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Sample records for anti-cyclic citrullinated peptide-positive

  1. Strong combined gene-environment effects in anti-cyclic citrullinated peptide-positive rheumatoid arthritis

    DEFF Research Database (Denmark)

    Pedersen, Line Merete Blak; Jacobsen, Søren; Garred, Peter;

    2007-01-01

    To study the role of shared epitope (SE) susceptibility genes, alone and in combination with tobacco smoking and other environmental risk factors, for risk of subtypes of rheumatoid arthritis (RA) defined by the presence or absence of serum antibodies against cyclic citrullinated peptides (CCPs)....

  2. Anti-cyclic citrullinated peptide (anti-CCP) antibodies with brucellosis.

    Science.gov (United States)

    Kisacik, Bunyamin; Dag, Muhammet Said; Pehlivan, Yavuz; Ugurlu, Kenan; Mercan, Ozge Kaya; Aydinli, Musa; Devay, Seda Duygulu; Sayarlioglu, Mehmet; Onat, Ahmet Mesut

    2014-06-01

    Anti-cyclic citrullinated peptide (anti-CCP) was positive in 11.5 % and rheumatoid factor was positive in 8.8 % of the patients with Brucella. After a comparative evaluation, we have found out that there was not a statistical significance concerning the anti-CCP levels between the patients with brucellosis and healthy control.

  3. Anti-Cyclic Citrullinated Peptide Antibody-Positive Meningoencephalitis in the Preclinical Period of Rheumatoid Arthritis

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    Tomoya Shibahara

    2016-07-01

    Full Text Available Rheumatoid meningoencephalitis (RM is a rare complication of rheumatoid arthritis (RA. This report describes a 63-year-old man with complaints of high-grade fever, headache, and vomiting for several days before admission. Both his serum and cerebrospinal fluid were positive for anti-cyclic citrullinated peptide (CCP antibody and rheumatoid factor, and contrast-enhanced fluid-attenuated inversion recovery magnetic resonance imaging (MRI showed abnormal gadolinium enhancement of the meninges and high-intensity lesions in the subarachnoid spaces. The patient was diagnosed with RM despite lack of signs suggesting RA. His symptoms drastically improved with intravenous infusion of high-dose methylprednisolone. Two months later, he developed RA. The findings in this patient suggest that RM could develop prior to the onset of RA. Anti-CCP antibody and MRI findings may be useful for the diagnosis of RM, regardless of RA history.

  4. The prognostic value of anti-cyclic citrullinated peptide antibody in patients with recent-onset rheumatoid arthritis

    NARCIS (Netherlands)

    Kroot, EJJA; de Jong, BAW; van Leeuwen, MA; Swinkels, H; van den Hoogen, FHJ; van't Hof, M; van de Putte, LBA; van Rijswijk, MH; van Venrooij, WJ; van Riel, PLCM

    2000-01-01

    Objective. To study the predictive value of anti-cyclic citrullinated peptide antibody (anti-CCP) in patients with recent-onset rheumatoid arthritis (RA). Methods. Outcome in terms of physical disability (Health Assessment Questionnaire) and radiologic damage (modified Sharp method) over 3-year and

  5. Profiling anti-cyclic citrullinated peptide antibodies in patients with juvenile idiopathic arthritis

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    Tebo Anne E

    2012-08-01

    Full Text Available Abstract Background Anti-citrullinated protein/peptide antibodies (ACPA, have high specificity for rheumatoid arthritis (RA. Some children with juvenile idiopathic arthritis (JIA, phenotypically resemble RA and test positive for rheumatoid factor (RF a characteristic biomarker of RA. We investigated the prevalence of ACPA and its relationship to other serologic markers associated with RA in a well-characterized JIA cohort. Methods Cases were 334 children with JIA, 30 of whom had RF + polyarticular JIA. Sera from all cases and 50 healthy pediatric controls were investigated by ELISA at a single time point for anti-cyclic citrullinated peptide (anti-CCP IgG, RF IgM, IgA and IgG, anti-RA33 IgG, and antinuclear antibodies (ANA. Comparisons between cases and controls were made using Chi-square or Fisher exact tests and T-tests. Results The prevalence of RF was 8% among controls, and 12% among cases (ns. The prevalence of ACPA was 2% in controls and 14.3% in cases (OR 8.2, p Conclusions ACPAs are detectable in 14% of children with JIA. Children with positive ACPA but negative RF are frequent, and may define a distinct subset of children with JIA. ACPA testing should be included in the classification of JIA.

  6. Anti-cyclic citrullinated peptide antibodies in children with Juvenile Idiopathic Arthritis

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    Hamooda, Mohamed; Fouad, Hala; Galal, Nermeen; Sewelam, Nadia; Megahed, Dina

    2016-01-01

    Aim The purpose of present study was to access the prevalence of anti-cyclic citrullinated peptide (anti-CCP) antibodies in children with Juvenile Idiopathic Arthritis (JIA), and to investigate the clinical significance and diagnostic value of the anti-CCP antibodies in correlation with age, sex & activity. Methods This case-control study was performed on 50 patients with JIA in addition to 40 sex and age-matched children as a control group. The participants were recruited from rheumatology Outpatient Clinic of Cairo University Specialized Pediatric Hospital. Patients were subjected to full history taking, clinical examination, routine laboratory investigations and x-rays on involved joints. Both patients and controls underwent assay of anti-CCP antibodies by AxSYM Anti-CCP IgG Microparticle Enzyme Immunoassay (MEIA) which is a semi-quantitative determination of the IgG class of autoantibodies specific to cyclic citrullinated peptide (CCP) in patients’ serum or plasma. Data were analyzed using Mann-Whitney U test, ANOVA, and independent-samples t-test by SPSS version 15. Results Anti-CCP positivity was identified amongst patients with JIA, particularly those JIA patients experiencing RF positive polyarticular disease onset. Above all, it is important that anti-CCP positivity and bone erosions, degree of joint damage, and ESR levels were significantly correlated. Conclusion Anti-CCP could be utilized as a valuable marker in the polyarticular form of JIA to direct early, and could be aggressive therapeutic intervention. PMID:27790341

  7. Anti-Cyclic Citrullinated Peptide (Anti-CCP) and Anti-Mutated Citrullinated Vimentin (Anti-MCV) Relation with Extra-Articular Manifestations in Rheumatoid Arthritis

    OpenAIRE

    2014-01-01

    We evaluated the association between anti-cyclic citrullinated peptide antibodies (anti-CCP) and anti-mutated citrullinated vimentin antibodies (anti-MCV) with the presence of extra-articular (ExRA) manifestations in 225 patients with rheumatoid arthritis (RA). Ninety-five patients had ExRA and 130 had no ExRA. There was no association of anti-CCP and anti-MCV levels with the presence of ExRA as total group (P = 0.40 and P = 0.91, resp.). Making an analysis of individual manifestations, rheum...

  8. RHEUMATOID FACTOR AND ANTI-CYCLIC CITRULLINATED PEPTIDE ANTIBODIES IN PATIENTS WITH PSORIATIC ARTHRITIS

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    V. V. Badokin

    2011-01-01

    Full Text Available Objective: to define the clinical value of rheumatoid factor (RF and anti-cyclic citrullinated peptide antibodies (anti-CCP in early psori- atic arthritis (PA. Subjects and methods. Fifty-six patients (32 females and 24 males with early PA with a mean duration of 12±6.7 months were studied. The examinees' age ranged from 18 to 76 years (mean age 44±15.5 years. Mean psoriasis duration was 12.5±2.2 years. RF IgM was determined using a high-sensitive nephelometric method on a BN Pro-Spec analyzer (Siemens, Germany and serum anti-CCP concentra- tions were measured by immunochemiluminescence on a COBAS e411 analyzer (Roche, Switzerland. Group 1 included 10 patients with anti-CCP and/or RF (a study group; Group 2 comprised 46 patients without anti-CCP and RF (a control group. Results. There was anti-CCP in 7 (12.5% of the patients with early PA, RF in 8 (14.3%, both of them in 5 (9%. The study group had a severer course of PA accompanied by polyarthritis, inflamed distal interphalangeal joints, axial arthritis, dactylitis, enthesitis, and, in some cases spondylitis and sacroiliitis. In groups 1 and 2, the number of tender joints was 17.6±4 and 10±1.5, respectively (p = 0.04; that of swollen ones, 12.6±1.5 and 7.0±1.1 (p = 0.02; DAS28 index, 5.9±1.7 and 4.5±1.5 (p = 0.02; ESR, 34.5±5.9 and 22±2.3 (p = 0.04, high-sensitive C reactive protein, 70±25.3 and 24.9±5.0 (p = 0.06; and Sharp ratio, 68.7±14.3 and 21.3±3.8 (p < 0.004. Conclusion. In patients with early PA, anti-CCP and RF were encountered with an approximately equal frequency; at the same time, they were associated with polyarthritis, high disease activity, and an erosive process. 

  9. Anti-cyclic Citrullinated Peptide Antibody (Anti-CCP and Diagnostic Value for Rheumatoid Arthritis

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    Mehmet Agilli

    2014-02-01

    Full Text Available Rheumatoid arthritis (RA is an inflammatory multisystem disease of unknown etiology characterized by chronic destructive synovitis. It and #8217;s prevalence is about 1% all over the world. Serologic markers are also important beside some clinical situations upon RA diagnosis. Today, the most commonly used laboratory test is rheumatoid factor (RF in patients with suspected RA. RF is sensitive but not a specific biomarker for diagnosing RA. Early diagnosis of RA is essential to prevent of progressive joint damage. In recent years, anticyclic citrullinated peptide/protein antibody (anti-CCP attracts the attention as a remarkable biomarker for early diagnosis. Anti-CCP which is a family of anti-citrullinated protein antibodies (ACPA family, showed quite satisfactory specificity in the diagnosis of RA. Due to the prescence of ACPA was included to 2010 RA diagnostic criteria, in a manner of speaking, importance of anti-CCP was registered. [TAF Prev Med Bull 2014; 13(1.000: 83-88

  10. Association analysis of anti-Epstein-Barr nuclear antigen-1 antibodies, anti-cyclic citrullinated peptide antibodies, the shared epitope and smoking status in Brazilian patients with rheumatoid arthritis

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    Michel Alexandre Yazbek

    2011-01-01

    Full Text Available INTRODUCTION: Epstein-Barr virus exposure appears to be an environmental trigger for rheumatoid arthritis that interacts with other risk factors. Relationships among anti-cyclic citrullinated peptide antibodies, the shared epitope, and smoking status have been observed in patients with rheumatoid arthritis from different populations. OBJECTIVE: To perform an association analysis of anti-Epstein-Barr nuclear antigen-1 antibodies, anti-cyclic citrullinated peptide antibodies, the shared epitope, and smoking status in Brazilian patients with rheumatoid arthritis. METHODS: In a case-control study, 140 rheumatoid arthritis patients and 143 healthy volunteers who were matched for age, sex, and ethnicity were recruited. Anti-Epstein-Barr nuclear antigen-1 antibodies and anti-cyclic citrullinated peptide antibodies were examined using an enzyme-linked immunosorbent assay, and shared epitope alleles were identified by genotyping. Smoking information was collected from all subjects. A comparative analysis of anti-Epstein-Barr nuclear antigen-1 antibodies, anti-cyclic citrullinated peptide antibodies, the shared epitope, and smoking status was performed in the patient group. Logistic regression analysis models were used to analyze the risk of rheumatoid arthritis. RESULTS: Anti-Epstein-Barr nuclear antigen-1 antibodies were not associated with anti-cyclic citrullinated peptide antibodies, shared epitope alleles, or smoking status. Anti-cyclic citrullinated peptide antibody positivity was significantly higher in smoking patients with shared epitope alleles (OR = 3.82. In a multivariate logistic regression analysis using stepwise selection, only anti-cyclic citrullinated peptide antibodies were found to be independently associated with rheumatoid arthritis (OR = 247.9. CONCLUSION: Anti-Epstein-Barr nuclear antigen-1 antibodies did not increase the risk of rheumatoid arthritis and were not associated with the rheumatoid arthritis risk factors studied. Smoking

  11. Circulating anti-cyclic citrullinated peptide antibody in patients with rheumatoid arthritis and chronic obstructive pulmonary disease.

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    Yang, Deng-Ho; Tu, Chuan-Chou; Wang, Shou-Cheng; Wei, Cheng-Chung; Cheng, Ya-Wen

    2014-07-01

    Anti-cyclic citrullinated peptide (anti-CCP) antibody is highly specific for diagnosing rheumatoid arthritis (RA). Cigarette smoking is a lifestyle and environmental factor associated with anti-CCP production and is strongly associated with chronic obstructive pulmonary disease (COPD). This study assessed levels of anti-CCP antibodies and rheumatoid factor (RF) among patients with RA and COPD. The study sample comprised 63 patients with RA and 70 patients with COPD, all of whom underwent assessment of anti-CCP antibody and RF levels. Testing revealed that 54.2% of RA patients and 0% of COPD patients were positive for anti-CCP antibodies. Additionally, 82.5% of RA patients and 42% of COPD patients were positive for RF. Among RA patients, levels of anti-CCP antibodies were higher among smokers than among nonsmokers (242.7 ± 128.3 vs. 68.1 ± 112.1, P < 0.001). COPD patients had low titers of RF but were negative for anti-CCP antibodies. The presence of anti-CCP antibodies was a reliable serologic marker in RA diagnosis and was associated with cigarette smoking.

  12. Anti-Cyclic Citrullinated Peptide (Anti-CCP and Anti-Mutated Citrullinated Vimentin (Anti-MCV Relation with Extra-Articular Manifestations in Rheumatoid Arthritis

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    Laura Gonzalez-Lopez

    2014-01-01

    Full Text Available We evaluated the association between anti-cyclic citrullinated peptide antibodies (anti-CCP and anti-mutated citrullinated vimentin antibodies (anti-MCV with the presence of extra-articular (ExRA manifestations in 225 patients with rheumatoid arthritis (RA. Ninety-five patients had ExRA and 130 had no ExRA. There was no association of anti-CCP and anti-MCV levels with the presence of ExRA as total group (P=0.40 and P=0.91, resp.. Making an analysis of individual manifestations, rheumatoid nodules were associated with positivity for rheumatoid factor (RF; (P=0.01, anti-CCP (P=0.048, and anti-MCV (P=0.02. Instead, RF, anti-CCP, or anti-MCV were not associated with SS, chronic anemia, or peripheral neuropathy. Levels of anti-CCP correlated with the score of the Health Assessment Questionnaire-Disability Index (HAQ-Di (r=0.154, P=0.03, erythrocyte sedimentation rate (ESR; (r=0.155, P=0.03, and RF (P=0.254, P<0.001, whereas anti-MCV titres only correlated with RF (r=0.169, P=0.02. On adjusted analysis, ExRA was associated with longer age (P=0.015, longer disease duration (P=0.007, higher DAS-28 score (P=0.002, and higher HAQ-DI score (P=0.007, but serum levels of anti-CCP and anti-MCV were not associated. These findings show the need to strengthen the evaluation of the pathogenic mechanisms implied in each specific ExRA manifestation.

  13. Anti-Cyclic Citrullinated Peptide (Anti-CCP) and Anti-Mutated Citrullinated Vimentin (Anti-MCV) Relation with Extra-Articular Manifestations in Rheumatoid Arthritis

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    Gonzalez-Lopez, Laura; Rocha-Muñoz, Alberto Daniel; Ponce-Guarneros, Manuel; Flores-Chavez, Alejandra; Salazar-Paramo, Mario; Cardona-Muñoz, Ernesto German; Fajardo-Robledo, Nicte Selene; Zavaleta-Muñiz, Soraya Amali; Garcia-Cobian, Teresa; Gamez-Nava, Jorge Ivan

    2014-01-01

    We evaluated the association between anti-cyclic citrullinated peptide antibodies (anti-CCP) and anti-mutated citrullinated vimentin antibodies (anti-MCV) with the presence of extra-articular (ExRA) manifestations in 225 patients with rheumatoid arthritis (RA). Ninety-five patients had ExRA and 130 had no ExRA. There was no association of anti-CCP and anti-MCV levels with the presence of ExRA as total group (P = 0.40 and P = 0.91, resp.). Making an analysis of individual manifestations, rheumatoid nodules were associated with positivity for rheumatoid factor (RF); (P = 0.01), anti-CCP (P = 0.048), and anti-MCV (P = 0.02). Instead, RF, anti-CCP, or anti-MCV were not associated with SS, chronic anemia, or peripheral neuropathy. Levels of anti-CCP correlated with the score of the Health Assessment Questionnaire-Disability Index (HAQ-Di) (r = 0.154, P = 0.03), erythrocyte sedimentation rate (ESR); (r = 0.155, P = 0.03), and RF (P = 0.254, P < 0.001), whereas anti-MCV titres only correlated with RF (r = 0.169, P = 0.02). On adjusted analysis, ExRA was associated with longer age (P = 0.015), longer disease duration (P = 0.007), higher DAS-28 score (P = 0.002), and higher HAQ-DI score (P = 0.007), but serum levels of anti-CCP and anti-MCV were not associated. These findings show the need to strengthen the evaluation of the pathogenic mechanisms implied in each specific ExRA manifestation. PMID:24804270

  14. Significance of Anti-cyclic Citrullinated Peptide Autoantibodies in Immune-mediated Inflammatory Skin Disorders with and without Arthritis

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    Grover, Chander; Kashyap, Bineeta; Daulatabad, Deepashree; Dhawan, Amit; Kaur, Iqbal R

    2016-01-01

    Background: Anti-cyclic citrullinated peptides (CCPs) are autoantibodies directed against citrullinated peptides. Rheumatoid factor (RF), an antibody against the Fc portion of IgG, is known to form immune complexes and contribute to the etiopathogenesis of various skin disorders. C-reactive protein (CRP), an acute-phase protein, increases following secretion of interleukin-6 from macrophages and T cells. Anti-CCP, RF, and CRP are well-established immune-markers, their diagnostic potential in immune-mediated skin disorders remains less widely studied. Aims and Objectives: To determine the correlation between anti-CCP, RF, and CRP in immune-mediated inflammatory skin diseases. Materials and Methods: About 61 clinically diagnosed cases of various immune-mediated skin diseases (psoriasis [n = 38], connective tissue diseases such as systemic lupus erythematosus and systemic sclerosis [n = 14], and immunobullous disorders including pemphigus vulgaris and pemphigus foliaceus [n = 9]) were included in the study. These patients were subclassified on the basis of presence or absence of arthritis. Arthritis was present in nine cases of psoriasis and seven connective tissue disorder patients. Detection of serum anti-CCP was done using enzyme-linked immunosorbent assay, whereas CRP and RF levels were detected using latex agglutination technique. Results: Of the 61 specimens, 14.75% had elevated serum anti-CCP levels. RF and CRP levels were elevated in 18.03% and 39.34% specimens, respectively. RF was elevated in 13.16% of inflammatory and 42.88% of connective tissue disorders, whereas anti-CCP was raised in 10.53% of inflammatory and 35.71% of connective tissue disorders. CRP positivity was highest in connective tissue disorders (50%), followed by 39.47% in inflammatory and 22.22% in immunobullous conditions. In none of the immunobullous patients, anti-CCP or RF levels were found to be elevated. Association of the presence of arthritis with elevated anti-CCP was found to be

  15. Usefulness of anti-cyclic citrullinate peptide antibody determination in synovial fluid analysis of patients with rheumatoid arthritis

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    G. Valesini

    2011-09-01

    Full Text Available Objective: To assess the role of anti-cyclic citrullinated peptide (CCP antibody detection in synovial fluid (SF of RA patients compared to OA patients. Methods: We evaluated in 25 RA subjects and 14 OA patients, presenting a knee-joint effusion, the main clinical and laboratory parameters including the number of painful and/or swollen joints, Ritchie index, morning stiffness, ESR, CRP and analysis of SF obtained by therapeutic arthrocentesis. IgG anti-CCP (ELISA, rheumatoid factor (RF and total IgG (nephelometry method were measured in SF and paired serum samples. Results: We found anti-CCP antibodies and RF in 64% (16/25 and 60% (15/25 of RA sera, respectively; 72% (18/25 of RA patients were positive for anti-CCP antibodies or RF. We found a higher SF/serum ratio for anti-CCP (p<0.004 compared to that for total IgG. The calculation of anti-CCP concentration as IgG anti-CCP (units/total IgG (g L-1 revealed higher values in SF than in serum (p<0.046 in RA patients. Among these, correlation analysis showed that anti-CCP/total IgG values in SF correlated with the relative concentration of serum anti-CCP/total IgG (rs=0.842; p<0.00001 and serum anti-CCP antibody levels (rs=0.799; p<0.0001. We did not find any correlation between SF anti-CCP levels and the main characteristics of SF as well as the clinical or laboratory parameters. Conclusion: Our study give evidence for a preferential production of anti-CCP antibodies at RA joint level, confirming the pathogenetic role of these autoantibodies. Moreover, SF determination of anti-CCP, corrected for the total amount of the corresponding immunoglobulin, may be helpful as diagnostic tool in selected cases.

  16. Frequency and diagnostic significance of anti-cyclic citrullinated peptide antibodies (ACCP and anti-modified citrullinated vimentin antibodies (AMCV in children with early juvenile arthritis

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    S O Salugina

    2008-01-01

    Full Text Available Objective. To determine frequency of anti-cyclic citrullinated peptide antibodies (ACCP and anti-modified citrullinated vimentin antibodies (AMCV elevation and their diagnostic significance in children with early juvenile arthritis (JA. Material and methods. ACCP were evaluated in serum of 80 pts with early JA (36 girls, 44 boys, mean age 8,5±5,03 years, AMCV — in 85 pts with early JA (49 girls and 36 boys aged from 1,5 to 16 years (mean age 8,7±4,9 years. Disease duration in all children was less than 6 months. Control group included 54 grown up pts with early rheumatoid arthritis (RA, 27 - with undifferentiated arthritis (UDA and 37 conditionally healthy children. АССР was assessed by immuno-enzyme assay (IEA with commercial kits “Axis Shield Diagnostics" (Great Britain, upper normal limit 5,0 U/ml. AMCV was examined by IEA with commercial kits “Orgentec Diagnostics” (Germany, upper normal limit — 25 U/ml. Results. ACCP was elevated in 7 children with early JA (8,8%. Frequency was higher than in healthy children but lower than in grown up pts with early RA and comparable with UDA. In juvenile rheumatoid arthritis (JRA ACCP were more frequent than in juvenile chronic arthritis (JCA. Concentration was higher in rheumatoid factor (RF positive pts with polyarticular JA. AMCV level was elevated in in 23 (27,1% pts with early JA (more frequent than in healthy donors but less frequent than in grown up pts with early RA and UDA. AMCV was significantly more frequent in JRA than in JCA and in RF positive than in RF negative pts. AMCV concentration in JA was higher than in healthy children but lower than in grown up pts with RA. It was also higher in RF+ than RF- JA. ACCP and AMCV correlated with swollen joint count, tender joint count and RF. AMCV also correlated with ESR and CRP. Conclusion. In pts with early JA ACCP and AMCV are equally or more frequent than RF. In spite of low sensitivity they have high specificity for JRA in contrast

  17. Onset of polyarticular juvenile idiopathic arthritis with both anti-cyclic citrullinated peptide antibodies and rheumatoid factor in a 3-year-old girl

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    Yasui Kozo

    2012-12-01

    Full Text Available Abstract This report describes 3 year old girl with the unusual presentation of polyarticular juvenile idiopathic arthritis (JIA with anti-cyclic citrullinated peptide (anti-CCP antibodies and a positive rheumatoid factor (RF. She was initially treated with a nonsteroidal anti-inflammatory drug (NSAID; ibuprofen followed by methotrexate (MTX, 10 mg/m2/week and prednisolone (0.25 mg/kg/day, but these treatments were ineffective. Administration of tocilizumab, a humanized antihuman interleukin-6 receptor monoclonal antibody, promptly improved her clinical manifestations, and she has been in complete remission (DAS28

  18. The Diagnostic Utility of Anti-cyclic Citrullinated Peptide Antibodies, Matrix Metalloproteinase-3, Rheumatoid Factor, Erythrocyte Sedimentation Rate, and C-reactive Protein in Patients with Erosive and Non-erosive Rheumatoid Arthritis

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    O. Shovman

    2005-01-01

    Full Text Available Objective: To compare the diagnostic utility of laboratory variables, including matrix metalloproteinase-3 (MMP-3, anti-cyclic citrullinated peptide (CCP antibodies, rheumatoid factor (RF, erythrocyte sedimentation rate (ESR, and C-reactive protein (CRP in patients with erosive and non-erosive rheumatoid arthritis (RA.

  19. Anti-cyclic citrullinated peptide (CCP) antibody in patients with wood-smoke-induced chronic obstructive pulmonary disease (COPD) without rheumatoid arthritis.

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    Sigari, Naseh; Moghimi, Nasrin; Shahraki, Farhad Saber; Mohammadi, Shilan; Roshani, Daem

    2015-01-01

    Citrullination, a post-translational modification of proteins, is increased in inflammatory processes and is known to occur in smokers. It can induce anti-cyclic citrullinated peptide (CCP) antibodies, the most specific serologic marker for rheumatoid arthritis. Thus far, the incidence of autoimmunity in patients with wood-smoke-induced chronic obstructive pulmonary disease (COPD) resulting in anti-CCP production has not been examined. We hypothesise that anti-CCP antibody level in these patients should be higher than that in healthy subjects. A total of 112 non-rheumatoid arthritis patients, including 56 patients with wood-smoke-induced COPD and 56 patients with tobacco-induced COPD, and 56 healthy non-smoker controls were included. The serum anti-CCP antibody levels were measured and compared between the groups and against smoke exposure and clinical characteristics. The mean anti-CCP antibody levels in wood-smoke-induced COPD group were significantly higher than those in tobacco-induced COPD group (p = 0.03) and controls (p = 0.004). Furthermore, 8 (14.2 %) patients with wood-smoke-induced COPD, 4 (7.14 %) with tobacco-induced COPD and 2 (3.57 %) controls exceeded the conventional cut-off of anti-CCP antibody positivity. No relationship was found between the anti-CCP antibody level and age, gender, duration of disease, Pack-years of smoking, and duration of exposure to wood smoke. Moreover, correlations between anti-CCP antibodies and severity of airflow limitation, CAT scores, mMRC scores of dyspnoea, and GOLD staging of COPD severity were not significant. Wood-smoke-induced COPD could significantly increase the anti-CCP antibody level in non-rheumatoid arthritis patients when compared with that in patients with tobacco-induced COPD and healthy controls.

  20. Anti-Cyclic Citrullinated Peptide Antibodies and Severity of Interstitial Lung Disease in Women with Rheumatoid Arthritis

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    Ponce-Guarneros, Manuel; Mejía, Mayra; Juárez-Contreras, Pablo; Corona-Sánchez, Esther Guadalupe; Rodríguez-Hernández, Tania Marlen; Salazar-Páramo, Mario; Cardona-Muñoz, Ernesto German; Celis, Alfredo; González-Lopez, Laura

    2015-01-01

    Objective. To evaluate whether serum titers of second-generation anticyclic citrullinated peptide antibodies (anti-CCP2) are associated with the severity and extent of interstitial lung disease in rheumatoid arthritis (RA-ILD). Methods. In across-sectional study, 39 RA-ILD patients confirmed by high-resolution computed tomography (HRCT) were compared with 42 RA without lung involvement (RA only). Characteristics related to RA-ILD were assessed in all of the patients and serum anti-CCP2 titers quantified. Results. Higher anti-CCP2 titers were found in RA-ILD compared with RA only (medians 77.9 versus 30.2 U/mL, P < 0.001). In the logistic regression analysis after adjustment for age, disease duration (DD), smoke exposure, disease activity, functioning, erythrocyte sedimentation rate, and methotrexate (MTX) treatment duration, the characteristics associated with RA-ILD were higher anti-CCP2 titers (P = 0.003) and + RF (P = 0.002). In multivariate linear regression, the variables associated with severity of ground-glass score were anti-CCP2 titers (P = 0.02) and with fibrosis score DD (P = 0.01), anti-CCP2 titers (P < 0.001), and MTX treatment duration (P < 0.001). Conclusions. Anti-CCP2 antibodies are markers of severity and extent of RA-ILD in HRCT. Further longitudinal studies are required to identify if higher anti-CCP2 titers are associated with worst prognosis in RA-ILD. PMID:26090479

  1. Anti-Cyclic Citrullinated Peptide Antibodies and Severity of Interstitial Lung Disease in Women with Rheumatoid Arthritis

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    Alberto Daniel Rocha-Muñoz

    2015-01-01

    Full Text Available Objective. To evaluate whether serum titers of second-generation anticyclic citrullinated peptide antibodies (anti-CCP2 are associated with the severity and extent of interstitial lung disease in rheumatoid arthritis (RA-ILD. Methods. In across-sectional study, 39 RA-ILD patients confirmed by high-resolution computed tomography (HRCT were compared with 42 RA without lung involvement (RA only. Characteristics related to RA-ILD were assessed in all of the patients and serum anti-CCP2 titers quantified. Results. Higher anti-CCP2 titers were found in RA-ILD compared with RA only (medians 77.9 versus 30.2 U/mL, P<0.001. In the logistic regression analysis after adjustment for age, disease duration (DD, smoke exposure, disease activity, functioning, erythrocyte sedimentation rate, and methotrexate (MTX treatment duration, the characteristics associated with RA-ILD were higher anti-CCP2 titers (P=0.003 and + RF (P=0.002. In multivariate linear regression, the variables associated with severity of ground-glass score were anti-CCP2 titers (P=0.02 and with fibrosis score DD (P=0.01, anti-CCP2 titers (P<0.001, and MTX treatment duration (P<0.001. Conclusions. Anti-CCP2 antibodies are markers of severity and extent of RA-ILD in HRCT. Further longitudinal studies are required to identify if higher anti-CCP2 titers are associated with worst prognosis in RA-ILD.

  2. Relation of rheumatoid factor and anti-cyclic citrullinated peptide antibody with disease activity in rheumatoid arthritis: cross-sectional study.

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    Choe, Jung-Yoon; Bae, Jisuk; Lee, Hwajeong; Bae, Sang-Cheol; Kim, Seong-Kyu

    2013-09-01

    To analyze the association of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (anti-CCP) with non-remission and with disease activity measures in rheumatoid arthritis (RA). Cross-sectional study of consecutive RA patients. Non-remission was defined as a disease activity score (DAS28) ≥ 2.6 at study enrollment. The Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) were additionally measured. Serum titers of RF and anti-CCP were transformed into incremental levels (100/units) and log-transformed levels. Analysis of association with non-remission was done with logistic regression models, with and without adjustment for age, sex, disease duration, and corticoid use. Multiple regression models, raw and similarly adjusted, were used to measure the association of RF and anti-CCP with the disease activity measures. A total of 385 patients were included, of whom 286 (74 %) were not in remission. Log-transformed RF level was associated with an increased risk of non-remission after adjustment (OR = 1.32, 95 % CI 1.04-1.67). This association was especially evident in patients with less than 10 years of disease duration (OR = 1.51, 95 % CI 1.15-1.99) and in those using steroids (OR = 2.06, 95 % CI 1.22-3.48). Serum RF titers and log-transformed RF levels showed a small but significant association with DAS28 score (adjusted beta coefficients 0.002 and 0.18, respectively; both p ≤ 0.01), but neither with SDAI or CDAI nor with anti-CCP antibody. : Log-transformed RF levels might be associated with non-remission in RA, especially in patients with short disease duration or on steroids.

  3. Detection of anti-cyclic citrullinated peptide antibodies in patients with rheumatoid arthritis: the clinical significance%抗环瓜氨酸抗体检测在类风湿关节炎中的临床意义

    Institute of Scientific and Technical Information of China (English)

    殷健; 李婷; 包军; 徐沪济

    2011-01-01

    类风湿关节炎( rheumatoid arthritis,RA)是一种主要累及全身多关节的自身免疫性疾病.目前RA仍具有很高的关节致残率和病死率.早期诊断并进行积极治疗可有效减少关节畸形的可能.近年发现的抗瓜氨酸抗体( anti-citrullinated peptide antibodies,ACPA)可在关节破坏发生前即表现出阳性,该抗体与经典的类风湿因子(rheumatoid factor,RF)相比,在RA的诊断中具有相似的敏感性,但具有更高的特异性.研究发现抗环瓜氨酸抗体(anti-cyclic citrullinated peptide antibodies)在RA的早期诊断、预后判断等方面都有重要意义,并有流行病学证据显示其可能在RA的发病中扮演重要角色.%Rheumatoid arthritis (RA) is an autoimmune disease involving multiple joints, and currently it still leads to high disability rate of the joints and high mortality. Early diagnosis and treatment can effectively reduce joint deformities. The recently discovered anti-citrullinated peptide antibodiesC ACPA) can be detected before damage to the joints occurs. Compared with classical rheumatoid factor (RF) ACPA has higher specificity and similar sensitivity in diagnosing RA. Some studies have showned that anti-cyclic citrullinated peptide antibodies play an important role in the early diagnosis of RA and prediction of prognosis; epidemiological evidences also show that ACPA plays an important role on the pathogenesis of RA.

  4. Mannose-binding lectin gene polymorphisms are associated with disease activity and physical disability in untreated, anti-cyclic citrullinated peptide-positive patients with early rheumatoid arthritis

    DEFF Research Database (Denmark)

    Jacobsen, Søren; Garred, Peter; Madsen, Hans Ole;

    2009-01-01

    high producers (YA/YA). Anti-CCP was present in 93 patients (59%). High scores of disease activity, C-reactive protein-based DAS28 (p=0.02), and physical disability by HAQ (p=0.01) were associated with high MBL2 expression genotypes in a gene-dose dependent way, but only in anti-CCP-positive patients......OBJECTIVE: To study the association between polymorphisms in the mannose-binding lectin gene (MBL2) and disease activity, physical disability, and joint erosions in patients with newly diagnosed rheumatoid arthritis (RA). METHODS: Patients with early RA (n=158) not previously treated with disease...... activity by Disease Activity Score-28 (DAS28 score), physical disability by Health Assessment Questionnaire (HAQ) score, and erosive changes in hands and feet (Sharp-van der Heijde score). RESULTS: Eight patients were homozygous MBL2 defective (O/O), 101 belonged to an intermediate group, and 49 were MBL2...

  5. Prevalência de anticorpos contra peptídeos cíclicos citrulinados na artrite idiopática juvenil The prevalence of anti-cyclic citrullinated peptide antibodies in juvenile idiopathic arthritis

    Directory of Open Access Journals (Sweden)

    Sandra H. Machado

    2005-12-01

    Full Text Available OBJETIVOS: Avaliar a presença de anticorpos contra peptídeos cíclicos citrulinados em uma coorte de pacientes com artrite idiopática juvenil. MÉTODOS: A presença de anticorpos contra peptídeos cíclicos citrulinados foi avaliada por ensaio imunoenzimático (ELISA no soro de pacientes com artrite idiopática juvenil com idade inferior a 18 anos, acompanhados no ambulatório de reumatologia pediátrica do Hospital de Clínicas de Porto Alegre, com tempo de diagnóstico de doença de, no mínimo, 6 meses. Também foi estudada a presença do fator reumatóide IgM e do fator antinuclear em células Hep-2 RESULTADOS: Foram analisadas amostras séricas de 45 pacientes com artrite idiopática juvenil. A presença de títulos elevados de anticorpos contra peptídeos cíclicos citrulinados foi encontrada somente no soro de uma criança (2%, a qual apresentava quadro de poliartrite com fator reumatóide reagente. CONCLUSÕES: O anticorpo contra peptídeos cíclicos citrulinados pode ser detectado em crianças com artrite idiopática juvenil, mas em freqüência muito inferior aos adultos com artrite reumatóide. Torna-se importante avaliar se anticorpos contra peptídeos cíclicos citrulinados podem identificar os pacientes com artrite idiopática juvenil com potencial de evolução para artrite reumatóide do adulto.OBJECTIVES: To assess the presence of anti-cyclic citrullinated peptide antibodies in a cohort of patients with juvenile idiopathic arthritis. METHODS: Anti-cyclic citrullinated peptide antibodies was tested for with an enzyme linked immunoabsorbent assay (ELISA in serum samples of patients from the Hospital de Clínicas de Porto Alegre, all less than 18 years old and with previous diagnosis for at least 6 months. IgMRF (rheumatoid factor and antinuclear antibodies in Hep-2 cells were also assayed. RESULTS: Serum samples were analyzed from 45 patients. The presence of high levels of anti-cyclic citrullinated peptide antibodies was found

  6. Macrophage-inducible C-type lectin is associated with anti-cyclic citrullinated peptide antibodies-positive rheumatoid arthritis in men

    Institute of Scientific and Technical Information of China (English)

    WU Xin-yu; GUO Jian-ping; YIN Fang-rui; LU Xiao-lan; LI Ru; HE Jing; LIU Xu; LI Zhan-guo

    2012-01-01

    Background Macrophage-inducible C-type lectin (MINCLE) is an important member of C-type lectin superfamily,which has been shown evidence for susceptibility to arthritis in animal models.We aimed to investigate the possible association of MINCLE with rheumatoid arthritis (RA) susceptibility in Chinese Hart population.Methods Haplotypes from HapMap database (Chinese Hart Beijing,CHB) were used to select tag-single nucleotide polymorphism (SNP) (r2=0.8) residing in MINCLE gene.A total of 563 patients with RA and 404 healthy controls were TagMan genotyped for SNP rs10841845.Association analyses were performed on the whole data set and on RA subsets based on gender difference and the status of anti-cyclic citrullinated peptide (anti-CCP) antibody in RA patients.Association statistics were calculated by age and sex adjusted logistic regression.Results Overall,MINCLE SNP rs10841845 was not associated with susceptibility to RA.However,following anti-CCP stratification,rs10841845 GG genotypes conferred a significantly protective effects against anti-CCP-positive RA (OR 0.65,95% CI 0.430-0.995,P=0.048).Following gender stratification,SNP rs10841845 G allele appeared to insert its RA protective effect only in male patients,both at allele level (G vs.A OR 0.66,95% CI 0.46-0.93,P=0.018) and at genotype level (GG vs.AA+AG,OR 0.429,95% CI 0.20-0.95,P=0.036).Notably,the male RA protective effect of rs10841845 G allele was only seen in anti-CCP-positive RA (G vs.A:OR 0.64,95% CI 0.43-0.96,P=0.029; GG vs.AA+AG:OR 0.375,95% Cl 0.14-0.94,P=0.038).Furthermore,we observed a significant reduction of Disease Activity Score (DAS) 28 score (3.91±0.70 vs.5.66±0.31,P=0.022) and serum C-reactive protein levels (31.64±24.13 vs.91.80±12.02,P=0.012)in male anti-CCP-positive RA patients carrying rs10841845 GG genotype,compared with patients carrying AA+AG genotypes.Conclusions Our study provides the evidence for a gender specific association between MINCLE rs10841845 and RA

  7. Associação do anticorpo anticitrulina e gravidade da artrite reumatóide Association of anti-cyclic citrullinated peptide antibody and severe rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Aldifran Ferreira da Silva

    2006-06-01

    Full Text Available OBJETIVOS: Avaliar a associação do anticorpo antipeptídeo citrulinado cíclico (anti-CCP com distintos parâmetros clínicos, sorológicos e radiológicos. MÉTODOS: Anti-CCP e fator reumatóide (FR foram pesquisados no soro de 100 pacientes com artrite reumatóide (AR. A atividade da doença foi definida por meio de um índice combinado compreendendo cinco parâmetros: número de juntas inflamadas, número de juntas doloridas, rigidez matinal, escala visual analógica (EVA de dor e velocidade de hemossedimentação (VHS. A capacidade funcional foi medida pelo índice HAQ (Health Assessment Questionnaire e a classe funcional foi determinada mediante aplicação dos critérios revisados do American College of Rheumatology (ACR, de 1991. Erosão e pinçamento articular foram graduados pelo índice de Sharp modificado. A análise estatística empregou os testes do Qui-quadrado, Mann Whitney e Kruskal-Wallis. RESULTADOS: Nenhum dos dois anticorpos demonstrou associação significativa com atividade da doença, sexo, idade de início da doença, presença de nódulos subcutâneos e síndrome de Sjögren. A média de idade foi significativamente menor nos pacientes com AR anti-CCP positivos. A positividade para o FR e anti-CCP foi maior nos pacientes com AR com menos de 50 anos em comparação com os pacientes com mais de 50 anos. A AR de início recente (OBJECTIVE: Evaluate the association of Anti-Cyclic Citrullinated Peptide Antibody (anti-CCP with distinct clinic, serological and radiological parameters. METHODS: anti-CCP and rheumatoid factor (RF were determined in the serum of 100 patients with rheumatoid arthritis (RA. Disease activity was defined by means of a combined index with five parameters: number of swollen joints, number of painful joints, morning stiffness, pain visual analogue scale (VAS, and erythrocyte sedimentation rate (ESR. Functional capacity was measured by (Health Assessment Questionnaire HAQ index and the functional class

  8. 抗环瓜氨酸肽抗体在幼年特发性关节炎中的诊断意义%Significance of anti-cyclic citrullinated antibodies in Juvenile Idiopathic arthritis

    Institute of Scientific and Technical Information of China (English)

    刘小惠; 陈月; 刘建国; 蔡素芬; 邓宇虹

    2013-01-01

    Objective To investigate the anti-cyclic citrullinated peptide(anti-cyclic citrullinated petide) antibodies,anti-ker-atin antibodies(anti-keratin antibody,AKA) and anti-perinuclear factor antibody(antiperinuclear factor,APF) joint detection in the diagnosis of juvenile idiopathic arthritis in value. Methods 61 cases of children with JIA and 20 patients with other rheumatic diseases in children,40 cases of healthy children with three detection,and comparative analysis. Results Three testing positive indicators of children with JIA were significantly higher than normal,healthy children;the difference was statistically significant(P<0.01). In the group of children with JIA anti-CCP,AKA,APF a sensitivity of 55.73%,39.34%,26.23%,the sensitivity of anti-CCP was higher than antibodies AKA and APF;the difference was statistically significant (P<0.05). Conclusion Although the sensitivi-ty of anti-CCP antibodies in children with JIA is lower than the sensitivity of adults RA ,but the diagnosis of JIA has a higher sen-sitivity and specificity,especially for polyarticular and oligoarticular JIA diagnosis more valuable.%目的:探讨抗环瓜氨酸肽(anti-cyclic citrullinated petide)抗体、抗角蛋白抗体(anti-keratin antibody,AKA)和抗核周因子抗体(antiperinuclear factor,APF)联合检测在诊断幼年特发性关节炎中的价值。方法对61例JIA患儿与40例健康患儿进行3项检测,并进行比较分析。结果幼年特发性关节炎(juvenile idiopathic arthritis,JIA)患儿的3项检测指标阳性率均明显高于正常健康患儿,差异有统计学意义(P<0.01),在JIA组患儿中抗CCP、AKA、APF的敏感性分别为55.73%、39.34%、26.23%,抗CCP抗体的敏感性高于AKA和APF,差异有统计学意义(P<0.05)。结论抗CCP抗体在JIA患儿中的敏感性虽不及成人类风湿性关节炎(rheumatoid arthritis,RA),但对JIA的诊断仍具有较高的敏感性和特异性,特别是对多关

  9. The status of rheumatoid factor and anti-cyclic citrullinated peptide antibody are not associated with the effect of anti-TNFα agent treatment in patients with rheumatoid arthritis: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Qianwen Lv

    Full Text Available OBJECTIVES: This meta-analysis was conducted to investigate whether the status of rheumatoid factor (RF and anti-cyclic citrullinated peptide (anti-CCP antibody are associated with the clinical response to anti-tumor necrosis factor (TNF alpha treatment in rheumatoid arthritis (RA. METHODS: A systemic literature review was performed using the MEDLINE, SCOPUS, Cochrane Library, ISI Web of Knowledge, and Clinical Trials Register databases, and Hayden's criteria of quality assessment for prognostic studies were used to evaluate all of the studies. The correlation between the RF and anti-CCP antibody status with the treatment effect of anti-TNFα agents was analyzed separately using the Mantel Haenszel method. A fixed-effects model was used when there was no significant heterogeneity; otherwise, a random-effects model was applied. Publication bias was assessed using Egger's linear regression and a funnel plot. RESULTS: A total of 14 studies involving 5561 RA patients meeting the inclusion criteria were included. The overall analysis showed that the pooled relative risk for the predictive effects of the RF and anti-CCP antibody status on patient response to anti-TNFα agents was 0.98 (95% CI: 0.91-1.05, p=0.54 and 0.88 (95% CI: 0.76-1.03, p=0.11, respectively, with I(2 values of 43% (p=0.05 and 67% (p<0.01, respectively. Subgroup analyses of different anti-TNFα treatments (infliximab vs. etanercept vs. adalimumab vs. golimumab, response criteria (DAS28 vs. ACR20 vs. EULAR response, follow-up period (≥ 6 vs. <6 months, and ethnic group did not reveal a significant association for the status of RF and anti-CCP. CONCLUSIONS: Neither the RF nor anti-CCP antibody status in RA patients is associated with a clinical response to anti-TNFα treatment.

  10. The evaluation of rheumatoid factor, anti-cyclic citrullinated peptide antibody and antikeratin antibody in the diagnosis of rheumatoid arthritis%RF、抗CCP抗体和AKA对类风湿性关节炎诊断的评价

    Institute of Scientific and Technical Information of China (English)

    胥国强; 杨佳佳; 蒲泽宴; 康清秀

    2013-01-01

    目的 评价类风湿因子(RF)、抗环瓜氨酸肽(CCP)抗体以及抗角蛋白抗体(AKA)在类风湿性关节炎(RA)诊断中的意义.方法 对177例确诊为RA患者的上述3项指标进行回顾分析.RF、抗CCP抗体和AKA分别用速率散射比浊法、酶联免疫吸附法(ELISA)和间接免疫荧光法(ⅡF)检测.应用x2检验和Pearson相关分析,比较3种抗体在RA诊断中的价值及相关性,并讨论RF、抗CCP抗体与新诊断标准评分的关系.结果 RF、抗CCP抗体和AKA对RA诊断的灵敏度分别是77.40%、64.97%和21.47%;3种抗体中任一抗体阳性的联合检测对RA诊断的灵敏度为85.88%,任2种抗体阳性的灵敏度为58.76%,3种抗体平均阳性的灵敏度为19.21%.抗CCP抗体和AKA在6个不同RF水平组的阳性率均有显著性差异(P<0.05),其中抗CCP抗体阳性率在RF阳性各组与阴性组之间差异显著(P<0.01),并与RF呈正相关(r=0.339,P=0.000);而AKA阳性率在RF阳性各组与阴性组之间无显著性差异(P>0.01),仅在RF值500~1 000 U/mL组的阳性率显著高于RF<20 U/mL组(x2=16.485,P=0.000),AKA与RF呈正相关(r=0.184,P=0.014).抗CCP抗体与AKA呈正相关(r=0.326,P=0.000).2010年ACR/EULAR分类标准评分大于或等于6分在6个不同RF水平组的阳性率无显著性差异(x2 =8.547,P=o.129),且与RF相关(r=0.199,P=0.005);而抗CCP抗体与RA评分不相关(r=0.123,P=0.103).结论 RF、抗CCP抗体和AKA均可作为RA血清学诊断指标,三者两两相关,前两者灵敏度较高,联合检测有助于RA的早期诊断.%Objective To explore the significance of rheumatoid factor(RF),anti-cyclic citrullinated peptide(anti-CCP) antibody and anti keratin antibody(AKA) in the diagnosis of Rheumatoid Arthritis(RA).Methods 177 patients with RA,who had these three tests,were analyzed basing on retrospectively available data.RF,anti-CCP antibody and AKA were respectively detected by nephelometry,Enzyme linked immunosorbent assay(ELISA) and

  11. Rheumatoid factor and anti-cyclic citrullinated peptide antibodies Clinical application of combined detection%类风湿因子与抗环瓜氨酸肽抗体联合检测的临床应用价值

    Institute of Scientific and Technical Information of China (English)

    李韧; 袁斌; 张娟

    2013-01-01

    Objective To investigate the analysis of rheumatoid factor and anti-citrulline antibody combined detection for the clinical application value. Methods Using enzyme-linked immunosorbent assay(ELISA method) to our hospital for the treatment of 150 cases of rheumatoid arthritis(RA) patients(A group), 28 cases of non-RA patients(B group) and 34 cases of healthy people(C group) were detected in serum, compared three groups of serum rheumatoid factor, anti-citrulline antibody for use alone or in combination for the diagnosis of rheumatoid arthritis sensitivity, specificity and so on. Results A group of people for anti-citrulline antibodies and rheumatoid factor positive rate than the B group, C group high(P <0.01); A group of rheumatoid factor alone sensitive than anti-citrulline antibodies for the anti-citrulline antibody specificity for the above rheumatoid factor, combined use of anti-citrulline conversion and rheumatoid factor antibodies, the detection sensitivity and negative predictive values, and Youden index for other than anti-citrulline antibodies or rheumatoid factor when used alone. Conclusion Anti-changer citrulline antibody and rheumatoid factor used in combination for the diagnosis of rheumatoid arthritis with good clinical practice.%目的探讨类风湿因子(RF)与抗环瓜氨酸肽抗体(抗CCP抗体)联合检测的临床应用价值。方法使用酶联免疫吸附法(ELISA 法)检测我院150例类风湿关节炎(RA)患者(A组)、28例非RA患者(B组)以及34例健康人群(C组)的血清,比较三组人群血清中RF、抗CCP抗体单独或联合使用对诊断RA的敏感性、特异性等。结果 A组人群抗CCP抗体和RF阳性率比B组、C组高(P<0.01);A组中单独使用RF的敏感性高于抗CCP抗体,抗CCP抗体的特异性高于RF,联合使用抗CCP抗体和RF,其检测敏感性、阴性预测值及约登指数等高于抗CCP抗体或RF单独使用。结论抗CCP抗体和RF联合使用用于诊断RA具有良好的临床应用价值。

  12. 抗CCP抗体和RF联检在RA诊疗中的临床价值%Clinical Value of Combined Detection of Serum Anti-Cyclic Citrullinated Peptide Antibody(Anti-CCP Ab)and Rheumatoid Factor(RF)in Diagnosis of Rheumatoid Arthritis

    Institute of Scientific and Technical Information of China (English)

    葛文亮

    2010-01-01

    目的:研究抗环瓜氨酸肽(anti-cyclic citrullinated peptide,Anti-CCP)(抗CCP抗体)和RF的检测在类风湿关节炎(RA)诊疗中的临床价值.方法:分别用酶联免疫吸附试验(ELISA)、BeckMan全自动蛋白分析仪同时检测早期RA组(病程<1年)42例,RA组(病程>1年)40例,非RA对照组40例患者血清抗CCP抗体和RF.结果:早期RA组、RA组的抗CCP抗体、RF阳性率显著高于非RA对照组(P<0.05)RA组抗CCP水平显著高于早期RA组(P<0.01),两者RF无显著差别(P>0.05).RA组与早期RA组CCP抗体与RF二者无相关性.结论:联检抗CCP抗体、RF有助于类风湿的早期诊断和预测病情的进展.

  13. The Diagnostic Value of Combinate Determination of Anti-cyclic Citrullinated Peptide Antibody and Rheumatoid Factor for the Rheumatoid Arthritis%抗CCP抗体与RF联合检测对类风湿性关节炎的诊断价值

    Institute of Scientific and Technical Information of China (English)

    游其勇; 易朝阳

    2011-01-01

    目的 探讨联合检测抗环瓜氨酸肽抗体(抗CCP抗体)及类风湿因子(RF)对类风湿关节炎(RA)的临床诊断价值.方法 分别用胶体金免疫层析法(GICA)、速率散射比浊法联合检测52例RA患者、37例非RA的自身免疫性疾病患者和15例正常人血清中抗CCP抗体和RF.结果 抗CCP抗体和RF联合检测的特异性、阳性预测值、阳性似然比、阴性似然比与任何单一项检测比较差异均有统计学意义(P<0.05).结论 联合检测抗CCP抗体和RF可明显提高类风湿关节炎的诊断率.%Objective To evaluate the clinical diagnosic value of anti - cyclic citrullinated peptide(anti- CCP) antibody and rheumatoid factor(RF) in patients with rhetrnatoid arthritis(PA).Methods Anti - CCP antibody was determined by quantitative GICA and rheumatoid factor by BNP nephelometer in 52 cases of PA ,37 cases of non - PA rhetrnatic diseases and 15 healths.Results The diagnosis specificity, positive predictive value, positive/negative likelihood ratios of combinate determination of anti - CCP antibodyand RF were significantly higher than either one.Conclusion The combinate determination of anti - CCP antibody and rheumatoid factor will remarkably improve the accuracy for diagnosis of RA.

  14. Rheumatoid factor and anti-cyclic citrullinated peptides antibody in diagnosing significance in patients with rheumatoid arthritis and their correlation with disease activity%类风湿因子和抗环瓜酸抗体联合检测对类风湿关节炎的诊断价值及与疾病活动的相关性

    Institute of Scientific and Technical Information of China (English)

    李雪飞; 武加标; 任敏

    2011-01-01

    目的:比较类风湿因子(RF)和抗环瓜酸抗体(抗CCP抗体)在类风湿关节炎(RA)诊断及预测疾病活动性中的价值.方法:采用酶联免疫吸附法(ELISA)、速率散射比浊法检测RF和抗CCP抗体,比较它们单独或联合诊断RA的价值,分析RF和抗CCP抗体与疾病活动性的相关性.结果:RF和抗CCP抗体诊断RA的敏感性分别为81.5%和95.4%,特异性分别为58.8%和95.6%,联合诊断RA特异性增高;RF和抗CCP抗体均与C反应蛋白、红细胞沉降率显著相关.结论:RF联合抗CCP抗体应用可进一步提高RA的诊断准确性,RF和抗CCP抗体与RA疾病活动性密切相关.%Objective: To evaluate the diagnostic significance through detecting rheumatoid factor(RF-IgM) and anti-cyclic citrullinated peptide (CCP) antibody and their correlation with disease activity.Methods: We used enzyme-linked immunosorbent assay and rate nephelometry to detect CCP and RF in patients with 65 RA, 68 nonRA.Results: The sensitivity for RF and anti-CCP were 81.5% and 95.4%, respectively, and the specificity were 58.8%, 95.6%, respectively.The specificity was increased by combining the tests.A significant correlation was found between RF, anti-CCP and CRP, ESR, respectively.Conclusion: The higher specificity was achieved by combining the tests.There was an association between RF, anti-CCP and disease activity.

  15. Significance of serum anti-cyclic citrullinated peptide antibodies in diagnosis of juvenile idiopathic arthritis%血清抗环瓜氨酸肽抗体水平对幼年特发性关节炎的诊断价值

    Institute of Scientific and Technical Information of China (English)

    郭桂梅; 何威逊; 朱光华; 王娟

    2013-01-01

    Objective To investigate the clinical significance of serum anti-cyclic citrullinated peptide ( anti-CCP) antibodies in diagnosis of juvenile idiopathic arthritis (JIA). Methods Serum anti-CCP antibodies of 68 children suspected of JIA with fever and arthritis of unknown causes were determined by ELISA, and comprehensive analysis was carried out with clinical data and related laboratory findings. Results Among the 68 children suspected of JIA, there were 10 cases of polyarticular JIA, 13 cases of systemic onset JIA, 8 cases of oligoarticular JIA and 13 cases of enthesitis related JIA. There were 11 cases of other rheumatoid diseases, 8 cases of neoplastic diseases of blood and 5 cases of infectious diseases. The serum anti-CCP level in children suspected of polyarticular JIA was significantly higher than those, in children suspected of systemic onset JIA, oligoarticular JIA and enthesitis related JIA (P <0.05). With serum anti-CCP ≥15.8 RU/mL as the positive threshold value, the area under receiver operating characteristic curve was 0.80, and the sensitivity and specificity in diagnosis of polyarticular JIA were 80% and 67. 6% respectively. The serum anti-CCP level was positively related to serum C-reaction protein level in children suspected of polyarticular JIA (r = 0. 764, P = 0. 017). Conclusion Serum anti-CCP can be used for the diagnosis of polyarticular JIA, and 15.8 RU/mL may be a suitable cut-off level.%目的 探讨血清抗环瓜氨酸肽(anti-CCP)抗体对幼年特发性关节炎(JIA)的诊断价值.方法 采用ELISA法对68例因不明原因发热和关节痛疑诊为JIA患儿进行血清anti-CCP抗体水平检测,并结合临床资料及相关实验室检查指标进行综合分析.结果 68例疑诊JIA患儿中,多关节型JIA 10例,全身型JIA 13例,少关节型JIA 8例,与附着点炎症相关的JIA 13例;其他风湿性疾病11例,血液与肿瘤疾病8例,感染性疾病5例.多关节型JIA患儿的血清anti-CCP水平显著高于全身

  16. Clinical value of anti-cyclic citrullinated peptide antibody combined with rheumatoid factor IgA and IgM for diagnosing rheumatoid arthritis%抗环瓜氨酸肽抗体联合类风湿因子IgA和IgM诊断类风湿关节炎的临床价值

    Institute of Scientific and Technical Information of China (English)

    邢雪梅; 李艳琴; 沈钢; 张军

    2014-01-01

    Objective To evaluate the value of the single or combined detection of anti-keratin antibody (AKA) ,anti-cyclic citrullinated peptide(CCP) antibody and rheumatoid factor (RF) for the diagnosis of rheumatoid arthritis(RA) .Methods Serum AKA ,anti-CCP antibody ,IgA-RF and IgM-RF were detected in 195 cases of RA and 195 controls .AKA was detected by using the indirect immunofluorescence method ,RF and anti-CCP antibody were detected by using ELISA .The specificity and sensitivity of those antibodies in RA were analyzed in the diagnosis of RA .The sensitivity ,specificity ,positive predictive value(PPV) and negative predictive value(NPV) of anti-CCP anti-body combined IgA-RF and/or IgM-RF for diagnosing RA were compared .Results The combination detection of an-ti-CCP antibody ,IgA-RF and IGM-RF had the highest specificity .The positive predictive value of anti-CCP antibody+ IgA-RF was 87 .59% ,which was significantly higher than 78 .49% of anti-CCP antibody + IGM-RF .Conclusion The combined detection of anti-CCP antibody and IgA /IgM-RF can significantly improve the diagnostic efficiency and reduce the misdiagnosis rate .%目的:评估单独或联合检测抗角蛋白抗体(AKA)、抗环瓜氨酸肽(CCP)抗体、类风湿因子(RF)IgA和 IgM 对类风湿关节炎(RA)的诊断价值。方法分别检测195例 RA 患者和195例对照者血清中的 AKA 、抗-CCP 抗体、IgA-RF 和 IgM-RF ,AKA 采用间接免疫荧光的方法检测,抗-CCP 抗体、IgA-RF 和 IgM-RF 采用酶联免疫吸附试验检测,分析上述抗体在 RA 中的敏感性和特异性,比较抗-CCP 抗体联合 IgA-RF 或(和)IgM-RF 诊断RA 的敏感性、特异性、阳性预测值和阴性预测值。结果抗-CCP 抗体、IgA-RF 和 IgM-RF 3项联合检测特异性最高。抗-CCP 抗体+ IgA-RF 的阳性预测值(87.59%)要明显高于抗-CCP 抗体+ IgM-RF(78.49%)。结论抗-CCP抗体与 IgA/IgM-RF 联合检测可以显著提高 RA 的诊断效能,降低误诊率。

  17. Diagnostic value evaluation of serum anti-cyclic citrullinated peptide antibody by contrast detection for rheumatoid arthritis%对比检测血清中抗环瓜氨酸肽抗体对类风湿关节炎的诊断价值评估

    Institute of Scientific and Technical Information of China (English)

    邓毅; 吴雪峰; 雷鸣; 吴建华

    2015-01-01

    Objective To investigate the diagnostic value of serum anti-cyclic citrullinated peptide (anti-CCP) antibody detection for rheumatoid arthritis (RA). Methods There were 86 RA patients (RA group), 44 non-RA patients (non-RA group), and 32 health physical examination people (control group). The level of anti-CCP antibody was detected by enzyme linked immunosorbent assay, and rheumatoid factor (RF) was detected by immunity transmission turbidity. The detection results of every group were compared. Results The Anti-CCP antibody and RF levels of the RA group were significantly higher than those in the non-RA group and the control group (P<0.05). The sensitivity of anti-CCP of the RA group was 69.77%, which was obviously lower than 81.40%of RF (P<0.05). Anti-CCP had higher diagnostic specificity and positive predicted value for RA than RF (P<0.05). The sensitivity, specificity, and negative predicted value of anti-CCP combined with RF were all significantly increased. It had a statistically significant difference from single detection (P<0.05). Conclusion Serum anti-CCP antibody detection has high specificity for the diagnosis of RA, and its combination with RF in detection can improve the accuracy and sensitivity of diagnosis.%目的:探讨检测血清中抗环瓜氨酸肽(抗-CCP)抗体对类风湿关节炎(RA)的诊断价值。方法收集RA患者86例(RA组)、非RA患者44例(非RA组)和健康体检者32例(对照组),分别采用酶联免疫吸附法检测抗-CCP抗体水平,并以免疫透射比浊法检测类风湿因子(RF),比较各组的检测结果。结果 RA组的抗-CCP抗体及RF水平均显著高于非RA组与对照组(P<0.05);RA组的抗-CCP灵敏度为69.77%,显著低于RF的灵敏度81.40%(P<0.05);抗-CCP对RA的诊断特异度与阳性预测值显著高于RF(P<0.05);抗-CCP联合RF的灵敏度、特异度及阴性预测值均获得显著提高,与单项检测相比,差异具有统计学意义(P<0.05)。结论血清抗-CCP抗体

  18. Combined detection rheumatoid factor、anti-cyclic citrullinated peptide antibody and Anti-keratin Antibody in the diagnosis of rheumatoid arthritis%类风湿因子、抗环瓜氨酸肽抗体与抗角蛋白抗体联合测定对类风湿性关节炎诊断价值

    Institute of Scientific and Technical Information of China (English)

    陈建平; 杨曙梅; 杨春兰; 祝文彩

    2014-01-01

    Objective:In the study, we clarity the combined detection of rheumatoid factor(RF)、anti-cyclic citrullinated peptide antibody(Anti-CCP) and anti-keratin antibody(AKA) in the diagnosis of rheumatoid arthritis(RA).Methods:132 patients with RA, 51 patients with other arthritis. RF was measured by immune rate nephelometry. Anti-CCP was measured by chemiluminescence immunoassay. Indirect Immunofluorescence assay was used to detect AKA.Results:The diagnostic sensitivity of RF for RA was 78.0% and the specificity was 64.7%. Whereas the diagnostic sensitivity of Anti-CCP for RA was 75.0% and the specificity was 88.2%. The diagnostic sensitivity of AKA for RA was 75.8% and the specificity was 86.3%. The combined detection of RF、Anti-CCP and AKA had a sensitivity of 63.6%% and the specificity of 96.1%.Conclusions:The results suggest that for diagnosis RA, the sensitivity of RF is better than Anti-CCP and AKA, whereas the specificity of Anti-CCP and AKA is better than RF. Combination of RF、Anti-CCP and AKA may be more helpful in early cliagnosis of RA patients.%目的:本文旨在探讨联合测定类风湿因子(RF)、抗环瓜氨酸肽抗体(Anti-CCP)及抗角蛋白抗体(AKA)在诊断类风湿性关节炎(RA)中的应用价值。方法:分别运用免疫速率散射比浊法、化学发光法及间接免疫荧光法检测132例类RA患者及51例非RA患者血清中的RF、Anti-CCP及AKA。结果:RF对RA敏感性为78.0%,特异性为64.7%,阳性预测值85.1%;Anti-CCP对RA敏感性为75.0%,特异性为88.2%,阳性预测值94.2%;AKA对RA敏感性为75.8%,特异性为86.3%,阳性预测值93.5%;RF、Anti-CCP及AKA联合检测诊断RA的敏感性为63.6%,特异性为96.1%,阳性预测值97.7%。结论: RF在RA诊断中敏感性较Anti-CCP及AKA高,但特异性较Anti-CCP及AKA低;RF、Anti-CCP及AKA联合检测的应用,更有助于类风湿关节炎的早期诊断。

  19. Early diagnostic and predictive value of antikeratin antibody, anti-cyclic citrullinated peptide antibody, and rheumatoid factors in juvenile idiopathic arthritis%4种自身抗体在幼年特发性关节炎早期诊断和预后评估中的意义

    Institute of Scientific and Technical Information of China (English)

    曾萍; 李丰; 唐盈; 刘海英; 关启鸿; 刘云锋; 曾华松

    2011-01-01

    目的 探讨免疫学指标抗角蛋白抗体(AKA)、抗环瓜氨酸肽(抗CCP)、类风湿因子(RF)-IgG、RF-IgM与各分型幼年特发性关节炎(JIA)患儿早期诊断和预后之间的关系.方法 收集76名经系统治疗并坚持随访治疗至少6个月的JIA患儿,在诊断初期进行AKA、抗CCP、RF.IgG、RF-IgM等免疫指标的检测,对不同亚型和预后作阳性检出率的比较,进行敏感性、特异性、相关危险度的统计学分析,并与49例健康儿童作对照比较.结果 多关节炎型组的AKA、抗CCP、RF-IgG、RF-IgM的阳性检出率与正常对照组比较差异有统计学意义,全身型、少关节型、附着点炎相关型的自身抗体阳性检出率与正常对照组差异无统计学意义.4种抗体的检测对多关节炎型组的分型敏感件依次为AKA>抗CCP,RF-IgG>RF-1gM;特异性依次为RF-IgM>AKA>RF-IgG>抗CCP.难治型JIA患儿的AKA阳性检出率与普通JIA患儿差异有统计学意义;相对危险度OR为3.514.结论 AKA、抗CCP、RF-IgG、RF-IgM在JIA不同亚型早期诊断中的作用有区别;AKA、抗CCP抗体的检测对JIA多关节炎型有较好的敏感性和特异性;AKA抗体的出现与难治型JIA相关,是否能作为成为多关节炎型早期诊断和预后评估的血清学指标,有待大样本的研究证实.%Objective To investigate the value of antikeratin antibody ( AKA ), anti-cyclic citrullinated peptide antibody ( anti-CCP ) and rheumatoid factor ( RF-IgG, RF-IgM ) in early diagnosis and prediction of juvenile idiopathic arthritis (JlA). Methods Seventy-six palients with JlA were enrolled and follow-up at least 6 months. The blood samples were collected to measure AKA, anti-CCP, RF-IgG, RF-IgM upon admission. The fiequency of positive AKA, anti-CCP, RF-IgG and RF-IgM in different subtype and refiractoriness were compared. Forty-nine healthy children were enrolled as control group. Results Compared with control group, the positive rates of AKA, anti-CCP,RF-IgG and RF

  20. Detection of anti-cyclic citrullinated peptide antibody in patients with psoriatic arthritis disease and its significance%抗环瓜氨酸肽抗体在银屑病关节炎患者中的检测及意义

    Institute of Scientific and Technical Information of China (English)

    潘虹; 李明

    2013-01-01

    目的 研究抗环瓜氨酸肽(CCP)抗体在银屑病关节炎(PsA)患者中的临床意义,探讨抗CCP抗体与PsA患者伴发关节炎、骨侵蚀破坏的关系及判断预后的意义.方法 采用酶联免疫吸附法,分别检测56例PsA患者血清的抗CCP 抗体水平,分析比较抗CCP 抗体与患者临床特征的关系.结果 抗CCP抗体在PsA患者中的阳性率为12.5%(7/56).抗CCP抗体在PsA五种临床分型中的阳性率分别为7.1%、21.4%、0%、0%、0%,抗CCP抗体阳性率在对称性多关节炎型PsA中明显高于其他四种PsA(P<0.05).抗CCP抗体阳性与阴性PsA患者临床及其他实验室指标比较结果显示:抗CCP抗体阳性组外周关节肿胀数、腕关节受累比例及红细胞沉降率(ESR)均高于抗CCP阴性组(P<0.05);在发病年龄、关节炎病程、阳性家族史、肘关节受累、腊肠指(趾)、腰骶痛和C反应蛋白(CRP)之间比较,差异无统计学意义.结论 12.5%的PsA患者体内存在抗CCP抗体;抗CCP抗体的出现与PsA患者多发性关节炎和骨侵蚀密切相关,对判断PsA关节炎的预后具有重要的临床价值.%Objective To study the clinical significance of anti-cyclic citrullinated peptide antibody( anti-CCP )in patients with psoriatic arthritis( PsA ), and to explore the correlation between anti-CCP and the complicated arthritis and bone erosion and also the significance of anti-CCP in the judgment of prognosis. Methods Enzyme linked immunosorbent assay was used to detect the anti-CCP level in the serum of 56 patients with PsA. The correlation between anti-CCP and the clinical features of those patients was analyzed. Results The positive rate of anti-CCP in patients with PsA was 12. 5 %( 7/56 ). The positive rate of anti-CCP in the five clinical classification of PsA was 7. 1% ,21.4% ,0% ,0% ,0% , respectively. The positive rate of anti-CCP in symmetry polyarthritis PsA was significantly higher that those in the other four kinds of PsA( P <0. 05 ). The

  1. 血清抗环瓜氨酸肽抗体对幼年特发性关节炎和成人类风湿关节炎诊断意义的比较%Diagnostic Value of Anti-Cyclic Citrullinated Peptide Antibodies in Juvenile Idiopahtic Arthritis and Adult Rheumatoid Arthritis

    Institute of Scientific and Technical Information of China (English)

    许峥; 黄小兰; 吴凤岐; 崔小岱; 黄峰; 张江林

    2011-01-01

    目的 比较分析幼年特发性关节炎(JIA)和成人类风湿关节炎(RA)患儿血清抗环瓜氨酸肽(CCP)抗体水平,探讨抗CCP抗体在JIA诊断中的价值和意义.方法 2009年2- 12月首都儿科研究所风湿免疫科确诊的JIA患儿72例.男33例,女39例;年龄(7.58 ±3.93)岁,全身型29例,少关节型27例,多关节型16例.同期在中国人民解放军总医院风湿科确诊的RA患者共65例.男14例,女51例;年龄(47.38±14.28)岁.健康对照组22例,为同期健康查体儿童.男10例,女12例;年龄(14.10±0.38)岁.选用英国Axis- shield Diagnostics Limit公司、德国欧蒙公司和上海富莼科芯公司生产的CCP抗体ELISA检测试剂盒,分别检测JIA患儿、RA患者和健康儿童血清CCP抗体水平.结果 英国Axis- shield Diagnostics Limit公司检测JIA患儿血清抗CCP抗体的阳性率为12.5%(9/72例),RA患者血清阳性率高达73.85%(48/65例),健康对照组无阳性(0/22例).RA患者血清抗CCP抗体阳性率显著高于JIA患儿(P<0.01),其中JIA组中多关节型阳性率31.25%(5/16例),少关节型阳性率14.8% (4/23例),全身型阳性率为0(0/29例),差异有统计学意义(P<0.001).另2家公司试剂盒检测结果.HA患儿血清抗CCP抗体的阳性率为15.3%(11/72例),RA患者血清阳性率为73.85% (48/65例),健康儿童无阳性.RA患者血清和健康儿童血清结果3家公司检测试剂盒完全一致.JIA患儿3种抗CCP抗体试剂盒检测结果之间差异无统计学意义(P>0.05).结论 ELISA方法检测血清抗CCP抗体水平较为稳定可靠,抗CCP抗体在JIA患儿中血清阳性率低于成人RA,抗CCP抗体在JIA各亚型分布差异显著,抗CCP抗体与多关节型相关.%Objective To evaluate the value of anti - cyclic citrullinated peptide antibodies (CCP) in the diagnosis of juvenile idiopathic arthritis (JIA) by analyzing results of detection from both JIA and adult rheumatoid arthritis ( RA) patients. Methods Seventy - two samples with

  2. 探讨抗环瓜氨酸肽抗体和类风湿因子对类风湿关节炎的诊断价值%Evaluate the value of anti -cyclic citrullinated peptide antibody and rheumatoid factor in the diagnosis of rheumatoid ar-thritis

    Institute of Scientific and Technical Information of China (English)

    莫巧璇; 张间霞; 张劲丰; 苏荣

    2013-01-01

    Objective Evaluate the diagnosis value of anti-cyclic citrullinated antibody (anti CCP antibody ) combined with rheumatoid factor (RF) for rheumatoid arthritis (RA) .Methods From May 2011 to September 2011 ,202 patients with rheumatic disease were selected ,including RA group ,and non-RA group .The quantitative chemiluminescence method to detect anti-CCP antibody ,immune turbidimetric assay to test RF ,and the results were analyzed statistically .Results The diagnostic test sensitivity of anti-CCP antibody ,specificity ,positive and the nega-tive predictive value were ,78% ,80 .6% ,82 .5% ,75 .8% ;RF :89 .9% ,52 .7% ,69% ,81 .7% .To analyze parallel and series test after anti-CCP antibody combined with RF detection ,The above indexes were ,parallel:93 .6% ,51 .6% , 69 .4% ,87 .3% ;series :74 .3% ,81 .7% ,82 .7% ,73 .1% ;The result of comparison in the RA group sensitivity :RF and anti-CCP antibody+RF series testing compared to individual CCP testing was significantly different (P<0 .05) , Beside ,Anti-CCP antibody+RF parallel testing and RF testing was significantly different (P<0 .05) .In the mean of anti-CCP antibody and RF positive results ,RA group and RA group was significantly difference .Conclusion Detec-tion of anti CCP antibody Combined with RF could provide clinical diagnosis for RA than individual testing .It could avoid leakage diagnosis caused by the low anti-CCP antibody sensitivity ,and misdiagnosis caused by RF low specifici-ty ,and provided the basis for clinical early diagnosis .%  目的探讨抗环瓜氨酸肽抗体(抗CCP抗体)、类风湿因子(RF)联合检测对类风湿关节炎(RA)的诊断价值。方法收集2011年5~9月RA和非RA患者202例,分别采用电化学发光法定量检测抗CCP抗体,免疫比浊法检测RF并进行统计学处理。结果抗CCP抗体诊断试验的灵敏度、特异性和阳性、阴性预测值分别为:78.0%、80.6%、82.5%、75.8%;RF为:89.9%、52.7

  3. Application of Rheumatoid Factor and Anti Cyclic Citrullinated Peptide Combined Detection in the Early Diagnosis of Rheumatoid Arthritis%类风湿因子及抗环瓜氨酸肽联合检测在类风湿关节炎早期诊断中应用

    Institute of Scientific and Technical Information of China (English)

    曾频频

    2015-01-01

    目的:探讨类风湿关节炎早期诊断。方法采用整群抽样的方法,选取2013年1月~2015年1月到医院就诊的46例类风湿性关节炎疑似患者和52例确诊类风湿性关节炎1年以上, ELISA法检测血清类风湿因子(RF)、抗环瓜氨酸肽(CCP)水平。结果 RF联和抗CCP抗体诊断疑似类风湿性关节炎,1年以上的类风湿性关节炎的诊断阳性率分别为71.15%和82.61%,明显高于RF和抗CCP抗体单独测试(<0.05)。结论 RF联和抗CCP抗体对早期诊断类风湿性关节炎,效果优于RA和CCP的两中检测单用。%Objective To investigate the ef ect of RF and CCP in the early diagnosis of rheumatoid arthritis. Methods Using cluster sampling, selected in April 2009 to 2012 April to the hospital for treatment of rheumatoid arthritis suspected patients and 46 cases of diagnosed 1 year more than 52 cases that were, by ELISA detection of serum rheumatoid factor (RF) and anti cyclic citrul inated peptide (CCP) levels. Results RF and anti CCP for suspected rheumatoid arthritis and diagnosed for more than 1 year rheumatoid arthritis diagnosis positive rate was 71.15% and 82.61%, was significantly higher than that of RF and anti CCP testing alone ( <0.05). Conclusion In the early diagnosis of RF, the ef ect of RA and CCP was bet er than that of the two.

  4. 抗环瓜氨酸肽抗体和类风湿因子联合检测对类风湿关节炎的临床价值%Clinical value of combined detection of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rhenmatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    阮艳秋; 殷明刚; 刘伟平

    2016-01-01

    目的:探讨抗环瓜氨酸肽(CCP)抗体和类风湿因子(RF)联合检测对类风湿关节炎(RA )诊治的临床价值。方法收集2013年11月至2014年12月该院182例风湿性疾病患者血清,采用 ELISA 方法检测 CCP 抗体,使用免疫透射比浊终点法检测 RF 。结果(1)182例患者中 RA 99例,CCP 中位数是4.20,RF 是392,非类风湿疾病患者83例,CCP 中位数是2.30,RF 是20.1,健康对照者106例,CCP 中位数是1.23,RF 是12.3。健康对照者与非风湿性疾病患者比较,差异无统计学意义(P>0.05);与 RA 患者比较,差异有统计学意义(P <0.01)。(2) CCP 抗体诊断 RA 的特异度是90.5%,RF 是79.2%,CCP 抗体高于 RF ,差异有统计学意义(P <0.05);CCP 抗体和 RF 联合检测诊断 RA 的灵敏度是71.4%,特异度是96.2%,高于单项检测(P<0.01)。 CCP 抗体和 RF 的灵敏度比较,差异无统计学意义(P>0.05)。 CCP 抗体特异度高于 RF 。结论 CCP 抗体和 RF 联合检测有助于 RA 的诊断和疗效监测,具有较高的临床意义。%Objective To estimate the clinical value of combined detection of anti‐cyclic citrullinated peptide (anti‐ccp)antibody and rheumatoid factor(RF) for the rhenmatoid arthritis .Methods Having collected the serum of 182 patients with rheumatic diseases in our hospital from November 2013 to December 2014 .With ELISA method measuring CCP and use immunity transmission turbidity to measurement RF ,the results were compared and ana‐lyzed .Results (1)Among the serum of 182 cases of patients ,99 cases were with rheumatoid arthritis ,with median of CCP 4 .20 and RF 392 .83 cases were with non‐rheumatoid diseases ,that with median of CCP 2 .30 and RF 20 .1 .106 cases of healthy control were ,with median of CCP 1 .23 and RF 12 .3 .Compared with non‐rheumatoid diseases ,P>0 .05 and the difference was of no statistical

  5. Meta-Analysis: Diagnostic Accuracy of Anti-Cyclic Citrullinated Peptide Antibody for Juvenile Idiopathic Arthritis

    Directory of Open Access Journals (Sweden)

    Yan Wang

    2015-01-01

    Full Text Available Objective. To estimate the diagnostic accuracy of the anti-CCP test in JIA and to evaluate factors associated with higher accuracy. Methods. Two investigators performed an extensive search of the literature published between January 2000 and January 2014. The included articles were assessed by the Quality Assessment of Diagnostic Accuracy Studies tool. The meta-analysis was performed using a summary ROC (SROC curve and a bivariate random-effect model to estimate sensitivity and specificity across studies. Results. The bivariate meta-analysis yielded a pooled sensitivity and specificity of 10% (95% confidence interval (CI: 6.0%–15.0% and 99.0% (95% CI: 98.0%–100.0%. The area under the SROC curve was 0.96. Sensitivity estimates were highly heterogeneous, which was partially explained by the higher sensitivity in the rheumatoid factor-positive polyarthritis (RF+ PA subtype (48.0%; 95% CI: 31.0%–65.0% than in the other subtypes (17.0%; 95% CI: 14.0%–20.0% and the higher sensitivity of the Inova assay (17.0%; 95% CI: 14.0%–20.%% than the other assays (0.05%; 95% CI: 2.0%–11.0%. Conclusions. Anti-CCP antibody test has a high specificity for the diagnosis of JIA. The sensitivity of this test is low and varies across populations but is higher in RF+ PA than in other JIA subtypes.

  6. THE CLINICAL AND DIAGNOSTIC VALUE OF ANTI-CYCLIC CITRULLINATED PEPTIDE ANTIBODIES IN EARLY JUVENILEARTHRITIS

    Directory of Open Access Journals (Sweden)

    S O Salugina

    2009-01-01

    Conclusion. In patients with early JA, the detection rate of CCPA is significantly higher than that in healthy children and comparable with that of RF. CCPAs have a high specificity for the diagnosis of JRA (an independent nosological entity within JA are a risk factor of polyarthritis. The early detection of CCPA alone or in combination with RF in JA patients may serve the basis for the early use of active, frequently aggressive therapy.

  7. How citrullination invaded rheumatoid arthritis research

    OpenAIRE

    van Venrooij, W J; Pruijn, G.J.M.

    2014-01-01

    Citrullination and the immune response to citrullinated proteins have been fundamental for the early recognition of rheumatoid arthritis by serological tests and a better understanding of its pathophysiology. In the first years after the initial publications, the focus was on the antibodies directed to citrullinated proteins. It is now realized that citrullinating enzymes and citrullinated proteins may have important roles in the maintenance of the inflammatory processes in the joints. There ...

  8. Interrelationships between glutamine and citrulline metabolism

    Science.gov (United States)

    This article analyzes the contribution of glutamine to the synthesis of citrulline and reviews the evidence that glutamine supplementation increases citrulline production. Glutamine supplementation has been proposed in the treatment of critically ill patients; however, a recent large multicenter ran...

  9. Evidence of fibrinogen as a target of citrullination in IgM rheumatoid factor-positive polyarticular juvenile idiopathic arthritis

    Directory of Open Access Journals (Sweden)

    Dehlendorf Amanda B

    2011-03-01

    Full Text Available Abstract Background Several studies have noted the significance of measuring anti-cyclic citrullinated peptide (CCP antibodies in juvenile idiopathic arthritis (JIA as an important indicator for destructive disease, as is the case in rheumatoid arthritis (RA. While the role of anti-CCP antibodies in RA and JIA has become better understood, the identity of the target proteins of this modification has remained elusive. In this study, we evaluated serum from patients with various subtypes of JIA to investigate the presence of anti-deiminated (citrullinated fibrinogen and anti-citrullinated α-enolase antibodies, and their association with RF and anti-CCP antibody isotypes. Methods Sera were obtained from 96 JIA patients, 19 systemic lupus erythematosus (SLE patients, and 10 healthy children. All sera were measured for antibodies against citrullinated and native fibrinogen and α-enolase by an enzyme linked immunosorbent assay (ELISA. In addition, all sera were assayed for anti-CCP antibody isotypes and rheumatoid factor (RF isotypes by ELISA. The relationship between anti-citrullinated fibrinogen and anti-α-enolase antibodies and disease activity and joint damage were also investigated. All results were correlated with clinical and laboratory parameters using Spearman's rho correlation coefficient. Multiple logistic regression analysis was utilized to identify which variables were associated with joint erosions and diagnosis of JIA. Results Thirty-one JIA patients (32% demonstrated reactivity to citrullinated fibrinogen and 9 (9% to citrullinated α-enolase. Reactivity to citrullinated fibrinogen and α-enolase was predominantly found in IgM RF-positive polyarthritis patients. Fourteen JIA patients reacted with native α-enolase and a higher percentage of SLE patients reacted with citrullinated α-enolase when compared to JIA patients. Anti-citrullinated fibrinogen antibodies correlated with the presence of IgG anti-CCP antibodies and IgA and Ig

  10. Citrullinated Chemokines in Rheumatoid Arthritis

    Science.gov (United States)

    2014-10-01

    Clavel C, Arnaud J, Nogueira L, et al. Epitopes of human fibrin recognized by the rheumatoid arthritis-specific autoantibodies to citrullinated... Clavel C, Chapuy-Regaud S, Al Badine R, Mechin MC, et al. Peptidyl arginine deiminase type 2 (PAD-2) and PAD-4 but not PAD-1, PAD-3, and PAD-6 are

  11. Hearing impairment in patients with rheumatoid arthritis: association with anti-citrullinated protein antibodies.

    Science.gov (United States)

    Lobo, Fabrício Silva; Dossi, Mario Orlando; Batista, Lígia; Shinzato, Márcia Midori

    2016-09-01

    It has been suggested that hearing impairment (HI) is one of the extra-articular features of rheumatoid arthritis (RA). Nevertheless, the prevalence and nature of HI in RA is still uncertain. The objectives were to study hearing function in patients with RA using audiometric tests and to examine whether HI correlates with autoantibodies. Hearing functions were investigated in 43 consecutive RA patients and 23 control subjects (less than 60 years old). Their sera were evaluated for the presence of rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), and anti-mutated citrullinated vimentin (anti-MCV) antibodies. HI was observed in 46.5 % of RA patients and in 30.4 % of control subjects, p = 0.32. HI was characterized as sensorineural in 80 and 85.7 % of RA patients and control subjects with HI, respectively, p = 1.00. RA patients had a worse hearing threshold for air conduction at 6 kHz in the right ear (p = 0.019) and had a decreased amplitude of otoacoustic emissions (OAEs) at 2 kHz bilaterally (p = 0.04) compared with control subjects. In the RA group, patients with and without HI were 80 and 34.78 % anti-CCP positive, respectively, p = 0.008. RA patients with and without HI were 85 and 43.48 % anti-MCV positive, respectively, p = 0.013. HI in RA patients was mainly sensorineural and was associated with anti-CCP and anti-MCV antibodies.

  12. Phenylglyoxal-Based Visualization of Citrullinated Proteins on Western Blots

    Directory of Open Access Journals (Sweden)

    Sanne M. M. Hensen

    2015-04-01

    Full Text Available Citrullination is the conversion of peptidylarginine to peptidylcitrulline, which is catalyzed by peptidylarginine deiminases. This conversion is involved in different physiological processes and is associated with several diseases, including cancer and rheumatoid arthritis. A common method to detect citrullinated proteins relies on anti-modified citrulline antibodies directed to a specific chemical modification of the citrulline side chain. Here, we describe a versatile, antibody-independent method for the detection of citrullinated proteins on a membrane, based on the selective reaction of phenylglyoxal with the ureido group of citrulline under highly acidic conditions. The method makes use of 4-azidophenylglyoxal, which, after reaction with citrullinated proteins, can be visualized with alkyne-conjugated probes. The sensitivity of this procedure, using an alkyne-biotin probe, appeared to be comparable to the antibody-based detection method and independent of the sequence surrounding the citrulline.

  13. Intestinal and hepatic metabolism of glutamine and citrulline in humans.

    Science.gov (United States)

    van de Poll, Marcel C G; Ligthart-Melis, Gerdien C; Boelens, Petra G; Deutz, Nicolaas E P; van Leeuwen, Paul A M; Dejong, Cornelis H C

    2007-06-01

    Glutamine plays an important role in nitrogen homeostasis and intestinal substrate supply. It has been suggested that glutamine is a precursor for arginine through an intestinal-renal pathway involving inter-organ transport of citrulline. The importance of intestinal glutamine metabolism for endogenous arginine synthesis in humans, however, has remained unaddressed. The aim of this study was to investigate the intestinal conversion of glutamine to citrulline and the effect of the liver on splanchnic citrulline metabolism in humans. Eight patients undergoing upper gastrointestinal surgery received a primed continuous intravenous infusion of [2-(15)N]glutamine and [ureido-(13)C-(2)H(2)]citrulline. Arterial, portal venous and hepatic venous blood were sampled and portal and hepatic blood flows were measured. Organ specific amino acid uptake (disposal), production and net balance, as well as whole body rates of plasma appearance were calculated according to established methods. The intestines consumed glutamine at a rate that was dependent on glutamine supply. Approximately 13% of glutamine taken up by the intestines was converted to citrulline. Quantitatively glutamine was the only important precursor for intestinal citrulline release. Both glutamine and citrulline were consumed and produced by the liver, but net hepatic flux of both amino acids was not significantly different from zero. Plasma glutamine was the precursor of 80% of plasma citrulline and plasma citrulline in turn was the precursor of 10% of plasma arginine. In conclusion, glutamine is an important precursor for the synthesis of arginine after intestinal conversion to citrulline in humans.

  14. Citrullination and Carbamylation in the Pathophysiology of Rheumatoid Arthritis

    OpenAIRE

    Pruijn, Ger J. M.

    2015-01-01

    The discovery that citrullination was crucial for the recognition of antigens by the most disease-specific class of autoantibodies in rheumatoid arthritis had a huge impact on studies aimed at understanding autoimmunity in this disease. In addition to the detailed characterization of anti-citrullinated protein antibodies, various studies have addressed the identity of citrullinated antigens. These investigations were facilitated by new methods to characterize these proteins, the analysis of p...

  15. Glutamine: precursor or nitrogen donor for citrulline synthesis?

    Science.gov (United States)

    Marini, Juan C; Didelija, Inka Cajo; Castillo, Leticia; Lee, Brendan

    2010-07-01

    Although glutamine is considered the main precursor for citrulline synthesis, the current literature does not differentiate between the contribution of glutamine carbon skeleton vs. nonspecific nitrogen (i.e., ammonia) and carbon derived from glutamine oxidation. To elucidate the role of glutamine and nonspecific nitrogen in the synthesis of citrulline, l-[2-(15)N]- and l-[5-(15)N]glutamine and (15)N-ammonium acetate were infused intragastrically in mice. The amino group of glutamine labeled the three nitrogen groups of citrulline almost equally. The amido group and ammonium acetate labeled the ureido and amino groups of citrulline, but not the delta-nitrogen. D(5)-glutamine also infused in this arm of the study, which traces the carbon skeleton of glutamine, was utilized poorly, accounting for only 0.2-0.4% of the circulating citrulline. Dietary glutamine nitrogen (both N groups) incorporation was 25-fold higher than the incorporation of its carbon skeleton into citrulline. To investigate the relative contributions of the carbon skeleton and nonspecific carbon of glutamine, arginine, and proline to citrulline synthesis, U-(13)C(n) tracers of these amino acids were infused intragastrically. Dietary arginine was the main precursor for citrulline synthesis, accounting for approximately 40% of the circulating citrulline. Proline contribution was minor (3.4%), and glutamine was negligible (0.4%). However, the glutamine tracer resulted in a higher enrichment in the ureido group, indicating incorporation of nonspecific carbon from glutamine oxidation into carbamylphosphate used for citrulline synthesis. In conclusion, dietary glutamine is a poor carbon skeleton precursor for the synthesis of citrulline, although it contributes both nonspecific nitrogen and carbon to citrulline synthesis.

  16. Optimizing the identification of citrullinated peptides by mass spectrometry

    DEFF Research Database (Denmark)

    Bennike, Tue; Lauridsen, Kasper B.; Olesen, Michael Kruse

    2013-01-01

    using digested synovial fluid samples from a rheumatoid arthritis patient. The samples were analyzed using liquid chromatography/tandem MS with electrospray ionization. Our in vivo and in vitro studies clearly demonstrate the inability of trypsin to cleave after citrulline residues. Based on our......Citrullinated proteins have been associated with several diseases and citrullination can most likely function as a target for novel diagnostic agents and unravel disease etiologies. The correct identification of citrullinated proteins is therefore of most importance. Mass spectrometry (MS) driven...

  17. N-Carbamoylputrescine, a citrulline-derived polyamine, is not a significant citrulline metabolite in rats.

    Science.gov (United States)

    Ramani, D; Nakib, S; Chen, H; Garbay, C; Loukaci, A; Cynober, L; De Bandt, J P

    2012-04-01

    Citrulline, a key amino acid of the urea cycle, has been shown to play a regulatory role in protein and energy metabolism in mammals. We questioned whether N-carbamoyl-putrescine (NCP), the decarboxylated derivative of citrulline, could play a role in the biological properties of this amino acid. To evidence the presence of NCP in mammalian tissues, we developed a sensitive reverse-phase high-performance liquid chromatography (HPLC) with fluorimetric detection method with precolumn dansyl derivatization and solid-phase extraction for the determination of NCP together with polyamines in biological samples. Dansyl NCP was identified with a 5.85-min retention time. Linearity was obtained in a concentration range of 0.125 to 12.5 μM. Intraday and day-to-day relative coefficients of variation ranged from 8.9% to 12.3% and from 14% to 14.3%, respectively. Recovery rates in serum ranged from 75% to 83%. Thereafter, we used this method to search for the presence of NCP in serum, muscle, liver, jejunum, and ileum in rats after both short-term intraperitoneal injection and long-term oral citrulline supplementation. We failed to detect NCP in these animals. These data suggest that NCP is not a significant citrulline metabolite in rats.

  18. Citrullination regulates pluripotency and histone H1 binding to chromatin

    DEFF Research Database (Denmark)

    Christophorou, Maria A; Castelo-Branco, Gonçalo; Halley-Stott, Richard P

    2014-01-01

    Citrullination is the post-translational conversion of an arginine residue within a protein to the non-coded amino acid citrulline. This modification leads to the loss of a positive charge and reduction in hydrogen-bonding ability. It is carried out by a small family of tissue-specific vertebrate...

  19. Extrarenal citrulline disposal in mice with impaired renal function

    Science.gov (United States)

    The endogenous synthesis of arginine, a semiessential amino acid, relies on the production of citrulline by the gut and its conversion into arginine by the kidney in what has been called the "intestinal-renal axis" for arginine synthesis. Although the kidney is the main site for citrulline disposal,...

  20. Citrullination and carbamylation in the pathophysiology of rheumatoid arthritits

    Directory of Open Access Journals (Sweden)

    Ger J.M. Pruijn

    2015-04-01

    Full Text Available The discovery that citrullination was crucial for the recognition of antigens by the most disease-specific class of autoantibodies in rheumatoid arthritis had a huge impact on studies aimed at understanding autoimmunity in this disease. In addition to the detailed characterization of anti-citrullinated protein antibodies, various studies have addressed the identity of citrullinated antigens. These investigations were facilitated by new methods to characterize these proteins, the analysis of protein citrullination by peptidylarginine deiminases, the generation of a catalogue of citrullinated proteins present in the inflamed joints of patients and the finding that the formation of extracellular traps is dependent on the activity of peptidylarginine deiminase activity. Recently, it was found that in addition to citrullination also carbamylation, which results in chemically highly related modified proteins, yields antigens that are targeted by rheumatoid arthritis patient sera. Here, all of these aspects will be discussed, culminating in current ideas about the involvement of citrullination and carbamylation in pathophysiological processes in autoimmunity, especially rheumatoid arthritis.

  1. Citrullination and carbamylation in the pathophysiology of rheumatoid arthritis.

    Science.gov (United States)

    Pruijn, Ger J M

    2015-01-01

    The discovery that citrullination was crucial for the recognition of antigens by the most disease-specific class of autoantibodies in rheumatoid arthritis (RA) had a huge impact on studies aimed at understanding autoimmunity in this disease. In addition to the detailed characterization of anti-citrullinated protein antibodies, various studies have addressed the identity of citrullinated antigens. These investigations were facilitated by new methods to characterize these proteins, the analysis of protein citrullination by peptidylarginine deiminases, the generation of a catalog of citrullinated proteins present in the inflamed joints of patients and the finding that the formation of extracellular traps is dependent on the activity of peptidylarginine deiminase activity. Recently, it was found that in addition to citrullination also carbamylation, which results in chemically highly related modified proteins, yields antigens that are targeted by rheumatoid arthritis patient sera. Here, all of these aspects will be discussed, culminating in current ideas about the involvement of citrullination and carbamylation in pathophysiological processes in autoimmunity, especially RA.

  2. Arginine and citrulline supplementation in sports and exercise: ergogenic nutrients?

    Science.gov (United States)

    Sureda, Antoni; Pons, Antoni

    2012-01-01

    Dietary L-citrulline malate supplements may increase levels of nitric oxide (NO) metabolites, although this response has not been related to an improvement in athletic performance. NO plays an important role in many functions in the body regulating vasodilatation, blood flow, mitochondrial respiration and platelet function. L-Arginine is the main precursor of NO via nitric oxide synthase (NOS) activity. Additionally, L-citrulline has been indicated to be a second NO donor in the NOS-dependent pathway, since it can be converted to L-arginine. The importance of L-citrulline as an ergogenic support derives from the fact that L-citrulline is not subject to pre-systemic elimination and, consequently, could be a more efficient way to elevate extracellular levels of L-arginine by itself. L-Citrulline malate can develop beneficial effects on the elimination of NH(3) in the course of recovery from exhaustive muscular exercise and also as an effective precursor of L-arginine and creatine. Dietary supplementation with L-citrulline alone does not improve exercise performance. The ergogenic response of L-citrulline or L-arginine supplements depends on the training status of the subjects. Studies involving untrained or moderately healthy subjects showed that NO donors could improve tolerance to aerobic and anaerobic exercise. However, when highly-trained subjects were supplemented, no positive effect on performance was indicated.

  3. Mitochondria: role of citrulline and arginine supplementation in MELAS syndrome.

    Science.gov (United States)

    El-Hattab, Ayman W; Emrick, Lisa T; Chanprasert, Sirisak; Craigen, William J; Scaglia, Fernando

    2014-03-01

    Mitochondria are found in all nucleated human cells and generate most of the cellular energy. Mitochondrial disorders result from dysfunctional mitochondria that are unable to generate sufficient ATP to meet the energy needs of various organs. Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a frequent maternally inherited mitochondrial disorder. There is growing evidence that nitric oxide (NO) deficiency occurs in MELAS syndrome and results in impaired blood perfusion that contributes significantly to several complications including stroke-like episodes, myopathy, and lactic acidosis. Both arginine and citrulline act as NO precursors and their administration results in increased NO production and hence can potentially have therapeutic utility in MELAS syndrome. Citrulline raises NO production to a greater extent than arginine, therefore, citrulline may have a better therapeutic effect. Controlled studies assessing the effects of arginine or citrulline supplementation on different clinical aspects of MELAS syndrome are needed.

  4. Local administration of glucocorticoids decreases synovial citrullination in rheumatoid arthritis

    OpenAIRE

    2012-01-01

    Introduction Protein citrullination is present in the rheumatoid synovium, presumably contributing to the perpetuation of chronic inflammation, in the presence of specific autoimmunity. As a result, the present study examined the possibility that effective antirheumatic treatment will decrease the level of synovial citrullination. Methods Synovial biopsies were obtained from 11 rheumatoid arthritis (RA) patients before and after 8 weeks of treatment with 20 mg methotrexate weekly, 15 RA patie...

  5. COMBINATION DETECTION OF SERUM ANTI-CYCLIC CITRULLINATED PEPTIDE ANTIBODY AND RHEUMATOID FACTOR: ITS DIAGNOSTIC VALUE OF RHEUMATOID ARTHRITIS%抗CCP抗体与RF联合检测诊断类风湿关节炎的价值

    Institute of Scientific and Technical Information of China (English)

    陈华丽; 杨文东; 韩景银

    2007-01-01

    目的 探讨联合检测抗环瓜氨酸肽(CCP)抗体和类风湿因子(RF)诊断类风湿关节炎(RA)的价值,并了解抗CCP抗体与RF之间的相关性.方法 采用ELISA法和乳胶增强免疫比浊法,检测79例RA、52例非RA病人血清抗CCP抗体和RF.结果 79例RA病人中单一抗CCP抗体阳性12例,单一RF阳性20例,两项同时阳性40例,同时阴性7例,一致率为59.5%(47/79).52例非RA病人中单一抗CCP抗体阳性2例,单一RF阳性14例,无1例两项同时阳性.RA病人抗CCP抗体与RF阳性率显著高于非RA病人(χ2=49.713、30.666,P<0.01),RF阳性率高于抗CCP抗体,但差异无显著性(P>0.05);非RA病人RF阳性率显著高于抗CCP抗体(χ2=10.636,P<0.01).抗CCP抗体诊断RA的特异度和阳性预测值分别为96.2%、96.3%,灵敏度为65.8%.抗CCP抗体和RF联合检测诊断RA的灵敏度、阴性预测值及准确度分别为91.1%、83.7%、82.4%.抗CCP抗体与RF无相关性(P>0.05).结论 抗CCP抗体诊断RA具有满意的特异度及很高的阳性预测值,对RA有较高诊断价值.抗CCP抗体与RF联合检测更有助于RA的临床诊断.

  6. 抗CCP抗体与RF联合检测在RA诊断中的价值%Value of combined detection of serum anti-cyclic citrullinated peptide antibody and rheumatoid factor in diagnosis of rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    钱明; 袁君君; 郭兆旺; 舒晓春

    2010-01-01

    目的 探讨联合检测抗环瓜氨酸肽(CCP)抗体和类风湿因子(RF)在类风湿关节炎(RA)诊断中的价值.方法 抗-ccp采用化学发光(MEIA)法,RF采用散射速率比浊法检测,取70例RA、130例非RA患者血清检测抗-CCP和RF.结果 70例RA患者中抗-CCP阳性54例,RF阳性52例,两项同时阳性64例,同时阴性6例,故抗-CCP、RF及两者联合检测在RA患者中的阳性率分别为77.1%、74.3%和91.4%;130例非RA患者中抗-CCP阳性5例,RF阳性38例,无1例两项同时阳性,故抗-CCP、RF及抗-CCP和RF联合检测在非RA患者中的阳性率分别为3.85%、29.23%和0.经过统计学分析联合检测与单项检测比较,差异有统计学意义(P<0.01),且RA患者抗-CCP与RF阳性率显著高于非RA患者,差异有统计学意义(P<0.01).结论 抗-CCP和RE联合检测可明显提高RA的诊断率.

  7. Anti-CCP和RF联合检测在诊断RA中的意义%Significance of detecting anti-cyclic citrullinated peptide and rheumatoid factor in the diagnosis of rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    郭玉娟

    2012-01-01

    目的 分析比较抗环瓜氨酸肽抗体(Anti-CCP)和类风湿因子(RF)在类风湿关节炎(RA)中的灵敏度和特异性,探讨将两种指标联合检测在RA诊断中的价值.方法 利用酶联免疫吸附试验和乳胶增强免疫透射比浊法分别测定76例RA 患者,56例非RA 患者血清中的Anti-CCP和RF.结果 Anti-CCP和RF在RA组的阳性率明显高于非RA组.特异度和灵敏度RF分别为76.8%、78.9%,Anti-CCP分别为96.4%、60.5%,将两者联合检测则分别为86.6%、73.1%.结论 Anti-CCP在诊断RA中具有较高的特异性和灵敏度,可作为诊断RA的新的血清学指标.将Anti-CCP和RF联合检测有助于RA的临床诊断.%Objective To analyse the specificily and sensilivily of anli-cyclic cilrullinaled peplide (Anli-CCP) and rheumatoid factor (RF) in the diagnosis of rheumatoid arlhrilis (RA) to invesligale the value when the Iwo anlibodies were used togelher. Methods ELISA and Lalex enhanced immune lurbidimelric were used to deled serum levels of Anli-CCP and RF in 76 palienls wilh RA and 56 non- RA palienls. Results The positive rale of Anli-CCP and RF of palienls wilh RA was significantly higher lhan lhal of non-RA palienls. The diagnostic specificily of RF for RA was 76. 8% and the sensilivily was 78. 9% , whereas the diagnostic specificily of Anti-CCP for RA was 96. 4% and the sensitivity was 60. 5%. The diagnostic specificily of the Anli-CCP and RF was 86. 6% and the sensitivity was 73. 1%. Conclusion The Anti-CCP might have high specificity and sensitivity, which might be used as the new serum sign for the diagnosis of RA. Combined wilh the detection of Anti-CCP and RF , the sensitivity will be higher.

  8. Citrullination regulates pluripotency and histone H1 binding to chromatin

    Science.gov (United States)

    Christophorou, Maria A.; Castelo-Branco, Gonçalo; Halley-Stott, Richard P.; Oliveira, Clara Slade; Loos, Remco; Radzisheuskaya, Aliaksandra; Mowen, Kerri A.; Bertone, Paul; Silva, José C. R.; Zernicka-Goetz, Magdalena; Nielsen, Michael L.; Gurdon, John B.; Kouzarides, Tony

    2014-03-01

    Citrullination is the post-translational conversion of an arginine residue within a protein to the non-coded amino acid citrulline. This modification leads to the loss of a positive charge and reduction in hydrogen-bonding ability. It is carried out by a small family of tissue-specific vertebrate enzymes called peptidylarginine deiminases (PADIs) and is associated with the development of diverse pathological states such as autoimmunity, cancer, neurodegenerative disorders, prion diseases and thrombosis. Nevertheless, the physiological functions of citrullination remain ill-defined, although citrullination of core histones has been linked to transcriptional regulation and the DNA damage response. PADI4 (also called PAD4 or PADV), the only PADI with a nuclear localization signal, was previously shown to act in myeloid cells where it mediates profound chromatin decondensation during the innate immune response to infection. Here we show that the expression and enzymatic activity of Padi4 are also induced under conditions of ground-state pluripotency and during reprogramming in mouse. Padi4 is part of the pluripotency transcriptional network, binding to regulatory elements of key stem-cell genes and activating their expression. Its inhibition lowers the percentage of pluripotent cells in the early mouse embryo and significantly reduces reprogramming efficiency. Using an unbiased proteomic approach we identify linker histone H1 variants, which are involved in the generation of compact chromatin, as novel PADI4 substrates. Citrullination of a single arginine residue within the DNA-binding site of H1 results in its displacement from chromatin and global chromatin decondensation. Together, these results uncover a role for citrullination in the regulation of pluripotency and provide new mechanistic insights into how citrullination regulates chromatin compaction.

  9. Maternal citrulline supplementation prevents prenatal dexamethasone-induced programmed hypertension.

    Science.gov (United States)

    Tain, Y L; Sheen, J M; Chen, C C; Yu, H R; Tiao, M M; Kuo, H C; Huang, L T

    2014-05-01

    Glucocorticoids are administered to premature infants to accelerate pulmonary maturation. In experimental model, prenatal dexamethasone (DEX) results in reduced nephron number and adulthood hypertension. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), can cause oxidative stress and is involved in the development of hypertension. L-citrulline can be converted to l-arginine (the substrate for NOS) in the body. Thus we intended to determine if maternal L-citrulline therapy can prevent prenatal DEX-induced programmed hypertension by restoration ADMA/nitric oxide (NO) balance, alterations of renin-angiotensin system (RAS) and sodium transporters, and epigenetic regulation by histone deacetylases (HDACs). Male offspring were assigned to four groups: control, pregnancy rats received intraperitoneal DEX (0.2 mg/kg body weight) daily on gestational days 15 and 16 (DEX), pregnancy rats received 0.25% L-citrulline in drinking water during the entire pregnancy and lactation period (CIT), and DEX + CIT. We found DEX group developed hypertension at 16 weeks of age, which was prevented by maternal L-citrulline therapy. Prenatal DEX exposure increased plasma ADMA concentrations and reduced renal NO production. However, L-citrulline reduced plasma ADMA level and increased renal level of NO in DEX + CIT group. Next, prenatal DEX-induced programmed hypertension is related to increased mRNA expression of angiotensin and angiotensin II type 1 receptor, and class I HDACs in the kidney. Prenatal DEX exposure increased renal protein abundance of Na(+)/Cl(-) cotransporter (NCC), which was prevented by L-citrulline therapy. The beneficial effects of L-citrulline therapy include restoration of ADMA/NO balance and alteration of NCC, to prevent the prenatal DEX-induced programmed hypertension.

  10. Citrullinated peptides in the diagnosis of rheumatoid arthritis.

    Science.gov (United States)

    Gómara, María J; Haro, Isabel

    2013-01-01

    Antibodies directed against citrullinated proteins and peptides (ACPAs) are the most specific serological markers available for diagnosing rheumatoid arthritis (RA). ACPAs may be detected several years before symptoms of RA appear, and their presence at disease onset is a good predictor of the development of erosive joint lesions. RA patients can be classified into two major groups: those who have ACPAs and those who do not. The presence of ACPAs at early stages of RA predicts the development of earlier and more widespread joint erosions, and low remission rates.Synthetic peptides can replace cognate proteins in solid-phase assays for specific autoantibody recognition in RA patients. The use of synthetic peptides instead of proteins represents an advantage in terms of the reproducibility of such immunoassays. Proteins also contain non-citrullinated epitopes that are recognized by non-RA sera and this could reduce the specificity of the test. The use of synthetic citrullinated peptides gives absolute control over the exact epitopes presented. Furthermore, it is difficult to prepare sufficient amounts of high-quality antigenic proteins with a well-defined degree of citrullination. Synthetic citrullinated peptides, in contrast, are easily obtained in a pure form with a well-defined chemical structure and the epitopes can be precisely oriented in the plate by covalent binding of the peptides.Chimeric peptides bearing different citrullinated protein domains have recently been used in the design of RA diagnosis systems. The results of the application of those systems indicate that more than one serological test is required to classify RA patients based on the presence or absence of ACPAs. Each of the target molecules reported (fibrin, vimentin and filaggrin) helps to identify a particular subset of RA patients.

  11. Physical characteristics of a citrullinated pro-filaggrin epitope recognized by anti-citrullinated protein antibodies in rheumatoid arthritis sera

    DEFF Research Database (Denmark)

    Trier, Nicole Hartwig; Holm, Bettina Eide; Slot, Ole

    2016-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease of complex etiology. A characteristic feature of a subset of RA is the presence of anti-citrullinated protein antibodies (ACPA), which correlate with a progressive disease course. In this study, we employed streptavidin capture enzyme...

  12. Citrulline as a Biomarker in the Murine Total-Body Irradiation Model: Correlation of Circulating and Tissue Citrulline to Small Intestine Epithelial Histopathology.

    Science.gov (United States)

    Jones, Jace W; Tudor, Gregory; Li, Fei; Tong, Yan; Katz, Barry; Farese, Ann M; MacVittie, Thomas J; Booth, Catherine; Kane, Maureen A

    2015-11-01

    The use of plasma citrulline as a biomarker for gastrointestinal acute radiation syndrome via exposure to total-body irradiation in a murine model was investigated. The radiation exposure covered lethal, mid-lethal, and sub-lethal gastrointestinal acute radiation syndrome. Plasma citrulline profiles were generated over the first 6 d following total-body irradiation exposure of 6-15 Gy. In addition, plasma citrulline was comprehensively evaluated in the context of matching small intestine citrulline and histopathology. Higher plasma citrulline was significantly associated with lower irradiation doses over the first 6 d following the irradiation insult. Furthermore, higher plasma citrulline was significantly associated with higher crypt survival. The correlation of the plasma citrulline to crypt survival was more robust for higher irradiation doses and for later time points. The data suggested plasma citrulline was most informative for reflecting gastrointestinal injury resulting from exposure to 9-15 Gy total-body irradiation covering time-points 2-5 d post the irradiation insult.

  13. Restoration of impaired nitric oxide production in MELAS syndrome with citrulline and arginine supplementation.

    Science.gov (United States)

    El-Hattab, Ayman W; Hsu, Jean W; Emrick, Lisa T; Wong, Lee-Jun C; Craigen, William J; Jahoor, Farook; Scaglia, Fernando

    2012-04-01

    Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is one of the most common mitochondrial disorders. Although the pathogenesis of stroke-like episodes remains unclear, it has been suggested that mitochondrial proliferation may result in endothelial dysfunction and decreased nitric oxide (NO) availability leading to cerebral ischemic events. This study aimed to assess NO production in subjects with MELAS syndrome and the effect of the NO precursors arginine and citrulline. Using stable isotope infusion techniques, we assessed arginine, citrulline, and NO metabolism in control subjects and subjects with MELAS syndrome before and after arginine or citrulline supplementation. The results showed that subjects with MELAS had lower NO synthesis rate associated with reduced citrulline flux, de novo arginine synthesis rate, and plasma arginine and citrulline concentrations, and higher plasma asymmetric dimethylarginine (ADMA) concentration and arginine clearance. We conclude that the observed impaired NO production is due to multiple factors including elevated ADMA, higher arginine clearance, and, most importantly, decreased de novo arginine synthesis secondary to decreased citrulline availability. Arginine and, to a greater extent, citrulline supplementation increased the de novo arginine synthesis rate, the plasma concentrations and flux of arginine and citrulline, and NO production. De novo arginine synthesis increased markedly with citrulline supplementation, explaining the superior efficacy of citrulline in increasing NO production. The improvement in NO production with arginine or citrulline supplementation supports their use in MELAS and suggests that citrulline may have a better therapeutic effect than arginine. These findings can have a broader relevance for other disorders marked by perturbations in NO metabolism.

  14. Plasma citrulline levels predict intestinal toxicity in patients treated with pelvic radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Onal, Cem; Kotek, Ayse; Arslan, Gungor; Topkan, Erkan (Dept. of Radiation Oncology, Baskent Univ. Faculty of Medicine, Adana (Turkey)), E-mail: hcemonal@hotmail.com; Unal, Birsel (Dept. of Biochemistry, Baskent Univ. Faculty of Medicine, Ankara (Turkey)); Yavuz, Aydin; Yavuz, Melek (Dept. of Radiation Oncology, Akdeniz Univ. Faculty of Medicine, Antalya (Turkey))

    2011-11-15

    Background. Radiotherapy (RT) for abdominal and pelvic malignancies often causes severe small bowel toxicity. Citrulline concentrations are known to decrease with intestinal failure. We thus evaluated the feasibility of plasma citrulline levels in predicting radiation-induced intestinal toxicity. Material and methods. Fifty-three patients (36 prostate cancer, 17 endometrial cancer) who received 45 Gy pelvic RT using conventional fractionation were prospectively evaluated. Patients with prostate cancer received an additional 25-30.6 Gy conformal boost. Plasma citrulline levels were assessed on day 0, mid- (week 3) and post-RT (week 8), and four months post-RT. Dose-volume histogram, citrulline concentration changes, and weekly intestinal toxicity scores were analyzed. Results. Mean age was 63 years (range: 43-81 years) and mean baseline citrulline concentration was 38.0 +- 10.1 mumol/l. Citrulline concentrations were significantly reduced at week 3 (27.4 +- 5.9 mumol/l; p < 0.0001), treatment end (29.9 +- 8.8 mumol/l; p < 0.0001), and four months post-treatment (34.3 +- 12.1; p 0.01). The following factor pairs were significantly positively correlated: Citrulline concentration/mean bowel dose during, end of treatment, and four months post-RT; dose-volume parameters/citrulline change groups; cumulative mean radiation dose/intestinal toxicity at end and four months post-RT; citrulline changes/intestinal toxicity during and end of RT. Citrulline concentration changes significantly differed during treatment according to RTOG intestinal toxicity grades (p < 0.0001). Although the citrulline changes differed significantly within RTOG intestinal toxicity grades (p = 0.003), the difference between Grade 0 and Grade 1 did not differ significantly at the end of the treatment. At four months after RT, no significant differences were apparent. Conclusion. Citrulline-based assessment scores are objective and should be considered in measuring radiation-induced intestinal toxicity

  15. Application of synthetic peptides for detection of anti-citrullinated peptide antibodies

    DEFF Research Database (Denmark)

    Trier, Nicole Hartwig; Holm, Bettina Eide; Slot, Ole;

    2016-01-01

    Anti-citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis (RA) and represent an important tool for the serological diagnosis of RA. In this study, we describe ACPA reactivity to overlapping citrullinated Epstein-Barr virus nuclear antigen-1 (EBNA-1)-derived peptides...

  16. The effect of citrulline and arginine supplementation on lactic acidemia in MELAS syndrome.

    Science.gov (United States)

    El-Hattab, Ayman W; Emrick, Lisa T; Williamson, Kaitlin C; Craigen, William J; Scaglia, Fernando

    2013-12-01

    Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a mitochondrial disorder in which nitric oxide (NO) deficiency may play a role in the pathogenesis of several complications including stroke-like episodes and lactic acidosis. Supplementing the NO precursors arginine and citrulline restores NO production in MELAS syndrome. In this study we evaluated the effect of arginine or citrulline on lactic acidemia in adults with MELAS syndrome. Plasma lactate decreased significantly after citrulline supplementation, whereas the effect of arginine supplementation did not reach statistical significance. These results support the potential therapeutic utility of arginine and citrulline in MELAS syndrome and suggest that citrulline supplementation may be more efficacious. However, therapeutic efficacy of these compounds should be further evaluated in clinical trials.

  17. Physical Characteristics of a Citrullinated Pro-Filaggrin Epitope Recognized by Anti-Citrullinated Protein Antibodies in Rheumatoid Arthritis Sera

    DEFF Research Database (Denmark)

    Trier, Nicole Hartwig; Holm, Bettina Eide; Slot, Ole;

    2016-01-01

    whether biotin labelling influence antibody recognition. The full-length cyclic pro-filaggrin peptide and a linear form with a N-terminal biotin, was recognized to the same level, whereas, a notable difference in ACPA reactivity to the linear peptides with a C-terminal biotin was found, probably due...... amino acid in position 4 C-terminal to citrulline. Collectively, peptide structure, length, the presence of charged amino acids and biotin labelling markedly influence antibody reactivity. In relation to the clinical diagnostics of ACPA, these findings may reflect the differences in diagnostic assays...

  18. Structure and pathogenicity of antibodies specific for citrullinated collagen type II in experimental arthritis

    DEFF Research Database (Denmark)

    Uysal, Hüseyin; Bockermann, Robert; Nandakumar, Kutty S

    2009-01-01

    Antibodies to citrulline-modified proteins have a high diagnostic value in rheumatoid arthritis (RA). However, their biological role in disease development is still unclear. To obtain insight into this question, a panel of mouse monoclonal antibodies was generated against a major triple helical...... collagen type II (CII) epitope (position 359-369; ARGLTGRPGDA) with or without arginines modified by citrullination. These antibodies bind cartilage and synovial tissue, and mediate arthritis in mice. Detection of citrullinated CII from RA patients' synovial fluid demonstrates that cartilage-derived CII...

  19. Anticorpos antipeptídeos citrulinados e fator reumatoide em pacientes sudaneses com infecção por Leishmania donovani Anti-citrullinated peptide antibodies and rheumatoid factor in Sudanese patients with Leishmania donovani infection

    Directory of Open Access Journals (Sweden)

    Erik Ahlin

    2011-12-01

    Full Text Available OBJETIVO: Este estudo avaliou a presença de anticorpos antipeptídeos citrulinados cíclicos (anti-CCP, fator reumatoide (FR e imunocomplexos circulantes (ICC em pacientes sudaneses infectados por Leishmania donovani. PACIENTES E MÉTODOS: Os soros foram coletados de pacientes infectados por Leishmania (n = 116 e de sudaneses saudáveis (n = 93. Dezenove pacientes sudaneses com artrite reumatoide (AR e anti-CCP+ foram incluídos como controles positivos. Os níveis de ICC e anti-CCP foram medidos por ELISA. Para avaliar a reatividade citrulina-específica foi usada a placa-controle com peptídeos-controle cíclicos contendo arginina em vez de citrulina. RESULTADOS: Entre os pacientes infectados por Leishmania e os pacientes com AR e anti-CCP+, a maioria (86% era positiva para FR, enquanto a frequência de positividade para ICC foi maior entre pacientes com leishmaniose visceral (LV (LV 38%; AR e anti-CCP+ 24%. Quando foi analisada a reatividade anti-CCP, 12% dos pacientes com LV foram positivos. Os níveis de anti-CCP entre os pacientes com LV correlacionaram-se bem com os níveis de ICC encontrados (r = 0,65; P OBJECTIVE: The present study evaluated the presence of anti-cyclic citrullinated peptides antibodies (anti-CCP, rheumatoid factor (RF, and circulating immune complexes (CIC in Sudanese patients infected with the Leishmania donovani parasite. PATIENTS AND METHODS: Sera were collected from Leishmania infected patients (n = 116 and healthy Sudanese (n = 93. Nineteen Sudanese anti-CCP+ RA patients were included as positive controls. Levels of CIC and anti-CCP were measured by ELISA. Control plate with cyclic control peptides containing arginine instead of citrulline was used to evaluate citrulline specifi c reactivity. RESULTS: Among Leishmania-infected patients and anti-CCP+ RA patients, most were RF positive (86%, while the frequency of CIC positivity was higher among visceral leishmaniasis (VL patients (VL 38%; anti-CCP+ RA 24%. When

  20. Potential role for PADI-mediated histone citrullination in preimplantation development

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    Kan Rui

    2012-06-01

    Full Text Available Abstract Background The peptidylarginine deiminases (PADIs convert positively charged arginine residues to neutrally charged citrulline on protein substrates in a process that is known as citrullination or deimination. Previous reports have documented roles for histone citrullination in chromatin remodeling and gene regulation in several tissue types, however, a potential role for histone citrullination in chromatin-based activities during early embryogenesis has not been investigated. Results In the present study, we tested by laser scanning confocal indirect immunofluorescence microscopy whether specific arginine residues on the histone H3 and H4 N-terminal tails (H4R3, H3R2 + 8 + 17, and H3R26 were citrullinated in mouse oocytes and preimplantation embryos. Results showed that all of the tested residues were deiminated with each site showing a unique localization pattern during early development. Given these findings, we next tested whether inhibition of PADI activity using the PADI-specific inhibitor, Cl-amidine, may affect embryonic development. We found that treatment of pronuclear stage zygotes with Cl-amidine reduces both histone H3 and H4 tail citrullination and also potently blocks early cleavage divisions in vitro. Additionally, we found that the Cl-amidine treatment reduces acetylation at histone H3K9, H3K18, and H4K5 while having no apparent effect on the repressive histone H3K9 dimethylation modification. Lastly, we found that treatment of zygotes with trichostatin A (TSA to induce hyperacetylation also resulted in an increase in histone citrullination at H3R2 + 8 + 17. Conclusions Given the observed effects of Cl-amidine on embryonic development and the well documented correlation between histone acetylation and transcriptional activation, our findings suggest that histone citrullination may play an important role in facilitating gene expression in early embryos by creating a chromatin environment that is

  1. Citrulline as a Biomarker in the Non-human Primate Total- and Partial-body Irradiation Models: Correlation of Circulating Citrulline to Acute and Prolonged Gastrointestinal Injury.

    Science.gov (United States)

    Jones, Jace W; Bennett, Alexander; Carter, Claire L; Tudor, Gregory; Hankey, Kim G; Farese, Ann M; Booth, Catherine; MacVittie, Thomas J; Kane, Maureen A

    2015-11-01

    The use of plasma citrulline as a biomarker for acute and prolonged gastrointestinal injury via exposure to total- and partial-body irradiation (6 MV LINAC-derived photons; 0.80 Gy min) in nonhuman primate models was investigated. The irradiation exposure covered gastrointestinal injuries spanning lethal, mid-lethal, and sub-lethal doses. The acute gastrointestinal injury was assessed via measurement of plasma citrulline and small intestinal histopathology over the first 15 d following radiation exposure and included total-body irradiation at 13.0 Gy, 10.5 Gy, and 7.5 Gy and partial-body irradiation at 11.0 Gy with 5% bone marrow sparing. The dosing schemes of 7.5 Gy total-body irradiation and 11.0 Gy partial-body irradiation included time points out to day 60 and day 180, respectively, which allowed for correlation of plasma citrulline to prolonged gastrointestinal injury and survival. Plasma citrulline values were radiation-dependent for all radiation doses under consideration, with nadir values ranging from 63-80% lower than radiation-naïve NHP plasma. The nadir values were observed at day 5 to 7 post irradiation. Longitudinal plasma citrulline profiles demonstrated prolonged gastrointestinal injury resulting from acute high-dose irradiation had long lasting effects on enterocyte function. Moreover, plasma citrulline did not discriminate between total-body or partial-body irradiation over the first 15 d following irradiation and was not predictive of survival based on the radiation models considered herein.

  2. Citrulline Supplementation Improves Organ Perfusion and Arginine Availability under Conditions with Enhanced Arginase Activity

    Directory of Open Access Journals (Sweden)

    Karolina A.P. Wijnands

    2015-06-01

    Full Text Available Enhanced arginase-induced arginine consumption is believed to play a key role in the pathogenesis of sickle cell disease-induced end organ failure. Enhancement of arginine availability with l-arginine supplementation exhibited less consistent results; however, l-citrulline, the precursor of l-arginine, may be a promising alternative. In this study, we determined the effects of l-citrulline compared to l-arginine supplementation on arginine-nitric oxide (NO metabolism, arginine availability and microcirculation in a murine model with acutely-enhanced arginase activity. The effects were measured in six groups of mice (n = 8 each injected intraperitoneally with sterile saline or arginase (1000 IE/mouse with or without being separately injected with l-citrulline or l-arginine 1 h prior to assessment of the microcirculation with side stream dark-field (SDF-imaging or in vivo NO-production with electron spin resonance (ESR spectroscopy. Arginase injection caused a decrease in plasma and tissue arginine concentrations. l-arginine and l-citrulline supplementation both enhanced plasma and tissue arginine concentrations in arginase-injected mice. However, only the citrulline supplementation increased NO production and improved microcirculatory flow in arginase-injected mice. In conclusion, the present study provides for the first time in vivo experimental evidence that l-citrulline, and not l-arginine supplementation, improves the end organ microcirculation during conditions with acute arginase-induced arginine deficiency by increasing the NO concentration in tissues.

  3. Is there a link between carbamylation and citrullination in periodontal disease and rheumatoid arthritis?

    Science.gov (United States)

    Bright, R; Proudman, S M; Rosenstein, E D; Bartold, P M

    2015-06-01

    The remarkable similarity in inflammatory response and pathology of periodontal disease and rheumatoid arthritis has been recognized for several decades. However, how these two disease may be interrelated has been less clear. During the pathogenesis of rheumatoid arthritis there is a preclinical immunological phase which precedes the clinical manifestation of rheumatoid arthritis. During this phase serum autoantibodies appear many years before the clinical signs and symptoms of rheumatoid arthritis become apparent. To date, the two best studied autoantibodies have been rheumatoid factor and anti-citrullinated protein antibodies (ACPA). Of these the production of ACPA has been considered very important due to their high predictive value in future manifestation of rheumatoid arthritis. Citrullination is a common post-translational modification of proteins based on the enzymatic conversion of arginine into citrulline. Extra-articular citrullination and production of ACPA, as a priming immunological experience, is well documented in many tissues including the inflamed gingival tissues associated with periodontal disease. More recently, carbamylation of proteins has also been implicated in the pathogenesis of rheumatoid arthritis in a manner similar to citrullination. Carbamylation is a post translational modification of proteins by an enzyme-independent modification of lysine residues against which autoantibodies are subsequently induced. In this article we hypothesise that, like citrullination, carbamylation of proteins and associated antibody production during the gingival inflammation associated with gingivitis and periodontitis may play a role in the pathogenesis of rheumatoid arthritis.

  4. Plasma arginine and ornithine are the main citrulline precursors in mice infused with arginine-free diets.

    Science.gov (United States)

    Marini, Juan C; Didelija, Inka Cajo; Castillo, Leticia; Lee, Brendan

    2010-08-01

    Dietary arginine is the main dietary precursor for citrulline synthesis, but it is not known if other precursors can compensate when arginine is absent in the diet. To address this question, the contributions of plasma and dietary precursors were determined by using multitracer protocols in conscious mice infused i.g. either an arginine-sufficient diet [Arg(+)] or an arginine-free diet [Arg(-)]. The plasma entry rate of citrulline and arginine did not differ between the 2 diet groups (156 +/- 6 and 564 +/- 30 micromol kg(-1) h(-1), respectively); however, the entry rate of ornithine was greater in the mice fed the Arg(+) than the Arg(-) diet (332 +/- 33 vs. 180 +/- 16 micromol kg(-1) h(-1)). There was a greater utilization of plasma ornithine for the synthesis of citrulline (49 +/- 4 vs. 36 +/- 3 micromol kg(-1) h(-1), 30 +/- 3% vs. 24 +/- 2% of citrulline entry rate) in the mice fed the Arg(-) diet than the Arg(+) diet. The utilization of plasma arginine did not differ between the 2 diet groups for citrulline synthesis, either through plasma ornithine (approximately 29 +/- 3 micromol kg(-1) h(-1)) or at the site of citrulline synthesis (approximately 12 +/- 3 micromol kg(-1) h(-1)). The contribution of dietary proline to the synthesis of citrulline was mainly at the site of citrulline production (17 +/- 1 micromol kg(-1) h(-1)), rather than through plasma ornithine (5 +/- 0.4 micromol kg(-1) h(-1)). Dietary glutamine was utilized only at the site of citrulline synthesis (4 +/- 0.2 micromol kg(-1) h(-1)). Dietary glutamine and proline made a greater contribution to the synthesis of citrulline in mice fed the Arg(-) diet but remained minor sources for citrulline production. Plasma arginine and ornithine are able to support citrulline synthesis during arginine-free feeding.

  5. IgG reactivity against citrullinated myelin basic protein in multiple sclerosis.

    Science.gov (United States)

    de Seze, J; Dubucquoi, S; Lefranc, D; Virecoulon, F; Nuez, I; Dutoit, V; Vermersch, P; Prin, L

    2001-07-02

    An increased level of citrullinated myelin basic protein (MBP-C8) has been reported in the brains of multiple sclerosis (MS) patients. However, the involvement of the immune response to post-translational modified MBP in the pathophysiology of MS remains speculative. The aim of this study was to compare the levels of immunoglobulin G antibodies to several MBP epitopes, before and after citrullination, in the cerebrospinal fluid (CSF) and sera of MS patients using enzyme-linked immunosorbent assay (ELISA). We analyzed antibody reactivity against various MBP-peptides in the CSF and sera of 60 MS patients, and 30 patients with other neurological diseases (OND) as controls. The peptides tested were: MBP(75-98) (peptide 1), native (peptide 2) and citrullinated (peptide 3) MBP(108-126) (ARG(122)-->Cit(122)), and native (peptide 4) and citrullinated (peptide 5) MBP(151-170) (ARG(159, 170)-->Cit(159, 170)). All selected peptides could support an immune reactivity in CSF and sera of MS and OND patients. A higher reactivity against peptide 4 was found in the CSF of MS patients compared with OND patients (P<0.0001), but not against citrullinated peptides (peptides 3 and 5). However, we observed that the citrullination state of peptide 2 modified the patterns of immune reactivity more markedly in MS patients (P<0.0001) than in OND patients (P<0.02). Although some MBP epitopes could be a potential target in MS, our data did not demonstrate any difference of antibody response to MBP peptides in their citrullinated forms.

  6. The periodontium of periodontitis patients contains citrullinated proteins which may play a role in ACPA (anti-citrullinated protein antibody) formation

    NARCIS (Netherlands)

    Nesse, Willem; Westra, Johanna; van der Wal, Jacqueline E.; Abbas, Frank; Nicholas, Anthony P.; Vissink, Arjan; Brouwer, Elisabeth; Westra J., [No Value

    2012-01-01

    Aim To determine the presence and location (stroma versus epithelium) of citrullinated proteins in periodontitis tissue as compared to non-periodontitis tissue and synovial tissue of RA patients. Materials & Methods Periodontitis, healthy periodontal and RA-affected synovial tissue samples were coll

  7. L-citrulline-malate influence over branched chain amino acid utilization during exercise.

    Science.gov (United States)

    Sureda, Antoni; Córdova, Alfredo; Ferrer, Miguel D; Pérez, Gerardo; Tur, Josep A; Pons, Antoni

    2010-09-01

    Exhaustive exercise induces disturbances in metabolic homeostasis which can result in amino acid catabolism and limited L-arginine availability. Oral L-citrulline supplementation raises plasma L-arginine concentration and augments NO-dependent signalling. Our aim was to evaluate the effects of diet supplementation with L-citrulline-malate prior to intense exercise on the metabolic handle of plasma amino acids and on the products of metabolism of arginine as creatinine, urea and nitrite and the possible effects on the hormonal levels. Seventeen voluntary male pre-professional cyclists were randomly assigned to one of two groups: control or supplemented (6 g L-citrulline-malate 2 h prior exercise) and participated in a 137-km cycling stage. Blood samples were taken in basal conditions, 15 min after the race and 3 h post race (recovery). Most essential amino acids significantly decreased their plasma concentration as a result of exercise; however, most non-essential amino acids tended to significantly increase their concentration. Citrulline-malate ingestion significantly increased the plasma concentration of citrulline, arginine, ornithine, urea, creatinine and nitrite (p urea.

  8. Potential Role of Peptidylarginine Deiminase Enzymes and Protein Citrullination in Cancer Pathogenesis

    Directory of Open Access Journals (Sweden)

    Sunish Mohanan

    2012-01-01

    Full Text Available The peptidylarginine deiminases (PADs are a family of posttranslational modification enzymes that catalyze the conversion of positively charged protein-bound arginine and methylarginine residues to the uncharged, nonstandard amino acid citrulline. This enzymatic activity is referred to as citrullination or, alternatively, deimination. Citrullination can significantly affect biochemical pathways by altering the structure and function of target proteins. Five mammalian PAD family members (PADs 1–4 and 6 have been described and show tissue-specific distribution. Recent reviews on PADs have focused on their role in autoimmune diseases. Here, we will discuss the potential role of PADs in tumor progression and tumor-associated inflammation. In the context of cancer, increasing clinical evidence suggests that PAD4 (and possibly PAD2 has important roles in tumor progression. The link between PADs and cancer is strengthened by recent findings showing that treatment of cell lines and mice with PAD inhibitors significantly suppresses tumor growth and, interestingly, inflammatory symptoms. At the molecular level, transcription factors, coregulators, and histones are functional targets for citrullination by PADs, and citrullination of these targets can affect gene expression in multiple tumor cell lines. Next generation isozyme-specific PAD inhibitors may have therapeutic potential to regulate both the inflammatory tumor microenvironment and tumor cell growth.

  9. Myelin Basic Protein Citrullination in Multiple Sclerosis: A Potential Therapeutic Target for the Pathology.

    Science.gov (United States)

    Yang, Lei; Tan, Dewei; Piao, Hua

    2016-08-01

    Multiple sclerosis (MS) is a multifactorial demyelinating disease characterized by neurodegenerative events and autoimmune response against myelin component. Citrullination or deimination, a post-translational modification of protein-bound arginine into citrulline, catalyzed by Ca(2+) dependent peptidylarginine deiminase enzyme (PAD), plays an essential role in physiological processes include gene expression regulation, apoptosis and the plasticity of the central nervous system, while aberrant citrullination can generate new epitopes, thus involving in the initiation and/or progression of autoimmune disorder like MS. Myelin basic protein (MBP) is the major myelin protein and is generally considered to maintain the stability of the myelin sheath. This review describes the MBP citrullination and its consequence, as well as offering further support for the "inside-out" hypothesis that MS is primarily a neurodegenerative disease with secondary inflammatory demyelination. In addition, it discusses the role of MBP citrullination in the immune inflammation and explores the potential of inhibition of PAD enzymes as a therapeutic strategy for the disease.

  10. L-citrulline supplementation reverses the impaired airway relaxation in neonatal rats exposed to hyperoxia

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    Sopi Ramadan B

    2012-08-01

    Full Text Available Abstract Background Hyperoxia is shown to impair airway relaxation via limiting L-arginine bioavailability to nitric oxide synthase (NOS and reducing NO production as a consequence. L-arginine can also be synthesized by L-citrulline recycling. The role of L-citrulline supplementation was investigated in the reversing of hyperoxia-induced impaired relaxation of rat tracheal smooth muscle (TSM. Methods Electrical field stimulation (EFS, 2–20 V-induced relaxation was measured under in vitro conditions in preconstricted tracheal preparations obtained from 12 day old rat pups exposed to room air or hyperoxia (>95% oxygen for 7 days supplemented with L-citrulline or saline (in vitro or in vivo. The role of the L-citrulline/L-arginine cycle under basal conditions was studied by incubation of preparations in the presence of argininosuccinate synthase (ASS inhibitor [α-methyl-D, L-aspartate, 1 mM] or argininosuccinate lyase inhibitor (ASL succinate (1 mM and/or NOS inhibitor [Nω-nitro-L-arginine methyl ester; 100 μM] with respect to the presence or absence of L-citrulline (2 mM. Results Hyperoxia impaired the EFS-induced relaxation of TSM as compared to room air control (p ; 0.5 ± 0.1% at 2 V to 50.6 ± 5.7% at 20 V in hyperoxic group: 0.7 ± 0.2 at 2 V to 80.0 ± 5.6% at 20 V in room air group. Inhibition of ASS or ASL, and L-citrulline supplementation did not affect relaxation responses under basal conditions. However, inhibition of NOS significantly reduced relaxation responses (p in vivo and in vitro also reversed the hyperoxia-impaired relaxation. The differences were significant (p ; 0.8 ± 0.3% at 2 V to 47.1 ± 4.1% at 20 V without L-citrulline; 0.9 ± 0.3% at 2 V to 68.2 ± 4.8% at 20 V with L-citrulline. Inhibition of ASS or ASL prevented this effect of L-citrulline. Conclusion The results indicate the presence of an L-citrulline/L-arginine cycle in the airways of rat pups

  11. Effects of L-citrulline diet on stress-induced cold hypersensitivity in mice

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    Yoshinori Kobayashi

    2014-01-01

    Full Text Available Background: L-citrulline is an amino acid discovered in watermelon (Citrullus lanatus, Cucurbitaceae and is a known component of the nitric oxide (NO cycle that plays an important role in adjusting blood circulation and supplying NO and a key component of the endothelium-derived relaxing factor. Objective: The objective of this study is to evaluate the effect of L-citrulline on a newly established stress-induced cold hypersensitivity mouse model. Materials and Methods: When normal mice were forced to swim in water at 25°C for 15 min, their core body temperature dropped to 28.9°C, and then quickly recovered to normal temperature after the mice were transferred to a dry cage at room temperature (25°C. A 1-h immobilization before swimming caused the core body temperature to drop to ca. 24.1°C (4.8°C lower than normal mice, and the speed of core body temperature recovery dropped to 57% of the normal control. We considered this delay in recovery from hypothermia to be a sign of stress-induced cold hypersensitivity. Similar cold hypersensitivity was induced by administration of 50 mM L-NG-nitroarginine methyl ester, a NO synthesis inhibitor. Results: In this study, we showed that recovery speed from the stress-induced hypothermia remarkably improved in mice fed a 1% L-citrulline-containing diet for 20 days. Furthermore, the nonfasting blood level of L-arginine and L-citrulline increased significantly in the L-citrulline diet group, and higher serum nitrogen oxide levels were observed during recovery from the cold. Conclusions: These results suggested that oral L-citrulline supplementation strengthens vascular endothelium function and attenuates stress-induced cold hypersensitivity by improving blood circulation.

  12. Potential role for peptidylarginine deiminase 2 (PAD2 in citrullination of canine mammary epithelial cell histones.

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    Brian D Cherrington

    Full Text Available Peptidylarginine Deiminases (PADs convert arginine residues on substrate proteins to citrulline. Previous reports have documented that PAD2 expression and activity varies across the estrous cycle in the rodent uterus and pituitary gland, however, the expression and function of PAD2 in mammary tissue has not been previously reported. To gain more insight into potential reproductive roles for PAD2, in this study we evaluated PAD2 expression and localization throughout the estrous cycle in canine mammary tissue and then identified possible PAD2 enzymatic targets. Immunohistochemical and immunofluorescence analysis found PAD2 expression is low in anestrus, limited to a distinct, yet sparse, subset of epithelial cells within ductal alveoli during estrus/early diestrus, and encompasses the entire epithelium of the mammary duct in late diestrus. At the subcellular level, PAD2 is expressed in the cytoplasm, and to a lesser extent, the nucleus of these epithelial cells. Surprisingly, stimulation of canine mammary tumor cells (CMT25 shows that EGF, but not estrogen or progesterone, upregulates PAD2 transcription and translation suggesting EGF regulation of PAD2 and possibly citrullination in vivo. To identify potential PAD2 targets, anti-pan citrulline western blots were performed and results showed that citrullination activity is limited to diestrus with histones appearing to represent major enzymatic targets. Use of site-specific anti-citrullinated histone antibodies found that the N-terminus of histone H3, but not H4, appears to be the primary target of PAD activity in mammary epithelium. This observation supports the hypothesis that PAD2 may play a regulatory role in the expression of lactation related genes via histone citrullination during diestrus.

  13. Contribution of peptide backbone to Anti-citrulline-dependent antibody reactivity

    DEFF Research Database (Denmark)

    Trier, Nicole Hartwig; Dam, Catharina; Olsen, Dorthe

    2015-01-01

    Rheumatoid arthritis (RA) is one of the most common autoimmune diseases, affecting approximately 1–2% of the world population. One of the characteristic features of RA is the presence of autoantibodies. Especially the highly specific anti-citrullinated peptide antibodies (ACPAs), which have been...... homology rather than sequence homology are favored between citrullinated epitopes. These findings are important in relation to clarifying the etiology of RA and to determine the nature of ACPAs, e.g. why some Cit-Gly-containing sequences are not targeted by ACPAs....

  14. Circulating levels of citrullinated and MMP-degraded vimentin (VICM) in liver fibrosis related pathology

    DEFF Research Database (Denmark)

    Vassiliadis, E.; Oliveira, C. P.; Alvares-da-Silva, M. R.;

    2012-01-01

    -citrulline (VICM) was developed and evaluated in a carbon tetrachloride (CCl4) (n=52 + 28 controls) rat model of liver fibrosis and two clinical cohorts of adult patients with hepatitis C (HCV) (n=92) and non-alcoholic fatty liver disease (NAFLD) (n=62), and compared to healthy controls. Results: In CCl4-treated...

  15. Current Challenges and Limitations in Antibody-Based Detection of Citrullinated Histones

    Science.gov (United States)

    Neeli, Indira; Radic, Marko

    2016-01-01

    Studies on NETosis demand reliable and convenient markers to monitor the progress of this form of cell death. Because a determining step in the release of nuclear chromatin NETs requires the conversion of arginine residues to citrulline residues in histones by peptidylarginine deiminase, citrullinated histones can provide such a marker. Here, we evaluate antibody reagents for the detection of citrulline residues in histones and observe alarming differences between commercial antisera and mouse and rabbit monoclonal antibodies in their ability to detect their nominal target residues. Differences between antibodies that are currently used to detect citrulline residues in histones could jeopardize efforts to reach a scientific consensus and instead lead to inconsistent and even conflicting conclusions regarding the regulation of histone deimination. Our results will assist others in planning their initial or ongoing studies on peptidylarginine deiminase activity with the use of currently available antibodies. Furthermore, we argue that, along with the careful attention to experimental conditions and calcium concentrations, validated antibody reagents are urgently needed to avoid possible setbacks in the research on NETosis. PMID:27933065

  16. Current Challenges and Limitations in Antibody-Based Detection of Citrullinated Histones

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    Indira Neeli

    2016-11-01

    Full Text Available Studies on NETosis demand reliable and convenient markers to monitor the progress of this form of cell death. Because a determining step in the release of nuclear chromatin NETs requires the conversion of arginine residues to citrulline residues in histones by peptidylarginine deiminase, citrullinated histones can provide such a marker. Here, we evaluate antibody reagents for the detection of citrulline residues in histones and observe alarming differences between commercial antisera and mouse and rabbit monoclonal antibodies in their ability to detect their nominal target residues. Differences between antibodies that are currently used to detect citrulline residues in histones could jeopardize efforts to reach a scientific consensus and instead lead to inconsistent and even conflicting conclusions regarding the regulation of histone deimination. Our results will assist others in planning their initial or ongoing studies on peptidylarginine deiminase activity with the use of currently available antibodies. Further, we argue that, along with the careful attention to experimental conditions and calcium concentrations, validated antibody reagents are urgently needed to avoid possible setbacks in the research on NETosis.

  17. Post-translational modifications in rheumatoid arthritis and atherosclerosis: Focus on citrullination and carbamylation.

    Science.gov (United States)

    Spinelli, Francesca Romana; Pecani, Arbi; Conti, Fabrizio; Mancini, Riccardo; Alessandri, Cristiano; Valesini, Guido

    2016-09-01

    Coronary heart disease is the main cause of mortality in patients with rheumatoid arthritis (RA), a disease known to be associated with accelerated atherosclerosis. The role of inflammation and immunity in atherosclerotic process offers possible explanations for the increased cardiovascular risk in patients with RA. The immune response to citrullinated peptides has been extensively studied in RA; antibodies directed to citrullinated peptides are now a cornerstone for RA diagnosis. However, few studies have investigated the response to citrullinated peptides and the development of atherosclerotic plaque. Antibodies to carbamylated proteins can be detected before the clinical onset of RA, suggesting a potential predictive role for these antibodies; on the other hand, carbamylation of lipoproteins has been described in patients with cardiovascular disease. This review examines the role of citrullination and carbamylation, two post-translational protein modifications that appear to be involved in the pathogenesis of both RA and atherosclerosis, expanding the similarities between these two diseases. Further investigation on the role of the immune response to modified proteins may contribute to a better comprehension of cardiovascular disease in patients with RA.

  18. Impaired nitric oxide production in children with MELAS syndrome and the effect of arginine and citrulline supplementation.

    Science.gov (United States)

    El-Hattab, Ayman W; Emrick, Lisa T; Hsu, Jean W; Chanprasert, Sirisak; Almannai, Mohammed; Craigen, William J; Jahoor, Farook; Scaglia, Fernando

    2016-04-01

    Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is one of the most frequent maternally inherited mitochondrial disorders. The pathogenesis of this syndrome is not fully understood and believed to result from several interacting mechanisms including impaired mitochondrial energy production, microvasculature angiopathy, and nitric oxide (NO) deficiency. NO deficiency in MELAS syndrome is likely to be multifactorial in origin with the decreased availability of the NO precursors, arginine and citrulline, playing a major role. In this study we used stable isotope infusion techniques to assess NO production in children with MELAS syndrome and healthy pediatric controls. We also assessed the effect of oral arginine and citrulline supplementations on NO production in children with MELAS syndrome. When compared to control subjects, children with MELAS syndrome were found to have lower NO production, arginine flux, plasma arginine, and citrulline flux. In children with MELAS syndrome, arginine supplementation resulted in increased NO production, arginine flux, and arginine concentration. Citrulline supplementation resulted in a greater increase of these parameters. Additionally, citrulline supplementation was associated with a robust increase in citrulline concentration and flux and de novo arginine synthesis rate. The greater effect of citrulline in increasing NO production is due to its greater ability to increase arginine availability particularly in the intracellular compartment in which NO synthesis takes place. This study, which is the first one to assess NO metabolism in children with mitochondrial diseases, adds more evidence to the notion that NO deficiency occurs in MELAS syndrome, suggests a better effect for citrulline because of its greater role as NO precursor, and indicates that impaired NO production occurs in children as well as adults with MELAS syndrome. Thus, the initiation of treatment with NO precursors may be

  19. Increased plasma citrulline in mice marks diet-induced obesity and may predict the development of the metabolic syndrome.

    Science.gov (United States)

    Sailer, Manuela; Dahlhoff, Christoph; Giesbertz, Pieter; Eidens, Mena K; de Wit, Nicole; Rubio-Aliaga, Isabel; Boekschoten, Mark V; Müller, Michael; Daniel, Hannelore

    2013-01-01

    In humans, plasma amino acid concentrations of branched-chain amino acids (BCAA) and aromatic amino acids (AAA) increase in states of obesity, insulin resistance and diabetes. We here assessed whether these putative biomarkers can also be identified in two different obesity and diabetic mouse models. C57BL/6 mice with diet-induced obesity (DIO) mimic the metabolic impairments of obesity in humans characterized by hyperglycemia, hyperinsulinemia and hepatic triglyceride accumulation. Mice treated with streptozotocin (STZ) to induce insulin deficiency were used as a type 1 diabetes model. Plasma amino acid profiling of two high fat (HF) feeding trials revealed that citrulline and ornithine concentrations are elevated in obese mice, while systemic arginine bioavailability (ratio of plasma arginine to ornithine + citrulline) is reduced. In skeletal muscle, HF feeding induced a reduction of arginine levels while citrulline levels were elevated. However, arginine or citrulline remained unchanged in their key metabolic organs, intestine and kidney. Moreover, the intestinal conversion of labeled arginine to ornithine and citrulline in vitro remained unaffected by HF feeding excluding the intestine as prime site of these alterations. In liver, citrulline is mainly derived from ornithine in the urea cycle and DIO mice displayed reduced hepatic ornithine levels. Since both amino acids share an antiport mechanism for mitochondrial import and export, elevated plasma citrulline may indicate impaired hepatic amino acid handling in DIO mice. In the insulin deficient mice, plasma citrulline and ornithine levels also increased and additionally these animals displayed elevated BCAA and AAA levels like insulin resistant and diabetic patients. Therefore, type 1 diabetic mice but not DIO mice show the "diabetic fingerprint" of plasma amino acid changes observed in humans. Additionally, citrulline may serve as an early indicator of the obesity-dependent metabolic impairments.

  20. Increased plasma citrulline in mice marks diet-induced obesity and may predict the development of the metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Manuela Sailer

    Full Text Available In humans, plasma amino acid concentrations of branched-chain amino acids (BCAA and aromatic amino acids (AAA increase in states of obesity, insulin resistance and diabetes. We here assessed whether these putative biomarkers can also be identified in two different obesity and diabetic mouse models. C57BL/6 mice with diet-induced obesity (DIO mimic the metabolic impairments of obesity in humans characterized by hyperglycemia, hyperinsulinemia and hepatic triglyceride accumulation. Mice treated with streptozotocin (STZ to induce insulin deficiency were used as a type 1 diabetes model. Plasma amino acid profiling of two high fat (HF feeding trials revealed that citrulline and ornithine concentrations are elevated in obese mice, while systemic arginine bioavailability (ratio of plasma arginine to ornithine + citrulline is reduced. In skeletal muscle, HF feeding induced a reduction of arginine levels while citrulline levels were elevated. However, arginine or citrulline remained unchanged in their key metabolic organs, intestine and kidney. Moreover, the intestinal conversion of labeled arginine to ornithine and citrulline in vitro remained unaffected by HF feeding excluding the intestine as prime site of these alterations. In liver, citrulline is mainly derived from ornithine in the urea cycle and DIO mice displayed reduced hepatic ornithine levels. Since both amino acids share an antiport mechanism for mitochondrial import and export, elevated plasma citrulline may indicate impaired hepatic amino acid handling in DIO mice. In the insulin deficient mice, plasma citrulline and ornithine levels also increased and additionally these animals displayed elevated BCAA and AAA levels like insulin resistant and diabetic patients. Therefore, type 1 diabetic mice but not DIO mice show the "diabetic fingerprint" of plasma amino acid changes observed in humans. Additionally, citrulline may serve as an early indicator of the obesity-dependent metabolic

  1. Contribution of Peptide Backbone to Anti-Citrullinated Peptide Antibody Reactivity.

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    Nicole Hartwig Trier

    Full Text Available Rheumatoid arthritis (RA is one of the most common autoimmune diseases, affecting approximately 1-2% of the world population. One of the characteristic features of RA is the presence of autoantibodies. Especially the highly specific anti-citrullinated peptide antibodies (ACPAs, which have been found in up to 70% of RA patients' sera, have received much attention. Several citrullinated proteins are associated with RA, suggesting that ACPAs may react with different sequence patterns, separating them from traditional antibodies, whose reactivity usually is specific towards a single target. As ACPAs have been suggested to be involved in the development of RA, knowledge about these antibodies may be crucial. In this study, we examined the influence of peptide backbone for ACPA reactivity in immunoassays. The antibodies were found to be reactive with a central Cit-Gly motif being essential for ACPA reactivity and to be cross-reactive between the selected citrullinated peptides. The remaining amino acids within the citrullinated peptides were found to be of less importance for antibody reactivity. Moreover, these findings indicated that the Cit-Gly motif in combination with peptide backbone is essential for antibody reactivity. Based on these findings it was speculated that any amino acid sequence, which brings the peptide into a properly folded structure for antibody recognition is sufficient for antibody reactivity. These findings are in accordance with the current hypothesis that structural homology rather than sequence homology are favored between citrullinated epitopes. These findings are important in relation to clarifying the etiology of RA and to determine the nature of ACPAs, e.g., why some Cit-Gly-containing sequences are not targeted by ACPAs.

  2. Citrullination in Rheumatoid Arthritis—A Process Promoted by Neutrophil Lysis?

    Science.gov (United States)

    Gazitt, Tal; Lood, Christian; Elkon, Keith B.

    2016-01-01

    Anti-citrullinated protein antibodies (ACPAs) are highly specific serologic markers for rheumatoid arthritis (RA) and can pre-date clinical disease onset by up to 10 years, also predicting erosive disease. The process of citrullination, the post-translational conversion of arginine to citrulline residues, is mediated by peptidylarginine deiminase (PAD) enzymes present in polymorphonuclear cells (PMNs). Calcium ions (Ca2+) are required for PAD activation, but the intracellular Ca2+ concentration in normal cells is much lower than the optimal Ca2+ concentration needed for PAD activation. For this reason, it has been proposed that PAD activation, and thus citrullination, occurs only during PMN cell death when PAD enzymes leak out of the cells into the extracellular matrix, or extracellular Ca2+ enters the cells, with the high Ca2+ concentration activating PAD. Recently, using artificial in vitro systems to corroborate their hypothesis, Romero et al. demonstrated that “hypercitrullination,” citrullination of multiple intracellular proteins, occurs within synovial fluid (SF) cells of RA patients, and that only modes of death leading to membranolysis such as perforin-granzyme pathway or complement membrane attack complex activation cause hypercitrullination. In order for Romero’s hypothesis to hold, it is reasonable to surmise that PMN-directed lysis should occur in the rheumatoid joint or the circulation of RA patients. Research conducted thus far has shown that immunoglobulin G (IgG) targeting PMNs are present in RA SF and mediate PMN activation. However, the role of anti-PMN IgG in mediating complement activation and subsequent PMN lysis and hypercitrullination has not been fully evaluated. PMID:27824546

  3. Citrullination in Rheumatoid Arthritis—A Process Promoted by Neutrophil Lysis?

    Directory of Open Access Journals (Sweden)

    Tal Gazitt

    2016-10-01

    Full Text Available Anti-citrullinated protein antibodies (ACPAs are highly specific serologic markers for rheumatoid arthritis (RA and can pre-date clinical disease onset by up to 10 years, also predicting erosive disease. The process of citrullination, the post-translational conversion of arginine to citrulline residues, is mediated by peptidylarginine deiminase (PAD enzymes present in polymorphonuclear cells (PMNs. Calcium ions (Ca2+ are required for PAD activation, but the intracellular Ca2+ concentration in normal cells is much lower than the optimal Ca2+ concentration needed for PAD activation. For this reason, it has been proposed that PAD activation, and thus citrullination, occurs only during PMN cell death when PAD enzymes leak out of the cells into the extracellular matrix, or extracellular Ca2+ enters the cells, with the high Ca2+ concentration activating PAD. Recently, using artificial in vitro systems to corroborate their hypothesis, Romero et al. demonstrated that “hypercitrullination,” citrullination of multiple intracellular proteins, occurs within synovial fluid (SF cells of RA patients, and that only modes of death leading to membranolysis such as perforin-granzyme pathway or complement membrane attack complex activation cause hypercitrullination. In order for Romero’s hypothesis to hold, it is reasonable to surmise that PMN-directed lysis should occur in the rheumatoid joint or the circulation of RA patients. Research conducted thus far has shown that immunoglobulin G (IgG targeting PMNs are present in RA SF and mediate PMN activation. However, the role of anti-PMN IgG in mediating complement activation and subsequent PMN lysis and hypercitrullination has not been fully evaluated.

  4. The Comparision of Anti-cyclic Citrullinated Peptide Antibody and Rheumatoid Factor in Rheumatoid Arthritis Diagnosis%抗环瓜氨酸多肽抗体和类风湿因子在类风湿性关节炎诊断中的比较

    Institute of Scientific and Technical Information of China (English)

    周厚清; 许赤多; 张辉; 董敏

    2009-01-01

    目的:检测抗环瓜氨酸肽(CCP)抗体在类风湿性关节炎(RA)中的阳性率,探讨抗CCP抗体检测在RA中的意义.方法:用ELISA方法检测30例RA,35例其他风湿性疾病,20例非风湿性疾病中的抗CCP抗体的分布.用免疫比浊法测定类风湿因子(RF),比较抗CCP抗体与RF的相关性.结果:30例RA病人中,抗CCP抗体的阳性率为73.33%.抗CCP抗体对RA的敏感性和特异性分别为73.33%和94.54%.RF的阳性率为76.67%.RF抗体对RA的敏感性和特异性分别为76.67%和80.0%.抗CCP抗体与RF之间呈正相关性.结论:抗CCP抗体对RA具有良好的敏感性和特异性,可视为RA新的血清学诊断指标,能用于RA的诊断.同时联合检测抗CCP抗体和RF有助于提高RA检测的敏感性和特异性.

  5. Evaluation of Clinical Usefulness of Antikeratin Antibody, Antiperinuclear Factor and Anti-Cyclic Citrullinated Peptide Antibody in Juvenile Rheumatoid Arthritis%血清抗角蛋白抗体、抗核周因子和抗环瓜氨酸肽抗体在幼年类风湿关节炎应用中的评价

    Institute of Scientific and Technical Information of China (English)

    韩彤昕; 李彩凤; 何晓琥; 王江; 邝伟英; 周怡芳

    2007-01-01

    目的 评价抗角蛋白抗体(AKA)、抗核周因子(APF)和抗环瓜氨酸肽抗体(anti-CCP)在幼年类风湿关节炎(JRA)应用中的意义.方法 收集76例JRA及54例非JRA患儿,健康对照30例血清,测定其AKA、APF和抗CCP水平,对JRA诊断敏感性、特异性进行评价,并对JRA患儿中3种抗体阳性和阴性组的临床症状、体征及实验室检查指标进行比较,并作统计学分析.结果 AKA、APF和抗CCP及联合检测ROC曲线下面积略高于0.5, 但Pa>0.05.单一抗体检测灵敏度为30%~50%,联合检测灵敏度无增加.单一抗体检测的特异度为50%~80%,联合检测特异度增加至80%~85%.JRA组AKA(+)病例较多出现关节强直,心包积液,骨质稀疏,肺炎支原体抗体阳性率相对高,且ASO、ESR、CRP水平较高,Pa<0.05;APF(+)病例较多出现关节强直,骨质稀疏,肺炎支原体抗体阳性率相对高,而且ASO、ESR、CRP水平较高,有显著差异(P<0.05),抗CCP(+)病例与抗CCP(-)病例比较,在临床表现、实验室检查方面无显著差异.结论 AKA、APF、抗CCP抗体对JRA缺乏早期诊断意义及特异性,AKA、APF对判断疾病的活动性、病理损害程度和预后有临床意义.

  6. 类风湿因子、抗环瓜氨酸肽抗体和葡萄糖-6-磷酸酶联合检测在类风湿关节炎中的临床意义%Clinical value of rheumatoid factor combined with anti-cyclic citrullinated peptide antibodies and glucose-6-phosphatase in diagnosis of rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    胡玲

    2012-01-01

    目的 探讨及评价类风湿因子(RF)联合抗环瓜氨酸肽(CCP)抗体和G-6-磷酸酶(GPI)检测在自身类风湿性关节炎(RA)诊断中的意义.方法 选择我院2009~2010年收治的RA患者80例(A组),非RA自身免疫病患者60例(B组),健康体检者52例(C组),取空腹血制备血清,采用速率散射免疫比浊法检测RF,以酶联免疫固相吸附试验法(ELISA)检测抗CCP抗体,采用双抗体夹心酶联免疫固相吸附试验法检测血清GPI水平,并分析RF、抗CCP抗体和GPI在诊断RA中的价值.结果 RA患者中RF、抗CCP抗体、GPI的敏感性分别为63.75%,70.00%和83.75%,以GPI最高;三者特异性分别为66.25%、90.00%和91.25%;三项指标联合检测敏感性为96.25%,显著高于任意单项指标(P < 0.05),且阳性符合率为91.25%.结论 抗CCP抗体和GPI可作为RA诊断的实验室有效指标,临床中与RF联合应用可以起到增加敏感性,提高阳性符合率的互补作用.%Objective To explore and evaluate the clinical value of RF combined with CCP and GPI in diagnosis of rheumatoid arthritis. Methods 80 patients with rheumatoid arthritis, 60 patients with other autoimmune diseases and 52 normal people were selected and divided into A, B and C group, blood serums were prepared and RF, anti-CCP and GPI were detected by immunization rate nephelometry, enzyme-linked immunosorbent assay and double antibody sandwich enzyme-linked immunosorbent. Results The sensitivity of RF, anti-CCP and GPI in RA patients were 63.75%, 70.00% and 83.75% respectively, the GPI was higher than the other index, and the specificity of the three index were 66.25%, 90.00% and 91.25% respectively. The sensitivity in combination was 96.25%, which was higher than any single index (P < 0.05), and the positive coincidence rate was 91.25%. Conclusion Anti-CCP and GPI are effective indicators in diagnosis of RA, the two index combination with RF have the effects on improvement of the sensitivity and the positive coincidence rate.

  7. 抗环瓜氨酸肽抗体与类风湿因子IgM联合检测在类风湿关节炎早期诊断中的应用%Application of combined detection of anti-cyclic citrullinated peptide antibody and rheumatoid factor IgM-RF in rheumatoid arthritis early diagnosis

    Institute of Scientific and Technical Information of China (English)

    李光迪; 刘芳; 张长菊

    2007-01-01

    目的 探讨抗环瓜氨酸肽抗体(anti-CCP)、类风湿因子IgM(IgM-RF)联合检测在类风湿关节炎(RA)早期诊断中的价值.方法 用ELISA法对84例RA、96例非 RA和26例健康献血者中anti-CCP抗体及IgM-RF进行检测;分析anti-CCP抗体、IgM-RF及两者联合检测的敏感度、特异度、阳性似然比、阴性似然比.结果 RA患者anti-CCP抗体的含量约为15.73±3.35 RU/ml;IgM-RF约为79.93±33.83 RU/mL,均显著高于非RA组和健康对照组(P<0.01).anti-CCP抗体及IgM-RF对诊断RA的敏感度、特异度、阳性似然比、阴性似然比分别为: anti-CCP抗体(67.9%、94.8%、13.02、0.34),IgM-RF(71.4%、79.2%、3.43、0.36).anti-CCP抗体与IgM-RF联合检测敏感度和特异度分别为65.5%、96.9%,阳性似然比、阴性似然比分别为21.13、0.36.提示anti-CCP抗体的特异度、阳性似然比明显高于IgM-RF,IgM-RF较anti-CCP抗体有较高的敏感度,两者联合检测可提高诊断的特异度和阳性似然比,但不能提高敏感度.结论 anti-CCP抗体和IgM-RF联合检测可提高诊断的特异度和阳性似然比,对RA的早期诊断有较好的临床价值.

  8. Diagnostic value of anti-cyclic citrullinated peptide antibody, antikeratin antibody and rheumatoid factor in patients with rheumatoid arthritis%类风湿关节炎患者血清自身抗体对其诊断价值分析

    Institute of Scientific and Technical Information of China (English)

    尹海琴; 李宝全; 巩路

    2011-01-01

    目的:分析抗环瓜氨酸肽抗体(抗CCP抗体)、抗角质蛋白抗体(AKA)及各型类风湿因子(RF)联合检测对类风湿关节炎(RA)诊断与病情活动等方面的作用.方法:选取80例RA患者和75例非RA患者,进行相关实验室指标测定,并对结果进行统计学分析.结果:RF-IgG、RF-IgA、RF-lgM、AKA及抗CCP抗体对RA的敏感性为:RF-IgM>抗CCP抗体>RF-IgG>RF-IgA>AKA;特异性为:AKA>抗CCP抗体>RF-IgG>RF-IgA>RF-IgM;联合检测2种、3种、5种抗体对RA的敏感性和特异性分别是:RF-IgA+RF-lgM为51.3%/81.3%,RF-IgG+RF-IgA+RF-lgM为43.8%/89.3%,RF-IgA+RF-lgM+抗CCP抗体为45%/98.7%,RF-lgA+RF-lgM+AKA为22.5%/98.7%,RF-IgG+RF-IgA+RF-lgM+抗CCP抗体+AKA为18.8%/100%;抗CCP抗体阳性和阴性患者在RF滴度值、ESR和晨僵方面差异存在统计学意义(P<0.05).结论:抗CCP抗体在诊断RA中的价值优于AKA和RF;抗CCP抗体在一定程度上可能有助于早期诊断和活动性的监测;RF与抗CCP抗体、AKA联合检测可进一步提高对RA诊断的特异性.%Objective: To analyze the value of anti-CCP,anti-AKA and rheumatoid factor antibodies(RF-IgA, RF-IgG, RF-IgM) in diagnosis and prognosis in patients with rheumatoid arthritis (RA). Methods: 80 RA patients and 75 patients with other rheumatic diseases were investigated,the relationship between them was analysed with SPSS17.0 software. Results:The sensitivity of RF-IgG, RF-IgA, RFIgM, anti-AKA and anti-CCP was RF-IgM>anti-CCP>RF-IgG> RF-IgA>AKA;and the specificity was AKA>anti-CCP>RF-IgG>RF-IgA>RF-IgM ;The sensitivity and specificity of combined detection of RF-IgA and RF-IgM were 51.3% and 81.3%, that of combined detection of RF-IgG, RF-IgA and RF-IgM were 43.8% and 89.3%, that of combined detection of RF-IgA, RF-IgM and anti-CCP were 45% and 98.7%,that of combined detection of RF-IgA, RF-lgM and AKA were 22.5% and 98.7%,that of combined detection of RF-IgG,RF-IgA,RF-IgM,anti-CCP and AKA were 18.8% and 100%; There were statistically significant (P<0.05) in RF titer values, ESR and morning stiffness in anti-CCP antibody-positive and-negative patients. Conclusion:Anti-CCP antibodies in the diagnosis of RA is more valuable than the AKA and RF;Anti-CCP antibodies, in a certain extent, may contribute to judgments and disease activity monitoring;the specificity of diagnosis of RA can be enhanced by joint detection of RF,AKA and anti-CCP.

  9. Value of anti-cyclic peptide containing citrulline antibody for the early diagnosis of rheumatoid arthritis%类风湿关节炎早期诊断中抗环瓜氨酸肽抗体检测的意义

    Institute of Scientific and Technical Information of China (English)

    葛艳玲; 宋慧; 刘武征; 杨凯楠

    2015-01-01

    目的 探讨单独或联合检测抗环瓜氨酸肽抗体(anti-CCP)、类风湿因子(RF)对类风湿关节炎(RA)早期诊断的价值. 方法 选取2012-2014年门诊及住院患者1 961例,已确诊为RA患者共509例(RA组),非RA患者共1 028例(非RA组),初步诊断非RA,随诊确诊为RA患者424例(初诊非RA随诊为RA组),分别采用速率散射比浊法检测RF;电化学发光法检测anti-CCP.结果 RA组与非RA组比较,单独检测anti-CCP与联合检测anti-CCP/RF的敏感度比较差异无统计学意义(P>0.05),而特异度(88.6%比60.4%)比较差异有统计学意义(P0.05), but the specificity between two groups (88.6%vs. 60.4%) was significant difference ( P<0.05). There were significant differences in the sensitivity (81.7% vs. 74.3%) and specificity (88.6% vs. 66.0%) between by using anti-CCP antibody alone and RF alone.In firstly was not diagnosed RA but later was diagnosed RA group, there were significantly difference in sensitivity (98.3%vs. 82.1%) and specificity (91.6%vs. 81.5%) by using anti-CCP antibody alone and RF alone. Conclusion There is important clinical value by using anti-CCP antibody alone for the early diagnosis of RA.

  10. 抗环瓜氨酸肽抗体与类风湿因子联合检测在类风湿关节炎诊断中的意义%Diagnostic significance of combined detection of serum anti cyclic citrullinated-peptide antibody and rheumatoid factor in rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    范云燕; 余静

    2009-01-01

    目的 探讨联合检测抗环瓜氨酸肽(CCP)抗体和类风湿因子(RF)在类风湿关节炎(RA)诊断中的意义.方法 抗-CCP采用ELISA法,RF采用散射速率比浊法检测,检测59例RA、48例非RA患者血清抗抗-CCP和RF.结果 59例RA患者中单一抗-CCP阳性8例,单一RF阳性16例,两项同时阳性30例,同时阴性5例,故抗-CCP、RF及两者联合检测在RA患者中的阳性率分别为64.40% 、77.97%和91.53%;48例非RA患者中单一抗-CCP阳性2例,单一RF阳性14例,无1例两项同时阳性,故抗-CCP、RF及抗-CCP和RF联合检测在非RA患者中的阳性率分别为4.16% 、29.16%和0.经过统计学分析联合检测与单项检测比较差异有统计学意义(P<0.01),且RA患者抗-CCP与RF阳性率显著高于非RA患者,差异有统计学意义(χ2= 41.15、25.60,P<0.01 ).结论 抗-CCP和RF联合检测可明显提高RA的诊断率.

  11. Mitochondrial citrulline synthesis from ammonia and glutamine in the liver of ureogenic air-breathing catfish, Clarias batrachus (Linnaeus).

    Science.gov (United States)

    Kharbuli, Zaiba Y; Biswas, Kuheli; Saha, Nirmalendu

    2007-12-01

    The possible synthesis of citrulline, a rate limiting step for urea synthesis via the ornithine-urea cycle (OUC) in teleosts was tested both in the presence of ammonia and glutamine as nitrogen-donating substrates by the isolated liver mitochondria of ureogenic air-breathing walking catfish, C. batrachus. Both ammonia and glutamine could be used as nitrogen-donating substrates for the synthesis of citrulline by the isolated liver mitochondria, since the rate of citrulline synthesis was almost equal in presence of both the substrates. The citrulline synthesis by the isolated liver mitochondria requires succinate at a concentration of 0.1 mM as an energy source, and also requires the involvement of intramitochondrial carbonic anhydrase activity for supplying HCO3 as another substrate for citrulline synthesis. The rate of citrulline synthesis was further stimulated significantly by the isolated liver mitochondria of the fish after pre-exposure to 25 mM NH4Cl for 7 days. Due to possessing this biochemical adaptational strategy leading to the amelioration of ammonia toxicity mainly by channeling ammonia directly and/or via the formation of glutamine to the OUC, this air-breathing catfish could succeed in surviving in high external ammonia, which it faces in its natural habitat in certain seasons of the year.

  12. The 2007 ESPEN Sir David Cuthbertson Lecture: amino acids between and within organs. The glutamate-glutamine-citrulline-arginine pathway.

    Science.gov (United States)

    Deutz, Nicolaas E P

    2008-06-01

    In daily practice, the plasma concentration of amino acids is usually viewed as a parameter of production. However, both a high production and/or a reduced disposal capacity can result in an increased plasma concentration. In this presentation, I will discuss my research on interorgan relationships of the amino acids glutamate, glutamine, citrulline and arginine to explain the regulation of the plasma arginine level. The reduced glutamine disposal during liver failure is related to enhanced plasma glutamine level without any change in muscle and gut production or consumption rate. In contrast during sepsis, a small reduction in plasma glutamine is related to a substantially enhanced organ glutamate and glutamine production or consumption rate. These observations are a good example that plasma levels are directly related to production or consumption rates. Because glutamine breakdown in the gut produces citrulline, there is a good relation between the amount of metabolically active gut tissue and gut and whole body citrulline production. Arginine is produces from citrulline in the kidney and a reduced gut glutamine to citrulline conversion during sepsis explains the reduced de novo arginine production that is related to the reduced plasma arginine level. The interorgan route between muscle, gut, liver and kidney of the amino acids glutamate, glutamine, citrulline and arginine is a very good example of how complicated the regulation of plasma amino acid levels can be. However, in-depth research is necessary and will give us important clues to new nutritional strategies.

  13. Peptidylarginine deiminase 2-catalyzed histone H3 arginine 26 citrullination facilitates estrogen receptor α target gene activation.

    Science.gov (United States)

    Zhang, Xuesen; Bolt, Michael; Guertin, Michael J; Chen, Wei; Zhang, Sheng; Cherrington, Brian D; Slade, Daniel J; Dreyton, Christina J; Subramanian, Venkataraman; Bicker, Kevin L; Thompson, Paul R; Mancini, Michael A; Lis, John T; Coonrod, Scott A

    2012-08-14

    Cofactors for estrogen receptor α (ERα) can modulate gene activity by posttranslationally modifying histone tails at target promoters. Here, we found that stimulation of ERα-positive cells with 17β-estradiol (E2) promotes global citrullination of histone H3 arginine 26 (H3R26) on chromatin. Additionally, we found that the H3 citrulline 26 (H3Cit26) modification colocalizes with ERα at decondensed chromatin loci surrounding the estrogen-response elements of target promoters. Surprisingly, we also found that citrullination of H3R26 is catalyzed by peptidylarginine deiminase (PAD) 2 and not by PAD4 (which citrullinates H4R3). Further, we showed that PAD2 interacts with ERα after E2 stimulation and that inhibition of either PAD2 or ERα strongly suppresses E2-induced H3R26 citrullination and ERα recruitment at target gene promoters. Collectively, our data suggest that E2 stimulation induces the recruitment of PAD2 to target promoters by ERα, whereby PAD2 then citrullinates H3R26, which leads to local chromatin decondensation and transcriptional activation.

  14. Circulating levels of citrullinated and MMP-degraded vimentin (VICM) in liver fibrosis related pathology

    DEFF Research Database (Denmark)

    Vassiliadis, Efstathios; Oliveira, Claudia P; Alvares-da-Silva, Mario R;

    2012-01-01

    -citrulline (VICM) was developed and evaluated in a carbon tetrachloride (CCl(4)) (n=52 + 28 controls) rat model of liver fibrosis and two clinical cohorts of adult patients with hepatitis C (HCV) (n=92) and non-alcoholic fatty liver disease (NAFLD) (n=62), and compared to healthy controls. RESULTS: In CCl(4.......75, PNAFLD cohort, VICM levels were 20.6% higher in F0 (339...... ±12 ng/mL, PNAFLD patients. These data...

  15. Streptococcus pyogenes arginine and citrulline catabolism promotes infection and modulates innate immunity.

    Science.gov (United States)

    Cusumano, Zachary T; Watson, Michael E; Caparon, Michael G

    2014-01-01

    A bacterium's ability to acquire nutrients from its host during infection is an essential component of pathogenesis. For the Gram-positive pathogen Streptococcus pyogenes, catabolism of the amino acid arginine via the arginine deiminase (ADI) pathway supplements energy production and provides protection against acid stress in vitro. Its expression is enhanced in murine models of infection, suggesting an important role in vivo. To gain insight into the function of the ADI pathway in pathogenesis, the virulence of mutants defective in each of its enzymes was examined. Mutants unable to use arginine (ΔArcA) or citrulline (ΔArcB) were attenuated for carriage in a murine model of asymptomatic mucosal colonization. However, in a murine model of inflammatory infection of cutaneous tissue, the ΔArcA mutant was attenuated but the ΔArcB mutant was hyperattenuated, revealing an unexpected tissue-specific role for citrulline metabolism in pathogenesis. When mice defective for the arginine-dependent production of nitric oxide (iNOS(-/-)) were infected with the ΔArcA mutant, cutaneous virulence was rescued, demonstrating that the ability of S. pyogenes to utilize arginine was dispensable in the absence of nitric oxide-mediated innate immunity. This work demonstrates the importance of arginine and citrulline catabolism and suggests a novel mechanism of virulence by which S. pyogenes uses its metabolism to modulate innate immunity through depletion of an essential host nutrient.

  16. Does Citrulline Have Protective Effects on Liver Injury in Septic Rats?

    Directory of Open Access Journals (Sweden)

    Bin Cai

    2016-01-01

    Full Text Available Citrulline (Cit supplementation was proposed to serve as a therapeutic intervention to restore arginine (Arg concentrations and improve related functions in sepsis. This study explored whether citrulline had positive effects on liver injury and cytokine release in the early stages of sepsis. The cecal ligation and puncture (CLP model was utilized in our study. Rats were divided into four groups: normal, Cit, CLP, and CLP+Cit. The CLP group and CLP+Cit group were separated into 6-, 12-, and 24-hour groups, according to the time points of sacrifice after surgery. Intragastric administration of L-citrulline was applied to rats in Cit and CLP+Cit groups before surgery. Serum AST and ALT levels and levels of MDA, SOD, NO, and iNOS in the liver tissues were evaluated. Plasma concentrations of Cit and Arg were assessed using HPLC-MS/MS. Serum concentrations of cytokines and chemokines were calculated by Luminex. Results showed SOD activities of CLP+Cit groups were significantly higher than that of CLP groups, contrasting with the MDA and NO levels which were significantly lower in CLP+Cit groups than in CLP groups. In addition, plasma concentrations of TNF-α, IL-6, and IL-1β were significantly lower in the CLP+Cit 6-hour group than in the CLP 6-hour group.

  17. The effects on plasma L-arginine levels of combined oral L-citrulline and L-arginine supplementation in healthy males.

    Science.gov (United States)

    Suzuki, Takashi; Morita, Masahiko; Hayashi, Toshio; Kamimura, Ayako

    2017-02-01

    We investigated the effects of combining 1 g of l-citrulline and 1 g of l-arginine as oral supplementation on plasma l-arginine levels in healthy males. Oral l-citrulline plus l-arginine supplementation more efficiently increased plasma l-arginine levels than 2 g of l-citrulline or l-arginine, suggesting that oral l-citrulline and l-arginine increase plasma l-arginine levels more effectively in humans when combined.

  18. Reduced TCR-dependent activation through citrullination of a T-cell epitope enhances Th17 development by disruption of the STAT3/5 balance

    NARCIS (Netherlands)

    Tibbitt, Christopher; Falconer, Jane; Stoop, Jeroen; van Eden, Willem; Robinson, John H.; Hilkens, Catharien M U

    2016-01-01

    Citrullination is a post-translational modification of arginine that commonly occurs in inflammatory tissues. Because T-cell receptor (TCR) signal quantity and quality can regulate T-cell differentiation, citrullination within a T-cell epitope has potential implications for T-cell effector function.

  19. Quantitative analysis of 15N labeled positional isomers of glutamine and citrulline via electrospray ionization tandem mass spectrometry of their dansyl derivatives

    Science.gov (United States)

    The enteral metabolism of glutamine and citrulline are intertwined because, while glutamine is one of the main fuel sources for the enterocyte, citrulline is one of its products. It has been shown that the administration of 15N labeled glutamine results in the incorporation of the 15N label into cit...

  20. Extracellular citrulline levels in the nucleus accumbens during the acquisition and extinction of a classical conditioned reflex with pain reinforcement.

    Science.gov (United States)

    Savel'ev, S A; Saul'skaya, N B

    2007-03-01

    Studies on Sprague-Dawley rats using in vivo microdialysis and HPLC showed that the acquisition and performance of a classical conditioned reflex with pain reinforcement was accompanied by increases in the concentrations of citrulline (a side product of nitric oxide formation) and arginine (the substrate of NO synthase) in the intercellular space of the nucleus accumbens. During extinction of the reflex, there was a decrease in the elevation of extracellular citrulline in this brain structure, which correlated with the extent of extinction of the reflex. Recovery of the reflex led to increases in arginine and citrulline levels in the nucleus accumbens. These data suggest that there is an increase in nitric oxide production in the nucleus accumbens during the acquisition and performance of a classical conditioned reflex with pain reinforcement, which decreases as the reflex is extinguished and recovers with recovery of the reflex.

  1. Enzymatic syntheses of carbamyl phosphate, L-citrulline, and N-carbamyl L-aspartate labeled with either 13N or 11C.

    Science.gov (United States)

    Gelbard, A S; Kaseman, D S; Rosenspire, K C; Meister, A

    1985-01-01

    [13N]- and [11C]carbamyl phosphate, L-[omega-13N]citrulline, L-[ureido-11C]citrulline, [carbamyl-13N]- and [carbamyl-11C]carbamyl-L-aspartate were synthesized using carbamyl phosphate synthetase co-immobilized with either aspartate transcarbamylase or ornithine transcarbamylase. Carbamyl L-[13N]aspartate was enzymatically prepared from carbamyl phosphate and L-[13N]aspartate. The tissue distribution of radioactivity in mice after injection of radiolabeled ammonia, carbamyl phosphate or citrulline was studied. The tissue distribution of isotope derived from [13N]carbamyl phosphate and [13N]ammonia were similar, with the exception of liver, brain and pancreas, in which 13NH3 uptake was higher after retroorbital injection. The distribution of label derived from L-[omega-13N]- and L-[ureido-11C]citrulline was similar. Substantial tumor (Sarcoma-180) uptake of label from L-citrulline was observed.

  2. Citrullination of histone H3 interferes with HP1-mediated transcriptional repression.

    Directory of Open Access Journals (Sweden)

    Priyanka Sharma

    2012-09-01

    Full Text Available Multiple Sclerosis (MS is an autoimmune disease associated with abnormal expression of a subset of cytokines, resulting in inappropriate T-lymphocyte activation and uncontrolled immune response. A key issue in the field is the need to understand why these cytokines are transcriptionally activated in the patients. Here, we have examined several transcription units subject to pathological reactivation in MS, including the TNFα and IL8 cytokine genes and also several Human Endogenous RetroViruses (HERVs. We find that both the immune genes and the HERVs require the heterochromatin protein HP1α for their transcriptional repression. We further show that the Peptidylarginine Deiminase 4 (PADI4, an enzyme with a suspected role in MS, weakens the binding of HP1α to tri-methylated histone H3 lysine 9 by citrullinating histone H3 arginine 8. The resulting de-repression of both cytokines and HERVs can be reversed with the PADI-inhibitor Cl-amidine. Finally, we show that in peripheral blood mononuclear cells (PBMCs from MS patients, the promoters of TNFα, and several HERVs share a deficit in HP1α recruitment and an augmented accumulation of histone H3 with a double citrulline 8 tri-methyl lysine 9 modifications. Thus, our study provides compelling evidence that HP1α and PADI4 are regulators of both immune genes and HERVs, and that multiple events of transcriptional reactivation in MS patients can be explained by the deficiency of a single mechanism of gene silencing.

  3. Newborn screening for dihydrolipoamide dehydrogenase deficiency: Citrulline as a useful analyte

    Directory of Open Access Journals (Sweden)

    Shane C. Quinonez

    2014-01-01

    Full Text Available Dihydrolipoamide dehydrogenase deficiency, also known as maple syrup urine disease (MSUD type III, is caused by the deficiency of the E3 subunit of branched chain alpha-ketoacid dehydrogenase (BCKDH, α-ketoglutarate dehydrogenase (αKGDH, and pyruvate dehydrogenase (PDH. DLD deficiency variably presents with either a severe neonatal encephalopathic phenotype or a primarily hepatic phenotype. As a variant form of MSUD, it is considered a core condition recommended for newborn screening. The detection of variant MSUD forms has proven difficult in the past with no asymptomatic DLD deficiency patients identified by current newborn screening strategies. Citrulline has recently been identified as an elevated dried blood spot (DBS metabolite in symptomatic patients affected with DLD deficiency. Here we report the retrospective DBS analysis and second-tier allo-isoleucine testing of 2 DLD deficiency patients. We show that an elevated citrulline and an elevated allo-isoleucine on second-tier testing can be used to successfully detect DLD deficiency. We additionally recommend that DLD deficiency be included in the “citrullinemia/elevated citrulline” ACMG Act Sheet and Algorithm.

  4. l-Citrulline ameliorates cerebral blood flow during cortical spreading depression in rats: Involvement of nitric oxide- and prostanoids-mediated pathway.

    Science.gov (United States)

    Kurauchi, Yuki; Mokudai, Koichi; Mori, Asami; Sakamoto, Kenji; Nakahara, Tsutomu; Morita, Masahiko; Kamimura, Ayako; Ishii, Kunio

    2017-02-17

    l-Citrulline is a potent precursor of l-arginine, and exerts beneficial effect on cardiovascular system via nitric oxide (NO) production. Migraine is one of the most popular neurovascular disorder, and imbalance of cerebral blood flow (CBF) observed in cortical spreading depression (CSD) contributes to the mechanism of migraine aura. Here, we investigated the effect of l-citrulline on cardiovascular changes to KCl-induced CSD. in rats. Intravenous injection of l-citrulline prevented the decrease in CBF, monitored by laser Doppler flowmetry, without affecting mean arterial pressure and heart rate during CSD. Moreover, l-citrulline attenuated propagation velocity of CSD induced by KCl. The effect of l-citrulline on CBF change was prevented by l-NAME, an inhibitor of NO synthase, but not by indomethacin, an inhibitor of cyclooxygenase. On the other hand, attenuation effect of l-citrulline on CSD propagation velocity was prevented not only by l-NAME but also by indomethacin. In addition, propagation velocity of CSD was attenuated by intravenous injection of NOR3, a NO donor, which was diminished by ODQ, an inhibitor of soluble guanylyl cyclase. These results suggest that NO/cyclic GMP- and prostanoids-mediated pathway differently contribute to the effect of l-citrulline on the maintenance of CBF.

  5. Enzymatic production of l-citrulline by hydrolysis of the guanidinium group of l-arginine with recombinant arginine deiminase.

    Science.gov (United States)

    Song, Wei; Sun, Xia; Chen, Xiulai; Liu, Dongxu; Liu, Liming

    2015-08-20

    In this study, a simple, efficient enzymatic production process for the environmentally friendly synthesis of l-citrulline from l-arginine was developed using arginine deiminase (ADI) from Lactococcus lactis. Following overexpression of L. lactis ADI in Escherichia. coli BL21 (DE3) and experimental evolution using error-prone PCR, mutant FMME106 was obtained with a Km for l-arginine of 3.5mM and a specific activity of 195.7U/mg. This mutant exhibited a maximal conversion of 92.6% and achieved a final l-citrulline concentration of 176.9g/L under optimal conditions (190g/L l-arginine, 15g/L whole-cell biocatalyst treated with 2% isopropanol for 30min, 50°C, pH 7.2, 8h). The average l-citrulline synthesis rate of 22.1g/L/h is considerably higher than that reported for other similar biocatalytic approaches, therefore the process developed in the present work has great potential for large-scale production of l-citrulline.

  6. Environmental risk factors differ between rheumatoid arthritis with and without auto-antibodies against cyclic citrullinated peptides

    DEFF Research Database (Denmark)

    Pedersen, Line Merete Blak; Jacobsen, Søren; Klarlund, Mette;

    2006-01-01

    The aim of this study was to evaluate new and previously hypothesised non-genetic risk factors for serologic subtypes of rheumatoid arthritis (RA) defined by the presence or absence of auto-antibodies to cyclic citrullinated peptides (CCP). In a national case-control study, we included 515 patients...

  7. Apo AIV and Citrulline Plasma Concentrations in Short Bowel Syndrome Patients: The Influence of Short Bowel Anatomy

    Science.gov (United States)

    Targarona, Jordi; Ruiz, Jorge; García, Natalia; Oró, Denise; García-Villoria, Judit; Creus, Gloria; Pita, Ana M.

    2016-01-01

    Introduction Parenteral nutrition (PN) dependence in short bowel syndrome (SBS) patients is linked to the functionality of the remnant small bowel (RSB). Patients may wean off PN following a period of intestinal adaptation that restores this functionality. Currently, plasma citrulline is the standard biomarker for monitoring intestinal functionality and adaptation. However, available studies reveal that the relationship the biomarker with the length and function of the RSB is arguable. Thus, having additional biomarkers would improve pointing out PN weaning. Aim By measuring concomitant changes in citrulline and the novel biomarker apolipoprotein AIV (Apo AIV), as well as taking into account the anatomy of the RSB, this exploratory study aims to a better understanding of the intestinal adaptation process and characterization of the SBS patients under PN. Methods Thirty four adult SBS patients were selected and assigned to adapted (aSBS) and non-adapted (nSBS) groups after reconstructive surgeries. Remaining jejunum and ileum lengths were recorded. The aSBS patients were either on an oral diet (ORAL group), those with intestinal insufficiency, or on oral and home parenteral nutrition (HPN group), those with chronic intestinal failure. Apo AIV and citrulline were analyzed in plasma samples after overnight fasting. An exploratory ROC analysis using citrulline as gold standard was performed. Results Biomarkers, Apo AIV and citrulline showed a significant correlation with RSBL in aSBS patients. In jejuno-ileocolic patients, only Apo AIV correlated with RSBL (rb = 0.54) and with ileum length (rb = 0.84). In patients without ileum neither biomarker showed any correlation with RSBL. ROC analysis indicated the Apo AIV cut-off value to be 4.6 mg /100 mL for differentiating between the aSBS HPN and ORAL groups. Conclusions Therefore, in addition to citrulline, Apo AIV can be set as a biomarker to monitor intestinal adaptation in SBS patients. As short bowel anatomy is shown

  8. Accuracy and standardization of diagnostic methods for the detection of antibodies to citrullinated peptides

    Directory of Open Access Journals (Sweden)

    M. Tampoia

    2011-06-01

    Full Text Available Anti-citrullinated peptide antibodies (ACPA have a very high specificity for rheumatoid arthritis, much more than that of the rheumatoid factor. In addition, ACPA can be found in sera in the pre-clinical phase, are associated with more severe joint destruction and with higher disease activity. In recent years, keeping pace with new knowledge and with progress made in the antigenic composition of tests and in the characterization of immunogenic epitopes, many immunoenzymatic (ELISA methods of second and third generation have been produced and marketed commercially, and their use has spread among clinical laboratories. Today, completely automated methods are also available, which are easy to use and with a higher throughput, rendering the diagnostic utility of testing ever faster and more effective. This review takes into consideration the more important characteristics of the new ACPA-ELISA tests now commercially available, and also considers recent progress in standardizing test results.

  9. A putative transport protein is involved in citrulline excretion and re-uptake during arginine deiminase pathway activity by Lactobacillus sakei.

    Science.gov (United States)

    Rimaux, Tom; Rivière, Audrey; Hebert, Elvira María; Mozzi, Fernanda; Weckx, Stefan; De Vuyst, Luc; Leroy, Frédéric

    2013-04-01

    Arginine conversion through the arginine deiminase (ADI) pathway is a common metabolic trait of Lactobacillus sakei which is ascribed to an arc operon and which inquisitively involves citrulline excretion and re-uptake. The aim of this study was to verify whether a putative transport protein (encoded by the PTP gene) plays a role in citrulline-into-ornithine conversion by L. sakei strains. This was achieved through a combination of fermentation experiments, gene expression analysis via quantitative real-time reverse transcription PCR (RT-qPCR) and construction of a PTP knock-out mutant. Expression of the PTP gene was modulated by environmental pH and was highest in the end-exponential or mid-exponential growth phase for L. sakei strains CTC 494 and 23K, respectively. In contrast to known genes of the arc operon, the PTP gene showed low expression at pH 7.0, in agreement with the finding that citrulline-into-ornithine conversion is inhibited at this pH. The presence of additional energy sources also influenced ADI pathway activity, in particular by decreasing citrulline-into-ornithine conversion. Further insight into the functionality of the PTP gene was obtained with a knock-out mutant of L. sakei CTC 494 impaired in the PTP gene, which displayed inhibition in its ability to convert extracellular citrulline into ornithine. In conclusion, results indicated that the PTP gene may putatively encode a citrulline/ornithine antiporter.

  10. Environmental pH determines citrulline and ornithine release through the arginine deiminase pathway in Lactobacillus fermentum IMDO 130101.

    Science.gov (United States)

    Vrancken, G; Rimaux, T; Weckx, S; De Vuyst, L; Leroy, F

    2009-11-15

    Sourdough lactic acid bacteria (LAB) need to be adapted to a highly acidic and, therefore, challenging environment. Different mechanisms are employed to enhance competitiveness, among which conversion of arginine into ornithine through the arginine deiminase (ADI) pathway is an important one. A combined molecular and kinetic approach of the ADI pathway in Lactobacillus fermentum IMDO 130101, a highly competitive sourdough LAB strain, identified mechanisms with advantageous technological effects and quantified the impact of these effects. First, molecular analysis of the arcBCAD operon of 4.8 kb revealed the genes encoding the enzymes ornithine transcarbamoylase, carbamate kinase, arginine deiminase, and an arginine/ornithine (A/O) antiporter, respectively, with an additional A/O antiporter 702.5 kb downstream of the ADI operon. The latter could play a role in citrulline transport. Second, pH-controlled batch fermentations were carried out, generating data for the development of a mathematical model to describe the temporal evolution of the three amino acids involved in the ADI pathway (arginine, citrulline, and ornithine) as a result of the activity of these enzymes and transporter(s). Free arginine in the medium was converted completely into a mixture of citrulline and ornithine under all conditions tested. However, the ratio between these end-products and the pattern of their formation showed variation as a function of environmental pH. Under optimal pH conditions for growth, citrulline release and some further conversion into ornithine was observed. When growing under sub-optimal pH conditions, ornithine was the main product of the ADI pathway. These kinetic data suggest a role in adaptation of L. fermentum IMDO 130101 to growth under sub-optimal conditions.

  11. Modular pathway engineering of Corynebacterium glutamicum for production of the glutamate-derived compounds ornithine, proline, putrescine, citrulline, and arginine.

    Science.gov (United States)

    Jensen, Jaide V K; Eberhardt, Dorit; Wendisch, Volker F

    2015-11-20

    The glutamate-derived bioproducts ornithine, citrulline, proline, putrescine, and arginine have applications in the food and feed, cosmetic, pharmaceutical, and chemical industries. Corynebacterium glutamicum is not only an excellent producer of glutamate but also of glutamate-derived products. Here, engineering targets beneficial for ornithine production were identified and the advantage of rationally constructing a platform strain for the production of the amino acids citrulline, proline, and arginine, and the diamine putrescine was demonstrated. Feedback alleviation of N-acetylglutamate kinase, tuning of the promoter of glutamate dehydrogenase gene gdh, lowering expression of phosphoglucoisomerase gene pgi, along with the introduction of a second copy of the arginine biosynthesis operon argCJB(A49V,M54V)D into the chromosome resulted in a C. glutamicum strain producing ornithine with a yield of 0.52 g ornithine per g glucose, an increase of 71% as compared to the parental ΔargFRG strain. Strains capable of producing 0.41 g citrulline per g glucose, 0.29 g proline per g glucose, 0.30 g arginine per g glucose, and 0.17 g putrescine per g glucose were derived from the ornithine-producing platform strain by plasmid-based overexpression of appropriate pathway modules with one to three genes.

  12. The Supplementation of Branched-Chain Amino Acids, Arginine, and Citrulline Improves Endurance Exercise Performance in Two Consecutive Days

    Directory of Open Access Journals (Sweden)

    I-Shiung Cheng, Yi-Wen Wang, I-Fan Chen, Gi-Sheng Hsu, Chun-Fang Hsueh, Chen-Kang Chang

    2016-09-01

    Full Text Available The central nervous system plays a crucial role in fatigue during endurance exercise. Branched-chain amino acids (BCAA could reduce cerebral serotonin synthesis by competing with its precursor tryptophan for crossing the blood brain barrier. Arginine and citrulline could prevent excess hyperammonemia accompanied by BCAA supplementation. This study investigated the combination of BCAA, arginine, and citrulline on endurance performance in two consecutive days. Seven male and three female endurance runners ingested 0.17 g·kg-1 BCAA, 0.05 g·kg-1 arginine and 0.05 g·kg-1 citrulline (AA trial or placebo (PL trial in a randomized cross-over design. Each trial contained a 5000 m time trial on the first day, and a 10000 m time trial on the second day. The AA trial had significantly better performance in 5000 m (AA: 1065.7 ± 33.9 s; PL: 1100.5 ± 40.4 s and 10000 m (AA: 2292.0 ± 211.3 s; PL: 2375.6 ± 244.2 s. The two trials reported similar ratings of perceived exertion. After exercise, the AA trial had significantly lower tryptophan/BCAA ratio, similar NH3, and significantly higher urea concentrations. In conclusion, the supplementation could enhance time-trial performance in two consecutive days in endurance runners, possibly through the inhibition of cerebral serotonin synthesis by BCAA and the prevention of excess hyperammonemia by increased urea genesis.

  13. Diagnostic significance of combined testing of anti-cyclic citrullinated peptide antibody and hidden rheumatoid factor immunoglobulin M in patients with juvenile rheumatoid arthritis%抗环瓜氨酸肽抗体和隐匿性类风湿因子免疫球蛋白M型在诊断早期幼年类风湿关节炎中的意义

    Institute of Scientific and Technical Information of China (English)

    滕庆; 刘永革; 何晓琥

    2004-01-01

    目的检测抗环瓜氨酸肽(CCP)抗体及隐匿性类风湿因子IgM型(HRF-IgM),并探讨其在幼年类风湿关节炎(JRA)早期诊断中的临床意义.方法用人工合成CCP链为抗原检测抗CCP抗体;对27例早期诊断的JRA做动态检测,通过阳性预测值(PPV)和阴性预测值(NPV)确定抗CCP抗体和HRF-IgM对早期诊断的JRA的特异性和敏感性.结果抗CCP抗体和HRF-IgM总阳性率分别为58.5%、65.0%.后者敏感性要高于前者,病情越重或受累的关节越多,抗体检出率越高.对早期JRA的PPV、抗CCP抗体特异性要高于HRF-IgM.当两种实验联合应用时,对具有早期关节炎表现发展成JRA的PPV为93.7%.结论抗C℃P抗体和HRF-IgM在JRA患儿均有较高的检出率,并与疾病严重程度有关.抗CCP抗体与HRF-IgM联合应用时,可使JRA的PPV进一步提高.

  14. Comparison of Two Assays to Determine Anti-Citrullinated Peptide Antibodies in Rheumatoid Arthritis in relation to Other Chronic Inflammatory Rheumatic Diseases: Assaying Anti-Modified Citrullinated Vimentin Antibodies Adds Value to Second-Generation Anti-Citrullinated Cyclic Peptides Testing

    Science.gov (United States)

    Díaz-Toscano, Miriam Lizette; Olivas-Flores, Eva Maria; Zavaleta-Muñiz, Soraya Amali; Gamez-Nava, Jorge Ivan; Cardona-Muñoz, Ernesto German; Ponce-Guarneros, Manuel; Castro-Contreras, Uriel; Nava, Arnulfo; Salazar-Paramo, Mario; Celis, Alfredo; Fajardo-Robledo, Nicte Selene; Corona-Sanchez, Esther Guadalupe; Gonzalez-Lopez, Laura

    2014-01-01

    Determination of anti-citrullinated peptide antibodies (ACPA) plays a relevant role in the diagnosis of rheumatoid arthritis (RA). To date, it is still unclear if the use of several tests for these autoantibodies in the same patient offers additional value as compared to performing only one test. Therefore, we evaluated the performance of using two assays for ACPA: second-generation anti-citrullinated cyclic peptides antibodies (anti-CCP2) and anti-mutated citrullinated vimentin (anti-MCV) antibodies for the diagnosis of RA. We compared three groups: RA (n = 142), chronic inflammatory disease (CIRD, n = 86), and clinically healthy subjects (CHS, n = 56) to evaluate sensitivity, specificity, predictive values, and likelihood ratios (LR) of these two assays for the presence of RA. A lower frequency of positivity for anti-CCP2 was found in RA (66.2%) as compared with anti-MCV (81.0%). When comparing RA versus other CIRD, sensitivity increased when both assays were performed. This strategy of testing both assays had high specificity and LR+. We conclude that adding the assay of anti-MCV antibodies to the determination of anti-CCP2 increases the sensitivity for detecting seropositive RA. Therefore, we propose the use of both assays in the initial screening of RA in longitudinal studies, including early onset of undifferentiated arthritis. PMID:25025037

  15. Comparison of Two Assays to Determine Anti-Citrullinated Peptide Antibodies in Rheumatoid Arthritis in relation to Other Chronic Inflammatory Rheumatic Diseases: Assaying Anti-Modified Citrullinated Vimentin Antibodies Adds Value to Second-Generation Anti-Citrullinated Cyclic Peptides Testing

    Directory of Open Access Journals (Sweden)

    Miriam Lizette Díaz-Toscano

    2014-01-01

    Full Text Available Determination of anti-citrullinated peptide antibodies (ACPA plays a relevant role in the diagnosis of rheumatoid arthritis (RA. To date, it is still unclear if the use of several tests for these autoantibodies in the same patient offers additional value as compared to performing only one test. Therefore, we evaluated the performance of using two assays for ACPA: second-generation anti-citrullinated cyclic peptides antibodies (anti-CCP2 and anti-mutated citrullinated vimentin (anti-MCV antibodies for the diagnosis of RA. We compared three groups: RA (n=142, chronic inflammatory disease (CIRD, n=86, and clinically healthy subjects (CHS, n=56 to evaluate sensitivity, specificity, predictive values, and likelihood ratios (LR of these two assays for the presence of RA. A lower frequency of positivity for anti-CCP2 was found in RA (66.2% as compared with anti-MCV (81.0%. When comparing RA versus other CIRD, sensitivity increased when both assays were performed. This strategy of testing both assays had high specificity and LR+. We conclude that adding the assay of anti-MCV antibodies to the determination of anti-CCP2 increases the sensitivity for detecting seropositive RA. Therefore, we propose the use of both assays in the initial screening of RA in longitudinal studies, including early onset of undifferentiated arthritis.

  16. Asymmetric Dimethylarginine Is a Well Established Mediating Risk Factor for Cardiovascular Morbidity and Mortality-Should Patients with Elevated Levels Be Supplemented with Citrulline?

    Science.gov (United States)

    McCarty, Mark F

    2016-07-08

    The arginine metabolite asymmetric dimethylarginine (ADMA) is a competitive inhibitor and uncoupler of endothelial nitric oxide synthase (eNOS), an enzyme that acts in multifarious ways to promote cardiovascular health. This phenomenon likely explains, at least in part, why elevated ADMA has been established as an independent risk factor for cardiovascular events, ventricular hypertrophy, and cardiovascular mortality. Fortunately, the suppressive impact of ADMA on eNOS activity can be offset by increasing intracellular arginine levels with supplemental citrulline. Although the long-term impact of supplemental citrulline on cardiovascular health in patients with elevated ADMA has not yet been studied, shorter-term clinical studies of citrulline administration demonstrate effects suggestive of increased NO synthesis, such as reductions in blood pressure and arterial stiffness, improved endothelium-dependent vasodilation, increased erection hardness, and increased ejection fractions in patients with heart failure. Supplemental citrulline could be a practical option for primary or secondary prevention of cardiovascular events and mortality, as it is inexpensive, has a mild flavor, and is well tolerated in doses (3-6 g daily) that can influence eNOS activity. Large and long-term clinical trials, targeting patients at high risk for cardiovascular events in whom ADMA is elevated, are needed to evaluate citrulline's potential for aiding cardiovascular health.

  17. A novel role for protein arginine deiminase 4 in pluripotency: the emerging role of citrullinated histone H1 in cellular programming.

    Science.gov (United States)

    Slade, Daniel J; Horibata, Sachi; Coonrod, Scott A; Thompson, Paul R

    2014-08-01

    Histone post-translational modifications (PTMs) alter the chromatin architecture, generating "open" and "closed" states, and these structural changes can modulate gene expression under specific cellular conditions. While methylation and acetylation are the best-characterized histone PTMs, citrullination by the protein arginine deiminases (PADs) represents another important player in this process. In addition to "fine tuning" chromatin structure at specific loci, histone citrullination can also promote rapid global chromatin decondensation during the formation of extracellular traps (ETs) in immune cells. Recent studies now show that PAD4-mediated citrullination of histone H1 at promoter elements can also promote localized chromatin decondensation in stem cells, thus regulating the pluripotent state. These observations suggest that PAD-mediated histone deimination profoundly affects chromatin structure, possibly above and beyond that of other PTMs. Additionally, these recent findings further enhance our understanding of PAD biology and the important contributions that these enzymes play in development, health, and disease.

  18. Demonstration of extracellular peptidylarginine deiminase (PAD) activity in synovial fluid of patients with rheumatoid arthritis using a novel assay for citrullination of fibrinogen

    DEFF Research Database (Denmark)

    Damgaard, Dres; Senolt, Ladislav; Nielsen, Michael Friberg

    2014-01-01

    INTRODUCTION: Members of the peptidylarginine deiminase (PAD) family catalyse the posttranslational conversion of peptidylarginine to peptidylcitrulline. Citrullination of proteins is well described in rheumatoid arthritis (RA), and hypercitrullination of proteins may be related to inflammation...... in general. PAD activity has been demonstrated in various cell lysates, but so far not in synovial fluid. We aimed to develop an assay for detection of PAD activity, if any, in synovial fluid from RA patients. METHODS: An enzyme-linked immunosorbent assay using human fibrinogen as the immobilized substrate...... for citrullination and anti-citrullinated fibrinogen antibody as the detecting agent were used for measurement of PAD activity in synovial fluid samples from five RA patients. The concentrations of PAD2 and calcium were also determined. RESULTS: Approximately 150 times lower levels of recombinant human PAD2 (rhPAD2...

  19. Genetic markers of rheumatoid arthritis susceptibility in anti-citrullinated peptide antibody negative patients

    Science.gov (United States)

    Viatte, Sebastien; Plant, Darren; Bowes, John; Lunt, Mark; Eyre, Stephen; Barton, Anne; Worthington, Jane

    2012-01-01

    Introduction There are now over 30 confirmed loci predisposing to rheumatoid arthritis (RA). Studies have been largely undertaken in patients with anticyclic citrullinated peptide (anti-CCP) positive RA, and some genetic associations appear stronger in this subgroup than in anti-CCP negative disease, although few studies have had adequate power to address the question. The authors therefore investigated confirmed RA susceptibility loci in a large cohort of anti-CCP negative RA subjects. Methods RA patients and controls, with serological and genetic data, were available from UK Caucasian patients (n=4068 anti-CCP positive, 2040 anti-CCP negative RA) and 13,009 healthy controls. HLA-DRB1 genotypes and 36 single nucleotide polymorphisms were tested for association between controls and anti-CCP positive or negative RA. Results The shared epitope (SE) showed a strong association with anti-CCP positive and negative RA, although the effect size was significantly lower in the latter (effect size ratio=3.18, p<1.0E-96). A non-intronic marker at TNFAIP3, GIN1/C5orf30, STAT4, ANKRD55/IL6ST, BLK and PTPN22 showed association with RA susceptibility, irrespective of the serological status, the latter three markers remaining significantly associated with anti-CCP negative RA, after correction for multiple testing. No significant association with anti-CCP negative RA was detected for other markers (eg, AFF3, CD28, intronic marker at TNFAIP3), though the study power for those markers was over 80%. Discussion In the largest sample size studied to date, the authors have shown that the strength of association, the effect size and the number of known RA susceptibility loci associated with disease is different in the two disease serotypes, confirming the hypothesis that they might be two genetically different subsets. PMID:22661644

  20. The clinical significance of antibody determination to cyclic citrullinated peptides in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Stamenković Bojana

    2012-01-01

    Full Text Available Introduction. Anti-citrullinated peptides antibodies (ACPA are present in 80% of sera of rheumatoid arthritis (RA patients with high specificity for diagnosis and prediction for the development of early erosive arthritis. A few studies have reported a low frequency ACPA in systemic sclerosis (SSc patients with the presence of arthritis. Objective. The aim of our study was to determine the frequency of ACPA in systemic sclerosis (SSc patients, their correlation with clinical manifestations and radiographic features. Methods. The study included 82 patients with SSc, mean age 54.4 years, 59 with the limited (lSSc and 23 with the diffuse (dSSc form of the disease. The control group included 28 healthy age and sex matched subjects. ACPA and rheumatoid factor (RF were determined in all SSc patients and healthy subjects in whom standard radiography of hands and wrists was also done. Results. The presence of ACPA was detected in 11 (13.4% of SSc patients. Their level was not increased in any of the controls. Positive RF was found in 15.9% of SSc patients. Arthritis was present in 17.1%, as well as marginal bone erosions. There was a statistically significant association between positive ACPA and arthritis (p<0.0001 and positive ACPA and marginal bone erosions (p=0.0002. Conclusion. The research confirmed the correlation between ACPA with clinical signs of arthritis and radiographic damage of hand joints. ACPA is a useful diagnostic marker in the identification of SSc patients with arthritis and anatomic bone damage enabling the use of adequate therapy in order to prevent joint damage and poor quality of life.

  1. Anti-citrullinated peptide antibodies in lupus patients with or without deforming arthropathy.

    Science.gov (United States)

    Damián-Abrego, G N; Cabiedes, J; Cabral, A R

    2008-04-01

    The objective was to study the association of antibodies against cyclic citrullinated peptides (anti-CCP) in patients with lupus articular damage. We studied 34 systemic lupus erythematosus patients (30 women) with (n = 14) or without (n = 20) deforming arthropathy. Anti-DNA and arthritis were mandatory inclusion criteria for both groups. As controls, 34 patients with rheumatoid arthritis and nine patients with rheumatoid arthritis and systemic lupus erythematosus (rhupus) were included. Anti-CCP and rheumatoid factor were determined by ELISA and nephelometry respectively. All patients had recent x-ray films of the hands that were evaluated according to Sharp's method. Systemic lupus erythematosus patients had a mean 6.50 +/- 0.86 (SD, range 5-8) American College of Rheumatology (ACR) criteria, rheumatoid arthritis patients met 5.38 +/- 0.60 (range 4-6) ACR criteria for rheumatoid arthritis and rhupus patients had 5.78 +/- 0.44 (range 5-6) criteria for rheumatoid arthritis and 5.11 +/- 0.78 (range 4-6) for systemic lupus erythematosus. Systemic lupus erythematosus patients, with or without deforming arthropathy, had normal serum anti-CCP concentrations. In contrast, rheumatoid arthritis and rhupus patients had 30- and 23-fold higher than normal amounts of anti-CCP (p lupus deforming arthropathy were more frequently positive for rheumatoid factor (65%) than patients with non-deforming arthritis (15%) (p = 0.005). Patients with lupus deforming arthropathy had similar frequency of erosions and mean Sharp's score than rhupus patients. Anti-CCP antibodies do not associate with lupus arthropathy, whether deforming, non-deforming or erosive.

  2. Reduced TCR‐dependent activation through citrullination of a T‐cell epitope enhances Th17 development by disruption of the STAT3/5 balance

    Science.gov (United States)

    Tibbitt, Christopher; Falconer, Jane; Stoop, Jeroen; van Eden, Willem; Robinson, John H.

    2016-01-01

    Citrullination is a post‐translational modification of arginine that commonly occurs in inflammatory tissues. Because T‐cell receptor (TCR) signal quantity and quality can regulate T‐cell differentiation, citrullination within a T‐cell epitope has potential implications for T‐cell effector function. Here, we investigated how citrullination of an immunedominant T‐cell epitope affected Th17 development. Murine naïve CD4+ T cells with a transgenic TCR recognising p89‐103 of the G1 domain of aggrecan (agg) were co‐cultured with syngeneic bone marrow‐derived dendritic cells (BMDC) presenting the native or citrullinated peptides. In the presence of pro‐Th17 cytokines, the peptide citrullinated on residue 93 (R93Cit) significantly enhanced Th17 development whilst impairing the Th2 response, compared to the native peptide. T cells responding to R93Cit produced less IL‐2, expressed lower levels of the IL‐2 receptor subunit CD25, and showed reduced STAT5 phosphorylation, whilst STAT3 activation was unaltered. IL‐2 blockade in native p89‐103‐primed T cells enhanced the phosphorylated STAT3/STAT5 ratio, and concomitantly enhanced Th17 development. Our data illustrate how a post‐translational modification of a TCR contact point may promote Th17 development by altering the balance between STAT5 and STAT3 activation in responding T cells, and provide new insight into how protein citrullination may influence effector Th‐cell development in inflammatory disorders. PMID:27173727

  3. L-citrulline protects from kidney damage in type 1 diabetic mice.

    Directory of Open Access Journals (Sweden)

    Maritza J Romero

    2013-12-01

    Full Text Available Rationale. Diabetic nephropathy is a major cause of end-stage renal disease, associated with endothelial dysfunction. Chronic supplementation of L-arginine (L-arg, the substrate for endothelial nitric oxide synthase (eNOS, failed to improve vascular function. L-citrulline (L-cit supplementation not only increases L-arg synthesis, but also inhibits cytosolic arginase I (Arg I, a competitor of eNOS for the use of L-arg, in the vasculature. Aims. To investigate whether L-cit treatment reduces diabetic nephropathy in streptozotocin (STZ-induced type 1 diabetes in mice and rats and to study its effects on arginase II (ArgII function, the main renal isoform. Methods. STZ-C57BL6 mice received L-cit or vehicle supplemented in the drinking water. For comparative analysis, diabetic ArgII knock out mice and L-cit-treated STZ-rats were evaluated. Results. L-cit exerted protective effects in kidneys of STZ-rats, and markedly reduced urinary albumin excretion, tubulo-interstitial fibrosis and kidney hypertrophy, observed in untreated diabetic mice. Intriguingly, L-cit treatment was accompanied by a sustained elevation of tubular ArgII at 16 wks and significantly enhanced plasma levels of the anti-inflammatory cytokine IL-10. Diabetic ArgII knock out mice showed greater BUN levels, hypertrophy, and dilated tubules than diabetic wild type mice. Despite a marked reduction in collagen deposition in ArgII knock out mice, their albuminuria was not significantly different from diabetic wild type animals. L-cit also restored NO/ROS balance and barrier function in high glucose-treated monolayers of human glomerular endothelial cells. Moreover, L-cit also has the ability to establish an anti-inflammatory profile, characterized by increased IL-10 and reduced IL-1beta and IL-12(p70 generation in the human proximal tubular cells. Conclusions. L-cit supplementation established an anti-inflammatory profile and significantly preserved the nephron function during type 1

  4. Are plasma citrulline and glutamine biomarkers of intestinal absorptive function in patients with short bowel syndrome?

    Science.gov (United States)

    Luo, Menghua; Fernández-Estívariz, Concepción; Manatunga, Amita K; Bazargan, Niloofar; Gu, Li H; Jones, Dean P; Klapproth, Jan-Michael; Sitaraman, Shanthi V; Leader, Lorraine M; Galloway, John R; Ziegler, Thomas R

    2007-01-01

    Sensitive biomarkers for intestinal absorptive function would be clinically useful in short bowel syndrome (SBS). Citrulline (Cit) is a product of the metabolism of glutamine (Gln) and derived amino acids by enterocytes. Cit is produced almost exclusively by the gut, which is also a major site of Gln metabolism. The goals of this study were to examine whether plasma Cit and Gln concentrations are biomarkers of residual small intestinal length and nutrient absorptive functions in adult SBS patients followed prospectively. We studied 24 stable adults with severe SBS receiving chronic parenteral nutrition (PN) in a double-blind, randomized trial of individualized dietary modification +/- recombinant human growth hormone (GH). During a baseline week, intestinal absorption studies (% absorption of fluid, kcal, nitrogen, fat, carbohydrate, sodium, phosphorus, and magnesium) were performed and concomitant plasma Cit and Gln concentrations determined. Individualized dietary modification and treatment with subcutaneous injection of placebo (n = 9) or GH (0.1 mg/kg daily x 21 days, then 3 times/week; n = 15) were then begun. PN weaning was initiated after week 4 and continued as tolerated for 24 weeks. Repeat plasma amino acid determination and nutrient absorption studies were performed at weeks 4 and 12. Residual small bowel length at baseline was positively correlated with baseline plasma Cit (r = 0.467; p = .028). However, no significant correlations between absolute Cit or Gln concentrations and the percent absorption of nutrient substrates at any time point were observed. Similarly, no correlation between the change in Cit or GLN concentration and the change in % nutrient absorption was observed (baseline vs weeks 4 and 12, respectively). By weeks 12 and 24, 7 and 13 subjects were weaned completely from PN, respectively. However, baseline plasma Cit or Gln did not predict PN weaning at these time points. We concluded that plasma Cit (but not Gln) concentrations appeared

  5. Asymmetric Dimethylarginine Is a Well Established Mediating Risk Factor for Cardiovascular Morbidity and Mortality—Should Patients with Elevated Levels Be Supplemented with Citrulline?

    Science.gov (United States)

    McCarty, Mark F.

    2016-01-01

    The arginine metabolite asymmetric dimethylarginine (ADMA) is a competitive inhibitor and uncoupler of endothelial nitric oxide synthase (eNOS), an enzyme that acts in multifarious ways to promote cardiovascular health. This phenomenon likely explains, at least in part, why elevated ADMA has been established as an independent risk factor for cardiovascular events, ventricular hypertrophy, and cardiovascular mortality. Fortunately, the suppressive impact of ADMA on eNOS activity can be offset by increasing intracellular arginine levels with supplemental citrulline. Although the long-term impact of supplemental citrulline on cardiovascular health in patients with elevated ADMA has not yet been studied, shorter-term clinical studies of citrulline administration demonstrate effects suggestive of increased NO synthesis, such as reductions in blood pressure and arterial stiffness, improved endothelium-dependent vasodilation, increased erection hardness, and increased ejection fractions in patients with heart failure. Supplemental citrulline could be a practical option for primary or secondary prevention of cardiovascular events and mortality, as it is inexpensive, has a mild flavor, and is well tolerated in doses (3–6 g daily) that can influence eNOS activity. Large and long-term clinical trials, targeting patients at high risk for cardiovascular events in whom ADMA is elevated, are needed to evaluate citrulline’s potential for aiding cardiovascular health. PMID:27417628

  6. Asymmetric Dimethylarginine Is a Well Established Mediating Risk Factor for Cardiovascular Morbidity and Mortality—Should Patients with Elevated Levels Be Supplemented with Citrulline?

    Directory of Open Access Journals (Sweden)

    Mark F. McCarty

    2016-07-01

    Full Text Available The arginine metabolite asymmetric dimethylarginine (ADMA is a competitive inhibitor and uncoupler of endothelial nitric oxide synthase (eNOS, an enzyme that acts in multifarious ways to promote cardiovascular health. This phenomenon likely explains, at least in part, why elevated ADMA has been established as an independent risk factor for cardiovascular events, ventricular hypertrophy, and cardiovascular mortality. Fortunately, the suppressive impact of ADMA on eNOS activity can be offset by increasing intracellular arginine levels with supplemental citrulline. Although the long-term impact of supplemental citrulline on cardiovascular health in patients with elevated ADMA has not yet been studied, shorter-term clinical studies of citrulline administration demonstrate effects suggestive of increased NO synthesis, such as reductions in blood pressure and arterial stiffness, improved endothelium-dependent vasodilation, increased erection hardness, and increased ejection fractions in patients with heart failure. Supplemental citrulline could be a practical option for primary or secondary prevention of cardiovascular events and mortality, as it is inexpensive, has a mild flavor, and is well tolerated in doses (3–6 g daily that can influence eNOS activity. Large and long-term clinical trials, targeting patients at high risk for cardiovascular events in whom ADMA is elevated, are needed to evaluate citrulline’s potential for aiding cardiovascular health.

  7. A combination of autoantibodies to cyclic citrullinated peptide (CCP) and HLA-DRB1 locus antigens is strongly associated with future onset of rheumatoid arthritis

    NARCIS (Netherlands)

    Berglin, E.; Padyukov, L.; Sundin, U.; Hallmans, G.; Stenlund, H.; Venrooij, W.J.W. van; Klareskog, L.; Dahlqvist, S.R.

    2004-01-01

    Antibodies against cyclic citrullinated peptide (CCP) and rheumatoid factors (RFs) have been demonstrated to predate the onset of rheumatoid arthritis ( RA) by years. A nested case control study was performed within the Northern Sweden Health and Disease study cohort to analyse the presence of share

  8. A tale of two citrullines--structural and functional aspects of myelin basic protein deimination in health and disease.

    Science.gov (United States)

    Harauz, George; Musse, Abdiwahab A

    2007-02-01

    Myelin basic protein (MBP) binds to negatively charged lipids on the cytosolic surface of oligodendrocyte membranes and is responsible for adhesion of these surfaces in the multilayered myelin sheath. The pattern of extensive post-translational modifications of MBP is dynamic during normal central nervous system (CNS) development and during myelin degeneration in multiple sclerosis (MS), affecting its interactions with the myelin membranes and with other molecules. In particular, the degree of deimination (or citrullination) of MBP is correlated with the severity of MS, and may represent a primary defect that precedes neurodegeneration due to autoimmune attack. That the degree of MBP deimination is also high in early CNS development indicates that this modification plays major physiological roles in myelin assembly. In this review, we describe the structural and functional consequences of MBP deimination in healthy and diseased myelin.

  9. Effects of Supplemental Citrulline-Malate Ingestion on Blood Lactate, Cardiovascular Dynamics, and Resistance Exercise Performance in Trained Males.

    Science.gov (United States)

    Wax, Benjamin; Kavazis, Andreas N; Luckett, William

    2016-01-01

    Citrulline-malate (CM) has been proposed to provide an ergogenic effect during resistance exercise; however, there is a paucity of research investigating these claims. Therefore, we investigated the impact that CM supplementation would have on repeated bouts of resistance exercise. Fourteen resistance-trained males participated in a randomized, counterbalanced, double-blind study. Subjects were randomly assigned to placebo (PL) or CM (8 g) and performed three sets each of chin-ups, reverse chin-ups, and push-ups to failure. One week later, subjects ingested the other supplement and performed the same protocol. Blood lactate (BLa), heart rate (HR), and blood pressure (BP) were measured preexercise, with BLa measured a second time immediately following the last set, while HR and BP were measured 5 and 10 min postexercise. Citrulline-malate ingestion significantly increased the amount of repetitions performed for each exercise (chin-ups: PL = 28.4 ± 7.1, CM = 32.2 ± 5.6, p = .003; reverse chin-ups: PL = 26.6 ± 5.6, CM = 32.1 ± 7.1, p = .017; push-ups: PL = 89.1 ± 37.4, CM = 97.7 ± 36.1, p < .001). Blood lactate data indicated a time effect (p < .001), but no treatment differences (p = .935). Systolic BP data did not show differences for time (p = .078) or treatment (p = .119). Diastolic BP data did not show differences for time (p = .069), but indicated treatment differences (p = .014) for subjects ingesting CM. Collectively, these findings suggests that CM increased upper-body resistance performance in trained college-age males.

  10. Periodontitis increases rheumatic factor serum levels and citrullinated proteins in gingival tissues and alter cytokine balance in arthritic rats

    Science.gov (United States)

    Corrêa, Mônica G.; Sacchetti, Silvana B.; Ribeiro, Fernanda Vieira; Pimentel, Suzana Peres; Casarin, Renato Corrêa Viana; Cirano, Fabiano Ribeiro; Casati, Marcio Z.

    2017-01-01

    This study investigated some immunological features by experimental periodontitis (EP) and rheumatoid arthritis (RA) disease interact in destructive processes in arthritic rats. Rats were assigned to the following groups: EP +RA; RA; EP; and Negative Control. RA was induced by immunizations with type-II collagen and a local immunization with Complete Freund’s adjuvant in the paw. Periodontitis was induced by ligating the right first molars. The serum level of rheumatoid factor (RF) and anti-citrullinated protein antibody (ACCPA) were measured before the induction of EP (T1) and at 28 days after (T2) by ELISA assay. ACCPA levels were also measured in the gingival tissue at T2. The specimens were processed for morphometric analysis of bone loss, and the gingival tissue surrounding the first molar was collected for the quantification of interleukin IL-1β, IL-4, IL-6, IL-17 and TNF-α using a Luminex/MAGpix assay. Paw edema was analyzed using a plethysmometer. Periodontitis increased the RF and ACCPA levels in the serum and in the gingival tissue, respectively. Besides, the level of paw swelling was increased by EP and remained in progress until the end of the experiment, when EP was associated with RA. Greater values of IL-17 were observed only when RA was present, in spite of PE. It can be concluded that periodontitis increases rheumatic factor serum levels and citrullinated proteins level in gingival tissues and alter cytokine balance in arthritic rats; at the same time, arthritis increases periodontal destruction, confirming the bidirectional interaction between diseases. PMID:28358812

  11. To evaluate the clinical diagnosic value of anti-cyclic citrul inated peptide(anti-CCP) antibody and rheumatoid factor(RF) in patients with rheumatoid arthritis(RA)%联合检测抗CCP抗体与RF对类风湿关节炎诊断的临床意义

    Institute of Scientific and Technical Information of China (English)

    赵海燕

    2014-01-01

    目的:探讨联合检测抗环瓜氨酸肽抗体(抗CCP抗体)及类风湿因子(RF)对类风湿性关节炎(RA)的临床诊断价值。方法:分别检测130例RA患者,98例非RA的风湿病患者及40例正常人血清的抗CCP抗体和RF。结果:抗CCP抗体和RF联合检测的特异性,阳性预测值,阳性似然比,阴性似然比与任何单一项检测比较均有显著差异(P<0.05)。结论:联合检测抗CCP抗体和RF可明显提高类风湿性关节炎的诊断率。%Objective: To evaluate the clinical diagnosic value of anti-cyclic citrul inated peptide(anti-CCP) antibody and rheumatoid factor(RF) in patients with rheumatoid arthritis(RA). Methods: Anti-CCP antibody was defected by quantitative ELISA and rheumatoid factor by BNP nephelometer in 130 cases of RA, 98 cases of non-RA rheumatic diseases and 40 cases of healthy individuals. Results: The diagnosis specificity, positive predictive value, positive/negative likelihood ratios of combinate determination of anti-CCP antibody and RF were significantly higher than either one. Conclusion: The measurements of anti-CCP antibody and rheumatoid factor wil remarkably improve the accuracy of diagnosis of RA.

  12. Effect of an hyperbaric nitrogen narcotic ambience on arginine and citrulline levels, the precursor and co-product of nitric oxide, in rat striatum.

    Science.gov (United States)

    Vallée, Nicolas; Rissoe, Jean-Jacques; Blatteau, Jean-Eric

    2011-07-05

    Previous studies performed in the laboratory have shown that nitrogen narcosis induces a decrease in striatal glutamate and dopamine levels. Although we stimulated the N-methyl-D-aspartate (NMDA) receptor, an important glutamate receptor required for motor and locomotor activity managed by the striatum, and demonstrated that the receptor was effective when exposed to nitrogen at 3MPa, it was not possible to return the striatal glutamate level to its base values. We conclude that it was the striatopetal neurons of the glutamatergic pathways that were mainly affected in this hyperbaric syndrome, without understanding the principal reasons. Hence we sought to establish what happens in the vicinity of the plasma membrane, downstream the NMDA-Receptor, and we used the hypothesis that there could be neuronal nitric oxide synthase (nNOS) disturbances. A microdialysis study was performed in rat striatum in order to analyse levels of citrulline, the NO co-product, and arginine, the NO precursor. Those both NO metabolites were detectable with an HPLC coupled to a fluorimetric detector. Exposure to pressurized nitrogen induced a reduction in citrulline (-18.9%) and arginine (-10.4%) levels. Under the control normobaric conditions, the striatal NMDA infusion enhanced the citrulline level (+85.6%), whereas under 3 MPa of nitrogen, the same NMDA infusion did not change the citrulline level which remains equivalent to that of the baseline. The level of arginine increased (+45.7%) under normobaric conditions but a decrease occurred in pressurized nitrogen (-51.6%). Retrodialysis with Saclofen and KCl in the prefrontal cortex under normobaric conditions led to an increase in striatal levels of citrulline (+30.5%) and a decrease in arginine levels (-67.4%). There was no significant difference when nitrogen at 3MPa was added. To conclude, the synthesis of citrulline/NO is reduced in nitrogen narcosis while it seems possible to activate it artificially by infusion. We have suggested

  13. Effect of an hyperbaric nitrogen narcotic ambience on arginine and citrulline levels, the precursor and co-product of nitric oxide, in rat striatum

    Directory of Open Access Journals (Sweden)

    Vallée Nicolas

    2011-07-01

    Full Text Available Abstract Previous studies performed in the laboratory have shown that nitrogen narcosis induces a decrease in striatal glutamate and dopamine levels. Although we stimulated the N-methyl-D-aspartate (NMDA receptor, an important glutamate receptor required for motor and locomotor activity managed by the striatum, and demonstrated that the receptor was effective when exposed to nitrogen at 3MPa, it was not possible to return the striatal glutamate level to its base values. We conclude that it was the striatopetal neurons of the glutamatergic pathways that were mainly affected in this hyperbaric syndrome, without understanding the principal reasons. Hence we sought to establish what happens in the vicinity of the plasma membrane, downstream the NMDA-Receptor, and we used the hypothesis that there could be neuronal nitric oxide synthase (nNOS disturbances. A microdialysis study was performed in rat striatum in order to analyse levels of citrulline, the NO co-product, and arginine, the NO precursor. Those both NO metabolites were detectable with an HPLC coupled to a fluorimetric detector. Exposure to pressurized nitrogen induced a reduction in citrulline (-18.9% and arginine (-10.4% levels. Under the control normobaric conditions, the striatal NMDA infusion enhanced the citrulline level (+85.6%, whereas under 3 MPa of nitrogen, the same NMDA infusion did not change the citrulline level which remains equivalent to that of the baseline. The level of arginine increased (+45.7% under normobaric conditions but a decrease occurred in pressurized nitrogen (-51.6%. Retrodialysis with Saclofen and KCl in the prefrontal cortex under normobaric conditions led to an increase in striatal levels of citrulline (+30.5% and a decrease in arginine levels (-67.4%. There was no significant difference when nitrogen at 3MPa was added. To conclude, the synthesis of citrulline/NO is reduced in nitrogen narcosis while it seems possible to activate it artificially by infusion

  14. Effects of type II collagen epitope carbamylation and citrullination in human leucocyte antigen (HLA)-DR4(+) monozygotic twins discordant for rheumatoid arthritis.

    Science.gov (United States)

    De Santis, M; Ceribelli, A; Cavaciocchi, F; Generali, E; Massarotti, M; Isailovic, N; Crotti, C; Scherer, H U; Montecucco, C; Selmi, C

    2016-09-01

    The aim of this study is to investigate the effect of the native, citrullinated or carbamylated type II human collagen T cell- and B cell-epitopes on the adaptive immune response in rheumatoid arthritis (RA). Peripheral blood T and B cells obtained from a human leucocyte D4-related (antigen DR4(-) HLA-DR4)(+) woman with early RA, her healthy monozygotic twin and an unrelated HLA-DR3(+) woman with early RA were analysed for activation (CD154/CD69), apoptosis (annexin/7-aminoactinomycin), cytokine production [interferon (IFN)γ/interleukin (IL)-17/IL-4/IL-10/IL-6] and functional phenotype (CD45Ra/CCR7) after stimulation with the collagen native T cell epitope (T261-273), the K264 carbamylated T cell epitope (carT261-273), the native B cell epitope (B359-369) or the R360 citrullinated B cell epitope (citB359-369), and the combinations of these. The T cell memory compartment was activated by T cell epitopes in both discordant DR4(+) twins, but not in the DR3(+) RA. The collagen-specific activation of CD4(+) T cells was induced with both the native and carbamylated T cell epitopes only in the RA twin. Both T cell epitopes also induced IL-17 production in the RA twin, but a greater IL-4 and IL-10 response in the healthy twin. The citrullinated B cell epitope, particularly when combined with the carbamylated T cell epitope, induced B cell activation and an increased IL-6/IL-10 ratio in the RA twin compared to a greater IL-10 production in the healthy twin. Our data suggest that circulating collagen-specific T and B cells are found in HLA-DR4(+) subjects, but only RA activated cells express co-stimulatory molecules and produce proinflammatory cytokines. Carbamylation and citrullination further modulate the activation and cytokine polarization of T and B cells.

  15. Smoking, Porphyromonas gingivalis and the immune response to citrullinated autoantigens before the clinical onset of rheumatoid arthritis in a Southern European nested case–control study

    OpenAIRE

    Fisher, Benjamin A; Cartwright, Alison J; Quirke, Anne-Marie; de Pablo, Paola; Romaguera, Dora; Panico, Salvatore; Mattiello, Amalia; Gavrila, Diana; Navarro, Carmen; Sacerdote, Carlotta; Vineis, Paolo; Tumino, Rosario; Lappin, David F; Apazidou, Danae; Culshaw, Shauna

    2015-01-01

    Background: \\ud Antibodies to citrullinated proteins (ACPA) occur years before RA diagnosis. Porphyromonas gingivalis expresses its own peptidylarginine deiminase (PPAD), and is a proposed aetiological factor for the ACPA response. Smoking is a risk factor for both ACPA-positive RA and periodontitis. We aimed to study the relation of these factors to the risk of RA in a prospective cohort.\\ud \\ud Methods: \\ud We performed a nested case–control study by identifying pre-RA cases in four populat...

  16. In ACPA-positive RA patients, antibodies to EBNA35-58Cit, a citrullinated peptide from the Epstein-Barr nuclear antigen-1, strongly cross-react with the peptide β60-74Cit which bears the immunodominant epitope of citrullinated fibrin.

    Science.gov (United States)

    Cornillet, M; Verrouil, E; Cantagrel, A; Serre, G; Nogueira, L

    2015-02-01

    Although several infectious agents and particularly Epstein-Barr virus (EBV) have been suspected to be involved in aetiology of rheumatoid arthritis (RA), their role still remains elusive. Almost 80% of RA sera contain antibodies to citrullinated proteins/peptides. Among them, the autoantibodies to citrullinated human fibrinogen (AhFibA) are composed of two non-cross-reactive subsets directed to immunodominant epitopes borne by the α36-50Cit and β60-74Cit fibrin peptides. RA sera also contain antibodies towards the citrullinated EBNA35-58Cit peptide derived from the EBNA-1 protein of EBV. Here, using a large cohort of RA patients and controls, we showed that for a diagnostic specificity of 98.5%, 47% of the AhFibA-positive patients were anti-EBNA35-58Cit-positive and that almost all (98.5%) the anti-EBNA35-58Cit-positive were AhFibA-positive, whereas 86% were anti-β60-74Cit-positive and only 43% anti-α36-50Cit-positive. AhFibA, anti-EBNA35-58Cit- and anti-β60-74Cit-antibody titres were significantly correlated. Competition assays showed that anti-EBNA35-58Cit antibodies are highly cross-reactive with the β60-74Cit peptide. The demonstration that a citrullinated peptide derived from the EBNA-1 protein of EBV presents a molecular mimicry with human citrullinated fibrin constitutes an additional argument for a possible role of EBV in RA aetiopathogeny.

  17. Roles of export genes cgmA and lysE for the production of L-arginine and L-citrulline by Corynebacterium glutamicum.

    Science.gov (United States)

    Lubitz, Dorit; Jorge, João M P; Pérez-García, Fernando; Taniguchi, Hironori; Wendisch, Volker F

    2016-10-01

    L-arginine is a semi-essential amino acid with application in cosmetic, pharmaceutical, and food industries. Metabolic engineering strategies have been applied for overproduction of L-arginine by Corynebacterium glutamicum. LysE was the only known L-arginine exporter of this bacterium. However, an L-arginine-producing strain carrying a deletion of lysE still accumulated about 10 mM L-arginine in the growth medium. Overexpression of the putative putrescine and cadaverine export permease gene cgmA was shown to compensate for the lack of lysE with regard to L-arginine export. Moreover, plasmid-borne overexpression of cgmA rescued the toxic effect caused by feeding of the dipeptide Arg-Ala to lysE-deficient C. glutamicum and argO-deficient Escherichia coli strains. Deletion of the repressor gene cgmR improved L-arginine titers by 5 %. Production of L-lysine and L-citrulline was not affected by cgmA overexpression. Taken together, CgmA may function as an export system not only for the diamine putrescine and cadaverine but also for L-arginine. The major export system for L-lysine and L-arginine LysE may also play a role in L-citrulline export since production of L-citrulline was reduced when lysE was deleted and improved by 45 % when lysE was overproduced.

  18. Single cell cloning and recombinant monoclonal antibodies generation from RA synovial B cells reveal frequent targeting of citrullinated histones of NETs

    Science.gov (United States)

    Corsiero, Elisa; Bombardieri, Michele; Carlotti, Emanuela; Pratesi, Federico; Robinson, William; Migliorini, Paola; Pitzalis, Costantino

    2016-01-01

    Objectives Rheumatoid arthritis (RA) is characterised by breach of self-tolerance towards citrullinated antigens with generation of anti-citrullinated peptide/proteins antibodies (ACPA). Currently, the nature and source of citrullinated antigens driving the humoral autoimmune response within synovial ectopic lymphoid structures (ELS) is a crucial unknown aspect of RA pathogenesis. Here we characterised the autoreactive B-cell response of lesional B cells isolated from ELS+RA synovium. Methods Single synovial tissue CD19+cells were Fluorescence Activated Cell Sorting (FACS)-sorted and VH/VL Ig genes cloned to generate recombinant monoclonal antibodies (rmAbs) from patients with ELS+/ACPA+RA. Results RA-rmAbs immunoreactivity analysis provided the following key findings: (1) in a chIP-based array containing 300 autoantigens and in a ‘citrullinome’ multiplex assay, a strong reactivity against citrullinated histones H2A/H2B (citH2A/H2B) was observed in ∼40% of RA-rmAbs, followed by cit-fibrinogen and cit-vimentin; (2) anti-citH2A/H2B-reactive RA-rmAbs (but not anti-citH2A/H2B negative) selectively recognised neutrophil extracellular traps (NETs) from peripheral blood and/or RA joint neutrophils; (3) anti-citH2A/citH2B and anti-NET immunobinding was dependent on affinity maturation and was completely abrogated following reversion of hypermutated IgVH/VL genes to germline sequences; (4) ELS+ (not ELS−) RA synovial tissues engrafted into Severe Combined ImmunoDeficiency (SCID) mice released human anti-citH2A/citH2B and anti-NET antibodies in association with the intra-graft expression of CXCL13 and lymphotoxin (LT)-β, two master regulators of ELS. Conclusion We provided novel evidence that B cells differentiated within synovial ELS in the RA joints frequent target deiminated proteins which could be generated during NETosis of RA synovial neutrophils including histones. Thus, NETs could represent a source of citrullinated antigens fuelling the ACPA autoimmune

  19. Isotypes of Epstein-Barr Virus Antibodies in Rheumatoid Arthritis: Association with Rheumatoid Factors and Citrulline-Dependent Antibodies

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    Marie Wulff Westergaard

    2015-01-01

    Full Text Available In order to study the humoral immune response against Epstein-Barr virus (EBV in patients with rheumatoid arthritis (RA and to compare it with the two major autoantibody types in RA, plasma samples from 77 RA patients, 28 patients with systemic lupus erythematosus (SLE, and 28 healthy controls (HCs were investigated by enzyme-linked immunosorbent assays (ELISA. Increased percentages of positives and concentrations of IgG/IgA/IgM antibodies against the latent EBV nuclear antigen-1 (EBNA-1 were observed in RA patients compared to SLE patients and HCs. Increased concentrations and percentages of positives of IgG/IgA/IgM against the early lytic EBV antigen diffuse (EAD were also found in RA patients compared to HCs but were highest in SLE patients. Furthermore, associations between the elevated EBNA-1 IgA and EBNA-1 IgM levels and the presence of IgM and IgA rheumatoid factors (RFs and anti-citrullinated protein antibodies (ACPAs, IgG and between elevated IgA concentrations against EAD and the presence of RFs and ACPAs in RA patients were found. Thus, RA patients had elevated antibodies of all isotypes characteristic of latent EBV infection (whereas SLE patients had elevated antibodies characteristic of lytic EBV infection. Notably, for IgM and IgA (but not IgG, these were associated with the presence of characteristic RA autoantibodies.

  20. Extracellular expression of natural cytosolic arginine deiminase from Pseudomonas putida and its application in the production of L-citrulline.

    Science.gov (United States)

    Su, Lingqia; Ma, Yue; Wu, Jing

    2015-11-01

    The Pseudomonas putida arginine deiminase (ADI), a natural cytosolic enzyme, and Thermobifida fusca cutinase were co-expressed in Escherichia coli, and the optimized cutinase gene was used for increasing its expression level. 90.9% of the total ADI protein was released into culture medium probably through a nonspecific leaking mechanism caused by the co-expressed cutinase. The enzymatic properties of the extracellular ADI were found to be similar to those of ADI prepared by conventional cytosolic expression. Extracellular production of ADI was further scaled up in a 3-L fermentor. When the protein expression was induced by IPTG (25.0μM) and lactose (0.1gL(-1)h(-1)) at 30°C, the extracellular ADI activity reached 101.2UmL(-1), which represented the highest ADI production ever reported. In addition, the enzymatic synthesis of l-citrulline was performed using the extracellularly expressed ADI, and the conversion rate reached 100% with high substrate concentration at 650gL(-1).

  1. Positive association between serum thymic stromal lymphopoietin and anti-citrullinated peptide antibodies in patients with rheumatoid arthritis

    Science.gov (United States)

    Koyama, K; Ohba, T; Haro, H; Nakao, A

    2015-01-01

    Thymic stromal lymphopoietin (TSLP) has been suggested recently to play an important role in the pathophysiology of rheumatoid arthritis (RA). However, there is little information on serum TSLP concentrations in RA and its clinical significance. The present study investigated whether serum TSLP concentrations were affected in patients with RA. Using an enzyme-linked immunosorbent assay (ELISA), we measured TSLP concentrations in the serum obtained from 100 patients with RA, 60 patients with osteoarthritis (OA) and 34 healthy volunteers. We also investigated the correlation between serum TSLP concentrations and clinical parameters of disease activity in RA [disease activity score using 28 joint counts (DAS28)-C-reactive protein (CRP), DAS28-erythrocyte sedimentation rate (ESR), Clinical Disease Activity Index (CDAI]), patient’s/-physician’s Visual Analogue Scale (VAS), swollen joints count, tender joints count, CRP, ESR and matrix metalloproteinase-3 (MMP-3) concentrations]. In addition, we investigated the correlation between serum TSLP concentrations and anti-citrullinated peptide antibody (ACPA) and serum tumour necrosis factor (TNF)-α. Serum TSLP levels in patients with RA were significantly higher than those in patients with OA and in healthy volunteers. Interestingly, serum TSLP concentrations were correlated significantly with ACPA titres, but not with other clinical parameters. There was a significant increase in serum TSLP concentrations in patients with RA, which was correlated positively with serum ACPA titres. These findings suggest that in patients with RA, TSLP may play a role in ACPA production by B cells. PMID:25817699

  2. The feeding route (enteral or parenteral) affects the plasma response of the dipetide Ala-Gln and the amino acids glutamine, citrulline and arginine, with the administration of Ala-Gln in preoperative patients.

    Science.gov (United States)

    Melis, Gerdien C; Boelens, Petra G; van der Sijp, Joost R M; Popovici, Theodora; De Bandt, Jean-Pascal; Cynober, Luc; van Leeuwen, Paul A M

    2005-07-01

    Enhancement of depressed plasma concentrations of glutamine and arginine is associated with better clinical outcome. Supplementation of glutamine might be a way to provide the patient with glutamine, and also arginine, because glutamine provides the kidney with citrulline, from which the kidney produces arginine when plasma levels of arginine are low. The aim of the present study was to investigate the parenteral and enteral response of the administered dipeptide Ala-Gln, glutamine, citrulline and arginine. Therefore, seven patients received 20 g Ala-Gln, administered over 4 h, parenterally or enterally, on two separate occasions. Arterial blood samples were taken before and during the administration of Ala-Gln. ANOVA and a paired t test were used to test differences (Pglutamine was observed with parenteral infusion of the dipeptide, although enteral infusion also significantly increased plasma levels of glutamine. The highest plasma response of citrulline was observed with the enteral administration of the dipeptide, although parenteral administration also increased plasma levels of citrulline. Plasma arginine increased significantly with parenteral infusion, but not with enteral administration of Ala-Gln. In conclusion, administrations of Ala-Gln, parenteral or enteral, resulted in an increased plasma glutamine response, as compared with baseline. Interestingly, in spite of the high availability of citrulline with enteral administration of the dipeptide, only parenteral infusion of Ala-Gln increased plasma arginine concentration.

  3. Anticorpos antiproteínas citrulinadas e a artrite reumatóide Auto-antibodies to citrullinated proteins and rheumatoid arthritis

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    Renata Trigueirinho Alarcon

    2007-06-01

    Full Text Available Pacientes com artrite reumatóide (AR possuem uma variedade de auto-anticorpos no soro e no líquido sinovial. Entre esses auto-anticorpos, destacam-se aqueles direcionados a proteínas citrulinadas, que são específicos para AR, aparecem precocemente durante a evolução da enfermidade e são bastante úteis para auxiliar no diag-nóstico da doença. Entre os antígenos citrulinados reconhecidos por auto-anticorpos na AR, encontram-se a profilagrina, a filagrina e a vimentina. Células e tecidos ricos nessas proteínas serviram de substrato para os primeiros ensaios laboratoriais para detecção dessa classe de auto-anticorpos. A descoberta de que os epitopos reconhecidos por esses auto-anticorpos eram peptídeos contendo citrulina permitiu o desenvolvimento de uma plataforma baseada em ELISA. O formato de ELISA possibilitou maior padronização e reprodutibilidade dos ensaios, resultando em ampla aceitação mundial como os auto-anticorpos mais específicos e precoces para o diagnóstico da AR. Há controvérsia quanto à capacidade dos anticorpos contra proteínas citrulinadas predizerem a gravidade da doença. O papel dos antígenos citrulinados na fisiopatologia da artrite reumatóide é sugerido pela forte especificidade desses auto-anticorpos para a doença, pelo achado de proteínas citrulinadas na sinóvia inflamada, pela produção intra-articular desses auto-anticorpos e pela extrema afinidade de peptídeos citrulinados por moléculas de HLA-DRB1 que contêm o epitopo compartilhado. Esses achados acenam com a possibilidade de novas e fascinantes descobertas rumo à melhor compreensão da fisiopatologia da AR.Rheumatoid arthritis (RA patients have a variety of auto-antibodies in the serum and synovial fluid. Among these auto-antibodies, those directed against citrullinated proteins are distinguished because that are specific for RA, appear early during the evolution of the disease and they are important to assist in the diagnosis of

  4. Antibodies to mutated citrullinated vimentin in patients with chronic hepatitis C virus genotype IV infection-related arthropathy.

    Science.gov (United States)

    Zehairy, M; Soliman, E; Daghaidy, A

    2012-11-01

    One of the extra-hepatic manifestations of hepatitis C virus (HCV) infection is polyarthritis that mimics rheumatoid arthritis (RA). Anti-mutated citrullinated vimentin (MCV) was recently introduced in the diagnostic workup of RA, but its exact role in HCV infection and its related arthropathy is still unclear. The aim of the study is to determine the prevalence of anti-MCV antibodies in HCV-infected patients with or without articular involvement, and to investigate whether anti-MCV antibodies have an additional role to anticyclic citrullinated peptide (CCP) antibodies and rheumatoid factor (RF) in differentiating patients with RA from patients with HCV-related arthropathy. Fifty-five HCV-infected patients (HCV RNA positive) and 30 RA patients (fulfilling the American College of Rheumatology classification criteria for RA and negative for HCV) were included. Anti-MCV antibodies, anti-CCP antibodies, RF and cryoglobulins were measured. Articular involvement in hepatitis C patients was evaluated. Articular involvement was detected in 30/55 (54.5%) of HCV-infected patients. The most frequent pattern was symmetric polyarthralgias and the most frequent joints to be involved were the wrists, metacarpophalangeal joints, shoulders and knees. In HCV arthropathy, anti-MCV was positive in 9/30 (30%), anti-CCP in 0% and RF in 22/30 (73.3%). Whereas, in chronic HCV without arthropathy, anti-MCV was positive in 8 patients (32%), anti-CCP in one patient (4%) and RF in 23/25 (92.0%). There was no significant difference between the two HCV groups as regards the frequencies of anti-MCV (P = 0.89), anti-CCP (P = 0.93) and RF (P = 0.15). In RA, anti-MCV was positive in 93.3% anti-CCP in 96.7% and RF in 86.7%. There was no significant difference in RF between RA and HCV arthropathy (P = 0.33). Meanwhile, there was a highly significant difference between both groups regarding anti-MCV and anti-CCP (P < 0.0001 for each). The sensitivity of anti-MCV, anti-CCP and RF for RA was 93.3, 96

  5. Quantitative Metabolomic Analysis of Urinary Citrulline and Calcitroic Acid in Mice after Exposure to Various Types of Ionizing Radiation

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    Maryam Goudarzi

    2016-05-01

    Full Text Available With the safety of existing nuclear power plants being brought into question after the Fukushima disaster and the increased level of concern over terrorism-sponsored use of improvised nuclear devices, it is more crucial to develop well-defined radiation injury markers in easily accessible biofluids to help emergency-responders with injury assessment during patient triage. Here, we focused on utilizing ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS to identify and quantitate the unique changes in the urinary excretion of two metabolite markers, calcitroic acid and citrulline, in mice induced by different forms of irradiation; X-ray irradiation at a low dose rate (LDR of 3.0 mGy/min and a high dose rate (HDR of 1.1 Gy/min, and internal exposure to Cesium-137 (137Cs and Strontium-90 (90Sr. The multiple reaction monitoring analysis showed that, while exposure to 137Cs and 90Sr induced a statistically significant and persistent decrease, similar doses of X-ray beam at the HDR had the opposite effect, and the LDR had no effect on the urinary levels of these two metabolites. This suggests that the source of exposure and the dose rate strongly modulate the in vivo metabolomic injury responses, which may have utility in clinical biodosimetry assays for the assessment of exposure in an affected population. This study complements our previous investigations into the metabolomic profile of urine from mice internally exposed to 90Sr and 137Cs and to X-ray beam radiation.

  6. Serum anticyclic citrullinated protein antibody titers are correlated with the response to biological agents in patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Takahashi R

    2014-05-01

    Full Text Available Ryo Takahashi, Sakiko Isojima, Masayu Umemura, Yoko Miura, Nao Oguro, Syo Ishii, Shinya Seki, Takahiro Tokunaga, Hiroyuki Tsukamoto, Hidekazu Furuya, Ryo Yanai, Tsuyoshi KasamaDivision of Rheumatology, Department of Medicine, Showa University School of Medicine,Tokyo, Japan Abstract: Anticyclic citrullinated protein antibody (ACPA is known as an important indicator for diagnosis of rheumatoid arthritis (RA. Our aim was to examine the relationship between the serum ACPA titer at baseline and responsiveness to biological agents (antagonists of either tumor necrosis factor or interleukin 6 in patients with RA. ACPA was measured using second-generation chemiluminescent enzyme immunoassay. Disease activity was assessed using disease activity scores 28. Fifty-seven RA patients with biological agents were enrolled, and the median ACPA titer at baseline was 110.0 U/mL. The median ACPA titer was 23.3 U/mL and 183.0 U/mL in the good and moderate response groups, respectively, which were significantly lower than in the no response group (404.0 U/mL. In addition, 69.2% and 26.9% of patients with low (<100 U/mL and moderate (100–499 U/mL basal ACPA titers showed a moderate to good response. Of the patients with higher (≥500 U/mL basal ACPA titers, only 14.0% and 42.5% showed a good or moderate response, respectively. The remission rate was 77.8% in the ACPA-negative, which was significantly higher than the rate of 25% in the ACPA-positive patients. The results suggest that the ACPA titers are correlated with the efficacy of the biological agents used in patients with RA.Keywords: biological agents, remission

  7. Acute ingestion of citrulline stimulates nitric oxide synthesis but does not increase blood flow in healthy young and older adults with heart failure.

    Science.gov (United States)

    Kim, Il-Young; Schutzler, Scott E; Schrader, Amy; Spencer, Horace J; Azhar, Gohar; Deutz, Nicolaas E P; Wolfe, Robert R

    2015-12-01

    To determine if age-associated vascular dysfunction in older adults with heart failure (HF) is due to insufficient synthesis of nitric oxide (NO), we performed two separate studies: 1) a kinetic study with a stable isotope tracer method to determine in vivo kinetics of NO metabolism, and 2) a vascular function study using a plethysmography method to determine reactive hyperemic forearm blood flow (RH-FBF) in older and young adults in the fasted state and in response to citrulline ingestion. In the fasted state, NO synthesis (per kg body wt) was ∼ 50% lower in older vs. young adults and was related to a decreased rate of appearance of the NO precursor arginine. Citrulline ingestion (3 g) stimulated de novo arginine synthesis in both older [6.88 ± 0.83 to 35.40 ± 4.90 μmol · kg body wt(-1) · h(-1)] and to a greater extent in young adults (12.02 ± 1.01 to 66.26 ± 4.79 μmol · kg body wt(-1) · h(-1)). NO synthesis rate increased correspondingly in older (0.17 ± 0.01 to 2.12 ± 0.36 μmol · kg body wt(-1) · h(-1)) and to a greater extent in young adults (0.36 ± 0.04 to 3.57 ± 0.47 μmol · kg body wt(-1) · h(-1)). Consistent with the kinetic data, RH-FBF in the fasted state was ∼ 40% reduced in older vs. young adults. However, citrulline ingestion (10 g) failed to increase RH-FBF in either older or young adults. In conclusion, citrulline ingestion improved impaired NO synthesis in older HF adults but not RH-FBF, suggesting that factors other than NO synthesis play a role in the impaired RH-FBF in older HF adults, and/or it may require a longer duration of supplementation to be effective in improving RH-FBF.

  8. The role of citrullinated proteins in the pathogenesis of rheumatoid arthritis%蛋白质瓜氨酸化及其在类风湿关节炎中的意义

    Institute of Scientific and Technical Information of China (English)

    钟兵; 方勇飞

    2015-01-01

    类风湿关节炎(rheumatoid arthritis,RA)的发病机制至今尚未阐明。 RA 患者体内发现越来越多的抗瓜氨酸化蛋白抗体(ACPA)提示瓜氨酸化可能参与其发病过程。本文从蛋白质的瓜氨酸化过程、生理功能,ACPA 在 RA 的诊断、预后及发病机制中的作用进行综述,试图更全面地了解蛋白质的瓜氨酸化在 RA 发病各环节中的作用。%The mechanism of rheumatoid arthritis(RA)has not been clarified.More and more anti-citrullinated protein antibod-ies(ACPA)have been found in RA patients ,suggesting that citrullinated proteins may be involved in the pathogenesis of RA .This paper reviews the process of protein citrullination ,physiological function and the role of ACPA in the diagnosis ,prognosis and pathogenesis of RA in order to get a more comprehensive understanding of the role of citrullinated proteins in the pathogenesis of RA .

  9. Levels of l-arginine and l-citrulline in patients with erectile dysfunction of different etiology.

    Science.gov (United States)

    Barassi, A; Corsi Romanelli, M M; Pezzilli, R; Damele, C A L; Vaccalluzzo, L; Goi, G; Papini, N; Colpi, G M; Massaccesi, L; Melzi d'Eril, G V

    2017-03-01

    Nitric oxide is a physiologic signal essential to penile erection. l-citrulline (l-Cit) is converted into l-arginine (l-Arg), the precursor from which nitric oxide is generated. The level of l-Arg and l-Cit in the field of male sexual function remains relatively underexplored. The aim of the study was to evaluate the level of serum l-Arg and of l-Cit in a group of patients with erectile dysfunction. Diagnosis and severity of erectile dysfunction was based on the IIEF-5 and its etiology was classified as arteriogenic (A-ED), borderline (BL-ED), and non-arteriogenic (NA-ED) with penile echo-color-Doppler in basal condition and after intracaversous injection of prostaglandin E1. Serum l-Arg and l-Cit concentrations were measured by a cation-exchange chromatography system. l-Arg and l-Cit levels of men with A-ED were compared with those of male with BL-ED and NA-ED. Median level of l-Arg and l-Cit in 122 erectile dysfunction patients (41 A-ED, 23 ED-BL, 58 NA-ED) was 82.7 and 35.4 μmol/L, respectively. l-Arg and l-Cit levels in control patients were not significantly different (p = 0.233 and p = 0.561, respectively) than in total erectile dysfunction patients. l-Arg and l-Cit levels in control patients were significantly higher (p  0.50) was observed in controls and in both BL-ED and NA-ED patients. Patients with severe/complete-erectile dysfunction (IIEF-5 l-Arg or l-Cit level significantly lower (-17%, p L) than those with mild-erectile dysfunction (IIEF-5 = 16-20). l-Arg and l-Cit levels in A-ED were significantly lower (p l-Arg under 82.7 μmol/L or l-Cit under 35.4 μmol/L and in the same population, the median peak systolic velocity values were lower in l-Arg deficient (29 vs. 35; p l-Cit deficient (31 vs. 33, p > 0.3) but without reaching the statistical significance. Our study shows that a significant proportion of erectile dysfunction patients have low l-Arg or l-Cit level and that this condition is more frequent in patients with arteriogenic

  10. Uncoupling of collagen II metabolism in newly diagnosed, untreated rheumatoid arthritis is linked to inflammation and antibodies against cyclic citrullinated peptides

    DEFF Research Database (Denmark)

    Christensen, Anne Friesgaard; Hørslev-Petersen, Kim; Christgau, Stephan;

    2010-01-01

    Objective. To investigate the relationship between markers of collagen 11 synthesis and degradation with disease activity measures, autoantibodies, and radiographic outcomes in a 4-year protocol on patients with early rheumatoid arthritis (RA) who are naive to disease-modifying antirheumatic drugs....... Methods. One hundred sixty patients with newly diagnosed, untreated RA entered the Cyclosporine, Methotrexate, Steroid in RA (CIMESTRA) trial. Disease activity and radiograph status were measured at baseline and 4 years. The N-terminal propeptide of collagen IIA (PIIANP) and the crosslinked C......-telopeptide of collagen II (CTX-II) were quantified at baseline by ELISA. PIIANP was also assayed at 2 and 4 years. Anticyclic citrullinated peptide (anti-CCP) was recorded at baseline. An uncoupling index for cartilage collagen metabolism was calculated from PHANP and CTX-II measurements. Results. PIIANP was low...

  11. EPR investigation of gamma-irradiated L-citrulline, α-methyl-DL-serine, 3-fluoro-DL-valine and N-acetyl-L-cysteine

    Science.gov (United States)

    Osmanoğlu, Y. Emre; Sütçü, Kerem; Başkan, M. Halim

    2017-02-01

    The spectroscopic parameters of the paramagnetic species produced in gamma-irradiated L-citrulline, α-methyl-DL-serine, 3-fluoro-DL-valine and N-acetyl-L-cysteine were investigated at room temperature at a dose of 20 kGy by using EPR technique. The paramagnetic species were attributed to NH2CONH(CH2)3ĊNH2COOH, HOCH2ĊCH3COOH and HOĊHCCH3NH2COOH, CH3CH3ĊCHNH2COOH and SHCH2ĊNHCOCH3COOH radicals, respectively. EPR data of the unpaired electron with the environmental protons and 14N nucleus were used to characterize the contributing radicals produced in gamma irradiated compounds. In this paper, the stability of these compounds at room temperature after irradiation was also studied.

  12. Arginine methylation and citrullination of splicing factor proline- and glutamine-rich (SFPQ/PSF) regulates its association with mRNA.

    Science.gov (United States)

    Snijders, Ambrosius P; Hautbergue, Guillaume M; Bloom, Alex; Williamson, James C; Minshull, Thomas C; Phillips, Helen L; Mihaylov, Simeon R; Gjerde, Douglas T; Hornby, David P; Wilson, Stuart A; Hurd, Paul J; Dickman, Mark J

    2015-03-01

    Splicing factor proline- and glutamine-rich (SFPQ) also commonly known as polypyrimidine tract-binding protein-associated-splicing factor (PSF) and its binding partner non-POU domain-containing octamer-binding protein (NONO/p54nrb), are highly abundant, multifunctional nuclear proteins. However, the exact role of this complex is yet to be determined. Following purification of the endogeneous SFPQ/NONO complex, mass spectrometry analysis identified a wide range of interacting proteins, including those involved in RNA processing, RNA splicing, and transcriptional regulation, consistent with a multifunctional role for SFPQ/NONO. In addition, we have identified several sites of arginine methylation in SFPQ/PSF using mass spectrometry and found that several arginines in the N-terminal domain of SFPQ/PSF are asymmetrically dimethylated. Furthermore, we find that the protein arginine N-methyltransferase, PRMT1, catalyzes this methylation in vitro and that this is antagonized by citrullination of SFPQ. Arginine methylation and citrullination of SFPQ/PSF does not affect complex formation with NONO. However, arginine methylation was shown to increase the association with mRNA in mRNP complexes in mammalian cells. Finally we show that the biochemical properties of the endogenous complex from cell lysates are significantly influenced by the ionic strength during purification. At low ionic strength, the SFPQ/NONO complex forms large heterogeneous protein assemblies or aggregates, preventing the purification of the SFPQ/NONO complex. The ability of the SFPQ/NONO complex to form varying protein assemblies, in conjunction with the effect of post-translational modifications of SFPQ modulating mRNA binding, suggests key roles affecting mRNP dynamics within the cell.

  13. Long-term effects of maternal citrulline supplementation on renal transcriptome prevention of nitric oxide depletion-related programmed hypertension: the impact of gene-nutrient interactions.

    Science.gov (United States)

    Tain, You-Lin; Lee, Chien-Te; Huang, Li-Tung

    2014-12-15

    Maternal malnutrition can elicit gene expression leading to fetal programming. L-citrulline (CIT) can be converted to L-arginine to generate nitric oxide (NO). We examined whether maternal CIT supplementation can prevent N(G)-nitro-L-arginine-methyl ester (L-NAME, NO synthase inhibitor)-induced programmed hypertension and examined their effects on the renal transcriptome in male offspring using next generation RNA sequencing (RNA-Seq) technology. Pregnant Sprague-Dawley rats received L-NAME administration at 60mg/kg/day subcutaneously via osmotic minipump during pregnancy alone or with additional 0.25% L-citrulline solution in drinking water during the whole period of pregnancy and lactation. Male offspring were assigned to three groups: control, L-NAME, and L-NAME + CIT. L-NAME exposure induced hypertension in the 12-week-old offspring, which CIT therapy prevented. Identified differentially expressed genes in L-NAME and CIT-treated offspring kidneys, including Guca2b, Hmox1, Hba2, Hba-a2, Dusp1, and Serpine1 are related to regulation of blood pressure (BP) and oxidative stress. In conclusion, our data suggests that the beneficial effects of CIT supplementation are attributed to alterations in expression levels of genes related to BP control and oxidative stress. Our results suggest that early nutritional intervention by CIT has long-term impact on the renal transcriptome to prevent NO depletion-related programmed hypertension. However, our RNA-Seq results might be a secondary phenomenon. The implications of epigenetic regulation at an early stage of programming deserve further clarification.

  14. Valor crítico da citrulina para as complicações do enxerto no transplante de intestino Critical value of citrulline for complications of intestinal transplant graft

    Directory of Open Access Journals (Sweden)

    André Ibrahim David

    2008-10-01

    Full Text Available OBJETIVO: Analisar, numa ampla amostra, o valor crítico da citrulina que confirma a presença das principais complicações do enxerto: rejeição e infecção. MÉTODOS: Foram coletadas 2135 amostras de citrulina sérica, na forma de gota de sangue seca, de 57 doentes submetidos a transplante de intestino/multivisceral no Jackson Memorial Hospital na Universidade de Miami, de março de 2004 a abril de 2006. Todas as amostras são do pós-operatório três meses em diante, passada a conhecida curva de elevação da citrulina após a recuperação das lesões causadas pela isquemia e reperfusão do pós-transplante. RESULTADOS: Utilizando um valor limite menor que 13 µmoles/L, a sensibilidade da citrulina foi de 96,4% para detectar rejeicão celular aguda (RCA moderada ou grave. A especificidade para as complicações mais freqüentes, rejeição e infecção foi de 54%-74% nas crianças e 83%-88% nos adultos, e o valor preditivo negativo (VPN foi > 99%. CONCLUSÃO: A citrulina pode ser utilizada como método não-invasivo para avaliar a evolução do enxerto intestinal após três meses do TI. Os episódios de RCA moderado e grave podem ser afastados quando o valor da citrulina for maior que 13 µmoles/L devido ao alto valor preditivo negativo.OBJECITIVE: A biochemical marker for detection of acute cellular rejection following small intestine transplantation has been sought. Citrulline, a non- protein amino acid synthesized mainly by functioning enterocytes, has been proposed. Trial sensitivity has been reportedly high but with low specificity. Thus, the goal was to determine, in a sufficiently large analysis, the significant value of citrulline level in the post-transplant setting, which would correlate with complications such as rejection and infection. METHODS: Since March, 2004 2,135 dried blood spot (DBS citrulline samples were obtained from 57 small intestine transplant recipients three months or more after post-transplant, i.e., once

  15. Citrulina plasmática como marcador de pérdida de masa enterocitaria en la enfermedad celíaca en la infancia Plasma citrulline as a marker of loss of enterocitary mass in coeliac disease in childhood

    Directory of Open Access Journals (Sweden)

    J. Blasco Alonso

    2011-08-01

    Full Text Available Introducción: La citrulina plasmática no está incorporada a las proteínas endógenas ni exógenas y constituye un teórico marcador de la atrofia vellositaria. El objetivo del estudio es relacionar los niveles plasmáticos de citrulina y arginina con la severidad de la afectación de la mucosa intestinal en pacientes celiacos. Material y métodos: Estudio transversal de cohortes en niños entre 16 meses y 14 años: 46 con enfermedad celíaca al diagnóstico; 9 celíacos siguiendo dieta sin gluten y 42 controles. Se determina concentración plasmática de aminoácidos, en mmol/L, y variables clínicas y analíticas asociadas. Resultados: No diferencias estadísticamente significativas en IMC, edad o función renal, con ligero incremento de esteatorrea en celíacos. Citrulina, arginina y glutamina plasmáticas significativamente más bajas en los casos (17,7 μmol/l, 38,7 μmol/l, 479,6 μmol/l respectivamente que en controles (28,9 μmol/l, 56,2 μmol/l, 563,7 μmol/l. Citrulina plasmática significativamente más baja en grados avanzados de atrofia (13,8 μmol/l vs 19,7 μmol/l, p Introduction: Plasma citrulline is not incorporated in endogenous or exogenous proteins so it is a theoretical marker of villous atrophy. Our aim was to correlate plasma citrulline levels with severity of villous atrophy in celiac patients. Methods: Observational case-control study longitudinal in children 16 month-old to 14 year-old: 48 with untreated celiac disease, 9 celiac children under gluten free diet and 35 non-celiac healthy children. Plasma amino acids concentration is determined, expressed in μmol/L, and so are other clinical and analytical data. Results: No statistically significative difference found in the referring to BMI, age or renal function. Small increase in fecal fat in celiac children. Citrulline, arginine and glutamine are significantly lower in cases (17.7 μmol/l, 38.7 μmol/l, 479.6 μmol/l respectively than in controls (28.9 μmol/l, 56

  16. NITRIC OXIDE (NO, CITRULLINE - NO CYCLE ENZYMES, GLUTAMINE SYNTHETASE AND OXIDATIVE STRESS IN ANOXIA (HYPOBARIC HYPOXIA AND REPERFUSION IN RAT BRAIN

    Directory of Open Access Journals (Sweden)

    M. Swamy, Mohd Jamsani Mat Salleh, K. N .S. Sirajudeen, Wan Roslina Wan Yusof, G. Chandran

    2010-01-01

    Full Text Available Nitric oxide is postulated to be involved in the pathophysiology of neurological disorders due to hypoxia/ anoxia in brain due to increased release of glutamate and activation of N-methyl-D-aspartate receptors. Reactive oxygen species have been implicated in pathophysiology of many neurological disorders and in brain function. To understand their role in anoxia (hypobaric hypoxia and reperfusion (reoxygenation, the nitric oxide synthase, argininosuccinate synthetase, argininosuccinate lyase, glutamine synthetase and arginase activities along with the concentration of nitrate /nitrite, thiobarbituric acid reactive substances and total antioxidant status were estimated in cerebral cortex, cerebellum and brain stem of rats subjected to anoxia and reperfusion. The results of this study clearly demonstrated the increased production of nitric oxide by increased activity of nitric oxide synthase. The increased activities of argininosuccinate synthetase and argininosuccinate lyase suggest the increased and effective recycling of citrulline to arginine in anoxia, making nitric oxide production more effective and contributing to its toxic effects. The decreased activity of glutamine synthetase may favor the prolonged availability of glutamic acid causing excitotoxicity leading to neuronal damage in anoxia. The increased formation of thiobarbituric acid reactive substances and decreased total antioxidant status indicate the presence of oxidative stress in anoxia and reperfusion. The increased arginase and sustained decrease of GS activity in reperfusion group likely to be protective.

  17. Supplementation with Phycocyanobilin, Citrulline, Taurine, and Supranutritional Doses of Folic Acid and Biotin—Potential for Preventing or Slowing the Progression of Diabetic Complications

    Directory of Open Access Journals (Sweden)

    Mark F. McCarty

    2017-03-01

    Full Text Available Oxidative stress, the resulting uncoupling of endothelial nitric oxide synthase (eNOS, and loss of nitric oxide (NO bioactivity, are key mediators of the vascular and microvascular complications of diabetes. Much of this oxidative stress arises from up-regulated nicotinamide adenine dinucleotide phosphate (NADPH oxidase activity. Phycocyanobilin (PhyCB, the light-harvesting chromophore in edible cyanobacteria such as spirulina, is a biliverdin derivative that shares the ability of free bilirubin to inhibit certain isoforms of NADPH oxidase. Epidemiological studies reveal that diabetics with relatively elevated serum bilirubin are less likely to develop coronary disease or microvascular complications; this may reflect the ability of bilirubin to ward off these complications via inhibition of NADPH oxidase. Oral PhyCB may likewise have potential in this regard, and has been shown to protect diabetic mice from glomerulosclerosis. With respect to oxidant-mediated uncoupling of eNOS, high-dose folate can help to reverse this by modulating the oxidation status of the eNOS cofactor tetrahydrobiopterin (BH4. Oxidation of BH4 yields dihydrobiopterin (BH2, which competes with BH4 for binding to eNOS and promotes its uncoupling. The reduced intracellular metabolites of folate have versatile oxidant-scavenging activity that can prevent oxidation of BH4; concurrently, these metabolites promote induction of dihydrofolate reductase, which functions to reconvert BH2 to BH4, and hence alleviate the uncoupling of eNOS. The arginine metabolite asymmetric dimethylarginine (ADMA, typically elevated in diabetics, also uncouples eNOS by competitively inhibiting binding of arginine to eNOS; this effect is exacerbated by the increased expression of arginase that accompanies diabetes. These effects can be countered via supplementation with citrulline, which efficiently enhances tissue levels of arginine. With respect to the loss of NO bioactivity that contributes to

  18. 瓜氨酸化修饰对纤维蛋白原多肽抗原性的影响%Impact of citrullination upon antigenicity of fibrinogen

    Institute of Scientific and Technical Information of China (English)

    赵义; 田昕; 栗占国

    2010-01-01

    目的 研究瓜氨酸化修饰对人纤维蛋白原(Fg)多肽抗原性的影响,探讨针对瓜氨酸化Fg的自身免疫应答在类风湿关节炎(RA)发病中的分子机制.方法 体外对人Fg进行瓜氨酸化修饰,用修饰后Fg刺激RA患者及对照组外周血单个核细胞,通过~3H掺人法观察细胞增殖情况;通过计算机软件对人Fg α链进行瓜氨酸化修饰前后的抗原性分析,从中筛选出1条多肽,并体外合成原型肽和瓜氨酸替换肽,通过在表达HLA-DRB1细胞系中的直接肽结合试验和抗体竞争肽结合试验,评价瓜氨酸化修饰对Fg多肽与HLA-DRB1亲合力的影响;另外,在体外采用抗原提呈及活化系统,通过检测细胞增殖情况观察瓜氨酸化修饰对Fg多肽激活T细胞作用的影响.结果 瓜氨酸化修饰的Fg和野生型Fg对RA患者外周血单个核细胞的激活作用略高于对照组,但差异无统计学意义(P>0.05).多肽结合试验和细胞活化试验证实,瓜氨酸替换肽与HLA-DRB1的结合力明显高于原型肽,而且瓜氨酸替换肽对T细胞的活化作用强于原型肽,二者差异有统计学意义(SI为2.26±0.14比1.65±0.53,P 0. 05 ). As predicted, the citrullinated substitute peptide from fibrinogen alpha chain was more prone to bind to HLA-DR4 molecule than wild-type peptide and could induce a stronger proliferation of T cells than wild-type peptide (SI, 2. 26±0. 14 vs 1.65±0. 53, P<0. 01 ) in the experiments of cell lines.Conclusions Citrullination can enhance the antigenicity of fibrinogen peptides by increasing the binding of fibrinogen peptides to HLA-DR4 molecules and inducing the specific T cell activation.

  19. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of a health claim related to citrulline-malate and faster recovery from muscle fatigue after exercise pursuant to Article 13(5) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    to citrulline-malate and faster recovery from muscle fatigue after exercise. Citrulline-malate is sufficiently characterised. The claimed effect is “maintenance of ATP levels through reduction of lactates in excess for an improved recovery from muscle fatigue”. The target population proposed by the applicant...... is healthy children above six years of age and adults. The Panel considers that faster recovery from muscle fatigue after exercise contributing to the restoration of muscle function is a beneficial physiological effect. A total of 33 references were considered as pertinent to the claim by the applicant...... to the methodological limitations of the study. A number of mechanistic, animal and in vitro studies were submitted. In the absence of evidence for an effect of consumption of citrulline-malate on a faster recovery from muscle fatigue after exercise in humans, these studies cannot be used as a source of data...

  20. EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2014. Scientific Opinion on the substantiation of a health claim related to citrulline-malate and faster recovery from muscle fatigue after exercise pursuant to Article 13(5) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    the human study for the scientific substantiation of the claim. A health claim on citrulline-malate and faster recovery from muscle fatigue after exercise has already been assessed by the Panel with an unfavourable outcome. The additional information submitted by the applicant did not provide evidence...... on the scientific substantiation of a health claim related to citrulline-malate and faster recovery from muscle fatigue after exercise. The Panel considers that citrulline-malate is sufficiently characterised. The claimed effect proposed by the applicant is “improved recovery from muscle fatigue”. Faster recovery...... function. The evidence provided by the applicant did not establish that a faster reduction of blood lactate concentrations through a dietary intervention leads to faster recovery from muscle fatigue by contributing to the restoration of muscle function after exercise. No conclusions could be drawn from...

  1. Associations of rheumatoid factor and anti-citrullinated peptide antibody with disease progression and treatment outcomes in patients with rheumatoid arthritis.

    Science.gov (United States)

    Katchamart, Wanruchada; Koolvisoot, Ajchara; Aromdee, Emvalee; Chiowchanwesawakit, Praveena; Muengchan, Chayawee

    2015-10-01

    The objective of this study was to investigate the association of rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA) status with disease progression and treatment outcomes in patients with rheumatoid arthritis (RA). A total of 276 adult patients who fulfilled the American College of Rheumatology 1987 classification criteria for RA were recruited from the Rheumatology clinic, Siriraj Hospital, from January 2011 to December 2012. Demographic, clinical, and laboratory data were collected at baseline and every 3 months up to 1 year of follow-up. RF and ACPA were measured at baseline. Radiography of the hands and feet was performed at baseline and 1 year. Patients with RF+/ACPA+ had significantly more severe disease activity and impaired functional status than those who had RF-/ACPA-. Although they received more aggressive treatment with methotrexate and combination of non-biologic, disease-modifying antirheumatic drug than other groups, fewer patients in this group achieved remission at 1 year of follow-up, especially when compared to RF-/ACPA- group (12 vs. 18 %). For radiographic erosion, patients with the presence of either RF or ACPA had a higher proportion of hand erosion than seronegative patients at baseline (77, 73, 83, and 32 %, p < 0.001 for RF+/ACPA+, RF+/ACPA-, RF-/ACPA+, and RF-/ACPA-, respectively). After 1 year of follow-up, patients who developed new erosion at the hands were more prevalent in RF+/ACPA+ (32 %) and RF+/ACPA- (33 %) groups. However, "newly developed" feet erosion was most common in RF+/ACPA- group (40 %) than in other groups. Patients with positive either RF or ACPA or both have more severe and aggressive disease that requires intensive treatment to improve outcomes.

  2. Anti-citrullinated protein antibodies suppress let-7a expression in monocytes from patients with rheumatoid arthritis and facilitate the inflammatory responses in rheumatoid arthritis.

    Science.gov (United States)

    Lai, Ning-Sheng; Yu, Hui-Chun; Yu, Chia-Li; Koo, Malcolm; Huang, Hsien-Bin; Lu, Ming-Chi

    2015-12-01

    We hypothesized that anti-citrullinated protein antibodies (ACPAs) could affect the expression of miRNAs in monocytes and contribute to the inflammatory responses in rheumatoid arthritis (RA). The expression profiles of 270 human miRNAs, co-cultured with ACPAs or human immunoglobulin G (IgG), were analyzed using real-time polymerase chain reaction. Ten miRNAs exhibited differential expression in U937 cells after co-cultured with ACPAs compared with human IgG. The expression levels of these miRNAs were investigated in monocytes from 21 ACPA-positive RA patients and 13 controls. Among these miRNAs, the expression levels of let-7a was decreased in monocytes from ACPA-positive RA patients. The expression levels of let-7a showed a negative correlation with positivity of rheumatoid factor in patients sampled. We found that transfection of U937 cells with let-7a mimic suppressed K-Ras protein expression. In the ACPA-mediated signaling pathway, transfection of U937 cells with let-7a mimic suppressed the ACPA-enhanced phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), and the expression and secretion of interleukin (IL)-1β. In conclusion, ACPA-mediated decreased let-7a expression in monocytes from ACPA-positive RA patients. Decreased let-7a expression was associated with the positivity of RF in ACPA-positive RA patients. The decreased expression of let-7a could facilitate the inflammatory pathway via enhanced ACPA-mediated phosphorylation of ERK1/2 and JNK and increased expression of IL-1β through an increase in the expression of Ras proteins.

  3. Left ventricular function in treatment-naive early rheumatoid arthritis

    DEFF Research Database (Denmark)

    Løgstrup, Brian B; Deibjerg, Lone K; Nielsen, Agnete Desirèe;

    2014-01-01

    BACKGROUND: The role of inflammation and anti-cyclic citrullinated peptide antibodies (anti-CCP) in the pathogenesis of cardiovascular disease in early rheumatoid arthritis (RA) remains unclear. Previous studies have suggested that both disease activity and disease duration are associated...

  4. Use of anti-citrullinated peptide (Anti –CCP antibodies in distinguishing patients with systemic lupus erythematosus and rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Harry Isbagio

    2004-12-01

    Full Text Available Diagnosis of Rheumatoid arthritis (RA and systemic lupus erythematosus (SLE can be confused in their initial stages. The joints, especially the hands, are commonly affected in both disorders, many patients with SLE are initially misdiagnosed as having RA Given that the outcome for the two diseases is diverse, it would be helpful to have serological marker to distinguish between them at onset. Anti-citrullinated peptide antibodies (anti-CCP have recently been described as highly specific for RA. The objective of this study is to confirm the specificity of anti-CCP antibodies and to determine whether they might distinguish patients with RA from those with SLE. This study is a cross sectional study on a group of patients with RA (n=27, SLE with arthritis (n=20, other autoimmune diseases (non-rheumatic diseases, n = 8, and healthy adults (n=20. Anti-CCP was determined by a commercial Elisa test and Rheumatoid factor (RF was determined by the standard slide latex test. The sensitivity and specificity of anti-CCP for the diagnosis of RA was 63.0% and 97.9% respectively, comparing with RF for RA that was 40.7 % and 85.4 %. Only 1 healthy adult was anti-CCP+, no anti-CCP was detected from SLE and other autoimmune disease. The mean of titer anti CCP in normal healthy adult, other autoimmune diseases, SLE and RA was 1.35 Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 ± 2.04, 0.63 Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 ± 0.59, 0.75 Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 ± 0.59, and 38.17 Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 ± 44.22 RU/ml, respectively. There was a highly significant difference between the mean of titer anti CCP for RA with others diseases (p <0.001. We conclude that detection of anti-CCP is very useful for the diagnosis of RA and distinguishing RA from SLE. (Med J Indones 2004; 13: 227-31Keywords

  5. Prevalence of anti-citrullinated protein antibodies (ACPA in patients with diffuse large B-cell lymphoma (DLBCL: a case-control study.

    Directory of Open Access Journals (Sweden)

    Gunter Assmann

    Full Text Available BACKGROUND: Antibodies against citrullinated proteins (ACPA have been recognised as the most specific serum marker for rheumatoid arthritis. However, serum autoantibodies such as anti-nuclear antibodies have also been detected in the sera of different lymphatic malignancies without accompanying rheumatologic disease. Therefore, we conducted a study to evaluate the prevalence of ACPA in diffuse large B-cell non-Hodgkin lymphoma (DLBCL. METHODS: Sera of 395 DLBCL patients and 258 age-matched healthy controls were investigated to evaluate the prevalence of ACPA and RF. ACPA-positive data were stratified into subgroups of RF positivity and established prognostic parameters for DLBCL, including overall survival. In addition, the ACPA serum concentrations levels were compared to an ACPA-positive RA cohort (n = 175. The statistics were performed with χ2 test and Mann- Whitney-U test; Kaplan-Meyer curves (log rank test were used to analyse the overall survival. P-value <0.05 was statistically significant. RESULTS: ACPA, but not RF, occurred significantly more frequently in the sera of DLBCL patients than in healthy controls (3.5% versus 0.8%, p = 0.030. However, the ACPA serum concentration levels were significantly lower than in RA patients (median 10.4 versus 124.1 U/ml, p = 0.0001. After subgroup stratification, ACPA positivity in DLBCL was significantly associated with male gender (4.4% versus 0%, p = 0.022; odds ratio 1.046, CI 1.014-1.079 and with RF-IgM seropositivity (1.77% versus 0%, p = 0.043, but not with prognostic parameters for DLBCL. CONCLUSIONS: DLBCL is associated with a significantly higher prevalence of ACPA, with an increased prevalence in male patients, and simultaneous RF-IgM positivity. However, ACPA is not prognostic for DLBCL. The prevalence of RF-IgM, -IgA, or -IgG did not differ from healthy controls.

  6. 重组精氨酸脱亚胺酶制备L-瓜氨酸的工艺条件优化%Optimization of Preparing L-citrulline by Recombinant Arginine Deiminase

    Institute of Scientific and Technical Information of China (English)

    马越; 宿玲恰; 吴丹; 吴敬

    2015-01-01

    将来源于Pseudomonas putida ACCC 10185的ADI编码基因克隆到表达载体pET-24a(+)中,转化Escherichia coli BL21(DE3),通过超声波破碎得到粗酶液,酶活检测ADI酶活为26 U/mL发酵液。对酶转化L-精氨酸盐酸盐生成L-瓜氨酸的反应条件进行了优化,结果表明,当底物L-精氨酸盐酸盐浓度650 g/L,反应初始pH6.0,温度37℃,加酶量24 U/g底物,转速100-200 r/min,转化时间7 h,L-瓜氨酸转化率达到100%,是目前国内外报道的酶法制备L-瓜氨酸的最高水平。%ThearcAgene encoding ADI from Pseudomonas putida ACCC 10185 was cloned into the expression vector pET-24a (+). The vector was then transformed intoEscherichia coli BL21(DE3)for intracellular production of ADI. The crude enzyme was obtained by ultrasonic treatment, and activity in the fermentation broth of recombinantE. coli BL21(DE3)was 26 U/mL. Furthermore, the condition for enzymatic conversion of L-arginine monohydrochloride to L-citrulline by the recombinant ADI was optimized. At 650 g/L of L-arginine monohydrochloride, pH6.0, 37℃, 100-200 r/min, and 24 U ADI per gram substrate incubated for 7 hours, 100% of the L-arginine monohydrochloride was transformed into L-citrulline, which was the highest level of preparing L-citrulline by enzyme method in home and abroad presently.

  7. Study on the Production of L-citrulline by Engineering Bacteria and Applied to the Tobacco%L-瓜氨酸的工程菌制备及在卷烟中的应用

    Institute of Scientific and Technical Information of China (English)

    胡延奇

    2012-01-01

    L-citrulline was produced by arginine deiminase from engineering bacteria.Factors which affected the yield of L-citrulline were studied,including culture medium,inducing conditions and cell conversion.The optimum culture were found to be 5 g/L glucose,20 g/L tryptone,1 g/L K2HPO4·3H2O and 1 g/L MgSO4·7H2O.The optimum inducing conditions were found to be the cell OD600 1.0,the temperature 25 ℃,the time 7 h and lactose 5 g/L.Under the optimum cell conditions: the pH 6.0,the temperature 40 ℃,and substrate concentration 60 g/L,55.1 g/L of L-citrulline could be obtained.The cells could be used for 3 times and the yields were stable.The findings in cigarette show that it was the best effect when the amount was 0.02%.%利用工程菌中的精氨酸托亚氨基酶转化制备L-瓜氨酸,进行了培养基、诱导条件和细胞转化条件的研究。培养基最佳组成为:葡萄糖质量浓度5 g/L,胰蛋白胨20 g/L,K2HPO4.3H2O 1 g/L,MgSO4.7H2O 1 g/L;最佳诱导条件为:OD600值1.0,诱导温度25℃,诱导时间7 h,诱导剂(乳糖)5 g/L;最佳的细胞转化条件为:pH 6.0,温度40℃,精氨酸质量浓度60 g/L。在最佳条件下瓜氨酸的产量达55.1 g/L,细胞可连续使用三次,且产量稳定。在卷烟中的初步应用研究结果显示:当其用量为0.02%时综合效果最好。

  8. Cartilage oligomeric matrix protein associates differentially with erosions and synovitis and has a different temporal course in cyclic citrullinated peptide antibody (anti-CCP)-positive versus anti-CCP-negative early rheumatoid arthritis

    DEFF Research Database (Denmark)

    Christensen, Anne F; Lindegaard, Hanne; Hørslev-Petersen, Kim;

    2011-01-01

    -suppressive effect. We aimed to compare circulating cartilage oligomeric matrix protein (COMP), a marker of cartilage turnover, in untreated anti-CCP-positive and anti-CCP-negative RA, and to study the temporal pattern of COMP through 4 years of treatment, including the relationship to imaging and clinical findings......OBJECTIVE: Cyclic citrullinated peptide antibody (anti-CCP)-positive and anti-CCP-negative rheumatoid arthritis (RA) have been suggested as 2 distinctive disease subsets with respect to disease activity and prognosis. Previously, we proposed that anti-CCP antibodies might have a chondrocyte......-CCP, Health Assessment Questionnaire, visual analog scale scores for pain and global and physician assessment, and magnetic resonance imaging (MRI) of the nondominant hand were recorded at baseline. COMP in serum was measured by ELISA at inclusion and serially through 4 years. RESULTS: Median baseline COMP...

  9. Activity and Stability of Arginine Deiminase for Producing L-citrulline%L-瓜氨酸酶法制备中精氨酸脱亚氨酸酶的活性与稳定性研究

    Institute of Scientific and Technical Information of China (English)

    李加友; 曹瑜; 刘毅; 钱绍松; 焦庆才

    2005-01-01

    A novel Enterococcus faecalis strain designated NJ402 was found with high activity of arginine deiminase (ADI). The optimum condition for catalytic activity was determined in terms of temperature (about 40℃),thermostability (available 37℃) and pH (6-7). The effects of substrate and product concentration were studied.The effects of various metal ions added in reaction mixtures on the biocatalyst were investigated and ADI of NJ402was found to exhibit Co2+ dependence, different from previous reports. Surfactant, cetyl trimethyl ammonium bromide, was one of the most important keys for producing L-citrulline. The enzyme in resting cells possessed the quality of high stability for reuse.

  10. Diagnostic Values of Combined Detection of Rheumatoid Factor, Anticyclic Citrullinated Peptide Antibody and Antikeratin Antibody in Rheumatoid Arthritis%类风湿因子、抗环瓜氨酸多肽抗体和抗角蛋白抗体联合检测在类风湿关节炎诊断中的价值

    Institute of Scientific and Technical Information of China (English)

    张新刚; 张晓莉; 蒋莉; 郭韵; 王晓非

    2012-01-01

    Objective To evaluate the diagnostic values of combined detection of rheumatoid factor (RF), antieyclic citrullinated peptide antibody and antikeratin antibody (AKA) in rheumatoid arthritis (RA). Methods Sera from 278 RA patients and 510 controls were ana-lyzed. RF,antieyclic citrullinated peptide antibody and AKA were detected using immune turbidimetry,ELISA and indirect immunofluores-cence,respectively. The distributions of these antibodies were compared to determine the diagnostic values of combined detection of RF,anti-eyelie citrullinated peptide antibody and AKA in RA patients. Results In the single antibody detection,RF had the highest sensitivity (79.86% ), antieyclic citrullinated peptide antibody had the highest specificity (94.51 %) and the highest positive predictive value (88.03% ), RF( 87.16%) or antieyclic citrullinated peptide antil>ody (87%) had the highest negative predictive value, antieyclic citrullinated peptide an-tibody had the highest PLR( 13.5) ,RF(0.27) or antieyelie citrullinated peptide antibody(0.27) had the lowest NLR. In the combined de-tection, RF and antieyclic citrullinated peptide antibody showed the highest sensitivity (67.63%),and highest specificity (96.27%) was ob-served with antieyclic citrullinated peptide antibody and AKA;RF and AKA had the highest positive predictive value( 89.55%) ,RF and an-tieyclic citrullinated peptide antibody had the highest negative predictive value (84.32% ),RF and AKA had the highest PLR( 15.72),RF and antieyclic citrullinated peptide antibody had the lowest NLR (0.34). Conclusion The combined detection between the three antibodies obviously improved the earlier diagnosis of RA. The diagnostic value of antieyclic citrullinated peptide antibody was superior to AKA and RF. The combined detection of RF and antieyclic citrullinated peptide antibody had the most significant diagnostic value.%目的 评估类风湿因子(RF)、抗环瓜氨酸多肽(CCP)抗体和抗角蛋白抗体(AKA)联合检测在类

  11. A weighted genetic risk score using all known susceptibility variants to estimate rheumatoid arthritis risk

    Science.gov (United States)

    Yarwood, Annie; Han, Buhm; Raychaudhuri, Soumya; Bowes, John; Lunt, Mark; Pappas, Dimitrios A; Kremer, Joel; Greenberg, Jeffrey D; Plenge, Robert; Worthington, Jane; Barton, Anne; Eyre, Steve

    2015-01-01

    Background There is currently great interest in the incorporation of genetic susceptibility loci into screening models to identify individuals at high risk of disease. Here, we present the first risk prediction model including all 46 known genetic loci associated with rheumatoid arthritis (RA). Methods A weighted genetic risk score (wGRS) was created using 45 RA non-human leucocyte antigen (HLA) susceptibility loci, imputed amino acids at HLA-DRB1 (11, 71 and 74), HLA-DPB1 (position 9) HLA-B (position 9) and gender. The wGRS was tested in 11 366 RA cases and 15 489 healthy controls. The risk of developing RA was estimated using logistic regression by dividing the wGRS into quintiles. The ability of the wGRS to discriminate between cases and controls was assessed by receiver operator characteristic analysis and discrimination improvement tests. Results Individuals in the highest risk group showed significantly increased odds of developing anti-cyclic citrullinated peptide-positive RA compared to the lowest risk group (OR 27.13, 95% CI 23.70 to 31.05). The wGRS was validated in an independent cohort that showed similar results (area under the curve 0.78, OR 18.00, 95% CI 13.67 to 23.71). Comparison of the full wGRS with a wGRS in which HLA amino acids were replaced by a HLA tag single-nucleotide polymorphism showed a significant loss of sensitivity and specificity. Conclusions Our study suggests that in RA, even when using all known genetic susceptibility variants, prediction performance remains modest; while this is insufficiently accurate for general population screening, it may prove of more use in targeted studies. Our study has also highlighted the importance of including HLA variation in risk prediction models. PMID:24092415

  12. The presence of anti-citrullinated protein antibodies (ACPA) and rheumatoid factor on patients with rheumatoid arthritis (RA) does not interfere with the chance of clinical remission in a follow-up of 3 years.

    Science.gov (United States)

    da Mota, Licia Maria Henrique; Dos Santos Neto, Leopoldo Luiz; de Carvalho, Jozélio Freire; Pereira, Ivânio Alves; Burlingame, Rufus; Ménard, Henri A; Laurindo, Ieda Maria Magalhães

    2012-12-01

    Autoantibodies in early rheumatoid arthritis (RA) have important diagnostic value. The association between the presence of autoantibodies against cyclic citrullinated peptide and the response to treatment is controversial. To prospectively evaluate a cohort of patients with early rheumatoid arthritis (peptide antibodies (anti-CCP) and citrullinated anti-vimentin (anti-Sa) with the occurrence of clinical remission, forty patients diagnosed with early RA at the time of diagnosis were evaluated and followed for 3 years, in use of standardized therapeutic treatment. Demographic and clinical data were recorded, disease activity score 28 (DAS 28), as well as serology tests (ELISA) for RF (IgM, IgG, and IgA), anti-CCP (CCP2, CCP3, and CCP3.1) and anti-Sa in the initial evaluation and at 3, 6, 12, 18, 24, and 36 months of follow-up. The outcome evaluated was the percentage of patients with clinical remission, which was defined by DAS 28 lower than 2.6. Comparisons were made through the Student t test, mixed-effects regression analysis, and analysis of variance (significance level of 5%). The mean age was 45 years, and a female predominance was observed (90%). At the time of diagnosis, RF was observed in 50% of cases (RF IgA-42%, RF IgG-30%, and RF IgM-50%), anti-CCP in 50% (no difference between CCP2, CCP3, and CCP3.1) and anti-Sa in 10%. After 3 years, no change in the RF prevalence and anti-CCP was observed, but the anti-Sa increased to 17.5% (P = 0.001). The percentage of patients in remission, low, moderate, and intense disease activity, according to the DAS 28, was of 0, 0, 7.5, and 92.5% (initial evaluation) and 22.5, 7.5, 32.5, and 37.5% (after 3 years). There were no associations of the presence of autoantibodies in baseline evaluation and in serial analysis with the percentage of clinical remission during follow-up of 3 years The presence of autoantibodies in early RA has no predictive value for clinical remission in early RA.

  13. Rheumatoid Factors: Clinical Applications

    Directory of Open Access Journals (Sweden)

    Francesca Ingegnoli

    2013-01-01

    Full Text Available Rheumatoid factors are antibodies directed against the Fc region of immunoglobulin G. First detected in patients with rheumatoid arthritis 70 years ago, they can also be found in patients with other autoimmune and nonautoimmune conditions, as well as in healthy subjects. Rheumatoid factors form part of the workup for the differential diagnosis of arthropathies. In clinical practice, it is recommended to measure anti-cyclic citrullinated peptide antibodies and rheumatoid factors together because anti-cyclic citrullinated peptide antibodies alone are only moderately sensitive, and the combination of the two markers improves diagnostic accuracy, especially in the case of early rheumatoid arthritis. Furthermore, different rheumatoid factor isotypes alone or in combination can be helpful when managing rheumatoid arthritis patients, from the time of diagnosis until deciding on the choice of therapeutic strategy.

  14. Chronic tophaceous gout with anti-CCP positivity: A rare presentation

    Directory of Open Access Journals (Sweden)

    Vikram Haridas

    2016-07-01

    Full Text Available Persistent gout may progress into a condition termed as chronic tophaceous gout, which involves the deposition of nodular mass of uric acid crystals called tophi in various soft tissue areas of the body. Generally, the anti-cyclic citrullinated peptide (anti-CCP antibody testing is considered as a highly specific confirmatory test for RA. We present here a rare case report of chronic tophaceous gouty arthritis with anti-CCP positivity.

  15. 谷氨酸棒状杆菌发酵生产L 瓜氨酸及发酵条件优化%Optimization of L-citrulline production by Corynebacterium glutamicum

    Institute of Scientific and Technical Information of China (English)

    丁叶; 郝宁; 胡洁; 谭玉岩; 郭格格

    2016-01-01

    以代谢控制发酵理论为指导,重点对C. glutamicum 366菌株进行摇瓶发酵条件的优化。应用响应面法优化发酵培养基的配比,优化后的发酵培养基:葡萄糖63.33 g/L、精氨酸196.96 mg/L、( NH4)2 SO445.79 g/L、生物素35.72μg/L、K2 HPO4·3H2 O 1.0 g/L、KH2 PO41.0 g/L、MgSO4·7H2 O、0.25 g/L、MnSO4·H2 O 0.02 g/L、FeSO4·7H2 O 0.02 g/L、ZnCl21 mg/L、CuSO40.2 mg/L、VB1200μg/L、CaCO330 g/L。摇瓶发酵培养条件:温度30℃、摇床转速200 r/min、初始pH 7.0。在此发酵条件下,菌株进行摇瓶发酵72 h,产L 瓜氨酸14.96 g/L,相比优化之前提高了75.8%。%We optimized the fermentation for L-citrulline production by C. glutamicum 366 strain. Mediam was optimized by response surface analysis Design-Expert software. The fermentation conditions were also studied. The optimum medium was:glucose 63. 33 g/L,arginine 196. 96 mg/L,ammonium sulfate 45. 79 g/L,biotin 35. 72 μg/L,K2HPO4·3H2O 1. 0 g/L,KH2PO4 1. 0 g/L,MgSO4·7H2O 0. 25 g/L,MnSO4· H2 O 0. 02 g/L, FeSO4·7H2 O 0. 02 g/L, ZnCl2 1 mg/L, CuSO4 0. 2 mg/L, vitamin B1 200 μg/L and CaCO3 30 g/L.The optimum fermentation conditions were:temperature at 30 ℃,the rotate speed of 200 r/min,initial pH 7. 0.Under this condition,the production of L-citrulline was 14. 96 g/L after 72 h shake flask fermentation,increased by 75. 8% compared to the control.

  16. Intestinal renal metabolism of L-citrulline and L-arginine following enteral or parenteral infusion of L-alanyl-L-[2,15N]glutamine or L-[2,15N]glutamine in mice.

    Science.gov (United States)

    Boelens, Petra G; van Leeuwen, Paul A M; Dejong, Cornelis H C; Deutz, Nicolaas E P

    2005-10-01

    Previously, we observed increased plasma arginine (ARG) concentrations after glutamine (GLN)-enriched diets, in combination with clinical benefits. GLN delivers nitrogen for ARG synthesis, and the present study was designed to quantify the interorgan relationship of exogenous L-GLN or GLN dipeptide, by enteral or parenteral route, contributing to intestinal citrulline (CIT) and renal de novo ARG synthesis in mice. To study this, we used a multicatheterized mouse model with Swiss mice (n = 43) in the postabsorptive state. Stable isotopes were infused into the jugular vein or into the duodenum {per group either free L-[2,(15)N]GLN or dipeptide L-ALA-L-[2,(15)N]GLN, all with L-[ureido-(13)C-(2)H(2)]CIT and L-[guanidino-(15)N(2)-(2)H(2)]ARG} to establish renal and intestinal ARG and CIT metabolism. Blood flow was measured using (14)C-para-aminohippuric acid. Net intestinal CIT release, renal uptake of CIT, and net renal ARG efflux was found, as assessed by arteriovenous flux measurements. Quantitatively, more de novo L-[2,(15)N]CIT was produced when free L-[2,(15)N]GLN was given than when L-ALA-L-[2,(15)N]GLN was given, whereas renal de novo L-[2,(15)N]ARG was similar in all groups. In conclusion, the intestinal-renal axis is hereby proven in mice in that L-[2,(15)N]GLN or dipeptide were both converted into de novo renal L-[2,(15)N]ARG; however, not all was derived from intestinal L-[2,(15)N]CIT production. In this model, the feeding route and form of GLN did not influence de novo renal ARG production derived from GLN.

  17. Does Citrulline Malate Enhance Physical Performance

    Science.gov (United States)

    2010-10-01

    then returned for their second VO2 max test. After the second test, subjects ingested 6 g/d of the other condition’s capsules for 14 days, and then...returned for their third and final VO2 max test. VO2max, lactate threshold, maximum watts reached, ratings of perceived exertion and pre- and post...ingested 6 g/d of either CM or a placebo for 14 days. Subjects then returned for their second VO2 max test. After the second test, subjects

  18. Presence of antibodies to cyclic citrullinated peptides in juvenile-onset systemic lupus erythematosus%儿童系统性红斑狼疮抗环瓜氨酸肽抗体检测及其临床意义

    Institute of Scientific and Technical Information of China (English)

    刘海英; 刘云锋; 关启鸿; 钟艳玲; 皮蕾; 张白杜; 郭彩娇; 曾华松

    2010-01-01

    Objective To determine the prevalence of antibodies to cyclic citrullinated peptides (antiCCP) in patients with juvenile-onset systemic lupus erythematosus (JSLE) and its potential clinical significance. Methods Anti-CCP was measured in sera from patients with JSLE (n=47), juvenile idiopathic arthritis (JIA, n=54) and the sera from age-matched healthy children (n=40) using the third generation of anti-CCP ELISA commercial kit. The association of anti-CCP with other laboratory parameters and clinical features, especially arthritic symptoms in JSLE was also analyzed. T-test, Mann-Whitney U test, Chi-square and Fisher's exact test were used for statistical analysis. Results Out of the 47 JSLE patients, 6 (13%) were anti-CCP positive, which was significantly higher than that of the healthy controls( 13% vs 0, P<0.05 ), but not different from that of the JIA group (26%, P=0.098). RF was more prevalent in JSLE patients with anti-CCP than patients without (83% vs 15%, P<0.01 ), but there was no difference in other laboratory parameters and the clinical features ineluding the occurrence of arthritis (67% vs 51%, P>0.05). As one of the initial symptoms, arthritis was observed in 25 of 47 JSLE patients and no one had developed deforming arthropathy.There was no statistical difference in anti-CCP positivity between JSLE patients with and without articular involvement ( 16% vs 9%, P>0.05 ). Anti-CCP was not detected in any of the 3 patients with JSLE who had experienced joint pain and limited activity during 3 years follow-up. Conclusion Anti-CCP could be detected in patients with JSLE. It is noteworthy when differentiate from juvenile idiopathic arthritis, but the presence of anti-CCP does not relate with the occurrence of arthritis at presentation and persistence of arthritis in JSLE.%目的 检测儿童系统性红斑狼疮(JSLE)患者血清抗环瓜氨酸肽(CCP)抗体水平,了解抗CCP抗体在该病中的阳性检出率以及探讨其与

  19. 抗瓜氨酸化蛋白抗体特异性免疫复合物在类风湿关节炎中的作用%Pathogenic role of anti-citrullinated protein antibody specific immune complexes and its pathogenesis in rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    高德玉

    2013-01-01

    Rheumatoid arthritis(RA) is a common chronic immuine disease characterized by autoimmune inflammatory reaction in joints. Citmllination of peptide in synovial tissue is the post-translational conversion of arginine to citmlline,and involved in the generation of anti-citmllinated protein antibodies(ACPA)and pathogenesis of RA. High amounts of Immune complex are usually found in RA synovial fluids (SF) and on the surface of chondrocytes. IC in the sera and SF are involved in activation of complement cascade in RA synovial tissue and induction of cytokines secretion, which can cause the irreversible damage of joints. Because of the pathogenic nature of IC in RA, it is important to identify the antigens in these complexes. The interaction of citrullinated protein deposits with locally produced ACPA results in the formation of immune complexes were able to chronically maintain inflammation. Since anti-citmllinated protein antibodies and citrullinated immune complexes are noticeable higher than that in health)' control, it may contribute to the diagnosis and pathogenic evaluation of RA.%类风湿关节炎(rheumatoid arthritis,RA)是一种以关节组织内炎症损害为主要病理变化的自身免疫性疾病.蛋白质抗原或多肽的瓜氨酸化是一种蛋白质翻译后修饰过程,并且与RA的发病过程及抗瓜氨酸蛋白抗体(anti-citrullinated protein antibodies,ACPA)产生有关.在RA患者血液及关节滑膜液、血清和软骨细胞表层可发现大量免疫复合物(immune complex,IC)存在.IC可激活RA患者体内补体系统并促进细胞因子等炎性介质的释放,引起关节骨和软骨组织发生损伤,进而引起不可逆的关节畸变等功能损害.IC中抗原成分的鉴定对于深入了解RA的发病机制非常重要.含有抗瓜氨酸化蛋白的IC的沉积及作用可以诱发细胞因子的产生,进而引起持续性慢性炎症.RA患者滑膜液及血清中ACPA及其特异性IC显著高于正常人,提示ACPA特异

  20. Isolation,Identification and Characterization of Citrulline-producing Lactic Acid Bacteria from Fermenting Liquid of Yellow Rice Wine%黄酒发酵液中产瓜氨酸乳酸菌的分离鉴定与评价

    Institute of Scientific and Technical Information of China (English)

    李晓敏; 王霈虹; 吴殿辉; 孙军勇; 陆健

    2015-01-01

    为了解黄酒发酵过程中氨基甲酸乙酯前体物瓜氨酸的来源,从黄酒发酵醪液中分离得到9株乳酸菌,并通过生理生化鉴定和16S rDNA序列分析,结果表明,菌株z1为Lactobacillus plantarum,菌株z2和z3为L.hilgardii,菌株z4为L.diolivorans,菌株z5和z7为L.brevis,菌株z6和z9为L.casei,菌株z8为L.fermentum。采用平板检测法结合分子检测法对9株乳酸菌产瓜氨酸能力进行了评价,结果显示,其中6株菌均能不同程度地降解精氨酸产生瓜氨酸,且与菌株中是否存在ADI途径编码基因簇中的关键基因arcA、arcB和arcC直接相关。此外,还应用HPLC对各菌株产瓜氨酸能力进行了精确定量,发现无论是在添加了精氨酸的培养基还是在灭菌后的黄酒培养液中培养,乳酸菌在利用精氨酸的过程中不断向胞外分泌瓜氨酸,从而积累氨基甲酸乙酯。本研究结果为进一步用微生物手段控制黄酒中氨基甲酸乙酯形成提供了思路。%To find out the original source of citrulline, one precursor of ethyl carbamate (EC),nine lactic acid bacteria (LAB) strains were isolat-ed from fermenting liquid of yellow rice wine. By physiological and biochemical characterization and 16S rDNA sequencing, strain z1 was identified as Lactobacillus plantarum,z2 and z3 were L.hilgardii,z4 was L.diolivorans,z5 and z7 were L.brevis,z6 and z9 were L.casei,z8 was L. fermentum.The capabilities of each strain to catabolize arginine was determined by plate assay combined with molecular approaches.It was found that six strains were able to degrade arginine and produce citrulline,which was dependent on the existence of key genes arcA,arcB and arcC that involved in ADI (arginine deiminase) pathway.Furthermore,the six LAB strains could secrete citrulline when grown either on broth supplemented with arginine or on sterilized Chinese rice wine culture,and thus forming EC.The results of the present study provided clues

  1. 抗突变型瓜氨酸波形蛋白检测在类风湿关节炎诊断中的意义%Detection of the Antibodies of Anti-mutated Citrullinated Vimentin in Diagnosis of Rheumatoid Arthritis

    Institute of Scientific and Technical Information of China (English)

    陈霞

    2011-01-01

    Objective To analyze diagnostic value of anti-mutated citrullinated vimentin(anti-MCV),antibody for rheumatoid arthritis (RA). Methods Enzyme-linked immunosorbent assay(ELISA)was used to detect the level of serum anti-MCV antibody and anti-cyclin citrullinated peptides(CCP) antibody in 41 patients with RA,39 patients with other autoimmune diseases and 30 healthy controls.Mann-Whitney U test and Spearman correlation were used for statistical analysis, the diagnostic value of these two antibodies for RA were compared by receiver operating characteristic curve (ROC). Results The median level of anti-MCV was significantly higher in RA group (410. 00 U/ml) than that of other autoimmune diseases group (10. 60 U/ml) and healthy control group (8. 30 U/ml) (U=242. 0,P<0. 01,and (7 = 318. 0,P<0. 01,re-spectively). According to receiver operating characteristic curve analysis,area under the curve of anti-MCV was 0.901, standard error was 0. 032,95%CI (0. 838~0. 963) ;area under the curve of anti-CCP was 0. 918,standard error was 0. 027, 95%CI (0. 865~0. 970). The diagnostic value of them are similar. In RA the sensitivity of Anti-MCV super to that of Anti-CCP,but show lower specific than Anti-CCP. Anti-MCV has correlated to Anti-CCP(r=0. 615,P<0. 01). Conclusion Anti-MCV is a valuable index for the diagnosis of RA. And it could be a good new serum marker.%目的 探讨血清抗突变型瓜氨酸波形蛋白(MCV)抗体水平在诊断类风湿性关节炎(RA)中的意义.方法 用酶联免疫吸附试验(ELISA)测定41例RA患者、39例非RA患者和30例健康体检者血清抗MCV抗体、抗CCP抗体水平,采用Mann-Whitney U检验、Spearman相关分析,并用ROC曲线比较对RA的诊断价值.结果 RA组抗MCV抗体水平(中位数410.00 U/ml)明显高于非RA组(中位数10.60 U/ml)和健康对照组(中位数8.30 U/ml)(U值分别为242.0和318.0,P值均<0.01).抗MCV抗体ROC曲线下面积为0.901,标准误0.032,其95%的近似可信区间为0.838~0.963.

  2. Serum Levels of Anticyclic Citrullinated Peptide Antibodies, Interleukin-6, Tumor Necrosis Factor-α, and C-Reactive Protein Are Associated with Increased Carotid Intima-Media Thickness: A Cross-Sectional Analysis of a Cohort of Rheumatoid Arthritis Patients without Cardiovascular Risk Factors

    Directory of Open Access Journals (Sweden)

    Mónica Vázquez-Del Mercado

    2015-01-01

    Full Text Available The main cause of death in rheumatoid arthritis (RA is cardiovascular events. We evaluated the relationship of anticyclic citrullinated peptide (anti-CCP antibody levels with increased carotid intima-media thickness (cIMT in RA patients. Methods. Forty-five anti-CCP positive and 37 anti-CCP negative RA patients, and 62 healthy controls (HC were studied. All groups were assessed for atherogenic index of plasma (AIP and cIMT. Anti-CCP, C-reactive protein (CRP, and levels of tumor necrosis factor alpha (TNFα and interleukin-6 (IL-6 were measured by enzyme-linked immunosorbent assay (ELISA. Results. The anti-CCP positive RA patients showed increased cIMT compared to HC and anti-CCP negative (P<0.001. Anti-CCP positive versus anti-CCP negative RA patients, had increased AIP, TNFα and IL-6 (P<0.01, and lower levels of high density lipoprotein cholesterol (HDL-c (P=0.02. The cIMT correlated with levels of anti-CCP (r=0.513, P=0.001, CRP (r=0.799, P<0.001, TNFα (r=0.642, P=0.001, and IL-6 (r=0.751, P<0.001. In multiple regression analysis, cIMT was associated with CRP (P<0.001 and anti-CCP levels (P=0.03. Conclusions. Levels of anti-CCP and CRP are associated with increased cIMT and cardiovascular risk supporting a clinical role of the measurement of cIMT in RA in predicting and preventing cardiovascular events.

  3. Serum Levels of Anticyclic Citrullinated Peptide Antibodies, Interleukin-6, Tumor Necrosis Factor-α, and C-Reactive Protein Are Associated with Increased Carotid Intima-Media Thickness: A Cross-Sectional Analysis of a Cohort of Rheumatoid Arthritis Patients without Cardiovascular Risk Factors

    Science.gov (United States)

    Vázquez-Del Mercado, Mónica; Nuñez-Atahualpa, Lourdes; Figueroa-Sánchez, Mauricio; Gómez-Bañuelos, Eduardo; Rocha-Muñoz, Alberto Daniel; Martín-Márquez, Beatriz Teresita; Martínez-García, Erika Aurora; Macias-Reyes, Héctor; Gamez-Nava, Jorge Ivan; Navarro-Hernandez, Rosa Elena; Nuñez-Atahualpa, María Alejandra; Andrade-Garduño, Javier

    2015-01-01

    The main cause of death in rheumatoid arthritis (RA) is cardiovascular events. We evaluated the relationship of anticyclic citrullinated peptide (anti-CCP) antibody levels with increased carotid intima-media thickness (cIMT) in RA patients. Methods. Forty-five anti-CCP positive and 37 anti-CCP negative RA patients, and 62 healthy controls (HC) were studied. All groups were assessed for atherogenic index of plasma (AIP) and cIMT. Anti-CCP, C-reactive protein (CRP), and levels of tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). Results. The anti-CCP positive RA patients showed increased cIMT compared to HC and anti-CCP negative (P < 0.001). Anti-CCP positive versus anti-CCP negative RA patients, had increased AIP, TNFα and IL-6 (P < 0.01), and lower levels of high density lipoprotein cholesterol (HDL-c) (P = 0.02). The cIMT correlated with levels of anti-CCP (r = 0.513, P = 0.001), CRP (r = 0.799, P < 0.001), TNFα (r = 0.642, P = 0.001), and IL-6 (r = 0.751, P < 0.001). In multiple regression analysis, cIMT was associated with CRP (P < 0.001) and anti-CCP levels (P = 0.03). Conclusions. Levels of anti-CCP and CRP are associated with increased cIMT and cardiovascular risk supporting a clinical role of the measurement of cIMT in RA in predicting and preventing cardiovascular events. PMID:25821796

  4. T cell proliferative response and antibody formation to citrullinated collagen type Ⅱ in patients with rheumatoid arthritis%类风湿关节炎患者瓜氨酸化Ⅱ型胶原的T细胞增殖反应和抗体生成

    Institute of Scientific and Technical Information of China (English)

    田昕; 赵义; 栗占国

    2009-01-01

    目的 研究类风湿关节炎(RA)患者对瓜氨酸化Ⅱ型胶原(Cit-CⅡ)的T细胞增殖反应和抗体生成,探讨Cit-CⅡ在RA发病机制中的作用.方法 体外用肽基精氨酸脱亚胺酶(PAD)催化牛CⅡ中的精氨酸转变为瓜氨酸,生成Cit-CⅡ,用3H掺入法检测34例RA患者和18例对照者(包括6例骨关节炎患者和12名健康志愿者)的外周血单个核细胞(PBMC)对CⅡ和Cit-CⅡ的增殖反应,用酶联免疫吸附试验测定患者和对照者血清抗CⅡ抗体及抗Cit-CⅡ抗体水平.结果 RA患者的PBMC对CⅡ和Cit-CⅡ的增殖反应阳性率分别为35.3%(12/34)和32.4%(11/34),均分别高于对照组11.1%和0(均P0.05).RA患者抗Cit-CⅡ抗体阳性率(52.9%,18/34)高于抗CⅡ抗体阳性率(32.4%,11/34).CⅡ增殖反应阳性组抗CⅡ抗体的阳性率(58.3%,7/12)高于增殖反应阴性组(18.2%,4/22),Cit-CⅡ增殖反应阳性组抗Cit-CⅡ抗体的阳性率(72.7%,8/11)高于增殖反应阴性组(43.5%,10/23),差异均有统计学意义(均P<0.05).结论 抗Cit-CⅡ抗体在RA中有很高的特异性;RA患者抗CⅡ抗体的生成可能与CⅡ特异性T细胞介导的B细胞活化有关.但是Cit-CⅡ并没有比原型CⅡ引起RA患者更强的外周血T细胞增殖反应,Cit-CⅡ在RA细胞免疫发病中的作用仍需进一步研究.%Objective To investigate the T cell proliferative response and antibody formation to citrullinated collagen type Ⅱ ( Cit-C Ⅱ) in patients with rheumatoid arthritis (RA), and explore whether autoreactive T cells responding to Cit-C Ⅱ plays a role in the pathogenesis of RA. Methods Arginine residues of bovine collagen type Ⅱ (C Ⅱ) were converted to citrulline residues by peptidylarginine deiminase (PAD). Peripheral blood samples were collected from 34 RA patients, and 18 sex- and age-matched controls, including 6 osteoarthritis patients and 12 healthy blood donors. Peripheral blood mononuclear cells (PBMCs) were isolated and cultured with Cit-C Ⅱ, C Ⅱ, or

  5. 抗突变型瓜氨酸波形蛋白抗体及相关自身抗体在幼年特发性关节炎中的检测意义%Antibodies to mutated citrullinated vimentin and some associated autoantibodies in juvenile idiopathic arthritis

    Institute of Scientific and Technical Information of China (English)

    张露月; 茹晋丽; 颉晓香; 车国柱; 靳雪琴; 李小峰

    2015-01-01

    Objective To compare the diagnostic value of antibodies to mutated citrullinated vimentin (MCV) and some associated autoantibodies in juvenile idiopathic arthritis and to further analyze the relation between antibodies and inflammatory markers.Method Antibodies to cyclic citrullinated peptides (CCP) and anti-MCV antibodies were detected by enzyme-linked immunosorbent assay (ELISA), antiperinuclear factor (APF) and antikeratin antibody (AKA) by indirect immunofluorescent assay, as well as rheumatoid factor (RF) by latex agglutination test in serum samples from 113 patients with JIA and 56 children without rheumatoid arthritis.Result (1) The positive rate of anti-MCV antibodies, anti-CCP antibodies, and RF was 16.8%, 14.2%, and 21.2% in the JIA.In the other group, the positive rate was 2.2% , 2.2% , and 6.5%.There was a significant difference between the two groups (x2 =8.105,6.337, 7.036, P < 0.05).The positive rate of AKA and APF were not significantly different.The area under the ROC curve of anti-MCV antibodies, anti-CCP antibodies, RF, AKA, APF was 0.579, 0.561, 0.578, 0.539, 0.505.(2) The positive rate of anti-MCV antibodies and anti-CCP antibodies were higher than other antibodies.In the RF-positive polyarticular disease patients, they were higher than those in the other subtypes (P < 0.05).Antibody levels were not significantly different (P > 0.05) from other subtypes.(3) The swollen joint counts and tender joint counts had a low correlation to anti-MCV antibodies, anti-CCP antibodies, RF, AKA and APF.No correlation was found between ESR, CRP and anti-MCV antibodies, anti-CCP antibodies, RF, AKA and APF.Conclusion The diagnostic value of anti-MCV antibodies is low for JIA.The positive rate of anti-MCV antibodies was higher than the other antibodies in the classification of JIA.There was a low correlation between anti-MCV antibodies, anti-CCP antibodies, RF, AKA, APF and swollen joint counts, tender joint counts.%目的 比较抗突变型瓜

  6. Rheumatoid arthritis specific anti-Sa antibodies target citrullinated vimentin

    NARCIS (Netherlands)

    Vossenaar, E.R.; Despres, N.; Lapointe, E.; Heijden, A.G. van der; Lora, M.; Senshu, T.; Venrooij, W.J.W. van; Menard, H.A.

    2004-01-01

    Antibodies directed to the Sa antigen are highly specific for rheumatoid arthritis ( RA) and can be detected in approximately 40% of RA sera. The antigen, a doublet of protein bands of about 50 kDa, is present in placenta and in RA synovial tissue. Although it has been stated that the Sa antigen is

  7. Rheumatoid arthritis and periodontitis; a possible link via citrullination

    OpenAIRE

    Smit, M. J.; Tonckens-Brouwer, Elisabeth; Vissink, A; van Winkelhoff, A J

    2011-01-01

    Rheumatoid Arthritis (RA) and chronic and aggressive periodontitis are chronic inflammatory disorders characterized by deregulation of the host inflammatory response. Increased secretion of pro-inflammatory mediators results in soft and hard tissue destruction of the synovium and periodontium respectively. Both diseases share risk factors and have pathological pathways in common, resulting in loss of function and disability as a final clinical outcome. This article discusses possible interact...

  8. Rheumatoid arthritis and periodontitis; a possible link via citrullination

    NARCIS (Netherlands)

    de Smit, M J; Tonckens-Brouwer, Elisabeth; Vissink, A; van Winkelhoff, A J

    2011-01-01

    Rheumatoid Arthritis (RA) and chronic and aggressive periodontitis are chronic inflammatory disorders characterized by deregulation of the host inflammatory response. Increased secretion of pro-inflammatory mediators results in soft and hard tissue destruction of the synovium and periodontium respec

  9. 联合检测类风湿因子、抗环瓜氨酸多肽抗体和抗角蛋白抗体在类风湿关节炎诊断中的价值%Diagnostic Values of Combined Detection of Rheumatoid Factor,Anticyclic Citrullinated Peptide Antibody and Antikeratin Antibody in Rheumatoid Arthritis

    Institute of Scientific and Technical Information of China (English)

    陈朴; 张立营; 李熙建; 龙琴

    2013-01-01

    Objective:To evaluate the significance of the combination of serum rheumatoid factor(RF),anticyclic citrullinated peptide antibody(anti CCP)and antikeratin antibody in the diagnostic value of rheumatoid arthritis(RA).Method:Serum from 150 RA patients and 75 non-RA patients were analyzed.RF,anti CCP and AKA were detected using immune turbidimetry、ELISA and indirect immunofluorescence respectively.The distributions of these antibodies were compared to determine the diagnostic values of combined detection of RF,anti CCP and AKA in RA patients.Result:The sensitivity of single antibody detection in RF was the highest(82.0%),specificity of AKA was the highest(93.33%),the positive predictive value of AKA was the highest(94.05%),and negative predictive value of RF was the highest(67.47%);the sensitivity of combined detection of anti CCP antibody to RF+in the highest(43.33%),specificity to RF+anti CCP+AKA was the highest(100%),the positive predictive value for RF+anti CCP+AKA was the highest (100%),and negative predictive value of RF+anti CCP antibody was highest(44.81%).Conclusion:RF diagnosis of RA sensitivity is highest,but specific to RF+anti CCP+AKA is the highest,the three combined detection can improve the diagnostic value of the RA.%目的:研究类风湿因子(RF)、抗环瓜氨酸多肽(CCP)抗体和抗角蛋白抗体(AKA)联合检测在类风湿关节炎(RA)诊断中的价值。方法:分别应用免疫比浊法、ELISA法和间接免疫荧光染色法检测150例RA患者和75例非RA患者血清中的RF、抗CCP抗体和AKA水平,并分析三种抗体在RA诊断中的价值。结果:单一抗体检测中敏感性以RF最高(82.0%),特异性以AKA最高(93.33%),阳性预测值以AKA最高(94.05%),阴性预测值以RF最高(67.47%);联合检测中敏感性以RF+抗CCP抗体最高(43.33%),特异性以RF+抗CCP+AKA最高(100%),阳性预测值以RF+抗CCP+AKA最高(100%),阴性预

  10. Functional and Structural Characterization of a Novel HLA-DRB1*04:01-Restricted α-enolase T Cell Epitope in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Christina Gerstner

    2016-11-01

    Full Text Available Antibodies to citrullinated proteins, common in Rheumatoid Arthritis (RA patients, are strongly associated to a specific set of HLA-DR alleles including HLA-DRB1*04:01, *04:04 and *01:01. Here, we first demonstrate that autoantibody levels towards the dominant citrullinated B cell epitope from α-enolase are significantly elevated in HLA-DRB1*04:01-positive RA patients. Furthermore, we identified α-enolase-derived T cell epitopes and demonstrated that native and citrullinated versions of several peptides bind with different affinities to HLA-DRB1*04:01, *04:04 and *01:01. The citrulline residues in the eight identified peptides are distributed throughout the entire length of the presented epitopes and more specifically, localized at peptide positions p-2, p2, p4, p6, p7, p10 and p11. Importantly, in contrast to its native version peptide 26 (TSKGLFRAAVPSGAS, the HLA-DRB1*04:01-restricted citrullinated peptide Cit26 (TSKGLFCitAAVPSGAS elicited significant functional T cell responses in primary cells from RA patients. Comparative analysis of the crystal structures of HLA-DRB1*04:01 in complex with peptide 26 or Cit26 demonstrated that the post-translational modification did not alter the conformation of the peptide. And since citrullination is the only structural difference between the two complexes this indicates that the neo-antigen Cit26 is recognized by T cells with high specificity to the citrulline residue.

  11. Impact of tocilizumab therapy on fatigue in patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Anna Sergeyevna Starkova

    2012-01-01

    Full Text Available Objective: to study the impact of tocilizumab (TCZ therapy on fatigue symptom in patients with rheumatoid arthritis (RA. Subjects and methods. The study covered 43 RA patients receiving therapy with TCZ in a dose of 8 mg/kg once four times for 24 weeks. Most patients were females, they were aged 25 to 69 years with a one-to-10-year history of the disease; 86% of the patients were rheumatoid factor-positive; 84% were anti-cyclic citrullinated peptide-positive; 42 and 49% had X-ray Stage II or III, respectively; 81% had Functional Class II; and 77% had high DAS 28 scores. Twelve (28% of the 43 patients included into the study were found to have anemia with lower hemoglobin levels (< 110 g/l. Prior to TCZ therapy, all the patients had received for at least 6 months disease-modifying antirheumatic drugs, mainly methotrexate, in an average dose of 15.0+2.7 mg; 59.5% of the patients had taken glucocorticoids in the average dose of 7.5+2.22 mg/day, calculated with reference to prednisolone. Fatigue was rated in centimeters, by applying the visual analog scale of the RAPID-3 questionnaire. Results. The fatigue symptom was found to have the most pronounced correlations with depression (R = 0.49, pain (R = 0.48, DAS 28 scores (R = 0.47, erythrocyte sedimentation rate (ESR (R = 0.49, and total disease activity scores (R = 0.55. The relationships to the number of tender and swollen joints, hemoglobin and interleukin-6 (IL-6 levels turned out to be less significant. The level of fatigue significantly decreased from 5.3 to 4.5 cm after the first TCZ infusion just at 4 weeks of a follow-up. Later on, it continued to fall and reached 2.5 cm at 24 weeks. During the therapy, fatigue generally diminished by 52%. There were significant reductions in the scores of DAS 28 (from 6.3 to 2.23, SDAI (from 41.75 to 4.55, CDAI (from 44.03 to 4.07, RAPID-3 (p < 0.01, pain (from 6.6 to 1.2 cm, ESR, C-reactive protein, IL-6, and a considerable functional improvement in HAQ

  12. Relation Analysis of Synovial Anti-Citrullinated Epitope Peptide Expression and Peptidyl Arginine Deiminase 4 Gene in the Rheumatoid Arthritis Patient%类风湿关节炎患者滑膜抗环瓜氨酸肽表位表达与肽酰基精氨酸脱亚氨酶4基因的相关性分析

    Institute of Scientific and Technical Information of China (English)

    沈小辉; 喻伟; 杨菲

    2016-01-01

    Objective To investigate the relation of synovial anti-citrullinated epitope peptide(CCP)expression and peptidyl arginine deiminase 4 (PADI4)gene in the rheumatoid arthritis patient.Methods From February 2013 to 2015 in Dongfeng General Hospital Affiliated to Hubei University,selected 110 patients with rheumatoid arthritis as the observation group, and selected 110 healthy people at the same period in this hospital for medical examination as the control group,both groups were given the synovial CCP expression positive rate and PADI4 gene expression detecting and correlation analysis.Results The synovial anti-CCP expression positive rates in the observation group and the control group were 70.9% and 9.1% re-spectively,and the observation group were significantly higher than the control group (P<0.05).The PADI4-104 genotype expression frequency compared between the observation group and control group,the difference were statistically significant (P<0.05).The G/G expression was more in the observation group,while the control group was more wit the C/G expres-sion.Pearson correlation analysis showed that in the observation group,synovial CCP positive expression were significant correlated to the expression of genotype PADI4-104 (r=0.344,P<0.05).Logistic regression analysis showed PADI4-104 genotype frequency were the main factors for the synovial CCP epitope expression (P<0.05).Conclusion The rheumatoid arthritis was more with synovial anti-CCP positive expression.There were also PADI4 polymorphism disorder expression, and clear correlation between the two.Thus impact the incidence of rheumatoid arthritis.%目的探讨类风湿关节炎患者滑膜抗环瓜氨酸肽(CCP)表位表达与肽酰基精氨酸脱亚氨酶4(PADI4)基因的相关性。方法2013年2月~2015年选择在湖北医药学院附属东风医院风湿免疫科住院的类风湿关节炎患者110例作为观察组,同期选择在该院进行体检的健康者110例作为对照

  13. Case of interstitial lung disease with anti-EJ and anti-CCP antibodies preceding rheumatoid arthritis.

    Science.gov (United States)

    Tomioka, Hiromi; Kaneko, Masahiro; Kogata, Yoshinori; Katsuyama, Eiji; Ishikawa, Seiko; Fujii, Takao

    2012-06-01

    Autoantibodies against aminoacyl-tRNA synthetases (ARSs) are highly specific for myositis and/or interstitial lung disease. We report a rare case of double positive antibodies (anti-EJ antibody, the least common among anti-aminoacyl-tRNA synthetase antibodies, and anti-cyclic citrullinated peptide antibody, reported to be specific for rheumatoid arthritis) in a patient who presented with interstitial lung disease and later developed rheumatoid arthritis. The patient did not have clinically apparent myositis over a period of careful follow-up of several years. The initial pulmonary pathologic findings showed a nonspecific interstitial pneumonia pattern, with the formation of lymphoid follicles, which should be recognized as the first manifestation of rheumatoid arthritis.

  14. Interactions between smoking, increased serum levels of anti-CCP antibodies, rheumatoid factors, and erosive joint disease in patients with early, untreated rheumatoid arthritis

    DEFF Research Database (Denmark)

    Krol, A.; Garred, P; Heegaard, N H H;

    2015-01-01

    OBJECTIVES: To determine to what extent shared epitopes, smoking, and anti-cyclic citrullinated peptide (anti-CCP) antibodies are associated with disease activity and erosive disease in patients with rheumatoid arthritis (RA) at disease onset. METHOD: RA patients not previously treated with disease...... or antibodies. All antibody levels measured were associated with smoking and shared epitopes. CONCLUSIONS: Shared epitopes and smoking were associated with the production of anti-CCP antibodies and rheumatoid factors of IgM and IgA isotypes, which again were associated with erosive disease at presentation only...... in smokers. As shared epitopes and smoking were not directly associated with erosive disease, smoking may enhance the development of erosive disease in RA at different levels or through separate pathways....

  15. Left ventricular function in treatment-naive early rheumatoid arthritis

    DEFF Research Database (Denmark)

    Løgstrup, Brian B; Deibjerg, Lone K; Hedemann-Andersen, Agnete;

    2014-01-01

    BACKGROUND: The role of inflammation and anti-cyclic citrullinated peptide antibodies (anti-CCP) in the pathogenesis of cardiovascular disease in early rheumatoid arthritis (RA) remains unclear. Previous studies have suggested that both disease activity and disease duration are associated...... with atherosclerosis and a higher mortality rate caused primarily by coronary artery disease. OBJECTIVE: We investigated how disease activity, anti-CCP status and coronary calcium score in treatment-naive early RA impacts left ventricular (LV) systolic function. METHODS: Fifty-tree patients (30 women) with mean age 58...... by computed tomography by calculating the Agaston score. One experienced senior rheumatologist and one experienced cardiologist performed all the clinical assessments as well as all the transthoracic echocardiography (TTE) and coronary CT analysis. RESULTS: Disease activity scores before treatment at baseline...

  16. Identification of ESM-1 as a new endothelial biomarker in the pathogenesis of rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Gönül Gürol Ciftci

    2016-05-01

    Full Text Available The aim of this study was to investigate the use of ESM-1 (endothelial cell-specific molecule-1 as a new biomarker for the pathogenesis of rheumatoid arthritis (RA. The study cohort was divided into four groups according to the DAS28 disease activity score: 16 patients were classified as being in remission (DAS28 5.1; 20 healthy subjects were included as a control group. Serum samples were gathered from the patients with documented seropositivity for rheumatoid factor (RF and anti-cyclic citrullinated peptide antibodies in order to assess RF IgM and ESM-1. ESM-1 levels were significantly higher in patients with RA than in healthy subjects (p = 0.035. The data presented here strongly indicate ESM-1 as an attractive target for the treatment of inflammation-related diseases, such as RA.

  17. Increased soluble programmed death-1 (sPD-1) is associated with disease activity and radiographic progression in early rheumatoid arthritis

    DEFF Research Database (Denmark)

    Greisen, S. R.; Rasmussen, T. K.; Stengaard-Pedersen, K.

    2014-01-01

    OBJECTIVES: Programmed death-1 (PD-1) is an immunoregulatory molecule functioning by down-regulating immune responses. PD-1 is present on follicular helper T cells (TFH) and is important in the formation of plasma cells. PD-1 exists in a bioactive soluble form (sPD-1) and is thought to be implica......OBJECTIVES: Programmed death-1 (PD-1) is an immunoregulatory molecule functioning by down-regulating immune responses. PD-1 is present on follicular helper T cells (TFH) and is important in the formation of plasma cells. PD-1 exists in a bioactive soluble form (sPD-1) and is thought...... Questionnaire (HAQ) score, immunoglobulin M rheumatoid factor (IgM-RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, C-reactive protein (CRP), interleukin-21 (IL-21), and total Sharp score (TSS). We also measured sPD-1 in plasma from healthy volunteers (HV) (n = 20) and in plasma and synovial fluid...

  18. Differentiation of Boc-protected alpha,delta-/delta,alpha- and beta,delta-/delta,beta-hybrid peptide positional isomers by electrospray ionization tandem mass spectrometry.

    Science.gov (United States)

    Raju, G; Ramesh, V; Srinivas, R; Sharma, G V M; Shoban Babu, B

    2010-06-01

    Two new series of Boc-N-alpha,delta-/delta,alpha- and beta,delta-/delta,beta-hybrid peptides containing repeats of L-Ala-delta(5)-Caa/delta(5)-Caa-L-Ala and beta(3)-Caa-delta(5)-Caa/delta(5)-Caa-beta(3)-Caa (L-Ala = L-alanine, Caa = C-linked carbo amino acid derived from D-xylose) have been differentiated by both positive and negative ion electrospray ionization (ESI) ion trap tandem mass spectrometry (MS/MS). MS(n) spectra of protonated isomeric peptides produce characteristic fragmentation involving the peptide backbone, the Boc-group, and the side chain. The dipeptide positional isomers are differentiated by the collision-induced dissociation (CID) of the protonated peptides. The loss of 2-methylprop-1-ene is more pronounced for Boc-NH-L-Ala-delta-Caa-OCH(3) (1), whereas it is totally absent for its positional isomer Boc-NH-delta-Caa-L-Ala-OCH(3) (7), instead it shows significant loss of t-butanol. On the other hand, second isomeric pair shows significant loss of t-butanol and loss of acetone for Boc-NH-delta-Caa-beta-Caa-OCH(3) (18), whereas these are insignificant for its positional isomer Boc-NH-beta-Caa-delta-Caa-OCH(3) (13). The tetra- and hexapeptide positional isomers also show significant differences in MS(2) and MS(3) CID spectra. It is observed that 'b' ions are abundant when oxazolone structures are formed through five-membered cyclic transition state and cyclization process for larger 'b' ions led to its insignificant abundance. However, b(1)(+) ion is formed in case of delta,alpha-dipeptide that may have a six-membered substituted piperidone ion structure. Furthermore, ESI negative ion MS/MS has also been found to be useful for differentiating these isomeric peptide acids. Thus, the results of MS/MS of pairs of di-, tetra-, and hexapeptide positional isomers provide peptide sequencing information and distinguish the positional isomers.

  19. Somatostatin, substance P and calcitonin gene-related peptide-positive intramural nerve structures of the human large intestine affected by carcinoma.

    Directory of Open Access Journals (Sweden)

    Jerzy Kaleczyc

    2010-11-01

    Full Text Available The aim of this study was to investigate the arrangement and chemical coding of enteric nerve structures in the human large intestine affected by cancer. Tissue samples comprising all layers of the intestinal wall were collected during surgery form both morphologically unchanged and pathologically altered segments of the intestine (n=15, and fixed by immersion in buffered paraformaldehyde solution. The cryostat sections were processed for double-labelling immunofluorescence to study the distribution of the intramural nerve structures (visualized with antibodies against protein gene-product 9.5 and their chemical coding using antibodies against somatostatin (SOM, substance P (SP and calcitonin gene-related peptide (CGRP. The microscopic observations revealed distinct morphological differences in the enteric nerve system structure between the region adjacent to the cancer invaded area and the intact part of the intestine. In general, infiltration of the cancer tissue resulted in the gradual (depending on the grade of invasion first decomposition and reduction to final partial or complete destruction and absence of the neuronal elements. A comparative analysis of immunohistochemically labeled sections (from the unchanged and pathologically altered areas revealed a statistically significant decrease in the number of CGRP-positive neurons and nerve fibres in both submucous and myenteric plexuses in the transitional zone between morphologically unchanged and cancer-invaded areas. In this zone, a decrease was also observed in the density of SP-positive nerve fibres in all intramural plexuses. Conversely, the investigations demonstrated statistically insignificant differences in number of SP- and SOM-positive neurons and a similar density of SOM-positive nerve fibres in the plexuses of the intact and pathologically changed areas. The differentiation between the potential adaptive changes in ENS or destruction of its elements by cancer invasion should be a subject of further investigations.

  20. The Clinical Application of Anti-CCP in Rheumatoid Arthritis and Other Rheumatic Diseases

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    CT Chou

    2007-01-01

    Full Text Available Rheumatoid arthritis (RA is a common rheumatic disease in Caucasians and in other ethnic groups. Diagnosis is mainly based on clinical features. Before 1998, the only serological laboratory test that could contribute to the diagnosis was that for rheumatoid factor (RF. The disease activity markers for the evaluation of clinical symptoms or treatment outcome were the erythrocyte sedimentation rate (ESR and C-reactive protein (CRP. As a matter of fact, the diagnosis of early RA is quite impossible, as the clinical criteria are insuffi cient at the beginning stage of the disease. In 1998, Schelleken reported that a high percentage of RA patients had a specifi c antibody that could interact with a synthetic peptide which contained the amino acid citrulline. The high specifi city (98% for RA of this new serological marker, anti-cyclic citrullinated antibody (anti-CCP antibody, can be detected early in RA, before the typical clinical features appear. The presence or absence of this antibody can easily distinguish other rheumatic diseases from RA. Additionally, the titer of anti-CCP can be used to predict the prognosis and treatment outcome after DMARDs or biological therapy. Therefore, with improvement of sensitivity, the anti-CCP antibody will be widely used as a routine laboratory test in the clinical practice for RA.

  1. PADI4 Haplotypes in Association with RA Mexican Patients, a New Prospect for Antigen Modulation

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    Maria Guadalupe Zavala-Cerna

    2013-01-01

    Full Text Available Peptidyl arginine deiminase IV (PAD 4 is the responsible enzyme for a posttranslational modification called citrullination, originating the antigenic determinant recognized by anti-cyclic citrullinated peptide antibodies (ACPA. Four SNPs (single nucleotide polymorphisms have been described in PADI4 gene to form a susceptibility haplotype for rheumatoid arthritis (RA; nevertheless, results in association studies appear contradictory in different populations. The aim of the study was to analyze if the presence of three SNPs in PADI4 gene susceptibility haplotype (GTG is associated with ACPA positivity in patients with RA. This was a cross-sectional study that included 86 RA patients and 98 healthy controls. Polymorphisms PADI4_89, PADI4_90, and PADI4_92 in the PADI4 gene were genotyped. The susceptibility haplotype (GTG was more frequent in RA patients; interestingly, we found a new haplotype associated with RA with a higher frequency (GTC. There were no associations between polymorphisms and high scores in Spanish HAQ-DI and DAS-28, but we did find an association between RARBIS index and PADI4_89, PADI4_90 polymorphisms. We could not confirm an association between susceptibility haplotype presence and ACPA positivity. Further evidence about proteomic expression of this gene will determine its participation in antigenic generation and autoimmunity.

  2. Citrullination of central nervous system proteins during the development of experimental autoimmune encephalomyelitis.

    NARCIS (Netherlands)

    Raijmakers, R.; Vogelzangs, J.H.P.; Croxford, J.L.; Wesseling, P.; Venrooij, W.J.W. van; Pruijn, G.J.M.

    2005-01-01

    Immunization of mammals with central nervous system (CNS)-derived proteins or peptides induces experimental autoimmune encephalomyelitis (EAE), a disease resembling the human autoimmune disease multiple sclerosis (MS). Both diseases are accompanied by destruction of a part of the of the myelin sheat

  3. Citrulline as a Marker for Chemotherapy Induced Mucosal Barrier Injury in Pediatric Patients

    NARCIS (Netherlands)

    van Vilet, Michel J.; Tissing, Wim J. E.; Rings, Edmond H. H. M.; Koetse, Harma A.; Stellaard, Frans; Kamps, Willem A.; de Bont, Eveline S. J. M.

    2009-01-01

    Background. The Currently used National Cancer Institute (NCI) adverse events criteria for mucosal barrier injury (MBI) are insufficient for use in children. We searched for objective, easily measurable indicators for MBI in children with cancer. Purpose. In children with acute myeloid leukemia, var

  4. Anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis : linking genetic predisposition to clinical outcome

    NARCIS (Netherlands)

    Woude, Diane van der

    2012-01-01

    Rheumatoid arthritis (RA) is a disease characterized by arthritis of mainly the small joints of the hands and feet, which is thought to be the result of an autoimmune response. It is the most common inflammatory arthritis with a prevalence of 0.5-1.0% in European and North-American populations 1. Th

  5. In-Depth Analysis of Citrulline-Specific CD4 T-Cells in Rheumatoid Arthritis

    Science.gov (United States)

    2016-01-01

    Simponi); and Infliximab (Remicade); 2. CTLA-4Ig: Abatacept; 3. Anti-IL6R: Tocilizumab; 4. Methotrexate 5. DMARDs: Leflunomide , Azathioprine...consumed with MTX. A study commented that more patients refused Leflunomide , another DMARD which abstinence from alcohol is required, when told that

  6. In-Depth Analysis of Citrulline-Specific CD4 T Cells in Rheumatoid Arthritis

    Science.gov (United States)

    2016-01-01

    DMARDs: Leflunomide , Azathioprine, Sulfasalazine, and Hydroxychloroquine.*As of 12/15/2015, VA subjects have not yet started treatment Ex vivo...more patients refused Leflunomide , another DMARD which abstinence from alcohol is required, when told that they needed to abstain from alcohol

  7. Association of CD247 polymorphisms with rheumatoid arthritis: a replication study and a meta-analysis.

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    María Teruel

    Full Text Available Given the role of CD247 in the response of the T cells, its entailment in autoimmune diseases and in order to better clarify the role of this gene in RA susceptibility, we aimed to analyze CD247 gene variants previously associated with other autoimmune diseases (rs1052237, rs2056626 and rs864537 in a large independent European Caucasian population. However, no evidence of association was found for the analyzed CD247 single-nucleotide polymorphisms (SNPs with RA and with the presence/absence of anti-cyclic citrullinated polypeptide. We performed a meta-analysis including previously published GWAS data from the rs864537 variant, revealing an overall genome-wide significant association between this CD247 SNP and RA with anti-CCP (OR = 0.90, CI 95% = 0.87-0.93, Poverall = 2.1×10(-10. Our results show for first time a GWAS-level association between this CD247 polymorphism and RA risk.

  8. High Prevalence of Antinuclear Antibodies in Children with Thyroid Autoimmunity

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    Maria Segni

    2014-01-01

    Full Text Available Background. Antinuclear antibodies (ANA are a hallmark of many autoimmune diseases and can be detected many years before disease onset. Autoimmune thyroid diseases (AITD are frequently associated with other organ- and non-organ-specific autoimmune disorders. Objectives. To assess the prevalence of ANA in pediatric patients with AITD and their clinical correlations. Methods. Ninety-three consecutive pediatric patients with AITD were enrolled (86 children with chronic lymphocytic thyroiditis and 7 with Graves’ disease. ANA, anti-double DNA (anti-dsDNA antibodies, anti-extractable nuclear antigen (anti-ENA, anti-cyclic citrullinated peptide antibodies (anti-CCP, and rheumatoid factor (RF was obtained. Signs and symptoms potentially related to rheumatic diseases in children were investigated by a questionnaire. Results. ANA positivity was found in 66/93 children (71%, anti-ENA in 4/93 (4.3%, anti-dsDNA in 1/93 (1.1%, RF in 3/93 (3.2%, and anti-CCP in none. No significant differences were found between the ANA-positive and ANA-negative groups with respect to age, sex, L-thyroxine treatment, or prevalence of other autoimmune diseases. Overall, parental autoimmunity was found in 23%. Conclusions. ANA positivity was demonstrated in 71% of children with AITD. ANA positivity was not related to overt immune-rheumatic diseases. However, because the positivity of ANA can occur even many years before the onset of systemic autoimmune diseases, prospective studies are warranted.

  9. Analysis of foot structural damage in rheumatoid arthritis: clinical evaluation by validated measures and serological correlations

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    E. Bartoloni Bocci

    2011-06-01

    Full Text Available Objective: To examine foot involvement in rheumatoid arthritis (RA and to characterize structural alterations in patients with anti-cyclic citrullinated peptide (CCP antibody-positive and -negative disease. Methods: Seventy-eight patients with RA with foot pain were consecutively enrolled. The Manchester Hallux Valgus (MHV rating scale was used to evaluate the hallux valgus deformity degree. The Foot Posture Index (FPI6, a novel, foot-specific outcome measure, was adopted in order to quantify variation in the position of the foot. The findings were correlated with disease duration and presence or absence of anti-CCP antibodies. Results: About 84.6% patients had different degrees of hallux valgus and 65.4% subjects had a pronated foot. These two foot alterations were prevalently found in patients with long-standing disease and circulating anti-CCP antibodies. On the contrary, RA patients without anti-CCP and early disease essentially displayed a supinated foot without relevant hallux valgus deformity. Conclusion: Our findings allowed to identify different anatomic foot alterations in RA patients according to disease duration and negative prognostic factors such as anti-CCP antibodies. Our findings support the role of an accurate analysis of foot structural damage and may suggest the usefulness of a correct plantar orthosis prescription also in early phases of the disease.

  10. Joint Involvement in Primary Sjögren’s Syndrome: An Ultrasound “Target Area Approach to Arthritis”

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    Luis M. Amezcua-Guerra

    2013-01-01

    Full Text Available Objective. To characterize the ultrasound (US pattern of joint involvement in primary Sjögren’s syndrome (pSS. Methods. Seventeen patients with pSS, 18 with secondary Sjögren’s syndrome (sSS, and 17 healthy controls underwent US examinations of various articular regions. Synovitis (synovial hypertrophy/joint effusion, power Doppler (PD signals, and erosions were assessed. Results. In patients with pSS, synovitis was found in the metacarpophalangeal joints (MCP, 76%, wrists (76%, and knees (76%, while the proximal interphalangeal joints, elbows, and ankles were mostly unscathed. Intra-articular PD signals were occasionally detected in wrists (12%, elbows (6%, and knees (6%. Erosions were evident in the wrists of three (18% patients with pSS, one of these also having anti-cyclic citrullinated peptide (anti-CCP antibodies. While US synovitis does not discriminate between sSS and pSS, demonstration of bone erosions in the 2nd MCP joints showed 28.8% sensitivity and 100% specificity for diagnosing sSS; in comparison, these figures were 72.2 and 94.1% for circulating anti-CCP antibodies. Conclusions. In pSS, the pattern of joint involvement by US is polyarticular, bilateral, and symmetrical. Synovitis is the US sign most commonly found in patients with pSS, especially in MCP joints, wrists, and knees, and bone erosions also may occur.

  11. Joint Involvement in Primary Sjögren's Syndrome: An Ultrasound “Target Area Approach to Arthritis”

    Science.gov (United States)

    Amezcua-Guerra, Luis M.; Vargas, Angelica; Rodriguez-Henriquez, Pedro; Solano, Carla; Hernández-Díaz, Cristina; Castillo-Martinez, Diana; Ventura-Ríos, Lucio; Gutiérrez, Marwin; Pineda, Carlos

    2013-01-01

    Objective. To characterize the ultrasound (US) pattern of joint involvement in primary Sjögren's syndrome (pSS). Methods. Seventeen patients with pSS, 18 with secondary Sjögren's syndrome (sSS), and 17 healthy controls underwent US examinations of various articular regions. Synovitis (synovial hypertrophy/joint effusion), power Doppler (PD) signals, and erosions were assessed. Results. In patients with pSS, synovitis was found in the metacarpophalangeal joints (MCP, 76%), wrists (76%), and knees (76%), while the proximal interphalangeal joints, elbows, and ankles were mostly unscathed. Intra-articular PD signals were occasionally detected in wrists (12%), elbows (6%), and knees (6%). Erosions were evident in the wrists of three (18%) patients with pSS, one of these also having anti-cyclic citrullinated peptide (anti-CCP) antibodies. While US synovitis does not discriminate between sSS and pSS, demonstration of bone erosions in the 2nd MCP joints showed 28.8% sensitivity and 100% specificity for diagnosing sSS; in comparison, these figures were 72.2 and 94.1% for circulating anti-CCP antibodies. Conclusions. In pSS, the pattern of joint involvement by US is polyarticular, bilateral, and symmetrical. Synovitis is the US sign most commonly found in patients with pSS, especially in MCP joints, wrists, and knees, and bone erosions also may occur. PMID:23936829

  12. Differentially methylated DNA regions in monozygotic twin pairs discordant for rheumatoid arthritis.An epigenome - wide study.

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    Anders Jørgen Svendsen

    2016-11-01

    Full Text Available Objectives: In an explorative epigenome-wide association study (EWAS to search for gene independent, differentially methylated DNA positions (DMPs and regions (DMRs associated with rheumatoid arthritis (RA by studying monozygotic (MZ twin pairs discordant for rheumatoid arthritis.Methods: Genomic DNA was isolated from whole blood samples from 28 monozygotic (MZ twin pairs discordant for RA. DNA methylation was measured using the HumanMethylation450 BeadChips. Smoking, anti-cyclic citrullinated peptide antibodies and immunosuppressive treatment were included as covariates. Pathway analysis was performed using GREAT.Results: Smoking was significantly associated with hypomethylation of a DMR overlapping the promoter region of the RNF5 and the AGPAT1, which are implicated in inflammation and autoimmunity, whereas DMARD treatment induced hypermethylation of the same region. Additionally, the promotor region of both S100A6 and EFCAB4B were hypomethylated and both genes have previously been associated with RA. We replicated several candidate genes identified in a previous EWAS in treatment naïve RA singletons. Gene set analysis indicated the involvement of immunologic signatures and cancer-related pathways in RA.Conclusion: We identified several differentially methylated regions associated with RA which may represent environmental effects or consequences of the disease and plausible biological pathways pertinent to the pathogenesis of rheumatoid arthritis

  13. A Rare Case of Cardiac Tamponade Induced by Chronic Rheumatoid Arthritis.

    Science.gov (United States)

    Yousuf, Tariq; Kramer, Jason; Kopiec, Adam; Bulwa, Zachary; Sanyal, Shuvani; Ziffra, Jeffrey

    2015-09-01

    Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease primarily involving the joint synovium. RA is a systemic disease which has many known extra-articular manifestations. We present a unique case of a patient with long standing RA who presented with a primary complaint of chest and back pain. Echocardiography revealed borderline normal left ventricular function and a large pericardial effusion with the finding of elevated intrapericardial pressure suspicious for cardiac tamponade. Infectious workup was all found to be negative. The presence and elevation of anti-cyclic citrullinated peptide antibody, rheumatoid factor and C-reactive protein (CRP) confirmed the patient was having an active flare-up of RA. It was determined that this flare-up was the cause of the cardiac tamponade. A pericardiocentesis was performed and 850 mL of bloody fluid was drained. The patient remained stable following the pericardiocentesis. At his follow-up visit, repeat echocardiogram showed no signs for pericardial effusion. Although there has been extensive study of RA, there are only a few documented cases noting the occurrence of cardiac tamponade in these patients. Therefore, it is important for the clinician to be aware of and recognize this potentially serious cardiac outcome associated with a common rheumatologic condition.

  14. The Multifaceted Aspects of Interstitial Lung Disease in Rheumatoid Arthritis

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    Lorenzo Cavagna

    2013-01-01

    Full Text Available Interstitial lung disease (ILD is a relevant extra-articular manifestation of rheumatoid arthritis (RA that may occur either in early stages or as a complication of long-standing disease. RA related ILD (RA-ILD significantly influences the quoad vitam prognosis of these patients. Several histopathological patterns of RA-ILD have been described: usual interstitial pneumonia (UIP is the most frequent one, followed by nonspecific interstitial pneumonia (NSIP; other patterns are less commonly observed. Several factors have been associated with an increased risk of developing RA-ILD. The genetic background plays a fundamental but not sufficient role; smoking is an independent predictor of ILD, and a correlation with the presence of rheumatoid factor and anti-cyclic citrullinated peptide antibodies has also been reported. Moreover, both exnovo occurrence and progression of ILD have been related to drug therapies that are commonly prescribed in RA, such as methotrexate, leflunomide, anti-TNF alpha agents, and rituximab. A greater understanding of the disease process is necessary in order to improve the therapeutic approach to ILD and RA itself and to reduce the burden of this severe extra-articular manifestation.

  15. Vitamin D receptor gene polymorphism in rheumatoid arthritis and its association with atherosclerosis

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    Amal M El-Barbary

    2015-01-01

    Patients and methods This study included forty early rheumatoid arthritis patients and forty healthy controls. Disease activity score 28 (DAS-28, Modified Health Assessment Questionnaire (MHAQ, Carotid intima-media thickness (cIMT were assessed using B-mode ultrasound, Erythrocyte sedimentation rate (ESR, C reactive protein (CRP, Lipid profile, anti cyclic citrullinated PolyPeptid (anti-CCP, serum interleukin-6, Total serum vitamin D and genotype determination of BsmI, FokI polymorphism and allel frequency were measured. Results Vitamin D deficiency was observed in 25% of patients. There was no significant difference between RA patients and controls regarding the distribution of BsmI genotype frequencies and allele. However, a significant difference between rheumatoid arthritis patients and controls regarding the distribution of FokI genotype and allele frequencies was found. In addition, FokI polymorphism and the F allele was significantly associated with RA. anti-CCP, interleukin-6 levels, (cIMT and vitamin D deficiency were significantly higher in the presence of bb homozygote of BsmI genotypes and FF homozygote of FokI genotypes. A significant negative correlation between 25 hydroxy vitamin D levels with (DAS-28, ESR, (CRP, and IL-6 (P < 0.001. However, there was positive correlation between 25 hydroxyvitamin D levels and HDL-C (P < 0.001.

  16. Clinical value of combined detection of RF and anti-CCP antibody in diagnosis of rheumatoid arthritis%联合检测抗CCP抗体和RF在类风湿关节炎中的诊断价值

    Institute of Scientific and Technical Information of China (English)

    刘其爱; 马小燕; 张弘

    2013-01-01

    Objective To evaluate the clinical value of anti-cyclic citrullinated peptide(CCP) antibody in the diagnosis of rheumatoid arthritis( RA).Methods 87 cases of patients with RA and 69 cases of patients with other autoimmune diseases (control group) were detected for serum anti-CCP antibody by KLISA and for RF by turbidimetry method.36 healthy subjects were enrolled as healthy control group.Diagnostic sensitivity and specificity of anti - CCP antibodies and RF in RA were compared.Results The sensitivity of anti - CCP antibody was 60.9% ,of RF was 67.2% and there was no significant difference between them(P> 0.05).The specificity of anti -CCP antibody was 94.2% ,of RF was 72.5% ,and the difference was significant(P0.05).抗 CCP 抗体的特异度为94.2%,RF 为72.5 %,差异有统计学意义(P<0.05).两者联合检测特异性为97.1 %.结论 抗CCP 抗体在RA诊断中具有较高的特异性,可作为诊断RA的理想血清学指标.两者联合检测可提高检测的特异度.

  17. Recent paradigm shifts in the diagnosis and treatment of rheumatoid arthritis.

    Science.gov (United States)

    Jung, Young Ok; Kim, Hyun Ah

    2012-12-01

    Rheumatoid arthritis (RA) is a progressive inflammatory disease with severe symptoms of pain and stiffness. Chronic persistent inflammation of RA often leads to joint destruction, deformity and limitation of function, which ultimately results in significant deterioration of quality of life (QoL). RA is characterized pathogenetically by immunologically driven, chronic synovitis, and production of autoantibodies, such as rheumatoid factor and anti-cyclic citrullinated peptide antibodies. Although the cause of RA is yet unknown, advances in the molecular biology led to in-depth understanding of its pathogenesis, and have fostered the recent development of novel treatments. The last decade has seen the dramatic change in the landscape of RA treatment with more aggressive therapy early in the disease course and with treatment guided by a structured assessment of disease activity, with the ultimate goal of reaching remission. In addition, prevention and control of joint damage and improvement in QoL are important goals. To achieve these goals, a multidisciplinary approach to reduce disease activity with disease modifying antirheumatic drugs and biological therapy is needed. We also need to find ways to identify those patients who are at risk for more rapid disease progression who would benefit from intensive therapy early in the course of disease.

  18. GITRL modulates the activities of p38 MAPK and STAT3 to promote Th17 cell differentiation in autoimmune arthritis.

    Science.gov (United States)

    Tang, Xinyi; Tian, Jie; Ma, Jie; Wang, Jiemin; Qi, Chen; Rui, Ke; Wang, Yungang; Xu, Huaxi; Lu, Liwei; Wang, Shengjun

    2016-02-23

    The glucocorticoid-induced TNFR family-related protein (GITR) and its ligand play a critical role in the pathogenesis of autoimmune arthritis by enhancing the Th17 cell response, but their molecular mechanisms remain largely unclear. This study aims to define the role of p38 mitogen-activated protein kinases (MAPK) and signal transducer and activator of transcription 3 (STAT3) signaling in GITRL-induced Th17 cells in autoimmune arthritis. We found that the p38 phosphorylation was enhanced by GITRL in activated CD4+T cells, and the p38 inhibitor restrained the GITRL-induced Th17 cell expansion in a dose-dependent manner. Moreover, there was decreased STAT3 activity on Tyr705 and Ser727 with the p38 inhibitor in vitro. Notably, the p38 inhibitor could prevent GITRL-treated arthritis progression and markedly decrease the Th17 cell percentages. The phosphorylation of the Tyr705 site was significantly lower in the GITRL-treated CIA mice administrated with the p38 inhibitor. A significantly higher phosphorylation of p38 was detected in RA patients and had a positive relationship with the serum level of anti-cyclic citrullinated peptide (anti-CCP) antibody. Our findings have indicated that GITRL could promote Th17 cell differentiation by p38 MAPK and STAT3 signaling in autoimmune arthritis.

  19. The Effect of SHH-Gli Signaling Pathway on the Synovial Fibroblast Proliferation in Rheumatoid Arthritis.

    Science.gov (United States)

    Qin, Suping; Sun, Dexu; Li, Hui; Li, Xiangyang; Pan, Wei; Yan, Chao; Tang, Renxian; Liu, Xiaomei

    2016-04-01

    Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by chronic synovitis. This study aims to investigate the role of sonic hedgehog (SHH)-Gli signaling pathway in synovial fibroblast proliferation in rheumatoid arthritis. The expression of serum SHH in RA patients group was significantly increased compared with the systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), and healthy subject (healthy control, HC) groups, respectively; serum SHH expression of RA patients was positively correlated with rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP Ab), while there was no significant correlation between SHH expression and erythrocyte sedimentation rate (ESR). SHH, Ptch, Smo, and Gli molecules were highly expressed in rat RA-synovial fibroblast (RA-SF); after blocking the SHH-Gli signaling pathway with a Gli specific inhibitor, Gli-antagonist 61 (GANT61), RA-SF proliferation was inhibited in a dose-dependent manner and the apoptosis rate of RA-SF was increased as well; the expression levels of fibroblast growth factor receptor 1 (FGFR1) and FGFR3 declined in SF cells after GANT61 treatment. Our results suggest that SHH-Gli pathway is involved in the pathogenesis of RA, and blocking SHH-Gli pathway inhibits RA-SF cell proliferation and increases cell apoptosis, which may shed light on developing new ideas for RA treatment.

  20. Remission of rheumatoid arthritis and potential determinants: a national multi-center cross-sectional survey.

    Science.gov (United States)

    Wang, Guan-Ying; Zhang, Sa-Li; Wang, Xiu-Ru; Feng, Min; Li, Chun; An, Yuan; Li, Xiao-Feng; Wang, Li-Zhi; Wang, Cai-Hong; Wang, Yong-Fu; Yang, Rong; Yan, Hui-Ming; Wang, Guo-Chun; Lu, Xin; Liu, Xia; Zhu, Ping; Chen, Li-Na; Jin, Hong-Tao; Liu, Jin-Ting; Guo, Hui-Fang; Chen, Hai-Ying; Xie, Jian-Li; Wei, Ping; Wang, Jun-Xiang; Liu, Xiang-Yuan; Sun, Lin; Cui, Liu-Fu; Shu, Rong; Liu, Bai-Lu; Yu, Ping; Zhang, Zhuo-Li; Li, Guang-Tao; Li, Zhen-Bin; Yang, Jing; Li, Jun-Fang; Jia, Bin; Zhang, Feng-Xiao; Tao, Jie-Mei; Lin, Jin-Ying; Wei, Mei-Qiu; Liu, Xiao-Min; Ke, Dan; Hu, Shao-Xian; Ye, Cong; Han, Shu-Ling; Yang, Xiu-Yan; Li, Hao; Huang, Ci-Bo; Gao, Ming; Lai, Bei; Cheng, Yong-Jing; Li, Xing-Fu; Song, Li-Jun; Yu, Xiao-Xia; Wang, Ai-Xue; Wu, Li-Jun; Wang, Yan-Hua; He, Lan; Sun, Wen-Wen; Gong, Lu; Wang, Xiao-Yuan; Wang, Yi; Zhao, Yi; Li, Xiao-Xia; Wang, Yan; Zhang, Yan; Su, Yin; Zhang, Chun-Fang; Mu, Rong; Li, Zhan-Guo

    2015-02-01

    The aim of this study is to investigate the remission rate of rheumatoid arthritis (RA) in China and identify its potential determinants. A multi-center cross-sectional study was conducted from July 2009 to January 2012. Data were collected by face-to-face interviews of the rheumatology outpatients in 28 tertiary hospitals in China. The remission rates were calculated in 486 RA patients according to different definitions of remission: the Disease Activity Score in 28 joints (DAS28), the Simplified Disease Activity Index (SDAI), the Clinical Disease Activity Index (CDAI), and the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean definition. Potential determinants of RA remission were assessed by univariate and multivariate analyses. The remission rates of RA from this multi-center cohort were 8.6% (DAS28), 8.4% (SDAI), 8.2% (CDAI), and 6.8% (Boolean), respectively. Favorable factors associated with remission were: low Health Assessment Questionnaire (HAQ) score, absence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP), and treatment of methotrexate (MTX) and hydroxychloroquine (HCQ). Younger age was also predictive for the DAS28 and the Boolean remission. Multivariate analyses revealed a low HAQ score, the absence of anti-CCP, and the treatment with HCQ as independent determinants of remission. The clinical remission rate of RA patients was low in China. A low HAQ score, the absence of anti-CCP, and HCQ were significant independent determinants for RA remission.

  1. MRI bone oedema is the strongest predictor of subsequent radiographic progression in early rheumatoid arthritis. Results from a 2 year randomized controlled trial (CIMESTRA)

    DEFF Research Database (Denmark)

    Hetland, M L; Ejbjerg, B; Hørslev-Petersen, K

    2008-01-01

    /placebo-cyclosporine. Baseline magnetic resonance imaging (MRI) of the wrist (wrist-only-group:N=130) or MRI of wrist and MCP-joints (wrist+MCP-group:N=89) (OMERACT RAMRIS), x-rays of hands, wrists and forefeet (Sharp/vdHeijde Score (TSS)), disease activity score (DAS28), anti-cyclic-citrullinated-peptide-antibodies (anti...... variables. RESULTS: Baseline values: median DAS28: 5.6 (range: 2.4-8.0); anti-CCP positive: 61%; radiographic erosions: 56%. At 2 years: DAS28: 2.0 (0.5-5.7), in DAS-remission: 56%, radiographic progression: 26% (wrist+MCP-group, similar for wrist-only-group). MRI bone oedema score was the only independent.......50, respectively). The results were confirmed by sensitivity analyses. CONCLUSION: In a RCT aiming at remission in early RA patients, baseline RAMRIS MRI bone oedema score of MCP and wrist joints (and of wrist only) was the strongest independent predictor of radiographic progression in hands, wrists and forefeet...

  2. In rheumatoid arthritis patients treated with tocilizumab, the rate of clinical disease activity index (CDAI) remission at 24 weeks is superior in those with higher titers of IgM-rheumatoid factor at baseline.

    Science.gov (United States)

    Kawashiri, Shin-Ya; Kawakami, Atsushi; Iwamoto, Naoki; Fujikawa, Keita; Aramaki, Toshiyuki; Tamai, Mami; Yamasaki, Satoshi; Nakamura, Hideki; Origuchi, Tomoki; Ueki, Yukitaka; Migita, Kiyoshi; Mizokami, Akinari; Aoyagi, Kiyoshi; Eguchi, Katsumi

    2011-08-01

    We aimed to evaluate the efficacy of tocilizumab in patients with rheumatoid arthritis (RA), using the clinical disease activity index (CDAI), and to determine the baseline variables associated with CDAI remission. Fifty-eight patients with active RA were enrolled. We tried to evaluate whether baseline variables were associated with CDAI remission at 24 weeks. Twenty-two of the 58 patients (37.9%) had received tumor necrosis factor (TNF) inhibitors. The continuation rate of tocilizumab at 24 weeks was 87.9%. The seropositivity rates of IgM-rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies at baseline were both 91.4%. The rate of CDAI remission at 24 weeks was 20.7%. We selected baseline variables including age, gender, duration of disease, concomitant use of glucocorticoids, concomitant use of methotrexate (MTX), previous anti-TNF therapy, titer of anti-CCP antibodies (high or low toward median), titer of IgM-RF (high or low toward median), and CDAI, and found that a high titer of IgM-RF was the only variable to be associated with CDAI remission, according to univariate and logistic regression analyses. This is a new finding, and may be specific to tocilizumab as compared with previous observations in anti-TNF therapy.

  3. 抗环瓜氨酸肽抗体与RF、CRP、ESR联合检测在类风湿关节炎诊断中的意义%The significance of combined determination of anti-cyclic citrulinatedpeptide antibodies and RF,CRP,ESR in diagnosis of rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    王碧玉

    2011-01-01

    目的 探讨抗环瓜氨酸肽(CCP)抗体和类风湿因子(RF)、C反应蛋白(CRP)、血沉(ESR)联合检测在类风湿关节炎(RA)诊断中的意义.方法 通过检测40例RA患者,35例非RA患者和30例健康体检者血清中的抗CCP抗体和RF、CRP、ESR,分析其在诊断中的价值.结果 RA组抗CCP抗体和RF、CRP、ESR检测结果显著高于非RA对照组和健康对照组(P<0.01);RA组抗CCP抗体和RF诊断RA的阳性率显著高于非RA对照组和健康对照组(P<0.01);RF诊断RA的敏感性高于抗CCP抗体,抗CCP抗体诊断RA的特异性高于RF,两者联合诊断的敏感性高于单项检测.结论 抗CCP抗体对于RA的早期诊断优于RF;抗CCP抗体和RF联合检测可提高对RA诊断的敏感度;CRP和ESR对RA的诊断具有辅助作用.对疑似RA以及RA的患者定期检测抗CCP抗体和RF、CRP、ESR,在RA早期诊断、鉴别诊断、治疗观察、病情估计和判断预后中都有重要意义.

  4. Monitoring myeloablative therapy-induced small bowel toxicity by serum citrulline concentration: a comparison with sugar permeability tests.

    NARCIS (Netherlands)

    Lutgens, L.C.; Blijlevens, N.M.A.; Deutz, N.E.; Donnelly, J.P.; Lambin, P.; Pauw, B.E. de

    2005-01-01

    BACKGROUND: Intestinal mucositis is an important cause of cancer treatment-related morbidity and mortality, carrying a serious economic burden. Currently, objective parameters are lacking that would enable the monitoring of gut damage in routine clinical practice, thus hindering the development of c

  5. Autoantibodies to citrullinated proteins in rheumatoid arthritis: clinical performance and biochemical aspects of an RA-specific marker.

    NARCIS (Netherlands)

    Nijenhuis, S.; Zendman, A.J.W.; Vossenaar, E.R.; Pruijn, G.J.M.; Venrooij, W.J.W. van

    2004-01-01

    Rheumatoid arthritis (RA) is a common, systemic autoimmune disease of which the exact etiology is not known. In the past 10 years, substantial progress has been made in the identification of the antigens specifically recognized by the autoantibodies of RA patients. A central factor in this respect i

  6. Autoantibodies to cyclic citrullinated peptides predict progression to rheumatoid arthritis in patients with undifferentiated arthritis - A prospective cohort study

    NARCIS (Netherlands)

    Gaalen, F.A. van; Linn-Rasker, S.P.; Venrooij, W.J.W. van; Jong, B.A. de; Breedveld, F.C.; Verweij, C.L.; Toes, R.E.M.; Huizinga, T.W.J.

    2004-01-01

    Objective. Rheumatoid arthritis (RA) is a common, severe, chronic inflammatory joint disease. Since the disease may initially be indistinguishable from other forms of arthritis, early diagnosis can be difficult. Autoantibodies seen in RA can be detected years before clinical symptoms develop. In an

  7. Autoantibodies to cyclic citrullinated peptides predict progression to rheumatoid arthritis in patients with undifferentiated arthritis: a prospective cohort study.

    NARCIS (Netherlands)

    Gaalen, van FA; Linn-Rasker, SP; Venrooij, W.J.; Jong, B.A.; Breedveld, F.C.; Verweij, C.L.; Toes, RE; Huizinga, T.W.

    2004-01-01

    OBJECTIVE: Rheumatoid arthritis (RA) is a common, severe, chronic inflammatory joint disease. Since the disease may initially be indistinguishable from other forms of arthritis, early diagnosis can be difficult. Autoantibodies seen in RA can be detected years before clinical symptoms develop. In an

  8. Increased plasma citrulline in mice marks diet-induced obesity and may predict the development of the metabolic syndrome

    NARCIS (Netherlands)

    Sailer, M.; Dahlhoff, C.; Giesbertz, P.; Eidens, M.K.; Wit, de N.J.W.; Rubio-Aliaga, I.; Boekschoten, M.V.; Müller, M.R.; Daniel, H.

    2013-01-01

    Article About the Authors Metrics Comments Related Content Abstract Introduction Results Discussion Materials and Methods Supporting Information Acknowledgments Author Contributions References Reader Comments (0) Figures Abstract In humans, plasma amino acid concentrations of branched-chain amino ac

  9. Clinical feature of pleural effusion in 78 patients with rheumatoid arthritis%78例类风湿关节炎胸腔积液临床特点分析

    Institute of Scientific and Technical Information of China (English)

    陈文玉; 王娟娟; 王智明

    2016-01-01

    Objective To investigate the feature of pleural effusion in patients with rheumatoid arthritis for the recognition of the disease.Methods The clinical feature of pleural effusion in patients with rheumatoid arthritis was retrospectively analyzed.Results There was no pleural effusion in patients with remission of rheumatoid arthritis,all patients with pleural effusion were in active phase of the disease,especially in moderate and high active phase, significant difference in the number of patients was detected in low,moderate and high active phases of rheumatoid arthritis between groups (P <0.05).The average levels of erythrocyte sedimentation rate and C-reactive protein were significantly higher in pleural effusion group than in non-pleural effusion group.The positive rates of rheumatoid factor and anti-cyclic citrullinated peptide antibody were significantly higher in pleural effusion group than in non-pleural effusion group (P < 0.05 ).The average number of joint tenderness and swollen joint was significantly higher in pleural effusion group than in non-pleural effusion group and the average time of morning stiffness was significantly longer in pleural effusion group than in non-pleural effusion group (P <0.05 ).Compared with non-pleural effusion group,the remission number of patients was significantly decreased in pleural effusion group (P < 0.05 ),and the number of new joint deformity was significantly increased in pleural effusion group (P < 0.05 ).Conclusion Rheumatoid arthritis patients present pleural effusion as an active signal of disease,which was positively correlated with immune index and clinical symptom and should get rigorously treated.%目的:探讨类风湿关节炎胸腔积液的特点,提高对该病的认识。方法回顾分析类风湿关节炎胸腔积液的特点。结果类风湿关节炎缓解状态下无胸腔积液出现,胸腔积液发生在疾病活动期,且集中在疾病中度、高度活动期,两组低、中、高度患者构

  10. Multiparameter analysis of biomarkers in the laboratory diagnosis of early rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Aleksandr Aleksandrovich Novikov

    2013-01-01

    Full Text Available Subjects and methods. 102 patients with early RA (79 women and 23 men; median age 51 years [41 to 62, 25th to 75th percentile]; disease duration 4 months [2.5 to 6.0]; DAS28 5.4 [4.1 to 5.9] were examined. A comparison group consisted of 616 patients including 27 with systemic lupus erythematosus, 15 with Sjö gren’s syndrome, 25 with ankylosing spondyloarthritis; 33 with osteoarthritis, 20 with overlap syndrome, 9, 22, and 168 patients with gouty, psoriatic, and undifferentiated arthritis, respectively; as well as 297 healthy donors matched with the examinees for gender and age. The concentrations of 36 biomarkers were measured by an immunonephelometric method, enzyme immunoassay, and xMAP technology. The values of one variable from others were predicted using a multiple linear regression method (multivariate analysis. Results. The strongest predictors of early RA, such as the concentrations of interleukin-6, C-reactive protein, granulo-cyte-macrophage colony-stimulating factor, interferon-γ (IFN-γ, IFN^-inducible protein, anti-cyclic citrullinated peptide antibodies, were identified and a candidate for MDI was developed for early RA (MIRRA. After thorough validation, MIRRA may be regarded as a precision serological assay for the early diagnosis of RA. Conclusion. The development of MDI having a higher diagnostic precision than routinely used biomarkers is imperative for early RA diagnosis that allows one to initiate active antirheumatic therapy that is able to effectively delay progressive joint injury.

  11. Osteoprotegerin CGA haplotype protection against cerebrovascular complications in anti-CCP negative patients with rheumatoid arthritis.

    Directory of Open Access Journals (Sweden)

    Fernanda Genre

    Full Text Available Rheumatoid arthritis is an inflammatory disease with high incidence of cardiovascular disease due to accelerated atherosclerosis. Osteoprotegerin (OPG has been associated with increased risk of atherosclerotic disease in the general population. Several polymorphisms in the OPG gene with functional effects on cardiovascular disease in non-rheumatic individuals have been described. Therefore, we aimed to analyze the effect of three of these functional OPG polymorphisms on the risk of cardiovascular disease in a large and well-characterized cohort of Spanish patients with rheumatoid arthritis.Three OPG gene variants (rs3134063, rs2073618 and rs3134069 were genotyped by TaqMan assays in 2027 Spanish patients with rheumatoid arthritis. Anti-cyclic citrullinated peptide (anti-CCP antibody testing was positive in 997 of 1714 tested. Also, 18.3% of the whole series had experienced cardiovascular events, including 5.4% with cerebrovascular accidents. The relationship between OPG variants and cardiovascular events was assessed using Cox regression.No association between OPG gene variants and cardiovascular disease was observed in the whole group of rheumatoid arthritis patients or in anti-CCP positive patients. Nevertheless, a protective effect of CGA haplotype on the risk of cardiovascular disease in general, and specifically in the risk of cerebrovascular complications after adjusting for sex, age at disease diagnosis and traditional cardiovascular risk factors was disclosed in anti-CCP negative patients (HR = 0.54; 95%CI: 0.31-0.95; p = 0.032 and HR = 0.17; 95%CI: 0.04-0.78; p = 0.022, respectively.Our results indicate a protective effect of the OPG CGA haplotype on cardiovascular risk, mainly due to a protective effect against cerebrovascular events in anti-CCP negative rheumatoid arthritis patients.

  12. 抗环瓜氨酸肽抗体与类风湿关节炎患者成纤维样%Relationship between anti-CCP antibody and migration or invasion ability of fibroblast-like synoviocytes from rheumatoid arthritis patients

    Institute of Scientific and Technical Information of China (English)

    刘志昌; 肖游君; 劳敏曦; 黄明城; 曾珊; 许韩师; 杨岫岩; 梁柳琴

    2013-01-01

    目的:研究抗环瓜氨酸肽(anti-cyclic citrullinated peptide,CCP)抗体与类风湿关节炎(rheumatoid arthritis,RA)患者成纤维样滑膜细胞(fibroblast-like synoviocyte,FLS)迁移和侵袭的关系.方法:FLS分离自22例活动性RA患者、12例骨关节炎(OA)和6例无关节炎病史的外伤患者滑膜组织;FLS迁移和侵袭能力采用Transwell小室测定.结果:RA组、OA组和正常组FLS迁移数目分别为(29.33±10.93)、(9.28±7.87)和(7.00±4.07)个/视野,侵袭细胞数分别为(14.35±7.67)、(3.96±4.37)和(3.08±1.03)个/视野,RA组与其它2组的迁移细胞数和侵袭细胞数比较均有显著差异;抗CCP抗体阳性RA患者FLS与抗CCP阴性RA患者FLS相比,前者迁移和侵袭能力均强于后者;相关性分析亦发现,抗CCP抗体阳性及抗CCP抗体滴度与RA患者FLS的侵袭和迁移能力密切相关.结论:抗CCP抗体阳性的RA患者FLS的迁移和侵袭能力更强,抗CCP抗体可能与RA患者FLS的迁移和侵袭能力改变有关.

  13. Expression of Prostaglandin E2 Enzymes in the Synovium of Arthralgia Patients at Risk of Developing Rheumatoid Arthritis and in Early Arthritis Patients.

    Directory of Open Access Journals (Sweden)

    Maria J H de Hair

    Full Text Available Arthralgia may precede the development of synovial inflammation in autoantibody-positive individuals at risk of developing rheumatoid arthritis (RA. A major pathway involved in pain is the prostaglandin (PG E2 pathway. We investigated this pathway in the synovium of individuals with RA-specific autoantibodies and in early arthritis patients.Nineteen autoantibody-positive individuals (IgM-rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies with arthralgia (n=15 and/or a positive family history of RA (n=8, who had been prospectively followed for at least 2 years, were included. In addition, we included early arthritis patients (disease-modifying antirheumatic drug naïve who after 2 years follow up fulfilled classification criteria for RA (n=63, spondyloarthritis (SpA; n=14, or had unclassified arthritis (UA; n=27. In all subjects we assessed pain and performed synovial biopsy sampling by mini-arthroscopy at baseline. Tissue sections were examined by immunohistochemistry to detect and quantify PGE2 pathway enzymes expression levels (mPGES-1; COX-1 and -2; 15-PGDH.In both study groups synovial expression of PGE2 enzymes was not clearly related to pain sensation. Expression levels at baseline were not associated with the development of arthritis after follow up (6 out of 19 autoantibody-positive individuals. However, in early SpA patients the expression levels of mPGES-1 and COX-1 were significantly increased compared to RA and UA patients.Pain in autoantibody-positive individuals without synovial inflammation who are at risk of developing RA and in early arthritis patients may be regulated by pathways other than the PGE2 pathway or originate at sites other than the synovium. In contrast, in SpA, the PGE2 pathway may be inherently linked to the pathophysiology/etiology of the disease.

  14. Serum levels of IL-17, IL-4, and INFγ in Serbian patients with early rheumatoid arthritis

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    Voja Pavlovic

    2014-01-01

    Full Text Available Background: Rheumatoid arthritis (RA is a chronic, systemic, inflammatory disease with autoimmune etiology, characterized by synovial inflammation and destruction of joint cartilage and bone. There are controversial data about the profile of interleukin-17 (IL-17A, interleukin-4 (IL-4, and interferon-gamma (INFγ, indicating in some studies the key role of IL-17, while in others the Th1 cytokines. Materials and Methods: Serum samples of 31 early RA patients were evaluated for erythrocytes sedimentation rate (ESR, rheumatoid factor (RF, C-reactive protein (CRP, anti-cyclic citrullinated peptide antibodies (anti-CCP, and for the tested cytokines (IL-17A, IL-4, and INFγ. Disease activity score (DAS28 calculation was done for all patients. Control serum samples were obtained from 29 healthy volunteers. Results: The levels of tested cytokines were significantly higher (IL-17A, p < 0.001; INFγ, p < 0.001; IL-4, p < 0.01 in patients with early RA, compared to the healthy controls. In early RA patients, a strong correlation of serum IL-17A was found with DAS28, ESR, and CRP. Also, significant negative correlation was found between serum INFγ levels and the DAS28 score, indicating that INFγ may play a key role in maintaining immune homeostasis in patients with RA. Conclusion: The mean serum IL-17A levels in patients with early RA, corresponded with the disease activity and severity. This might highlight the usefulness of the serum IL-17A level in defining the activity and predictive patterns, for aggressive disease therapy, and it might express specific therapeutically targets.

  15. Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors

    Science.gov (United States)

    Westhovens, R; Robles, M; Ximenes, A C; Nayiager, S; Wollenhaupt, J; Durez, P; Gomez-Reino, J; Grassi, W; Haraoui, B; Shergy, W; Park, S-H; Genant, H; Peterfy, C; Becker, J-C; Covucci, A; Helfrick, R; Bathon, J

    2009-01-01

    Objectives: To assess the efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis (RA) and poor prognostic factors. Methods: In this double-blind, phase IIIb study, patients with RA for 2 years or less were randomly assigned 1 : 1 to receive abatacept (∼10 mg/kg) plus methotrexate, or placebo plus methotrexate. Patients were methotrexate-naive and seropositive for rheumatoid factor (RF), anti-cyclic citrullinated protein (CCP) type 2 or both and had radiographic evidence of joint erosions. The co-primary endpoints were the proportion of patients achieving disease activity score in 28 joints (DAS28)-defined remission (C-reactive protein) and joint damage progression (Genant-modified Sharp total score; TS) at year 1. Safety was monitored throughout. Results: At baseline, patients had a mean DAS28 of 6.3, a mean TS of 7.1 and mean disease duration of 6.5 months; 96.5% and 89.0% of patients were RF or anti-CCP2 seropositive, respectively. At year 1, a significantly greater proportion of abatacept plus methotrexate-treated patients achieved remission (41.4% vs 23.3%; p<0.001) and there was significantly less radiographic progression (mean change in TS 0.63 vs 1.06; p = 0.040) versus methotrexate alone. Over 1 year, the frequency of adverse events (84.8% vs 83.4%), serious adverse events (7.8% vs 7.9%), serious infections (2.0% vs 2.0%), autoimmune disorders (2.3% vs 2.0%) and malignancies (0.4% vs 0%) was comparable for abatacept plus methotrexate versus methotrexate alone. Conclusions: In a methotrexate-naive population with early RA and poor prognostic factors, the combination of abatacept and methotrexate provided significantly better clinical and radiographic efficacy compared with methotrexate alone and had a comparable, favourable safety profile. PMID:19124524

  16. Medical ozone increases methotrexate clinical response and improves cellular redox balance in patients with rheumatoid arthritis.

    Science.gov (United States)

    León Fernández, Olga Sonia; Viebahn-Haensler, Renate; Cabreja, Gilberto López; Espinosa, Irainis Serrano; Matos, Yanet Hernández; Roche, Liván Delgado; Santos, Beatriz Tamargo; Oru, Gabriel Takon; Polo Vega, Juan Carlos

    2016-10-15

    Medical ozone reduced inflammation, IL-1β, TNF-α mRNA levels and oxidative stress in PG/PS-induced arthritis in rats. The aim of this study was to investigate the medical ozone effects in patients with rheumatoid arthritis treated with methotrexate and methotrexate+ozone, and to compare between them. A randomized clinical study with 60 patients was performed, who were divided into two groups: one (n=30) treated with methotrexate (MTX), folic acid and Ibuprophen (MTX group) and the second group (n=30) received the same as the MTX group+medical ozone by rectal insufflation of the gas (MTX+ozone group). The clinical response of the patients was evaluated by comparing Disease Activity Score 28 (DAS28), Health Assessment Questionnaire Disability Index (HAQ-DI), Anti-Cyclic Citrullinated (Anti-CCP) levels, reactants of acute phase and biochemical markers of oxidative stress before and after 20 days of treatment. MTX+ozone reduced the activity of the disease while MTX merely showed a tendency to decrease the variables. Reactants of acute phase displayed a similar picture. MTX+ozone reduced Anti-CCP levels as well as increased antioxidant system, and decreased oxidative damage whereas MTX did not change. Glutathione correlated with all clinical variables just after MTX+ozone. MTX+ozone increased the MTX clinical response in patients with rheumatoid arthritis. No side effects were observed. These results suggest that ozone can increase the efficacy of MTX probably because both share common therapeutic targets. Medical ozone treatment is capable of being a complementary therapy in the treatment of rheumatoid arthritis.

  17. The clinical and pathogenetic value of Foxp3+ T regulatory cells in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    A. S. Avdeeva

    2016-01-01

    Full Text Available T regulatory cells (Tregs play a key role in the immune system due to the suppression of a hyperimmune response to autoantigens and opportunistic enteric microorganisms. In recent years, there has been evidence that Tregs can suppress various immunoinflammatory responses to a wide range of physiological and pathological stimuli, including microorganisms, tumor cells, allogeneic grafts, and fetal cells.Tregs express a broad spectrum of membrane molecules that determine their functional activity and make it possible to identify these cells; however, none has discovered a universal surface marker that would distinguish this cell subpopulation from a pool of T lymphocytes. The most specific intracellular marker for Tregs is the nuclear transcription factor Foxp3 that is of fundamental importance in the development of Tregs and their inhibitory function.The results of the vast majority of studies indicate that there are increased numbers of Tregs in the synovial fluid of patients with rheumatoid arthritis (RA; however, the data on the level of this cell population in their peripheral blood are very contradictory. The majority of investigators have observed a decrease in the percentage of circulating Tregs while other studies have revealed its increase or no differences from the corresponding value of healthy donors or patients with osteoarthritis. It is believed that a quantitative defect in CD4+CD25+Foxp3+CD127 regulatory cells is especially characteristic of early RA and associated with the risk of the latter in asymptomatic patients positive for anti-cyclic citrullinated peptide antibodies. The use of disease-modifying antirheumatic drugs and biologic agents is accompanied by a certain change in the level and functional activity of Tregs, which is responsible for the therapeutic effect of the medicaments.Thus, an important part is assigned to Tregs in the pathogenesis of autoimmune rheumatic diseases, RA in particular. The decrease in the level

  18. Efficacy of golimumab plus methotrexate in methotrexate-naïve patients with severe active rheumatoid arthritis.

    Science.gov (United States)

    Emery, Paul; Fleischmann, Roy M; Hsia, Elizabeth C; Xu, Stephen; Zhou, Yiying; Baker, Daniel

    2014-09-01

    The purpose of this study was to assess the treatment benefit of golimumab + methotrexate (MTX) vs. MTX monotherapy in MTX-naïve patients with severe active rheumatoid arthritis (RA). This was a post hoc analysis of MTX-naïve RA patients in the GO-BEFORE trial who were randomized to receive placebo + MTX (n = 160), golimumab 50 mg + MTX (n = 159), or golimumab 100 mg + MTX (n = 159). Subsets of patients with severe disease were identified using these baseline criteria: C-reactive protein (CRP) ≥1.5 mg/dL, CRP ≥3.0 mg/dL, swollen joint count (SJC) ≥10 and tender joint count (TJC) ≥12, SJC ≥ 20/TJC ≥ 12, 28-joint count Disease Activity Score using CRP (DAS28-CRP) >5.1, and anti-cyclic citrullinated peptide antibody-positive status. The treatment effect of golimumab + MTX vs. MTX alone was evaluated for these outcomes: the proportions of patients achieving ≥20, 50, and 70 % improvement in the American College of Rheumatology criteria; DAS28-CRP European League Against Rheumatism response; DAS28-CRP golimumab + MTX groups vs. placebo + MTX for all of the outcomes evaluated. Furthermore, the treatment effect of golimumab + MTX was consistently greater among patients in the severe disease subsets when compared with the overall GO-BEFORE trial population. The treatment benefit of golimumab + MTX vs. MTX monotherapy was most pronounced within the subsets of patients with CRP ≥3.0 mg/dL and SJC ≥ 20/TJC ≥ 12. Following treatment with golimumab + MTX, improvements in RA signs/symptoms and in progression of structural damage were evident for the overall GO-BEFORE population, with the treatment effect more pronounced among patients with severe active disease.

  19. Wrist ultrasound analysis of patients with early rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    J.A. Mendonça

    2011-01-01

    Full Text Available In the present study, we evaluated 42 wrists using the semi-quantitative scales power Doppler ultrasound (PDUS and gray scale ultrasound (GSUS with scores ranging from 0 to 3 and correlated the results with clinical, laboratory and radiographic data. Twenty-one patients (17 women and 4 men with rheumatoid arthritis according to criteria of the American College of Rheumatology were enrolled in the study from September 2008 to July 2009 at Universidade Estadual de Campinas (UNICAMP. The average disease duration was 14 months. The patients were 66.6% Caucasians and 33.3% non-Caucasians, with a mean age of 42 and 41 years, respectively. A dorsal longitudinal scan was performed by ultrasound on the radiocarpal and midcarpal joints using GE LOGIQ XP-linear ultrasound and a high frequency (8-10 MHz transducer. All patients were X-rayed, and the Larsen score was determined for the joints, with grades ranging from 0 to V. This study showed significant correlations between clinical, sonographic and laboratory data: GSUS and swollen right wrist (r = 0.546, GSUS of right wrist and swelling of left wrist (r = 0.511, PDUS of right wrist and pain in left wrist (r = 0.436, PDUS of right wrist and C-reactive protein (r = 0.466. Ultrasound can be considered a useful tool in the diagnosis of synovitis in early rheumatoid arthritis mainly when the anti-cyclic citrullinated peptide and rheumatoid factor are negative, and can lead to an early change in the therapeutic decision.

  20. PADI4 and the HLA-DRB1 shared epitope in juvenile idiopathic arthritis

    Science.gov (United States)

    Hisa, Kaori; Yanagimachi, Masakatsu D.; Naruto, Takuya; Miyamae, Takako; Kikuchi, Masako; Hara, Rhoki; Imagawa, Tomoyuki; Yokota, Shumpei; Mori, Masaaki

    2017-01-01

    Objective Both genetic and environmental factors are associated with susceptibility to juvenile idiopathic arthritis (JIA). Many studies have reported that both a ‘shared epitope’ (SE) encoded by several HLA-DRB1 alleles and the peptidyl arginine deiminase type 4 (PADI4) gene polymorphisms are associated with susceptibility to rheumatoid arthritis (RA). However, it is uncertain whether JIA and RA share the latter genetic risk factor. Therefore, here we investigated relationships between HLA-SE and PADI4 polymorphisms with clinical subtypes of JIA. Methods JIA patients (39 oligoarthritis, 48 RF-positive polyarthritis, 19 RF-negative polyarthritis and 82 systemic) and 188 healthy controls were genotyped for HLA-DRB1 by PCR-sequence-specific oligonucleotide probe methodology. Three PADI4 gene single nucleotide polymorphisms (SNPs), rs2240340, rs2240337 and rs1748033, were genotyped using TaqMan SNP Genotyping Assays. Results Frequencies of the HLA-SE were higher in RF-positive polyarticular JIA than in healthy controls. RF-positive polyarticular JIA was associated with HLA-SE (OR = 5.3, 95% CI = 2.5–11.9, pc < 0.001). No associations were found between clinical subtypes of JIA and PADI4 allele frequency. Nonetheless, rs2240337 in the PADI4 gene was significantly associated with anti-cyclic citrullinated peptide antibody (ACPA)-positivity in JIA. The A allele at rs2240337 was a significant risk factor for ACPA positivity in JIA (OR = 5.6, 95% CI = 1.71–23.7 pc = 0.03). Conclusion PADI4 gene polymorphism is associated with ACPA-positivity in JIA. The association of HLA-SE with RF-positive polyarticular JIA as well as RA is confirmed in Japanese. Thus, HLA-SE and PADI4 status both influence JIA clinical manifestations. PMID:28182665

  1. Clinical Diagnostic Value of Combined Determination of Serum RF,AKA and Anti- CCP Antibody Levels in Patients with Rheumatoid Arthritis%RF、AKA和抗CCP抗体联检对类风湿关节炎诊断的临床价值

    Institute of Scientific and Technical Information of China (English)

    赵洪灿; 项国谦

    2005-01-01

    目的:探讨类风湿因子(Rheumatoid factor,RF)、抗角质蛋白抗体(antikeratin antibody,AKA)及抗环瓜氨酸肽(anti-cyclic citrullinated peptide,CCP)抗体对类风湿关节炎(rheumatoid arthritis,RA)的临床意义和早期应用价值.方法:对40例类风湿关节炎患者、30例系统性红斑狼疮和30名正常健康体检者进行RF、AKA、抗CCP抗体检测,应用速率散射比浊法测定RF,间接免疫荧光法检测AKA,ELISA法测定抗CCP抗体.结果:40例RA患者血清中,RF灵敏度和特异性分别为70.0%、90.0%,AKA灵敏度和特异性分别为35.0%、96.7%,抗CCP抗体灵敏度和特异性分别为85.0%、93.3%,联检RF、AKA及抗CCP抗体灵敏度和特异性分别为97.07%、99.8%.结论:RF、AKA和抗CCP抗体可作为诊断RA比较特异的血清学指标,三项指标联检可在一定程度上弥补RF对RA的诊断不足,提高RA的阳性诊断率,且有助于疾病的预后判断.

  2. Concomitância de artrite reumatoide e espondilite anquilosante em um único paciente: importância dos novos critérios de classificação Concurrent rheumatoid arthritis and ankylosing spondylitis in one patient: the importance of new classification criteria

    Directory of Open Access Journals (Sweden)

    Valderilio Feijó Azevedo

    2013-02-01

    Full Text Available Relatamos um caso de concomitância de espondilite anquilosante e artrite reumatoide em um paciente caucasiano de 65 anos, com achados clínicos de poliartrite simétrica com erosão de metacarpofalangeana ao raio X convencional e dor lombar infl amatória, HLA-B27+, associada à sacroiliíte. O paciente apresentou valores elevados de fator reumatoide e antipeptídeo citrulinado cíclico (anti-CCP. Realizamos uma revisão da literatura na qual as principais características de casos previamente reportados foram comparadas às deste caso. Este é o primeiro relato de caso de concomitância das duas doenças em que se utilizou teste laboratorial para dosagem do anti-CCP associado ao preenchimento das últimas versões dos critérios ASAS axial e ACR/EULAR para a classificação de espondilite anquilosante e artrite reumatoide, respectivamente.We report the case of concomitant ankylosing spondylitis and rheumatoid arthritis in a 65-year-old Caucasian male, who had symmetric polyarthritis with erosion of the metacarpophalangeal joint on conventional X-ray, infl ammatory low back pain with HLA-B27 positivity, and sacroiliitis. Laboratory analysis showed high levels of rheumatoid factor and anti-cyclic citrullinated peptide antibody (anti-CCP. Clinical features of previously reported cases were compared with those of our case. This is the first case report on the coexistence of both diseases in the same patient, for whom anti- CCP testing and the latest versions of axial ASAS criteria and ACR/EULAR criteria for the classification of ankylosing spondylitis and rheumatoid arthritis, respectively, were used.

  3. Evaluation of the Canadian Rheumatology Association Choosing Wisely recommendation concerning anti-nuclear antibody (ANA) testing.

    Science.gov (United States)

    Ferrari, Robert

    2015-09-01

    The objective of this study was to evaluate the Canadian Rheumatology Association Choosing Wisely recommendation concerning anti-nuclear antibody (ANA) testing. Patients with joint pain/stiffness/swelling were assessed to determine if ANA testing was indicated. An a priori threshold was set before ANA testing would be considered. Those who did not have ANA testing ordered were followed for 1 year to determine if any of them went on to have a diagnosis of systemic lupus erythematosus (SLE) or other connective tissue disease. A parallel study was conducted with a similar a priori threshold for the use of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody testing in the diagnosis of rheumatoid arthritis (RA), and again, patients were followed for 1 year. A total of 866 subjects were examined, 509 females (58.8 %) and 357 males (41.2 %). The mean age of the group was 47.5 ± 16.8 years. The mean duration of symptoms was 12.0 ± 5.6 weeks. Of the 866 subjects, 68 met an a priori threshold for ordering ANA, RF, and anti-CCP testing. Of these 68, there was a newly diagnosed case of SLE, 4 newly diagnosed cases of RA, and 3 cases of polymyalgia rheumatica. The remaining 798 subjects were followed for approximately 1 year and none developed evidence of SLE, RA, or other connective tissue disease. In the evaluation of non-specific musculoskeletal symptoms, setting an a priori threshold for ordering serology in keeping with the spirit of the Canadian Rheumatology Association Choosing Wisely recommendation for antibody testing results in a very low risk of missing a case of systemic lupus erythematosus or rheumatoid arthritis.

  4. HIV/AIDS and rheumatoid arthritis.

    Science.gov (United States)

    Cunha, Bernardo M; Mota, Licia Maria H; Pileggi, Gecilmara S; Safe, Izabella P; Lacerda, Marcus V G

    2015-05-01

    The acquired immunodeficiency syndrome (AIDS) is an infectious disease caused by the human immunodeficiency virus (HIV). It was first recognized in the United States in 1981, and the HIV/AIDS epidemic has since spread to affect all countries. The interface of HIV/AIDS with opportunistic infectious diseases is well characterized, but further research is required into the concurrence of other chronic diseases. The objective of this review was to identify possible interferences of HIV infection in the diagnosis and management of rheumatoid arthritis (RA). A review of the available evidence was conducted using the GRADE approach. Overall, the quality of evidence was low. Our main conclusions were: (1) the occurrence of rheumatoid-like arthritis in patients with HIV/AIDS is quite rare; therefore, it is not recommended that HIV infection be considered routinely as a differential diagnosis in this condition (C2); (2) HIV infection may lead to rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody positivity, but usually at low titers (C1); (3) RA might cause false-positive HIV serology and ELISA seems to be a more specific test for HIV in patients with RA (C2); (4) RA and AIDS may coexist, even in cases of severe immunosuppression (C1); (5) RA emergence may seldom occur during or after immune reconstitution (C1); and (6) there is insufficient safety data to recommend use of specific disease-modifying antirheumatic drugs (DMARDs) in RA patients with HIV/AIDS. Therefore, these drugs should be used cautiously (C1).

  5. Performance of the 2010 American College of Rheumatology/European League against Rheumatism (ACR/EULAR) criteria for classification of rheumatoid arthritis in an Indian population: An observational study in a single centre

    Science.gov (United States)

    Kedar, M. V. V. Pavan; Acharya, Raviraja V.; Prakashini, K.

    2016-01-01

    Background & objectives: The 1987 American College of Rheumatology (ACR) criteria were criticised for classifying patients only in the late stage. The 2010 ACR/European League against Rheumatism (ACR/EULAR) classification criteria for rheumatoid arthritis (RA) were thus formulated to recognize the early stage of disease with high sensitivity. This pilot study was designed to estimate and compare the sensitivities of the 1987 ACR and 2010 ACR/EULAR classification criteria for RA. Methods: In a tertiary care hospital, the medical records of 97 patients diagnosed with RA were reviewed. Case study forms were filled with relevant clinical data and investigation results after reviewing each medical record. The radiographs of hands were also reviewed. To each case, both the 1987 ACR and the 2010 ACR/EULAR criteria were applied and the results of the classification were noted. Results: The sensitivity of the 2010 ACR/EULAR criteria was found to be 79.38 per cent [95% confidence interval (CI) = 71.33-87.43%] and the sensitivity of the 1987 ACR criteria was found to be 63.92 per cent (95% CI = 54.36-73.48%). The difference in the sensitivities was significant (P< 0.01). There was a significant rise in sensitivity of the 2010 ACR/EULAR criteria when patients having anti-cyclic citrullinated peptide (CCP) titres were analysed. Interpretation & conclusions: The 2010 ACR/EULAR criteria were found to be more sensitive than the 1987 ACR criteria possibly owing to features of the criteria. Anti-CCP titres were found to increase the sensitivity of the 2010 ACR/EULAR criteria. PMID:27934811

  6. Plasma n-3 fatty acids and clinical outcomes in recent-onset rheumatoid arthritis.

    Science.gov (United States)

    Proudman, Susanna M; Cleland, Leslie G; Metcalf, Robert G; Sullivan, Thomas R; Spargo, Llewellyn D; James, Michael J

    2015-09-28

    A randomised controlled trial (RCT) of high-dose v. low-dose fish oil in recent-onset rheumatoid arthritis (RA) demonstrated that the group allocated to high-dose fish oil had increased remission and decreased failure of disease-modifying anti-rheumatic drug (DMARD) therapy. This study examines the relationships between plasma phospholipid levels of the n-3 fatty acids in fish oil, EPA and DHA, and remission and DMARD use in recent-onset RA. EPA and DHA were measured in blood samples from both groups of the RCT. The data were analysed as a single cohort, and Cox proportional hazards models were used to examine relationships between plasma phospholipid (PL) EPA and DHA and various outcome measures. When analysed as a single cohort, plasma PL EPA was related to time to remission, with a one unit increase in EPA (1% total fatty acids) associated with a 12% increase in the probability of remission at any time during the study period (hazard ratio (HR)=1.12; 95% CI 1.02, 1.23; P=0.02). Adjustment for smoking, anti-cyclic citrullinated peptide antibodies and 'shared epitope' HLA-DR allele status did not change the HR. Plasma PL EPA, adjusted for the same variables, was negatively related to time to DMARD failure (HR=0.85; 95% CI 0.72, 0.99; P=0.047). The HR for DHA and time to remission or DMARD failure were similar in magnitude to those for EPA, but not statistically significant. Biomarkers of n-3 status, such as plasma PL EPA, have the potential to predict clinical outcomes relevant to standard drug treatment of RA patients.

  7. 类风湿性关节炎心功能超声心动图的应用研究%Rheumatoid Arthritis Cardiac Echocardiography Application Research

    Institute of Scientific and Technical Information of China (English)

    王红峰; 吴晓萍

    2016-01-01

    Rheumatoid arthritis (rheumatoid arthritis,RA) is one of the causes are not known, chronic, inlfammatory SYNOVITIS is characterized by systemic autoimmune disease, the disease occurred in 30-50 young women, if left untreated, can lead to serious damage to other parts, especially the cardiovascular system, and most patients with occult disease. Prevalence of RA in the 0.36%, has a high morbidity and mortality. Existing research[1] showed that the mortality rate of cardiovascular events in patients with RA is 2-5 times the normal crowd, so the changes of heart function in patients with early RA is particularly important. On echocardiography in check mode is convenient, cheap, safe and simple advantages is the ideal technology testing heart function. Most cases of clinical study can be found early on the cardiac function of patients with RA caused signiifcant damage, but most are asymptomatic when RA patients with clinical symptoms, cardiovascular damage is more severe, reversible treatment was almost lost. However, the echocardiography for early RA patients symptom-free examination is highly sensitive, early detection of latent heart dysfunction in the pathogenesis of RA patients. According to clinical data displayed, for early RA patients right heart function damaged of change main performance for pulmonary contraction pressure (pulmonary arterial systolic pressure,PASP) of increased; and left heart function of injury is main for left room shot blood scores (ejection fraction,EF) of reduced, diastolic early e peak of reduced and diastolic late a, peak of increased and diastolic early e peak, and late a, peak ratio (E/A) of reduced. However, acute period is mostly in patients with rheumatoid factor in RA (Rheumatoid factors,RF) and Anti-Cyclic Citrullinated Peptide antibody (Anti-Cyclic Citrullinated Peptide antibody and anti-CCP) positive, erythrocyte sedimentation rate (erythrocyte sedimentation,ESR) and high sensitivity c-reactive protein (hypersensitivity

  8. Effect of an hyperbaric nitrogen narcotic ambience on arginine and citrulline levels, the precursor and co-product of nitric oxide, in rat striatum

    OpenAIRE

    Vallée Nicolas; Rissoe Jean-Jacques; Blatteau Jean-Eric

    2011-01-01

    Abstract Previous studies performed in the laboratory have shown that nitrogen narcosis induces a decrease in striatal glutamate and dopamine levels. Although we stimulated the N-methyl-D-aspartate (NMDA) receptor, an important glutamate receptor required for motor and locomotor activity managed by the striatum, and demonstrated that the receptor was effective when exposed to nitrogen at 3MPa, it was not possible to return the striatal glutamate level to its base values. We conclude that it w...

  9. Fragments of Citrullinated and MMP-degraded Vimentin and MMP-degraded Type III Collagen Are Novel Serological Biomarkers to Differentiate Crohn's Disease from Ulcerative Colitis

    DEFF Research Database (Denmark)

    Mortensen, Joachim Høg; Godskesen, Line Elbjerg; Jensen, Michael Dam;

    2015-01-01

    BACKGROUND AND AIMS: A hallmark of inflammatory bowel disease [IBD] is chronic inflammation, which leads to excessive extracellular matrix [ECM] remodelling and release of specific protein fragments, called neoepitopes. We speculated that the biomarker profile panel for ulcerative colitis [UC......-degraded vimentin [VICM] were studied with a competitive ELISA assay system in a cohort including 164 subjects [CD n = 72, UC n = 60, and non-IBD controls n = 32] and a validation cohort of 61 subjects [CD n = 46, and UC n = 15]. Receiver operating characteristic curve analysis and logistic regression modelling....... Furthermore, the biomarkers C1M [AUC = 0.81], C3M [AUC = 0.83], VICM [AUC = 0.83], and P1NP [AUC = 0.77] were best to differentiate UC from non-IBD. The best combinations of biomarkers to differentiate CD from UC and UC from non-IBD were VICM, C3M, C4M [AUC = 0.90] and VICM, C3M [AUC = 0.98] respectively...

  10. Expression and significance of soluble triggering receptor expressed on myloid cells-1 in the sera with rheumatoid arthritis%可溶性髓样细胞表达的触发因子受体-1在类风湿关节炎患者血清中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    崔刘福; 李慧娟; 杨文浩; 舒荣; 宋海澄; 韩依轩; 于萍

    2012-01-01

    Objective To investigate the correlation of expression of soluble triggering receptor expressed on myloid cells-1 ( sTREM-1 ) in the sera with the activity of rheumatoid arthritis(RA).Methods All 80 RA patients ( 15 remissive and 65 active) and 74 normal controls were enrolled in the study.Enzyme linked immunosorbent assay (ELISA) was applied to detect sTREM-1 in the sera from RA patients and normal controls.The correlation of sTREM-1 with medical history,painful joint count,swollen joint count,erythocyte sedimentation rate,highsensitivity C-reactive protein,rheumatoid factor and anti-cyclic citmllinated peptide antibody were observed.Results The level of sTREM-1 in RA patients was higher than that in the normal ones and the difference had a statistical significance [ ( 3.2 ± 1.3 ) μg/L vs (2.6 ± 1.4 ) μg/L,r =2.94,P < 0.05 ].The level of sTREM-1 in active RA patients was higher than that in the remissive ones [ ( 3.3 ± 1.2 ) μg/L vs (0.9 ± 0.6 ) μg/L,r =4.50,P <0.05 ].The sTREM-1 level in patients with X-ray damage of hands joint was higher than that in patients with non-X-ray damage of hand joint[ (3.7 ±1.1) μg/L vs (2.5 ± 1.1) μg/L,r =4.52,P<0.01 ].There was a significant association between sTREM-1 level and DAS28 score,swollen joint count,erythrocyte sedimentation rate,rheumatoid factor and anti-cyclic citrullinated peptide antibody in RA patients ( r1 =0.8500,r2 =0.6412,r3 =0.8263,r4 =0.4421,r5 =0.6635,all P < 0.01 ).Conclusions Level of sTREM-1 are high in sera of RA patients.Positive correlation with DAS28,the number of swollen joints,erythrocyte sedimentation rate,rheumatoid factor,anti-cyclic citrullinated peptide antibody and Serum sTREM-1 may be indicators of disease activity.%目的 探讨可溶性髓样细胞表达的触发因子受体-1(sTREM-1)在类风湿性关节炎(RA)患者血清中的表达及与RA病情活动的相关性.方法 80例RA患者(病例组)中,稳定期RA患者15例,活动期RA患者65例.选取健康体检者74

  11. SMAD3 rs17228212 gene polymorphism is associated with reduced risk to cerebrovascular accidents and subclinical atherosclerosis in anti-CCP negative Spanish rheumatoid arthritis patients.

    Directory of Open Access Journals (Sweden)

    Mercedes García-Bermúdez

    Full Text Available Rheumatoid arthritis (RA is a complex polygenic inflammatory disease associated with accelerated atherosclerosis and increased risk of cardiovascular (CV disease. Previous genome-wide association studies have described SMAD3 rs17228212 polymorphism as an important signal associated with CV events. The aim of the present study was to evaluate for the first time the relationship between this gene polymorphism and the susceptibility to CV manifestations and its potential association with the presence of subclinical atherosclerosis assessed by the evaluation of carotid intima-media thickness (cIMT in patients with RA.One thousand eight hundred and ninety-seven patients fulfilling classification criteria for RA were genotyped for SMAD3 rs17228212 gene polymorphism through TaqMan genotyping assay. Also, subclinical atherosclerosis determined by the assessment of cIMT was analyzed in a subgroup of these patients by carotid ultrasonography.No statistically significant differences were observed when allele frequencies of RA patients with or without CV events were compared. Nevertheless, when RA patients were stratified according to anti-cyclic citrullinated peptide (anti-CCP status, we found that in RA patients who were negative for anti-CCP antibodies, the presence of C allele of SMAD3 rs17228212 polymorphism conferred a protective effect against the risk of cerebrovascular accident (CVA after adjustment for demographic and classic CV risk factors (HR [95%CI]=0.36 [0.14-0.94], p=0.038 in a Cox regression model. Additionally, correlation between the presence of C allele of SMAD3 rs17228212 polymorphism and lower values of cIMT was found after adjustment for demographic and classic CV risk factors (p-value=0.0094 in the anti-CCP negative RA patients.Our results revealed that SMAD3 rs17228212 gene variant is associated with lower risk of CVA and less severe subclinical atherosclerosis in RA patients negative for anti-CCP antibodies. These findings may have

  12. Study of association of CD40-CD154 gene polymorphisms with disease susceptibility and cardiovascular risk in Spanish rheumatoid arthritis patients.

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    Mercedes García-Bermúdez

    Full Text Available OBJECTIVE: Rheumatoid arthritis (RA is a chronic inflammatory disease associated with increased cardiovascular (CV mortality. Since CD40-CD154 binding has direct consequences on inflammation process initiation, we aimed to replicate previous findings related to disease susceptibility in Spanish RA population. Furthermore, as the major complication in RA disease patients is the development of CV events due to accelerated atherosclerosis, and elevated levels of CD40L/CD154 are present in patients with acute myocardial infarction, we assessed the potential association of CD40 and CD154/CD40L gene variants with CV risk in Spanish RA patients. METHODS: One thousand five hundred and seventy-five patients fulfilling the 1987 ACR classification criteria for RA and 1600 matched controls were genotyped for the CD40 rs1883832, rs4810485 and rs1535045 and CD154 rs3092952 and rs3092920 gene polymorphisms, using predesigned TaqMan single nucleotide polymorphism genotyping assays. Afterwards, we investigated the influence of CD40-CD154 gene variants in the development of CV events. Also, in a subgroup of 273 patients without history of CV events, we assessed the influence of these polymorphisms in the risk of subclinical atherosclerosis determined by carotid ultrasonography. RESULTS: Nominally significant differences in the allele frequencies for the rs1883832 CD40 gene polymorphism between RA patients and controls were found (p=0.038. Although we did not observe a significant association of CD40-CD154 gene variants with the development of CV events, an ANCOVA model adjusted for sex, age at the time of the ultrasonography assessment, follow-up time, traditional CV risk factors and anti-cyclic citrullinated peptide antibodies disclosed a significant association (p=0.0047 between CD40 rs1535045 polymorphism and carotid intima media thickness, a surrogate marker of atherosclerosis. CONCLUSION: Data from our pilot study indicate a potential association of rs

  13. "Immune Complexes in Juvenile Idiopathic Arthritis"

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    Terry Lynn Moore

    2016-05-01

    Full Text Available Abstract for invited review in Molecular Mechanisms of Immune Complex Pathophysiology thematic issue to be published in Frontiers in Immunology. Immune Complexes(ICin Juvenile Idiopathic Arthritis (JIA Terry L. Moore, MD, FAAP, FACR, MACR Professor of Internal Medicine,Pediatrics, and Molecular Biology and Immunology Director of Adult and Pediatric Rheumatology Saint Louis University School of Medicine Saint Louis, Missouri 631`04,USA Juvenile idiopathic arthritis (JIA reflects a group of clinically heterogeneous, autoimmune disorders in children characterized by chronic arthritis and hallmarked by elevated levels of circulating immune complexes (CICs and associated complement activation by-products in their sera. ICs have been detected in patients’ sera with JIA utilizing a variety of methods, including the anti-human IgM affinity column,C1q solid phase assay, polyethylene glycol precipitation, Staphylococcal Protein A separation method, anti-C1q/C3 affinity columns, and FcγRIII affinity method. As many as 75% of JIA patients have had IC detected in their sera. The CIC proteome in JIA patients has been examined to elucidate disease-associated proteins that are expressed in active disease. Evaluation of these IC s have shown the presence of multiple peptide fragments by SDS-PAGE and 2-DE. Subsequently, all isotypes of rheumatoid factor (RF, isotypes of anti-cyclic citrullinated (CCP peptide antibodies, IgG, C1q, C4, C3, and the membrane attack complex (MAC were detected in these IC. Complement activation and levels of IC correlate with disease activity in JIA, indicating their role in the pathophysiology of the disease. This review will summarize the existing literature and discuss the role of possible protein modification that participates in the generation of immune response. We will address the possible role of these events in the development of ectopic germinal centers that become the secondary site of plasma cell development in JIA. We

  14. Rituximab therapy in Greek patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Haralampos M Moutsopoulos

    2008-10-01

    Full Text Available Aristotelis P Tsiakalos*, Nestor K Avgoustidis*, Haralampos M MoutsopoulosDepartment of Pathophysiology, Medical School, National Univercity of Athens, Athens, Greece. *These authors contributed equally to this workObjective: An open-label, prospective, uncontrolled study created to investigate clinical response, serological changes and side effects in Greek patients with rheumatoid arthritis (RA, after B-cell depletion with rituximab.Methods: Patients with high disease activity (disease activity score [DAS]-28 > 5.1 were selected for treatment with rituximab and received two infusions, 1 gr each, 2 weeks apart. Different disease parameters (visual analog scale, DAS-28, C-reactive protein [CRP], erythrocyte sedimentation rate, health assessment questionnaire, complement (C3, C4, rheumatoid factor [RF], anti-cyclic citrullinated peptide antibody [anti-CCP], swollen joint count, tender joint count, immunoglobulin M [IgM], IgG, IgA were performed at base line, 2, 4, and 6 months post-treatment. Response was defined according to the American College of Rheumatology (ACR criteria.Results: Seventeen patients received therapy. Treatment led to a reduction in various disease parameters. ACR20 was achieved in 41.11% of patients by week 8, 52.94% by week 16, and 82.35% by week 24. ACR50 was achieved in 5.88% by week 8, 41.17% by week 16, and 64.7% by week 24. ACR70 was achieved only by week 24 in 23.52% of patients. Statistical analysis has shown no differences in clinical response, between RF positive/negative patients, and anti-CCP-positive/negative patients, while decline of RF was better correlated with reduction of DAS-28 than with anti-CCP.Conclusions: Rituximab is a well tolerated and effective treatment in RA. Response was not correlated to RF or anti-CCP positivity. Decline of RF was associated with clinical response and reduction of DAS-28 and CRP.Keywords: rituximab, Greek patients, rheumatoid arthritis

  15. Changes of Serum CRP, CER, Hcy and Anti-CCP Concentrations in Patients with Depression%抑郁症患者血清CRP、CER、Hcy和Anti-CCP抗体的浓度变化

    Institute of Scientific and Technical Information of China (English)

    唐亚梅; 周利君; 刘勇; 秦立新

    2012-01-01

    目的 探讨抑郁症患者血清C-反应蛋白(C- reactive protein,CRP)、铜蓝蛋白(copper - protein,CER)、同型半胱氨酸(Homocysteinc,Hcy)及抗环瓜氨酸肽抗体(anti - CCP)与抑郁症的关系. 方法 收集本院确诊的抑郁症患者55例,健康体检者30例,采用速率散射比浊法测血清CRP和CER,酶法测血清Hcy,酶联免疫吸附法测血清anti - CCP抗体,比较抑郁患者和正常对照人群的组间差异. 结果 与对照组比较,抑郁患者血清CRP水平无显著性变化(P>0.05),CER水平显著降低(P<0.05),Hcy和Anti - CCP水平均显著升高(P<0.05). 结论 抑郁患者存在免疫炎症和自身免疫反应,CER、Hcy和anti - CCP均可能参与了抑郁症的病理进程.%Objective To investigate the correlations of the levels of serum C- reactive protein (CRP), ceruloplasmin (CER), homocysteine (Hcy) and anti - cyclic citrullinated peptide antibody (anti - CCP) with depression. Methods Serum was collected from 55 patients with depression (depression group) and 30 health adults (control group). The levels of serum CRP and CER were determined by rate nephelometry. Serum anti - CCP concentration was measured by enzymatic - linked immu-nosorbent assay (ELISA) and serum Hcy was detected by enzyme method. The differences of serum CRP, CER, Hcy and anti -CCP levels were compared between the depression group and the control group. Results Compared with the control group, the serum CRP level of the depression group was not statistically different(P >0.05), while the serum CER concentration was significantly decreased ( P < 0.05 ) and serum Hcy and anti - CCP were markedly incrcascd( P < 0. 05 ) . Conclusions Immu-nological inflammation and autoimmune reaction do exist in depression patients. CER, Hcy and anti - CCP may all participate in the pathological process of depression.

  16. COMORBIDITY IN RHEUMATOID ARTHRITIS

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    T. A. Panafidina

    2014-01-01

    Full Text Available The peak onset of rheumatoid arthritis (RA is at 30-55 years of age. At this age, the patients have also other concomi- tant diseases (comorbidities that affect the course and prognosis of RA, the choice of its treatment policy, quality of life of the patients. Objective: to identify the most important and common comorbidities in patients with RA. Subjects and methods. Two hundred patients (median age 55 [46; 61] years were enrolled; there was a preponderance of women (82.5% with median disease duration 5 [1; 10] years, seropositive for IgM rheumatoid factor (83.0% and anti-cyclic citrullinated peptide antibodies (81.6% with moderate and high disease activity (median DAS28 value 3.9 [3.1; 4.9]. Varying degrees of destructive changes in hand and foot joints were radiologically detected in 71.2% of the patients; 64.5% of the patients had Functional Class II. Methotrexate was given to 69.5% of the patients; therapy with biological agents was used in 21.0% of the cases. 15.5% of the patients did not receive DMARD or biologics. 43.0% of the patients with RA received glucocorticoids. Results. Comorbidities were present in 72.0% of the patients with RA. The most common diseases were hypertension (60.0%, dyslipidemia (45.0%, fractures at various sites (29.5%, and coronary heart disease (21.0%. Myocardial infarction and stroke were observed in 1.5 and 1.0% of cases, respectively. There was diabetes mellitus (DM in 7.5% of the cases and osteoporosis in 15.5% of the patients. 81.7% of the patients with RA and hypertension and 80.0% of those with RA and DM received antihypertensive and sugar-lowering therapy, respectively. At the same time the RA patients with dyslipidemia and osteoporosis received specific drugs far less frequently (30.0 and 29.0%, respectively. Conclusion. Comorbidities are frequently encountered in RA. By taking into account the fact that cardiovascular dis- eases are a main cause of death in RA; it is necessary to adequately and timely

  17. COMPARATIVE CLINICAL, LABORATORY, AND INSTRUMENTAL EVALUATION OF INTERSTITIAL LUNG CHANGES IN RHEUMATOID ARTHRITIS

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    D. V. Bestaev

    2014-01-01

    Full Text Available Interstitial lung disease (ILD is a common extra-articular manifestation of rheumatoid arthritis (RA. Objective: to study the associations of the data of high-resolution computed tomography (HRCT and the esti- mate of diffusing lung capacity (DLC with clinical and laboratory parameters in RA patients with and without ILD. Subjects and methods. 79 RA patients fulfilling the 1987 American College of Rheumatology criteria (61 women and 18 men admitted to the Nasonova Research Institute of Rheumatology were included. Results. HRCT revealed signs of ILD in 58 (73% cases. The patients with ILD were divided into three groups: 1 18 (31% patients with ground glass opacities; 2 34 (58.6% patients with fibrosis; 3 6 (10.4% patients with the honeycomb lung. Twenty-one (27% patients with ILD were included in Group 4. In the ILD patients with ground glass opacities, the levels of anti-cyclic citrullinated peptide (ACCP antibodies and rheumatoid factor (RF were much above those in the patients without ILD (240 [166; 410.5], 480 [140; 850.5] and 73 [31; 101], 330,5 [118.5; 604.8], respectively. In the patients with ILD, the concentration of C-reactive protein (CRP (46 [35; 91] was higher than that in those without ILD (24 [18; 31]; p < 0.05. In the ILD patients with ground glass opacities, DLC was considerably below that in those with ILD – 59.2±11.2 and 79.8±12.1% of the normal value, respectively (p < 0.001. Conclusion. The associations found between ACCP antibodies and DLC, DAS28 and DLC may suggest that ACCP antibodies are implicated in the pathogenesis of ILD and the lung is involved in the immunoinflammatory process. The high percent of smokers detected in our investigation confirms the considerable role of smoking in the pathogene- sis of RA-associated ILD. In the RA patients with ILD, ground glass opacities must be an indicator of the activity of an immunopathological process in the lung.

  18. 抗环瓜氨酸肽抗体和IgG-Rf因子在类风湿关节炎中的诊断价值%Diagnostic value of anti-CCP antibody and IgG-Rf in rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    李三中; 郑延梅; 代燕

    2009-01-01

    目的 探讨抗环瓜氨酸肽抗体(抗-CCP)和类风湿因子IgG-Rf联合检测对类风湿关节炎(RA)的诊断价值.方法 抗-CCP采用ELISA法定量检测,IgG一Rf采用速率散射免疫比浊法检测.结果 68例RA患者抗-CCP、IgG-Rf的灵敏度分别为57.4%和69.1%,61例非RA患者抗-CCP、IgG-Rf的特异度分别为97.6%和89.7%,两者联合检测灵敏度和特异度为30.9%和100%,21例IgG-Rf阴性中有6例抗-CCP阳性,阳性率为28.6%,47例IgG-Rf阳性中有42例抗-CCP阳性,阳性率为89.4%.结论 抗-CCP抗体能提高RA的早期诊断率,两者联合检测在RA诊断中可降低RA误诊率,同时提高RA诊断的特异性和阳性预测值.%Objective To explore the clinical value of the combined detection of anti - cyclic Cit-rullinated peptide(anti-CCP) antibody and rheumatoid factor (Rf) in the diagnosis of rheumatoid arthritis (RA). Methods Anti- CCP antibody was measured by ELISA and IgG- Rf were detected by rate nephe-lometry. Results In 68 patients with RA the sensitivity for anti - CCP antibody and IgG - Rf were 57.4%and 69.1% respectively. In 61 non-RA patients the speciality for anti -CCP was 97. 6% ,and for IgG- Rfwas 89.7%. If combined the detection of anti -CCP antibody and IgG -Rf,the sensitivity reached 30.9% ,the speciality reached 100%. In 21 patients with negative IgG - Rf 6 cases were anti - CCP antibody positive, the positive rate was 28.6%. In 47 patients with positive IgG - Rf 42 cases were anti - CCP antibody positive, the positive rate was 89.4%. Conclusions Anti -CCP antibody could improve the accuracy of early diagnosis of RA. The combined detection of anti - CCP antibody and IgG - Rf could reduce the misdiagnosis of RA. Mean-time the speciality and the positive predicative value could be raised.

  19. Diagnosis Values of Combined Determination of Serum Rheumatoid Factor,Antikeratin Antibody,C Reaction Protein and anti-CCP Antibody in Patients with Rheumatoid Arthritis%联合检测类风湿因子、抗角蛋白抗体、C 反应蛋白和抗环瓜氨酸抗体诊断类风湿关节炎的临床意义

    Institute of Scientific and Technical Information of China (English)

    张明; 孟和宝力高; 高智文

    2011-01-01

    目的:探讨联合检测类风湿因子(RF)、抗角蛋白抗体(AKA)、C反应蛋白(CRP)和抗环瓜氨酸肽(抗-CCP)抗体诊断类风湿关节炎(RA)的临床意义.方法:检测60例RA患者和60例其他风湿类疾病患者的RF 、AKA和CRP以及抗-CCP抗体.应用速率散射比浊法测定CRP、RF,应用酶联免疫吸附试验(ELISA)法测定AKA、抗-CCP抗体.结果:60例患者血清中,RF敏感性和特异性分别为67%和77%,AKA敏感性和特异性分别为72%和95%,CRP敏感性和特异性分别为80%和33%,抗-CCP抗体敏感性和特异性分别为73%和92%,4项联合检测敏感性和特异性分别为 98%和22%.结论:RF、AKA、CRP和抗-CCP抗体4项指标联合检测可明显提高诊断RA的敏感性,有助于RA的诊断.%Objective: To evaluate the diagnosis value of combined determination of serum rheumatoid factor(RF),antikeratin antibody(AKA) c-reaction protein(CRP)and anti-cyclic citr-ulline peptide(anti-CCP) anti-body in patients with rheumatoid arthritis(RA). Methods: The RF, AKA and CRP were detect by ate-nephelometryand the anti-CCP was measured by enzymelinked immunosor bentassay in 60 patients with RA and in 60 patients with other rheumatic dis-eases. Results: The diagnostic sensitivity of RF,AKA,CRP and anti-CCP were 67%, 72% ,83% and 73% respectively; and the speeifieity were 77% ,95%, 33% and 92%, respectively. The specificity was 22% and the sensitivity was 98% with combined determination of RF, CRP and anti-CCP. Conclusions: The combination of RF,AKA,CRP and anti-CCP may offer clinical benefits for diagnosis of RA and can significantly improve the sensitivity to diagnose RA.

  20. ESR、RF、抗CCP和AKA联合检测对类风湿性关节炎的诊断价值%The Value of Combined Detection of ESR,RF,Anti CCP and AKA in the Diagnosis of Rheumatoid Arthritis

    Institute of Scientific and Technical Information of China (English)

    杨芳; 郭春霞

    2015-01-01

    目的:探讨红细胞沉降率(ESR)、类风湿因子(RF)、抗环瓜氨酸多肽抗体(抗CCP)和抗角蛋白抗体(AKA)联合检测对类风湿性关节炎(RA)的临床诊断价值。方法:对100例RA患者和70例非RA的其他自身免疫病患者检测ESR、RF、抗CCP和AKA四种指标。结果:RA患者组的四项检查阳性率均明显高于其他自身免疫病组,单项检测RA诊断的敏感性为ESR>RF>抗CCP>AKA,特异性抗CCP>AKA>RF>ESR,联合检测对RA诊断的敏感性下降,特异性却升高甚至高达100%。结论:ESR、RF、抗CCP和AKA联合检测可提高对RA诊断的特异性,对RA的早期诊断有较高价值。%Objective:To investigate the clinical value of combined detection of erythrocyte sedimentation rate (ESR),rheumatoid factor(RF),anti-cyclic citrullinated peptide antibody(anti CCP) and anti keratin antibody (AKA) in diagnosis of rheumatoid arthritis(RA).Method: ESR, RF, anti CCP and AKA in 100 patients with RA and 70 patients with other autoimmune diseases were detected.Result: In RA group, positive rate of four indexs was obviously higher than those of other autoimmune disease group, individual testing RA diagnostic sensitivity for ESR>RF>CCP>AKA, the specificity of CCP>AKA>RF>ESR,combined detection of RA diagnostic sensitivity,specificity was elevated even higher amounts to 100%.Conclusion:Combined detection of ESR,RF,anti CCP and AKA can improve RA diagnostic specificity,has high value on early diagnosis of RA.

  1. The value of anti CCP antibody, RF and CRP combined detection in early diagnosis of rheumatoid arthritis%抗CCP抗体、RF和CRP联合检测在早期诊断类风湿关节炎中的价值

    Institute of Scientific and Technical Information of China (English)

    董丽珍; 李洁平; 陈妍

    2016-01-01

    Objective:To analyze sensitivity and specificity of anti cyclic citrullinated peptide antibody(anti CCP),rheumatoid factor(RF),C reactive protein(CRP) of rheumatoid arthritis(RA)patients.Methods:78 cases of RA patients and 86 cases of non RA patients were selected.The serum anti CCP antibody,RF and CRP were detected by enzyme-linked immunosorbent assay,and the value of 3 indexes in early diagnosis of RA was compared.Results:The positive rate of anti CCP antibody,RF and CRP in RA group were significantly higher than those in non RA group;the sensitivity and specificity of combined detection of the 3 were statistically significant(P<0.05).Conclusion:The sensitivity and specificity of anti RF antibody CCP and CRP were both improved compared with that of single detection.It has important significance for early diagnosis of RA.%目的:分析类风湿关节炎(RA)患者环瓜氨酸多肽抗体(抗CCP)、类风湿因子(RF)、C反应蛋白(CRP)联合检测的敏感性和特异性。方法:收治 RA 患者78例及非 RA 患者86例,采用酶联免疫吸附试验检测其血清抗 CCP 抗体,以免疫比浊法定量检测 RF 和 CRP,比较3种指标在 RA 早期诊断中的价值。结果:RA 组抗 CCP 抗体、RF 及CRP 的阳性率显著高于非 RA 组;三者联合检测的灵敏性和特异性与单独检测时的差异有统计学意义(P<0.05)。结论:抗CCP抗体RF和CRP三者联合检测其敏感性和特异性较单独检测都有所提高,对早期诊断RA具有重要意义。

  2. IgM-RF、IgG-RF、IgA-RF及抗CCP对类风湿性关节炎的诊断价值%The diagnostic significance of IgM-RF, IgG-RF, IgA-RF and anti-CCP on rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    蔡小慧; 吕星; 卿之驹

    2012-01-01

    Objective To investigate the sensitivity and specificity of IgM-rheumatoid factor ( RF ), IgG-RF, IgA-RF and anti-cyclic citrullinated peptide ( CCP ) antibody by respective detection and combined detection for the diagnosis of rheumatoid arthritis ( RA ) and their diagnosis significance. Methods A total of 105 patients with RA, 42 patients with other autoimmune diseases and 63 healthy subjects were enrolled. Serum IgM-RF, IgG-RF, IgA-RF and anti-CCP were detected by enzyme-linked immunosorbent assay ( ELISA ). The results were analyzed statistically. Results The positive rates and concentrations of IgM-RF, IgG-RF, IgA-RF and anti-CCP in RA group were higher than those of other autoimmune disease group and healthy control group ( P 5. 1 were higher than those with 2. 6 5.1患者的IgA-RF浓度显著高于2.6

  3. Meta-analysis of diagnostic tests for rheumatoid arthritis with the screening methods of Anti-CCP and RF%抗CCP抗体联合RF检测类风湿性关节炎诊断试验Meta分析

    Institute of Scientific and Technical Information of China (English)

    杨奕; 刁建萍; 刘重阳

    2012-01-01

    目的 通过诊断试验Meta分析,综合评价抗环瓜氨酸肽抗体(CCP)和类风湿因子(RF)联合诊断类风湿关节炎(RA)的效果.方法 通过检索万方、维普、CNKI等数据库,获得有关抗CCP和RF联合诊断RA的文献,提取相关数据;采用SAS 8.02进行诊断试验Meta分析.结果 抗CCP/RF并联的准确度为0.803,诊断优势比为16.590;抗CCP+ RF串联的准确度为0.841,诊断优势比为27.781;两种联合诊断准确度比较,差异无统计学意义(P>0.05).结论 抗CCP和RF联合诊断效果较好,并联能够提高灵敏度,串联能够提高特异度,联合诊断对RA具有较高的诊断价值.%[Objective]To comprehensively evaluate the effect of anti-cyclic citrullinated peptide antibody ( Anti-CCP) and rheumatoid factor ( RF) on diagnosis of rheumatoid arthritis (RA) through Meta-analysis of diagnostic tests. [ Methods ] By search literature database such as Wangfang, Weipu, CNKI, the related literatures were obtained for data extraction. SAS 8.02 was adopted for Meta-analysis. [Results] Meta analysis indicated that the accuracy of anti-CCP/RF was 0. 803 and diagnostic OR was 16. 590. Those of anti-CCP + RF screening method were 0.841 and 27.781 respectively. The difference of accuracy between 2 methods was not significant(P >0.05). [ Conclusion] Both anti-CCP/RF and anti-CCP + RF can be used in diagnosis of RA with good effect. Anti-CCP/RF can raise sensitivity, and Anti-CCP+ RF can heighten specificity. So this combination diagnosis has good value for RA diagnosis.

  4. Usefulness of anti -CCP antibodies in rheumatic diseases in Indian patients

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    Gupta Rajiva

    2009-03-01

    Full Text Available Background: The usefulness of anti-cyclic citrullinated peptide antibodies (anti-CCP antibodies to identify rheumatic arthritis (RA from other rheumatic diseases presenting with joint pain is not well studied. Aims: We aimed to determine the sensitivity and specificity of anti-CCP antibodies in Indian RA patients with respect to non-RA rheumatic diseases and to study the relationship of anti-CCP antibodies and IgG, IgM and IgA rheumatoid factor in RA. Settings and Design: Case-control cross-sectional study carried out in the rheumatology division of All India Institute of Medical Sciences.Materials and Methods: Sixty-three patients with rheumatoid arthritis (RA and 51 patients with non-RA rheumatic diseases having joint pain were included in the study. Sera were tested for anti-CCP antibodies (IgG and IgA, IgM, IgG rheumatoid factor, using a commercially available enzyme-linked immunosorbent assay. Statistical Analysis: Statistical analysis was performed using SPSS statistical software version 11.5. Results: Fifty-four of 63 RA patients (85.71% were positive for anti-CCP antibodies. In the non-RA group, anti-CCP antibody was positive in only 5 of 51 patients (9.8%. Our study found a sensitivity of 85% and a specificity of 90.19% with regard to the use of anti-CCP antibodies assay in patients with joint pain to correctly identify RA. Anti-CCP antibodies positive patients did not have more erosive disease. IgM-RF-positive patients had more erosion when compared to the IgM-RF-negative group. Thirty-two of 57 (56.1% IgM-RF-positive patients had erosions, while no patient (0/6 patients had erosions in the IgM-RF-negative group (P = 0.01 Conclusion: Anti-CCP antibodies have high sensitivity and specificity for diagnosis of RA, in Indian patients. Anti-CCP antibodies positive patients did not have more erosive disease in our study.

  5. Serum Jo-1 Autoantibody and Isolated Arthritis in the Antisynthetase Syndrome: Review of the Literature and Report of the Experience of AENEAS Collaborative Group.

    Science.gov (United States)

    Cavagna, Lorenzo; Nuño, Laura; Scirè, Carlo Alberto; Govoni, Marcello; Longo, Francisco Javier Lopez; Franceschini, Franco; Neri, Rossella; Castañeda, Santos; Sifuentes Giraldo, Walter Alberto; Caporali, Roberto; Iannone, Florenzo; Fusaro, Enrico; Paolazzi, Giuseppe; Pellerito, Raffaele; Schwarting, Andreas; Saketkoo, Lesley Ann; Ortego-Centeno, Norberto; Quartuccio, Luca; Bartoloni, Elena; Specker, Christof; Pina Murcia, Trinitario; La Corte, Renato; Furini, Federica; Foschi, Valentina; Bachiller Corral, Javier; Airò, Paolo; Cavazzana, Ilaria; Martínez-Barrio, Julia; Hinojosa, Michelle; Giannini, Margherita; Barsotti, Simone; Menke, Julia; Triantafyllias, Kostantinos; Vitetta, Rosetta; Russo, Alessandra; Bogliolo, Laura; Bajocchi, Gianluigi; Bravi, Elena; Barausse, Giovanni; Bortolotti, Roberto; Selmi, Carlo; Parisi, Simone; Salaffi, Fausto; Montecucco, Carlomaurizio; González-Gay, Miguel Angel

    2017-02-01

    Anti-Jo-1 is the most frequently detectable antibody in the antisynthetase syndrome (ASSD), an autoimmune disease characterized by the occurrence of arthritis, myositis, and interstitial lung disease (ILD). Recently, we organized an international collaborative group called American and European NEtwork of Antisynthetase Syndrome (AENEAS) for the study of this rare and fascinating disease. The group collected and published one of the largest series of ASSD patients ever described and with one of the longer follow-up ever reported. The number of participating centers is steadily increasing, as well as the available cohort. In the first paper, we showed that arthritis, myositis, and ILD may be frequently the only feature at disease onset, raising problems to reach a correct diagnosis of this syndrome. Nevertheless, we first observed that the ex novo appearance of further manifestations is common during the follow-up, strengthening the importance of a correct diagnosis. In our cohort, the 24 % of the 243 patients up to now collected had isolated arthritis as a presenting feature. These patients represent the most intriguing group in terms of differential diagnosis and clinical time course. Furthermore, data on this aspect are scanty, the reason that lead us to evaluate these aspects in our cohort of patients, reviewing also available literature. In fact, the most relevant aspect is that ASSD is rarely suspected in this setting of patients, in particular in case of poliarticular involvement, positive rheumatoid factor (RF), or anti-cyclic citrullinated peptide antibodies (ACPA) or evidence of joint erosions at plain radiographs. These findings were not rare in our cohort, and they have been also described in other series. Furthermore, manifestations such as Raynaud's phenomenon, mechanic's hands, and fever that may lead to the suspect of ASSD are observed only in a third of cases. If we consider the high rate of clinical picture progression in these patients, we feel

  6. Analysis of risk factors for rheumatoid arthritis-related interstitial lung disease%类风湿关节炎相关肺间质病变的危险因素分析

    Institute of Scientific and Technical Information of China (English)

    黄义鸿; 许赤多; 吴南辉

    2015-01-01

    目的:通过分析与探讨类风湿关节炎相关肺间质病变的危险因素,为临床上预防该种疾病提供相关依据。方法97例类风湿关节炎患者作为研究对象,其中单纯类风湿关节炎患者(单纯组)53例,类风湿关节炎相关肺间质病变患者(合并组)44例,对两组患者的临床资料进行对比分析。结果合并组患者的发病年龄、病程、抗环瓜氨酸肽(CCP)抗体值、吸烟率、类风湿因子(RF)、疾病活动性评分均明显高于单纯组,差异均有统计学意义(P<0.05)。结论类风湿关节炎患者年龄越大、病程越长、有吸烟史、疾病活动率越高、抗CCP抗体值越高越容易发生肺间质病变,应早期检查、早期诊治,以降低死亡率,促进患者早日康复。%Objective To analyze risk factors for rheumatoid arthritis-related interstitial lung disease, in order to provide related reference for clinical prevention.Methods Among the 97 patients with rheumatoid arthritis as study subjects, there were 53 cases with single rheumatoid arthritis (single group) and 44 cases with rheumatoid arthritis-related interstitial lung disease (complicated group). Clinical data of the two groups were comparative analyzed.Results The complicated group had much higher onset age, course of disease, anti-cyclic citrullinated peptide (CCP) antibody value, smoking rate, rheumatoid factors (RF), and disease activity score than the single group, and their differences all had statistical significance (P<0.05).Conclusion Interstitial lung disease occurs easily in rheumatoid arthritis patients with old onset age, long course of disease, smoking history, high disease activity and anti-CCP antibody value. Early examination and diagnosis are necessary for reducing mortality and accelerating rehabilitation of patients.

  7. ANALYSIS OF GENE EXPRESSION IN BLOOD AS AN ADDITIONAL TOOL TO MONITOR METHOTREXATE THERAPY IN PATIENTS WITH RHEUMATOID ARTHRITIS

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    Elena Vasilyevna Chetina

    2013-01-01

    Full Text Available Objective. To assess the changes in clinical, immunological, X-ray indicators and expression of the mTOR (mammalian target of rapamycin genes, the key regulator of cell growth and proliferation; ULK1 (autophagy marker; р21 (cyclindependent kinase inhibitor; caspase 3 (indicator of apoptotic activity; MMP9 (matrix metalloproteinase 9 and cathepsin K, which participate in joint destruction, and proinflammatory cytokine TNFα (tumor necrosis factor α in blood of patients with rheumatoid arthritis (RA receiving methotrexate (MT therapy.Materials and Methods. Thirty-three RA patients (21 with positive and 12 with negative rheumatoid factor (RF, respectively; median age, 47.1 years and 28 healthy volunteers (median age, 45.1 years were examined. All patients have been receiving MT for 2 years. The clinical response was assessed according to the DAS28 score. ESR and the serum levels of anti-cyclic citrullinated peptide antibodies (ACPA, C-reactive protein (CRP, and RF were also determined. Degenerative changes in the joints were evaluated by X-ray examination. Gene expression was measured in peripheral blood cells using reverse transcriptase reaction and real-time polymerase chain reaction.Results. MT therapy considerably reduced the disease severity according to DAS28 score, as well as the number of swollen and painful joints both in seropositive (RF+ and seronegative (RF- RA patients. Ten patients reached remission by the end of the study. In (RF- RA patients, the absence of progression of joint destruction was accompanied by the absence of any significant changes in expression of MMP9 and cathepsin K, as well as a stronger suppression of TGFα (its expression became comparable to that in the control group. Patients who achieved remission showed a significant decrease in the expression level of the cathepsin K gene as compared to that at the start of the study. In (RF+ RA patients, MT therapy significantly reduced the clinical and

  8. Immunological effects of adalimumab in rheumatoid arthritis: Results of a Russian national study

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    Dmitri Evgenyevich Karateev

    2013-01-01

    Full Text Available A reduction in immunological parameters during therapy for rheumatoid arthritis (RA can yield new data on the mechanisms of anti-inflammatory action and be of great practical importance since this allows judgment of the depth of impact on the immunological process and therefore may be regarded as one of the components of improvement and remission. Objective: to study the effect of the tumor necrosis factor-a (TNF-а inhibitor adalimumab (ADA on a number of key immunological parameters in RA. Subjects and methods. The study included 100 patients (11 men and 89 women diagnosed with RA from 5 research centers. The patients were observed to have high RA activity: at baseline, DAS28 6.22+0.84 scores; C-reactive protein (CRP 37.1+34.7 mg/l. The mean number of disease-modifying antirheumatic drugs (DMARDs used by a patient in the history was 2.1. During 24-week treatment, the patients took ADA in a subcutaneous dose of 40 mg every 2 weeks both alone and in combination with DMARDs. The time course of changes in the serum levels of CRP, IGM rheumatoid factor (RF and in the concentration of anti-cyclic citrullinated peptide 2 (anti-CCP2 antibodies was determined by enzyme immunoassay (EIA using the Axis-Shield Diagnostics commercial kits (United Kingdom. The levels of TNF-a, interleukin (IL 6, 12, matrix metalloproteinase 3 (MMP3 were measured in pg/ml by EIA using the Bender MedSystems commercial kits (USA according to the manufacturer's directions. Results. During ADA therapy, there was a rapid reduction in the level of CRP from 34.3 to 11.317.2 mg/l following 2 weeks (p<0.001, which thereafter remained low (11.9 mg/l, with some fluctuations, until week 24 of the study. There was a significant reduction in blood RF levels from 169.24 to 111.97 at 24 weeks (p<0.001. After 12 weeks of ADA treatment, there was virtually a two-fold decrease in IL-6 content from 8.87 to 4.87 pg/ml and later on to 4.03 pg/ml at week 24 (p>0,05. The mean levels of anti-CCP2

  9. Baseline Serum Osteopontin Levels Predict the Clinical Effectiveness of Tocilizumab but Not Infliximab in Biologic-Naive Patients with Rheumatoid Arthritis: A Single-Center Prospective Study at 1 Year (the Keio First-Bio Cohort Study.

    Directory of Open Access Journals (Sweden)

    Keisuke Izumi

    Full Text Available To explore the baseline predictors of clinical effectiveness after tocilizumab or infliximab treatment in biologic-naïve rheumatoid arthritis patients.Consecutive biologic-naïve patients with rheumatoid arthritis initiating infliximab (n = 57 or tocilizumab (n = 70 treatment were included in our prospective cohort study. Our cohort started in February 2010, and the patients observed for at least 1 year as of April 2013 were analysed. We assessed baseline variables including patients' characteristics (age, sex, disease duration, prednisolone dose, methotrexate dose, other disease-modifying antirheumatic drug use, Clinical Disease Activity Index [CDAI] and serum biomarker levels (C-reactive protein, immunoglobulin M-rheumatoid factor, anti-cyclic citrullinated protein/peptide antibodies, interferon-γ, interleukin (IL-1β, IL-2, IL-6, IL-8, IL-10, IL-17, tumor necrosis factor-α, soluble intercellular adhesion molecule-1, bone alkaline phosphatase, osteonectin, osteopontin to extract factors associated with clinical remission (CDAI ≤ 2.8 at 1 year using univariate analyses, and the extracted factors were entered into a multivariate logistic regression model. Similar analyses were also performed for Simplified Disease Activity Index (SDAI remission (≤ 3.3 and Disease Activity Score with 28 joint counts, erythrocyte sedimentation rate (DAS28-ESR remission (< 2.6.There were no significant differences in the baseline characteristics except for methotrexate use between the groups. In the multivariate analyses, the low baseline osteopontin levels (OR 0.9145, 95% CI 0.8399-0.9857 were identified as predictors of CDAI remission in the tocilizumab group, whereas no predictors of CDAI remission were found in the infliximab group. Similar results were obtained when using SDAI and DAS28-ESR remission criteria.Baseline low serum osteopontin levels predict clinical remission 1 year after tocilizumab treatment and not infliximab treatment in biologic

  10. Reduced glutathione as a physiological co-activator in the activation of peptidylarginine deiminase

    DEFF Research Database (Denmark)

    Damgaard, Dres; Bjørn, Mads Emil; Steffensen, Maria A

    2016-01-01

    BACKGROUND: Citrullination catalysed by peptidylarginine deiminases (PADs) plays an important pathogenic role in anti-citrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA) and, possibly, several other inflammatory diseases. Non-physiological reducing agents such as dithiothreit...

  11. Extracellular Proteome and Citrullinome of the Oral Pathogen Porphyromonas gingivalis

    NARCIS (Netherlands)

    Stobernack, Tim; Glasner, Corinna; Junker, Sabryna; Gabarrini, Giorgio; de Smit, Menke; de Jong, Anne; Otto, Andreas; Becher, Doerte; van Winkelhoff, Arie Jan; van Dijl, Jan Maarten

    2016-01-01

    Porphyromonas gingivalis is an oral pathogen associated with the inflammatory disease periodontitis. Periodontitis and P. gingivalis have been associated with rheumatoid arthritis. One of the hallmarks of rheumatoid arthritis is the loss of tolerance against citrullinated proteins. Citrullination is

  12. 一种基于量子点检测抗CCP抗体的免疫荧光层析法%Development of an Immunochromatographic Test Strip for the Detection of Anti-CCP Antibody Based on Quantum Dots

    Institute of Scientific and Technical Information of China (English)

    郭利宁; 何红秋

    2013-01-01

    抗环瓜氨酸多肽(cyclic citrullinated peptide,CCP)抗体是类风湿关节炎(rheumatoid arthritis,RA)早期诊断的重要生物标志物.为了实现对RA的早期诊断,本研究建立了一种基于CdTe量子点标记技术检测抗CCP抗体的免疫荧光层析法.将CCP多肽与小牛血清白蛋白(bovine serum albumin,BSA)连接,再将CCP-BSA和羊抗鼠IgG分别在硝酸纤维素膜(nitrocellulose membrane,NC膜)上划线,作为检测线(test line,T线)和质控线(control line,C线).制备量子点并在量子点上标记鼠抗人IgG,喷在玻璃纤维上并烘干,最后组装大卡、切割并封装制成检测试纸条.应用该试纸条检测了RA患者及健康人血清临床样本200份,以酶联免疫吸附测定法(enzyme-linked immunosorbent assay,ELISA)为对照,计算免疫荧光层析法的检测灵敏度和特异性.结果显示,建立的量子点免疫荧光层析试纸条检测抗CCP抗体的灵敏度为97.5%,特异性为95.8%.该方法操作简单、快速,可实现床旁检测(point-of-care testing,POCT),能应用于RA的早期诊断.%Anti-cyclic citrullinated peptide antibody ( anti-CCP antibody) is an important biomarker for early detection of rheumatoid arthritis ( RA). For clinical diagnosis of RA in the early stage, an immunochromatographic test strip for anti-CCP antibody detection was developed based on quantum dots. First, CCP was linked to bovine serum albumin (BSA) ; and then, the CCP-BSA and goat anti-mouse IgG were dotted on the nitrocellulose membrane as test line ( T line) and control line ( C line) , respectively. Subsequently, quantum dots solution was prepared and conjugated to the mouse anti-human IgG antibody; further more, the marked quantum dots were sprayed to the glass fibers and dried. Last, all components of immunochromatographic test strip were assembled, cut and packaged. The test strip has been applied to the detection of 200 clinic serum samples from RA patients and healthy people, and the sensitivity

  13. Diagnostic value of combined detection of anti-CCP, anti-MCV antibodies and RF in rheumatoid arthritis%血清抗CCP抗体、抗MCV抗体与RF联合检测诊断类风湿关节炎的临床价值

    Institute of Scientific and Technical Information of China (English)

    许军华; 刘树业

    2013-01-01

    目的 探讨抗环瓜氨酸肽(CCP)抗体、抗突变型瓜氨酸波形蛋白(MCV)抗体和类风湿因子(RF)联合检测诊断类风湿关节炎(RA)的价值.方法 采用ELISA法检测101例RA患者(RA组)、55例非RA自身免疫性疾病患者(非RA组)和55例健康查体者(对照组)血清抗CCP抗体、抗MCV抗体和RF诊断RA水平,并进行比较.结果 RA组抗CCP抗体、抗MCV抗体和RF阳性率均显著高于非RA组和对照组(P均<0.01).RA组抗CCP抗体、抗MCV抗体和RF的敏感性分别为83.2%、70.3%和79.2%,特异性分别为93.6%、94.5%和75.4%.三项指标联合检测诊断RA的特异性达99.1%,敏感性降至67.3%.结论 抗CCP抗体、抗MCV抗体和RF联合检测可提高诊断RA的准确性.%Objective To investigate the clinical value of combined detection of anti-cyclic citrullinated peptide (antiCCP) antibodies,anti-mutated citrullinated vimentin (anti-MCV) antibodies and rheumatoid factor (RF) in rheumatoid arthritis (RA) diagnosis.Methods Anti-CCP,anti-MCV antibodies and RF were detected by ELISA in 101 RA patients(RA group),55 patients with other rheumatic diseases (non-RA group),and 55 healthy controls (control group).The differences of anti-CCP,anti-MCV antibodies and RF in the three groups were compared.Results The positive ratios of anti-CCP,anti-MCV antibodies and RF were significantly higher in the RA group than those in the non-RA group and control group (P < 0.01).In the RA group,the sensitivity of anti-CCP antibodies was 83.2% with 93.6% specificity,the sensitivity of anti-MCV antibodies was 70.3% and the specificity was 94.5%,the sensitivity of RF was 79.2% with 75.4% specificity.The specificity of combined detection of anti-CCP,anti-MCV antibodies and RF was increased to 99.1%,with a lower 67.3% sensitivity.Conclusions The combined detection of anti-CCP,anti-MCV antibodies and RF could improve the diagnostic accuracy of rheumatoid arthritis (RA).

  14. Impact of tocilizumab therapy on immunological parameters in patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Anastasia Sergeyevna Avdeyeva

    2012-01-01

    Full Text Available Objective: to evaluate the impact of tocilizumab (TCZ therapy on the level of acute-phase indicators, autoantibodies, and immunoglobulins (Ig G, M, and A after 2, 4, 8, 12, and 24 weeks as compared to the clinical efficacy of TCZ using DAS 28, SDAI, and CDAI scores and to reveal the immunological predictors of effective TCZ therapy. Subjects and methods. Forty-two patients with rheumatoid arthritis (RA who had received 6 TCZ infusions in an intravenous dose of 8 mg/kg at a 4-week interval during stable therapy with disease-modifying antirheumatic drugs (DMARDs and glucocorticosteroids were examined. Erythrocyte sedimentation rate (ESR was determined by the Westergren method; the levels of C-reactive protein (CRP, IgM rheumatoid factor (RF, IgG, IgM, and IgA were measured by a nephelometric method; the content of anti-cyclic citrullinated peptide (anti-CCP antibodies was estimated by an electrochemiluminescence technique. Results. In the respondents to TCZ therapy, the baseline Me values [25 th; 75 th percentiles] were 6.44 (5.87; 7.04 for DAS 28; 41.5 (32; 53 for SDAI; and 36.4 (19.2; 62.7 mg for CRP; 262.0 (95.3; 663.0 IU/l for IgM RF; 342.5 (106.9; 789.9 IU/ml for IgA RF; 366.8 (76.9; 500.0 for anti-CCP antibodies; 770.5 (190.7; 2393.1 IU/ml for anti-modified citrullinated vimentin (anti-MCV antibodies; 16.1 (12.9; 21.1 g/l for IgG; 2.07 (1.68; 2.63 g/l for IgM; 4.19 (3.38; 5.71 g/l for IgA. At week 2 of TCZ therapy, there was a reduction in the levels of CRP to 0.5 (0.3; 1 mg/l, IgM RF to 191.5 (45.6; 507.5 IU/ml, IgA RF to 225.8 (74.2; 547.4 IU/ml; at week 4, there were decreases in anti-MCV titers to 312.15 (81.2; 925.5 IU/ml, which remained until week 24 (p < 0.01. By week 24 of therapy, there were falls of IgG to 9.41 (8.14; 11.8 g/l, IgM to 1.12 (0.89; 1.94 g/l, IgA to 2.15 (1.73; 2.73 g/l (р < 0.01; however, their mean level as a whole remained to be in the normal range. The anti-MCV-positive patients with RA more frequently achieved a

  15. Diagnostic significance of detection of anti-citrullinated peptide antibodies in juvenile rheumatoid arthritis%抗瓜氨酸肽抗体谱在幼年类风湿关节炎诊断中的意义

    Institute of Scientific and Technical Information of China (English)

    茹晋丽; 李小峰; 张莉芸; 魏华; 胡学芳; 牛红青

    2007-01-01

    目的 探讨抗环瓜氨酸肽抗体(抗CCP抗体)、类风湿因子(RF)、抗核周因子(APF)、抗角蛋白抗体(AKA)对幼年类风湿关节炎(JRA)诊断的意义,并与类风湿关节炎(RA)进行比较.方法 分别采用酶联免疫吸附试验(ELISA)、胶乳凝集法、间接免疫荧光法检测54例JRA患者、31例非RA对照组、116例成人RA患者血清中的抗CCP抗体、RF、APF、AKA.结果 54例JRA患者抗CCP抗体、RF、APF、AKA的敏感性分别为61.1%、57.4%、37.0%、18.5%,特异性分别为96.8%、93.6%、96.8%、100%.抗CCP抗体与RF在JRA的敏感性差异无统计学意义,但明显高于APF、AKA;4种抗体在JRA的特异性比较差异无统计学意义.RA患者中4种抗体敏感性分别为82.3%、78.3%、48.7%、25.4%,特异性分别为95.7%、73.7%、91.6%、94.0%.4种抗体在JRA诊断中的敏感性均明显低于RA组,RF在JRA患者中特异性明显高于RA患者,而其他3种抗体的特异性在两组患者比较差异无统计学意义.结论 虽然抗CCP抗体谱在JRA诊断中的敏感性不及RA组,但对JRA的诊断仍具有较好的敏感性和特异性,可用于JRA的诊断.

  16. Studies of Arginine Deiminase Activity and Conversion of L-Citrulline%精氨酸脱亚胺酶活性以及瓜氨酸转化研究

    Institute of Scientific and Technical Information of China (English)

    任丽梅; 成志远; 李晓静; 吴会广; 袁国强

    2015-01-01

    目前,L-瓜氨酸的主要生产方法为化学法水解L-精氨酸.利用精氨酸脱亚胺酶可以直接转化L-精氨酸获得L-瓜氨酸,条件温和、效率高、环境友好,因而在工业化生产中具有很好的应用前景.本研究将优化后的单增李斯特菌(Listeriamonocytogenes)精氨酸脱亚胺酶(ADI)基因序列分别克隆到相应的载体pET-21a、pWB980及pAO815中,并分别转化大肠杆菌BL21(DE3)、枯草芽胞杆菌WB600及毕赤酵母GS115中构建表达菌株.发现大肠杆菌能高效表达ADI.经过5L发酵罐验证,发酵后酶活力单位可达200 000~270 000 U·L-1.经过验证,该酶可以很好地应用于L-瓜氨酸生产.在7 920~17 600 U· L-1的ADI存在条件下,5.5h内,可使95%的浓度为94~258 g·L-1的精氨酸转化为瓜氨酸.该方法具备良好的工业化应用前景.

  17. An important step towards completing the rheumatoid arthritis cycle

    OpenAIRE

    Venrooij, W.J.W. van; Pruijn, G.J.M.

    2008-01-01

    In the previous issue of Arthritis Research & Therapy data are presented showing that circulating immune complexes containing citrullinated fibrin(ogen) are present in anti-citrullinated protein antibody-positive rheumatoid arthritis patients, and that such immune complexes co-localize with complement factor C3 in the rheumatoid synovium. These results corroborate the idea that citrullination is intimately involved in the pathophysiology of rheumatoid arthritis and complete our model (the rhe...

  18. Clinical Features and Risk Factors in Patients with Rheumatoid Arthritis Combined with Interstitial Lung Disease%类风湿关节炎合并肺间质病变的临床特点及相关因素

    Institute of Scientific and Technical Information of China (English)

    姜帆; 刘荣清

    2012-01-01

    目的 分析类风湿关节炎合并肺间质病变(RA-ILD)患者的临床特点及相关因素.方法 回顾性分析2006年9月-2011年5月我院住院及门诊病人93例RA-ILD及93例未合并ILD的类风湿关节炎(RA)患者的一般情况、临床特点及类风湿因子(RF)、血沉(ESR)、C反应蛋白(CRP)、抗核抗体(ANA)及抗角蛋白抗体(AKA)、抗环瓜氨酸肽(CCP)抗体、抗SSA/SSB抗体、红细胞计数(RBC)、血红蛋白(HGB)、血小板计数(PLT)进行比较.结果 RA-ILD组患者呼吸系统症状多数以咳嗽为首发症状.RA-ILD组患者年龄、RF滴度、吸烟构成比均显著高于无ILD的RA组,有统计学意义(P均<0.05).RA-ILD组病程、性别、ESR、CRP、ANA、抗SSA/SSB抗体,以及服用甲氨蝶呤与无ILD的RA组比较差异无统计学意义(P均>0.05).经过后退法建立Logistic回归分析模型,多因素分析显示年龄(OR=1.093,95%CI 1.053~1.136,P<0.05),年龄每增大1岁,危险性增加0.093倍.结论 年龄增大是RA发生ILD的相关因素,高龄的RA患者应警惕ILD的发生.%Objective To analyze the clinical features and risk factors of rheumatoid arthritis combined with interstitial lung disease (RA - ILD). Methods 93 cases with RA - ILDand 93 cases with RA without ILD from September,2006 to May,2011 were retrospectively analyzed. General,Clinical,rheumatoid factor (RF) , erythrocyte sedimentation rate (ESR) ,C -reactive protein (CRP) ,antinuclear antibody (ANA) ,anti -keratin antibody (AKA) ,anti -cyclic citrullinated peptide antibody (CCP) ,anti - SSA/anti -SSB,red blood cell (ESR) ,hemoglobin (HGB) and platelets (PLT) were compared between two groups. Results First symptoms of RA - ILD patients was cough. The age, RF level, prevalences of smoking in RA - ILD group were significantly higher than those in control group (P 0.05). The Logistic regression model showed that onset age were significantly associated with pulmonary disease ( OR = 1. 093 ,95% CI 1. 053 ~ 1. 136 , P < 0. 05

  19. 肿瘤标志物在类风湿性关节炎伴间质性肺病中的临床意义%Clinical value of tumor markers in rheumatoid arthritis with interstitial lung diseases

    Institute of Scientific and Technical Information of China (English)

    夏俊波; 严秀娟; 任振义; 陈灏; 王娇莉

    2012-01-01

    目的 探讨肿瘤标志物在类风湿性关节炎伴间质性肺病(RA-ILD)中的临床意义.方法 收集2008年1月至2011年1月住院的82例类风湿关节炎患者.根据是否伴有间质性肺病,将其分为RA-ILD组(38例)和RA组(44例),比较两组血清肿瘤标志物癌胚抗原(CEA)、糖蛋白抗原15-3(CA15-3)、糖蛋白抗原19-9(CA19-9)水平、抗环瓜氨酸肽(CCP)抗体水平和肺功能包括用力肺活量(FVC)、第1秒用力呼气量(FEV1)、一氧化碳弥散量(DL)占预计值百分比,分析两组患者肿瘤标志物表达差异以及RA-ILD组肿瘤标志物与肺功能、抗CCP抗体相关性.结果 RA-ILD组外周血CEA、CA15-3、CA19-9水平均明显高于RA组(均P<0.01);RA-ILD组FVC、FEV1和DLco占预计值百分比均明显低于RA组(均P<0.01),但RA-ILD组抗CCP抗体水平与RA组比较差异无统计学意义(P >0.05).RA-ILD组CEA水平与FVC、FEV1和DLco呈负相关(r=-0.499、-0.576、-0.512,均P<0.01),但CEA、CA15-3和CA19-9均与抗CCP抗体无相关性(r=-0.192、-0.264、-0.268,均P >0.05).结论 肿瘤标志物CEA、CA15-3和CA19-9在RA-ILD中表达升高,CEA可能反应RA-ILD肺间质受损的严重程度,而不是关节损害的严重程度.%Objective To assess the clinical significance of tumor markers (TMs) in rheumatoid arthritis (RA) with interstitial lung diseases (ILD). Methods Eighty-two RA inpatients were admitted in Hangzhou First People's Hospital from January 2008 to January 2011; among whom 38 were complicated by interstitial lung diseases (RA-ILD). Tumor markers (CEA, CA15-3, CA19-9), pulmonary function indexes (FVC, FEVi, DLco) and anti-cyclic citrullinated peptide antibody (anti-CCP) levels were measured in all patients. Correlation between TMs and pulmonary function indexes, level of anti-CCP antibody was analyzed by Spearman rank correlation. Results Serum levels of CEA, CA15-3 and CA19-9 in RA-ILD group were significantly higher than those in RA group (P0.05). Serum CEA level was

  20. 异基因脐带间充质干细胞移植治疗类风湿关节炎疗效及安全性%Allogenic Derived Mesenchymal Stem Cells Transplantation for 4 Patients with Rheumatoid Arthritis

    Institute of Scientific and Technical Information of China (English)

    王秦; 李小峰; 马丽辉; 李军霞; 陈俊伟; 李芳; 薛丽巾; 白洁

    2011-01-01

    目的:探讨异基因脐带间充质干细胞(uhcMSC)移植治疗难治性类风湿关节炎(RA)的疗效及安全性.方法:从足月顺产供者脐带中分离培养MSC,给予3例RA患者行MSCs移植治疗,移植细胞数(1 x10(6)/kg体重).评价患者移植前后的临床表现和实验室检查指标的改变.结果:异基因MSC移植后,3例RA患者随访9-11个月,所有患者均无移植相关并发症.移植后1月疾病活动评分(DAS-28)由5.13降低为2.16(n=3),1例血液系统受累患者血细胞(中性粒细胞、红细胞、血小板)均上升.移植前后比较抗环瓜氨酸(CCP)抗体滴度降低.1例患者移植前后比较Th17细胞明显升高,Treg细胞降低.结论:异基因脐带MSC移植治疗难治性RA有效、安全.uhcMSC取材方便,扩增迅速,输注安全经济.%Objective To explore the clinical efficacy and safety of allogenic derived mesenchymal stem cells transplantation (MSCT) in patients with refractory rheumatoid arthritis (RA). Methods Three patients with refractory RA ( all were female patients) aged 43 - 47 were enrolled in the study and the Ethics Committee of the Affiliated The Shanxi Medical University approved informed consent was obtained for each patient The umbilical cord of healthy donors were aspirated and the mesenchymal stem cells ( MSC) were expanded in vitro. MSC 1 X 106/kg body weight was infused intra-venously for each patient Before MSCT, all patients were administrated with cyclophosphamide ( CTX) 400 - 600 mg. The clinical manifestations and laboratory tests were compared before and after MSCT. Results The three patients were followed up for nine to eleven months after MSCT. No patient had developed transplantation related complications. The rheumatoid arthritis disease activity scord ( DAS-28 ) score decreased from 5. 13 to 2. 16 one month after MSCT (n =3). Erythrocyte sedimentation rate (ESR) decreased significantly one month after MSCT (n =3). Three patients were followed up for nine months, anti-cyclic

  1. Effect of glucocorticoids on the expression of BTLA in rheumatoid arthritis patients%糖皮质激素对类风湿关节炎患者血清中B、T淋巴细胞弱化因子表达的影响

    Institute of Scientific and Technical Information of China (English)

    邱群芳; 罗裕旋; 魏建伟

    2011-01-01

    Objective To investigate the BTLA in the serum level of patients with rheumatoid arthritis in the pathogenesis of the role and regulation of glucocorticoids.Methods ELISA was used to detect the serum levels of BTLA.Western blotting with anti-nuclear antibody ( ANA) spectroscopy, enzyme-linked immunosorbent assay (ELISA) detection of anti-cyclic citrullinated peptide (CCP)antibodies,detected by turbidimetry of rheumatoid factor(RF).Results In the control group, effective cases in 9 cases, 11 cases ineffective;effective cases in the observation group of 15 patients,12 cases ineffective.The clinical observation of 75% of the total effective rate was higher than 53%(P<0.05).The control group before treatment serum BTLA(89 ± 13) μg/L, after treatment, slightly elevated serum BTLA(110± ll)μg/L(P<0.05) ;the observation group before treatment serum BTLA(78 ± 11)μg/ L,the serum of BTLA(140±13)μg/L significantly increased.Conclusion BTLA in rheumatoid arthritis patients with lower levels of serum,glucocorticoids can upregulate the expression,BTLA increase of the disease can affect the outcome of rheumatoid arthritis, can be used as a new therapeutic target.%目的 探讨B、T淋巴细胞弱化因子(BTLA)在类风湿关节炎患者血清中的水平及其在发病机制中的作用和糖皮质激素对其表达的调节.方法 酶联免疫吸附试验(ELISA)法检测患者血清中BTLA的水平.采用免疫印迹法检测抗核抗体(ANA)谱,ELISA法检测抗环瓜氨酸肽(CCP)抗体,免疫比浊法检测类风湿因子(RF).结果 对照组治疗有效例数为9例,无效为11例;观察组有效例数为15例,无效为12例.观察组临床治疗总有效率(75%)明显高于对照组(53%),差异有统计学意义(P<0.05).对照组治疗前血清中BTLA为(89±13)μg/L,治疗后为稍微升高,为(110±11)μg/L,差异有统计学意义(P<0.05);而观察组治疗前血清中BTLA为(78±11)μg/L,治疗后为(140±13)μg/L,明显升高.结论 BTLA在类风湿关

  2. SUBCLINICAL INTERSTITIAL PULMONARY INJURY IN RHEUMATOID ARTHRITIS

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    D. V. Bestaev

    2015-01-01

    Full Text Available Subjects and methods. The study enrolled 61 inpatients diagnosed with RA (according to the 1987 American College of Rheumatology criteria who were treated at the V.A. Nasonova Research Institute of Rheumatology; in so doing, high-resolution computed tomography revealed lung changes as a ground glass pattern in 15 patients, reticular striation, traction bronchoectases, and lung tissue changes as honeycomb ones in 25 patients; no lung abnormalities were found in 21 patients. DAS28 was applied to determine the inflammatory activity of RA. The RA patients underwent X-ray studies of the hand, foot, and chest, by using accordingly X-Ray unit and spiral computed tomography scanner (section thickness, 0.65 mm. External respiration function (ERF indicators were studied with plethysmograph. IgM rheumatoid factor was measured using an immune nephelometer. Serum anti-cyclic citrullinated peptide antibodies were assayed by immunochemiluminescence technique on a Cobas e411 analyzer. The xMAP technology using a BioPlex200 analyzer was employed to determine the serum concentrations of 27 cytokines in 15 patients with subclinical IPI and in 25 with clinical IPI. Results and discussion. The major respiratory signs in patients with IPI proved to be cough (24 %, expectoration (20 %, dyspnea (16 %, and crepitation (64 % on auscultation. Three patients with subclinical IPI were found to have crepitation on auscultation. Respiratory symptoms were absent in the RA patients without IPI. It should be noted that there are a larger number of RA patients with a high smoking index among the RA patients with IPI than among those without IPI (p < 0.05. Investigation of ERF indicators revealed a statistically significantly lower lung diffusing capacity (LDC in the RA patients with subclinical IPI than in those without IPI (p < 0.05. Other ERF indicators showed no significant deviations of the reference values. LDC and total lung capacity appeared to be statistically

  3. 类风湿关节炎患者血纤维蛋白原免疫复合物的检测和意义%Significance of Detecting the Immune Complexes Contain Fibrinogen in Patients with Rheumatoid Arthritis

    Institute of Scientific and Technical Information of China (English)

    王艾丽; 吉滢; 郑田; 严孝岭; 刘国瑞; 贾煊

    2012-01-01

    Objective To explore the diagnostic value and significance of immune complexes contain fibrinogen(Fb-IC) in patients with rheumatoid arthritis (RA). Methods Fb-ICs were determined by ELISA using anti-human Fb antibody,the serum sample of 126 patients with RA,75 patients with non-RA diseases (lung cancer,systemic lupus erythematosus,undiffer-entiated connective tissue disease and kidney disease) and 34 healthy controls were involved in this study. The consistency of results was compared with that of Clq binding ELISA assay. The correlation of Fb-ICs to anti-cyclic citrullinated pepdide (CCP) and rheumatoid factor (RF) were analysed. Results The Fb-ICs positive rates of RA group,non-RA disease group and healthy control group were 53. 17% (67/126) ,10. 67% (8/75) and 5. 88% (2/34) respectively. The positive rate of RA group was significantly higher than other two groups (X2 = 36. 31 and 22. 16, P<0. 001). The sensitivity of Fb-ICs was 53. 17% with high specificity ( 90. 00%) in RA. The coincidence for both ELISA methods of anti- Fb and Clq was 75%,the results were related (Kappa values>0. 4). There was 55. 3% and 62. 2% Fb-ICs-positive patients with anti-CCP and RF-positive respectively. Conclusion Fb-ICs presents a reasonable sensitivity with high specificity to RA and it is valuable to RA diagnosis. More than 50% of anti-CCP antibodies and RF-positive RA patients existed Fb-ICs and it may be the pathogenic mechanism of RA and conduce to diagnostic value for RA.%目的 检测类风湿关节炎(RA)患者血清中含纤维蛋白原免疫复合物(Fb-IC),探讨Fb-IC在RA中的意义.方法 用抗Fb抗体建立ELISA法检测126例RA,75例其他疾病包括肺癌、系统性红斑狼疮(SLE)、未分化结缔组织病(UCTD)、肾脏疾病患者血清中Fb-ICs,另设健康对照34例.将该法结果与C1q结合法检测ICs的结果进行比较.分析RA患者Fb-IC与抗环瓜氨酸肽(CCP)抗体、类风湿因子( RF)的关系.结果 RA组、非RA疾病组和对

  4. Efficiency and safety of leflunomide in rheumatoid arthritis: Results of a Russian observational multicenter of trial

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    R. M. Balabanova

    2015-01-01

    Full Text Available Methotrexate or leflunomide is used as a first-line synthetic disease-modifying anti-rheumatic drug in the therapy of rheumatoid arthritis (RA. In 2011, the Russian Federation registered and since it has been successfully using leflunomide**.Objective: to evaluate the efficacy and tolerability of leflunomide** used to treat RA in routine clinical practice.Subjects and methods.The investigation enrolled patients with varying duration of RA that met the 1987 classification criteria. The patients were followed up in 33 healthcare facilities of Russia from March 2013 to October 2014. A total of 235 patients were randomized; the data of 196 patients were statistically processed. The mean age of the patients was 52.4±11.8 years; the mean duration of the disease was 75.4±69.1 months. The disease activity estimated by DAS28 and CDAI were 5.5±1.2 and 35.1±14.3 scores, respectively. 105 and 57 patients had X-ray Stages II and III disease, respectively. 80.1% of the patients were positive for rheumatoid factor and anti-cyclic citrullinated peptide antibodies. According to the instruction of its use, leflunomide was administered in a dose of 100 mg/day during the first 3 days and then in that of 20 mg/day. When adverse reactions (ARs occurred, it was recommended that the daily dose of the drug was decreased to 10 mg. The patients were examined before and 1, 3, and 6 months after treatment. The investigators measured the number of tender joints (NTJ and that of swollen joints (NSJ, and visual analog scale (VAS pain intensity, performed a laboratory examination involving clinical blood test, erythrocyte sedimentation rate (ESR, and C-reactive protein (CRP, in patients during their visits to physicians. The disease activity was assessed with DAS28 and CDAI and ARs were recorded.Results. Six-month therapy reduced the mean NSJ from 10.9 to 7.5%, NTJ from 12.3 to 8.9, VAS pain intensity from 64.1 to 39.3 mm, on average, ESR from 37.04 to 23.6 mm/hr, and

  5. 抗CCP、RF、CRP、ASO对类风湿关节炎的诊断意义%The significance of serum anti - CCP antibody, RF, CRP, ASO in the diagnosis of rheumatoid arthritis.

    Institute of Scientific and Technical Information of China (English)

    刘发河; 曾海莲; 郑小江; 杨春媚

    2011-01-01

    Objective To investigate the significance of serum anti - cyclic citrullinated peptide ( CCP ) antibody, C - reactive protein ( CRP ), antistreptolysin O ( ASO ) and rheumatoid factor ( RF ) in the diagnosis of rheumatoid arthritis ( RA ).Methods CCP was detected in serum samples from 115 patients with RA by ELISA and compared with serum samples from 131 cases of undifferentiated inflammatory arthritis ( UIA ) patients.CRP, ASO and RF were detected by immunoturbidimetry method.Results In RA , the positive rates of anti - CCP, CRP and RF were higher than UIA.The sensitivities of anti - CCP, CRP and RF for RA were 65.2% , 70.0% and 60.9% , respectively.The specificities of anti - CCP, RF and CRP for RA were 93.9%, 80.3% and 58.0%, respectively.Statistical test indicated that there were no significant differences in sensitivities of anti - CCP, CRP and RF, but the specificity of CCP was higher than those of RF and CRP for the diagnosis of RA.The positive rate of ASO in RA was only 12.5% and no significant difference in the positive rate of ASO between RA and UIA was found.Conclusion The anti - CCP assay has high sensitivity and specificity for the diagnosis of RA and the combined detection of anti - CCP, CRP and RF may further improve the sensitivity.ASO has no significance for the diagnosis of RA, but it can be an indication of streptococcal infection in RA patients.%目的 探讨抗环瓜氨酸肽(CCP)抗体、类风湿因子(RF)、C反应蛋白(CRP)、抗链球菌溶血素"O"(ASO)对类风湿关节炎(RA)的诊断意义.方法 收集115例RA患者和131例非RA的自身免疫病患者的血清,用酶联免疫吸附试验检测抗-CCP抗体,免疫比浊法检测RF、CRP、ASO.结果 抗CCP、RF、CRP的阳性率在RA组显著高于非RA组,抗-CCP对RA的敏感性为65.2%,CRP对RA的敏感性70.0%,RF的敏感性较抗-CCP和CRP稍低,为60.9%.特异性以抗CCP为最高93.9%,RF对RA的特异性为80.3%,CRP较低为58.0%,经统计学检验,抗CCP的灵

  6. Application of combined detection of anti-CCP, RF, and AKA in the diagnosis of rheumatoid arthritis%抗CCP抗体、抗角蛋白抗体及类风湿因子联合检测在类风湿关节炎诊断中的应用

    Institute of Scientific and Technical Information of China (English)

    张园; 张吟眉; 崔丽艳; 杨硕; 张捷

    2014-01-01

    目的 评价抗环瓜氨酸多肽抗体(anti-CCP)、类风湿因子(RF)、抗角蛋白抗体(AKA)的单一及联合检测在类风湿关节炎(RA)诊断中的应用价值.方法 前瞻性研究.随机表法选取2011年1月至2013年9月于北京大学第三医院就诊的门诊及住院的137例RA患者,265例非RA的自身免疫患者,111名健康人,检测血清中AKA、anti-CCP抗体及RF的水平.其中AKA测定采用间接免疫荧光法;RF测定采用速率散射比浊法;anti-CCP测定采用电化学发光法.检测方案分为单项目、双项目、三项目检测,一共18种方案.检测结果组间比较采用四格表卡方(x2)检验.结果 Anti-CCP检测的准确度(80.39%),YI(0.51),和κ值(0.55)在单项目检测方案中均最高.方案antiCCP+ (AKA/RF),AKA/(anti-CCP+ RF),和(AKA+ RF)/(anti-CCP+ RF)/(AKA+ anti-CCP)的准确度(80.94,80.94,80.66),YI(0.51,0.51,0.50),和κ值(0.55,0.56,0.54)在联合检测方案中最高.结论 Anti-CCP检测在辅助RA诊断中具有突出的价值.联合检测方案anti-CCP+(AKA/RF)、AKA/(anti-CCP+ RF)、与(AKA+ RF)/(anti-CCP+ RF)/(AKA+ anti-CCP)对于RA的诊断最有价值.%Objective To investigate the application of combined detection of three serum markers,anti-cyclic citrullinated peptide antibody (anti-CCP),rheumatoid factor (RF),anti-keratin antibodies (AKA),for the diagnosis of rheumatoid arthritis.Methods This was a prospective study.Serum samples were randomly obtained from 137 RA patients,265 other autoinmmune diease patients,and 111 normal controls.All of the volunteers were outpatients or inpatients of Peking University Third Hospital from January 2011 to September 2013.Levels of AKA,anti-CCP antibody,RF were measured by indirect immunofluorescence,chemiluminescence,and immune turbidimetry,respectively.The values of 3 serum biomarkers and their varied combinations for RA diagnosis were systemically assessed.The results were compared using fourfold table chi-square (x2) test.Results When using one

  7. Perfil dos pacientes com manifestações extra-articulares de artrite reumatoide de um serviço ambulatorial em Curitiba, Sul do Brasil Epidemiological profile of patients with extra-articular manifestations of rheumatoid arthritis from the city of Curitiba, South of Brazil

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    Mariana Costa Moura

    2012-10-01

    t and chi-square tests, and a significance level of 5% (α= 0.05. RESULTS: During the course of the disease, 120 patients (45.8% had ExRA. Pulmonary manifestation, rheumatoid nodules and Sjögren's syndrome were the most common manifestations found. Rheumatoid factor and anti-cyclic citrullinated peptide antibody were positive in most patients tested. Most patients were classified as Steinbrocker functional classes 1 and 2. The mean DAS-28 was 3.629, and the mean HAQ score, 1.12. Patients with ExRA had longer disease duration (P < 0.05, and current smoking habit associated with the presence of ExRA (P < 0.05. CONCLUSIONS: The prevalence of ExRA during disease course was 45.8%, and current smoking habit correlated with the presence of ExRA.

  8. The role of combined application of RF,AKA,anti-CCP antibody and CRP in diagnosing rheumatoid arthritis%联合检测 RF、AKA、抗 CCP 抗体和 CRP 对 RA 的诊断价值

    Institute of Scientific and Technical Information of China (English)

    王波; 牛莉莉; 常波

    2016-01-01

    Objective To explore the clinical value of combination detection of rheumatoid factor(RF),anti-cyclic citrullinated peptide antibody (CCP),anti-keratin antibody(AKA)and c-reactive protein (CRP)in the diagnosing rheu-matoid arthritis(RA).Methods The serum samples of 68 RA patients and 42 other autoimmune diseases patients were collected.Anti-CCP antibody was detected by chemiluminescent microparticle immunoassay(CMIA).AKA was meas-ured by indirect immunofluorescence.Both RF and CRP were detected by Immune turbidimetry (ITM).Then analyze the results.Results In RA group,positive rate of RF,Anti-CCP antibody,AKA,CRP was obviously higher than those of other autoimmune diseases patients(P <0.01 or P <0.05),the difference between both groups was statistically sig-nificant.Single diagnostic sensitivity of RA from high to low ranking is CRP Anti-CCP antibody RF AKA.The diagnos-tic specificity of RA from high to low ranking is AKA Anti-CCP antibody RF CRP.Four series of joint detection im-proves the sensitivity (91.2%)of RA diagnosis,parallel combined detection can improve the specificity and even reached 100%.Conclusion The RF,AKA,Anti-CCP antibody and CRP detection alone RA has good sensitivity and specificity,but a separate application index easily missed diagnosis or misdiagnosis.Combined detection of four indexes may offer clinical benefits for diagnosis of RA and can significantly improve the specificity and sensitivity to diagnose RA.%目的:探讨联合检测类风湿因子(RF)、抗角蛋白抗体(AKA)、抗环瓜氨酸多肽(CCP)抗体和 C 反应蛋白(CRP)在类风湿性关节炎(RA)诊断中的价值。方法收集68例 RA 病人和42例非 RA 的自身免疫病病人血清,化学发光微粒子免疫法测抗 CCP 抗体,间接免疫荧光法检测 AKA,免疫比浊法测 RF 和 CRP,然后对检测结果进行计算分析。结果RA 组 RF、AKA、抗 CCP 抗体和 CRP 的阳性率均明显高于非 RA 组,且差

  9. Early rheumatoid arthritis in Italy: study of incidence based on a two-level strategy in a sub-area of Florence (Scandicci-Le Signe).

    Science.gov (United States)

    Benucci, Maurizio; Cammelli, Emanuela; Manfredi, Mariangela; Saviola, Gianantonio; Baiardi, Paola; Mannoni, Alessandro

    2008-06-01

    The concept of Early Arthritis represents a new diagnostic-therapeutic strategy in modern rheumatology. Even if many Early Arthritis clinics are starting up, we do not yet know the frequency of this pathology in the Italian population. With the collaboration of 20 general practictioners (GPs) operating in the municipalities of Scandicci, Lastra a Signa and Signa, we assessed the incidence of rheumatoid arthritis and of new cases of Early Rheumatoid Arthritis (ERA) in the period from 1.09.2005 to 31.08.2006. The general population over 18 years old in the three municipalities according to the political electoral lists in April 2006 was as follows: Scandicci 42,474 (Males 20,290; Females 22,184), Lastra a Signa 15,368 (M 7,458; F 7,910) and Signa 13,372 (M 6,439; F 6,933). The total number of patients followed by the 20 GPs was 32,521 according to the records of ASL10 Florence. In one year 920 patients were referred by their GPs to a rheumatologist with suspected early undifferentiated arthritis according to Emery's criteria. The patients underwent a rheumatological examination and the rheumatoid factor IgM, hidden rheumatoid factors (IgG and IgA) and IgG antibodies anti-CCP (anti-cyclic citrullinate peptides) with a semiquantitative immuno-enzymatic test ELISA were investigated. In one year we observed 32 new cases of Rheumatoid Arthritis, of which 8 were males and 24 were females. The rate of incidence with respective intervals of confidence of 95% was 0.98 per thousand (0.64-1.32 per thousand). The average age was 47.7 +/- 10.5 in the females and 54.9 +/- 10.3 in the males. The patients had an average history of illness in months of 5.2 +/- 1.3 F versus 4.6 +/- 1.1 M, number of tender joints 6.2 +/- 2.3 F versus 5.3 +/- 2.2 M, number of swollen joints 4.8 +/- 1.4 F versus 4.2 +/- 1.5 M, a global assessment of 64.3 +/- 10 F versus 53 +/- 12 M, ESR (mm/h) 49.2 +/- 11.3 F versus 43.3 +/- 12.5 M, CRP (mg/dl) 2.8 +/- 1.3 F versus 2.3 +/- 1.4 M, DAS28 5.55 +/- 1.2 F

  10. 抗角蛋白抗体与抗环瓜氨酸肽抗体在早期类风湿关节炎诊断中的意义比较

    Institute of Scientific and Technical Information of China (English)

    王丽; 邱敏

    2013-01-01

      目的比较抗角蛋白(antikeratin antibody,AKA)抗体与抗环瓜氨酸肽(cyclic citrullinated peptides, CCP)抗体在早期类风湿关节炎诊断中的意义。方法对40例类风湿关节炎(rheumatoid arthritis,RA)患者、40例非RA患者和40例健康人采用酶联免疫吸附法(ELISA)检测抗CCP抗体,用免疫比浊法检测类风湿因子(rheumatoid factor,RF),用间接免疫荧光法检测抗AKA抗体,并作比较。结果 RA患者抗CCP抗体、抗AKA抗体、RF阳性率分别为82.5%、67.5%、90%,敏感性分别为82.5%、67.5%、90%,特异性分别为97.2%、95%、80%;非RA患者抗CCP抗体、AKA、RF的阳性率为分别2.5%、5%、32.5%;正常对照组1例抗CCP抗体弱阳性,2例AKA低滴度阳性。结论抗CCP抗体及AKA均为早期类风湿关节炎特异性诊断指标,但抗CCP抗体敏感性及特异性高于AKA,联合检测抗CCP抗体、AKA、RF有利于RA的早期诊断。%  Objective To explore the significance of anti-kerantin antibody(AKA)and anti-cyclic citrulinated peptides in the diagnosing rheumatoid arthritis. Methods All together 40 pateins with RA ,40 pateins without RA and 40 normal controls were employed in the study. The levels of Anti-CCP and rheumatoid factors(RF)and AKA were measured by ELISA methods and indirect immune fluorescence methods,respectively. Resluts In these 40 RA pateins,the diagnosing positive rates of anti-CCP,AKA and RF were 82.5%,67.5%and 90%,respectively. The sensitiveity of anti-CCP,AKA and RF were 82.5%,67.5%and 90%,respectively. The specificity were 97.2%,95%and 80%,respectively. Whereever,the diagnosing positive rates of anti-CCP,AKA and RF in these 40 pateins without RA were 2.5%,5%and 32.5%,respectively. However, there were 1 cases showing weak positive for anti-CCP and 2 case showing weak positive of AKA. Conclusion The anti-CCP and AKA are perfect index in diagnosing rheumatoid arthritis in early periods,though the sensitivity

  11. THE FIRST RUSSIAN STRATEGIC STUDY OF PHARMACOTHERAPY FOR RHEUMATOID ARTHRITIS (REMARCA TRIAL: RESULTS OF 12-MONTH TREATMENT IN 130 PATIENTS

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    D. E. Karateev

    2014-01-01

    Full Text Available To introduce treat-to-target recommendations is an important task of modern rheumatology; however, there is still a diversity of serious problems relating to a scientific rationale and a clinical one for this strategy and to the possibilities of its implementation in real clinical practice, in the rheumatology service of the Russian Federation in particular, by taking into account the specific features of funding for high-tech medical care.Objective: to determine the efficiency and safety of combined therapy with subcutaneous methotrexate (MT and biological agents (BA when using the treat-to-target strategy in patients with active early and extended-stage rheumatoid arthritis (RA who have risk factors for a poor prognosis.Subjects and methods.The results of the REMARCA (Russian InvEstigation of MethotrexAte and biologicals in eaRly aCtive inflammatory Arthritis trial of 130 patients followed up for 12 months or more were given. There was a female preponderance; mean age 48.9±13.9 years, rheumatoid factor positivity (86.9%; anti-cyclic citrullinated peptide antibody positivity (89.2%. Seventy patients formed a subgroup of early RA (disease duration ≤6 months (mean 4.17±1.39 months; 60 patients were a subgroup of advanced-stage RA (disease duration >6 months (mean 30.8±32.7 months. In all the patients, therapy was initiated by using subcutaneous MT with its rapid dose escalation up to 20–30 mg/week and the achievement of the treatment goal (low disease activity or remission was checked every 3 months and depending on the result a decision had been taken to add or not to add a biological agent (BA (a tumor necrosis factor inhibitor or abatacept. If the former was insufficiently effective, it was substituted for a BA from another class.Results. Subcutaneous MT monotherapy provided remission or low disease activity in 49 (37.7% patients; a BA was given to 81 (62.3% patients. Following 6 and 12 months, low activity or remission

  12. CHANGES OF CYTOKINE LEVELS DURING THERAPY WITH METHOTREXATE AND ADALIMUMAB IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS (REMARCA STUDY

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    A. S. Avdeeva

    2014-01-01

    Full Text Available Objective: to estimate changes in cytokine profile versus disease activity in patients with early rheumatoid arthritis (RA who use methotrexate (MTX and adalimumab (ADA in accordance with the treat-to-target concept. Subjects and methods. Forty-five patients (35 women; median age 53.5 [46; 59.5] years with early RA (median dura- tion 7.0 [4.0; 11.5] months; DAS28 5.8 [4.9; 6.4]; rheumatoid factor positivity (RF+ 91%; anti-cyclic citrullinated peptide antibody positivity (ACCP + 96% were examined. In all the patients, MTX as the first agent was subcuta- neously used in a dose of 10 mg/week with its rapid escalation up to 20-25 mg/week. Serum cytokine concentrations were determined using the xMAP multiplexing technology before and 12 and 24 weeks after therapy. Results. Following 12 weeks of therapy, DAS28 mean value decreased to 4.33 [3.5; 5.2] (p < 0.05 vs baseline. Twenty- nine (64.4% patients responded to treatment. It was decided to continue MTX monotherapy in 23 patients (a monotherapy group and in 22 patients ADA was added to therapy due to its inadequate effect in accordance with the standard regimen (a combined therapy group. At 24 weeks, mean DAS28 was 2.9 [2.1; 3.6] and 19 (82.6% patients responded to treatment in the monotherapy group. In the combined therapy group, DAS28 was 3.4 [3.2; 4.4]; nearly 30% of the patients achieved remission/low disease activity and the number of patients with the high activity of a pathological process also declined significantly (from 59.1 to 13.6%. At 12 weeks, the monotherapy group showed reduction of the level of proinflammatory (interleukin-6 (IL-6, IL-17, tumor necrosis factor-α (TNF-α, anti-inflammatory (IL-4, IL-5, IL-9, IL-13 cytokines, chemokines (interferon induced protein-10 (IP-10, and vascular endothelial growth factors (VEGF (p<0.05; at 24 weeks, there were reductions in IL-6, IL-9, and IL-10, and transforming GF-bb and an increase in IL-10 concentration (p<0.05. At 12 weeks of MTX therapy

  13. ASSOCIATION BETWEEN CLINICAL MANIFESTATIONS AND ULTRASONIC SIGNS OF INFLAMMATION IN PATIENTS WITH RHEUMATOID ARTHRITIS

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    O. G. Alekseeva

    2015-01-01

    Full Text Available Rheumatoid arthritis (RA is a systemic autoimmune rheumatic disease characterized by chronic inflammation of the synovial membrane and a wide range of extra-articular (systemic manifestations. The main goal of RA therapy is to achieve low disease activity or clinical remission. Power Doppler (PD ultrasonography (USG can significantly distinguish between active synovitis (hypervascularization of the synovial membrane and inactive synovial proliferation.Objective: to investigate the association between the ultrasonic signs of active inflammation and the clinical and laboratory parameters of disease activity in patients with RA.Subjects and methods. The investigation included RA patients followed up at the V.A. Nasonova Research Institute of Rheumatology within the first Russian strategic study of pharmacotherapy for RA – REMARCA (Russian invEstigation of MethotrexAte and biologicals for eaRly aCtive Arthritis. A total of 105 RA patients (mean age 51 years, among whom 80% were rheumatoid factor (RF-positive and 75% were anti-cyclic citrullinated peptide (ACCP-positive, were examined. In all the patients, methotrexate (metoject, MEDAC, Germany as the first diseasemodifying anti-rheumatic drug was subcutaneously injected in an initial dose of 10 mg/week with its rapid escalation up to 20–25 mg/week. Then the therapy was added by biologicals as the need arose. The clinical and laboratory parameters were analyzed immediately before and then 12, 24, 36, and 48 weeks following treatment. Therapeutic efficacy was evaluated using the European League Against Rheumatism (EULAR criteria and activity indices (DAS28, CDAI, and SDAI. USG of eight articular areas (the wrist, second and third metacarpophalangeal, second and third proximal interphalangeal, second and fifth metatarsophalangeal articulations in the hand and foot of the clinically dominant side was carried out in all the patients prior to treatment and at 12, 24, 36, and 48 weeks

  14. THE FIRST RUSSIAN STRATEGIC STUDY OF PHARMACOTHERAPY FOR RHEUMATOID ARTHRITIS (REMARCA TRIAL: RESULTS OF 12-MONTH TREATMENT IN 130 PATIENTS

    Directory of Open Access Journals (Sweden)

    D. E. Karatee

    2016-01-01

    Full Text Available To introduce treat-to-target recommendations is an important task of modern rheumatology; however, there is still a diversity of serious problems relating to a scientific rationale and a clinical one for this strategy and to the possibilitiesof its implementation in real clinical practice, in the rheumatology service of the Russian Federation in particular, by taking into account the specific features of funding for high-tech medical care.Objective: to determine the efficiency and safety of combined therapy with subcutaneous methotrexate (MT and biological agents (BA when using the treat-to-target strategy in patients with active early and extended-stage rheumatoid arthritis (RA who have risk factors for a poor prognosis.Subjects and methods. The results of the REMARCA (Russian InvEstigation of MethotrexAte and biologicals in eaRly aCtive inflammatory Arthritis trial of 130 patients followed up for 12 months or more were given. There was a female preponderance; mean age 48.9±13.9 years, rheumatoid factor positivity (86.9%; anti-cyclic citrullinated peptide anti body positivity (89.2%. Seventy patients formed a subgroup of early RA (disease duration ≤6 months (mean 4.17±1.39 months; 60 patients were a subgroup of advanced-stage RA (disease duration >6 months (mean 30.8±32.7 months. In all the patients, therapy was initiated by using subcutaneous MT with its rapid dose escalation up to 20–30 mg/week and the achievement of the treatment goal (low disease activity or remission was checked every 3 months and depending on the result a decision had been taken to add or not to add a biological agent (BA (a tumor necrosis factor inhibitor or abatacept. If the former was insufficientlyeffective, it was substituted for a BA from another class.Results. Subcutaneous MT monotherapy provided remission or low disease activity in 49 (37.7% patients; a BA was given to 81 (62.3% patients. Following 6 and 12 months, low activity or remission according to

  15. Use of tofacitinib in real clinical practice to treat patients with rheumatoid arthritis resistant to synthetic and biological disease-modifying antirheumatic drugs: Results of a multicenter observational study

    Directory of Open Access Journals (Sweden)

    D. E. Karateev

    2016-01-01

    Full Text Available Tofacitinib (TOFA, a member of a new class of targeted synthetic disease-modifying antirheumatic drugs (DMARDs, is a promising medication for the treatment of rheumatoid arthritis (RA and other immunoinflammatory diseases. The paper describes the Russian experi-ence with TOFA used to treat severe RA.Patients and methods. 101 RA patients (18 men and 83 women; mean age, 51.03±11.28 years; mean disease duration, 105.4±81.43 months who were positive for rheumatoid factor (89.1% and anti-cyclic citrullinated peptide antibodies (74.7% and resistant to therapy with synthetic DMARDs (sDMARDs (80.2% and biological agents (19.8% were given TOFA at a dose of 5 mg twice daily, which could be doubled if necessary. TOFA was used alone (n=9 or in combination with methotrexate (MT (n=75 or other sDMARDs (n=17. The achievement of low disease activity (LDA and clinical remission at 3 and 6 months of treatment by DAS28-ESR SDAI, and CDAI scores, and the indices of safety and tolerability were assessed.Results. A total of 93 (92.1% of the 101 patients completed a 24-week period of the investigation. 8 (7.9% patients prematurely discontinued TOFA after an average of 2.75±0.71 months. At the end of the study, the patients achieved the primary endpoint (LDA including remission in terms of DAS28-ESR ≤3.2 (34.7%, SDAI ≤11 (47.5%, and CDAI ≤10 (48.5% and the secondary endpoints (clinical remission in terms of DAS28-ESR ≤2.6 (17.8%, SDAI ≤3.3 (8.9%, and CDAI ≤2.8 (6.9%. When TOFA was combined with MT, the discontinuation rate for the former was significantly lower (2.7% than when TOFA was used in combination with other sDMARDs (29.4% or alone (11.1%; p<0.01. At 3 and 6 months of follow-up, LDA was achieved more frequently when TOFA was combined with MT than when other treatment regimens were used. Fatal outcomes and serious adverse events (AEs, as AEs previously undescribed in the literature, were not seen during a follow-up within

  16. THE FIRST RUSSIAN STRATEGIC STUDY OF PHARMACOTHERAPY FOR RHEUMATOID ARTHRITIS (REMARCA TRIAL: RESULTS OF 12-MONTH TREATMENT IN 130 PATIENTS

    Directory of Open Access Journals (Sweden)

    D. E. Karateev

    2015-01-01

    Full Text Available To introduce treat-to-target recommendations is an important task of modern rheumatology; however, there is still a diversity of serious problems relating to a scientific rationale and a clinical one for this strategy and to the possibilities of its implementation in real clinical practice, in the rheumatology service of the Russian Federation in particular, by taking into account the specific features of funding for high-tech medical care. Objective: to determine the efficiency and safety of combined therapy with subcutaneous methotrexate (MT and biological agents (BA when using the treat-to-target strategy in patients with active early and extended-stage rheumatoid arthritis (RA who have risk factors for a poor prognosis. Subjects and methods. The results of the REMARCA (Russian InvEstigation of MethotrexAte and biologicals in eaRly aCtive inflammatory Arthritis trial of 130 patients followed up for 12 months or more were given. There was a female preponderance; mean age 48.9±13.9 years, rheumatoid factor positivity (86.9%; anti-cyclic citrullinated peptide antibody positivity (89.2%. Seventy patients formed a subgroup of early RA (disease duration ≤6 months (mean 4.17±1.39 months; 60 patients were a subgroup of advanced-stage RA (disease duration >6 months (mean 30.8±32.7 months. In all the patients, therapy was initiated by using subcutaneous MT with its rapid dose escalation up to 20–30 mg/week and the achievement of the treatment goal (low disease activity or remission was checked every 3 months and depending on the result a decision had been taken to add or not to add a biological agent (BA (a tumor necrosis factor inhibitor or abatacept. If the former was insufficiently effective, it was substituted for a BA from another class. Results. Subcutaneous MT monotherapy provided remission or low disease activity in 49 (37.7% patients; a BA was given to 81 (62.3% patients. Following 6 and 12 months, low activity or remission according

  17. X-RAY PROGRESSION AND ITS IMPACT ON THE FUNCTIONAL STATUS OF PATIENTS WITH EARLY RHEUMATOID ARTHRITIS DURING A 5-YEAR FOLLOW-UP

    Directory of Open Access Journals (Sweden)

    Yu. A. Ermakova

    2015-01-01

    Full Text Available Objective: to assess progression of X-ray joint changes and their impact on functional status of patients with early rheumatoid arthritis (RA.Subjects and methods. The investigation enrolled 204 patients with early RA included in the RADICAL (Early Arthritis: Diagnosis, Outcomes, Criteria, Active Treatment program in the period 2003 to 2007. The duration of the disease at the inclusion was less than 2 years. RA was diagnosed according to 1987 American College of Rheumatology (ACR criteria. Rheumatoid factor was presentin 67.5% of the patients and anti-cyclic citrullinated peptide antibodies – in 57%. Women were 86.5%; median age was 49 [40; 58] years. The patients received traditional diseasemodifying antirheumatic drugs and biological agents (24%. Therapy response was monitored applying the tight control strategy. Main clinical and laboratory parameters, DAS28, and HAQ scores, and functional class and hand and foot X-ray were recorded every year.Results and discussion. After 5 years of follow-up, new erosions appeared in 57% of the patients. Joint erosions were present in 16.5% of the patients at the inclusion and in 73% following 5 years. At baseline, after 1, 2, 3, 4, and 5 years, the total erosion scores (modified Sharp score was equal to 0 [0; 0], 0 [0; 1], 0 [0; 4], 1 [0; 8], 3 [0; 12], 6 [0; 14], respectively. A significant functional improvement could be achieved just during the first year of follow-up. Thus, the median HAQ value decreased from 1.125 [0.625; 1.75] to 0.5 [0.125; 1.0], reaching the population level. Following 2, 3, 4, and 5 years, the median HAQ was 0.5 [0; 1.0], 0.5 [0; 1.0], 0.5 [0; 1.0], and 0.75 [0.125; 1.125], respectively. There was a weak positive correlation between total erosion scores and HAQ in the eаrly stage of the disease. However, it became more marked after 3, 4, and 5 years (correlation coefficient, 0.38, 0.39, and 0.40,respectively; p < 0.01. Conclusion.In spite of the stable pattern

  18. CARDIOVASCULAR RISK IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS BEFORE DISEASE-MODIFYING ANTIRHEUMATIC THERAPY (PRELIMINARY DATA OF THE REMARCА STUDY

    Directory of Open Access Journals (Sweden)

    Yu. N. Gorbunova

    2014-01-01

    peptide-positive patients with early RA and high disease activity have high and very high cardiovascular risks.

  19. Grr1p is required for transcriptional induction of amino acid permease genes and proper transcriptional regulation of genes in carbon metabolism of Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Eckert-Boulet, Nadine; Regenberg, Birgitte; Nielsen, Jens

    2005-01-01

    and a grr1 Delta strain and adding citrulline in the exponential phase. Whole-genome transcription analyses were performed on samples from each cultivation, both immediately before and 30 min after citrulline addition. Transcriptional induction of the AAP genes AGP1, BAP2, BAP3, DIP5, GNP1 and TAT1 is fully...

  20. Peptidyl arginine deiminase inhibitor effect on hepatic fibrogenesis in a CCl4 pre-clinical model of liver fibrosis

    DEFF Research Database (Denmark)

    Vassiliadis, E.; Veidal, Sanne Skovgård; Kristiansen, M. N.

    2013-01-01

    Having previously shown that levels of the citrullinated vimentin peptide VICM are raised in liver fibrosis in rats, we aimed to investigate whether inhibition of citrullination as measured by VICM levels could affect fibrogenesis. METHODS: Fibrogenesis was evaluated by quantitative histology and...

  1. Peptidylarginine deiminase activity in postmortem white matter of patients with multiple sclerosis

    NARCIS (Netherlands)

    De Keyser, J; Schaaf, M; Teelken, A

    1999-01-01

    The myelin sheath in multiple sclerosis (MS) appears to contain a higher proportion of the citrullinated isoform of myelin basic protein MBP-C8. In vitro, MBP-associated arginine is deiminated to citrulline by the enzyme peptidylarginine deiminase (PAD). We investigated PAD activity in white matter

  2. The Extracellular Proteome and Citrullinome of the Oral Pathogen Porphyromonas gingivalis

    NARCIS (Netherlands)

    Stobernack, Tim; Glasner, Corinna; Junker, Sabryna; Gabarrini, Giorgio; de Smit, Menke; de Jong, Anne; Otto, Andreas; Becher, Dörte; van Winkelhoff, Arie Jan; van Dijl, Jan Maarten

    2016-01-01

    Porphyromonas gingivalis is an oral pathogen associated with the inflammatory disease periodontitis. Periodontitis and P. gingivalis¬ have been associated with rheumatoid arthritis. One of the hallmarks of rheumatoid arthritis is the loss of tolerance against citrullinated proteins. Citrullination i

  3. The arginine deiminase pathway of koji bacteria is involved in ethyl carbamate precursor production in soy sauce.

    Science.gov (United States)

    Zhang, Jiran; Fang, Fang; Chen, Jian; Du, Guocheng

    2014-09-01

    Ethyl carbamate (EC) is a group 2A carcinogen generated from a few precursors in many fermented foods and alcoholic beverages. Citrulline, urea, carbamoyl phosphate, and ethanol are common precursors detected in fermented foods. In this study, citrulline was proved to be the main EC precursor in soy sauce, which was found to be accumulated in moromi mash period and correlated with the utilization of arginine by koji bacteria. Six koji isolates belonging to three genera were identified to be able to accumulate citrulline via the arginine deiminase (ADI) pathway. Among these strains, only Pediococcus acidilactici retained high activities in synthesis and accumulation of citrulline in the presence of high concentration of sodium chloride. These results suggested that P. acidilactici is responsible for the accumulation of citrulline, one of the EC precursors, in the process of soy sauce fermentation.

  4. 6种抗体联合检测类风湿性关节炎的临床意义%Clinical significance of combined detection of six kinds of antibodies in rheumatoid arthritis patients

    Institute of Scientific and Technical Information of China (English)

    韩叶光; 许聪敏; 符生苗; 符克英; 蔡俊宏; 王茹

    2012-01-01

    Objective To investigate the value detection of rheumatoid factors (RF-IgM,IgA,IgG),anti-keratin antibody (AKA),anti-perinuclear factor (APF) and anti-cyclic citrullinated peptide antibody (CCP) in diagnosis of rheumatoid arthritis (RA). Methods Enzyme immunoassay was used for detection of rheumatoid factor(RF-IgM,IgA, IgG),cyclic citrullinated peptide antibody (CCP);indirect immunofluorescence (IIF)was used for detection of anti-keratin antibody (AKA)and anti-perinuclear factor (APF)in 76 patients with RA.98 cases of non-RA patients and 30 healthy controls. Results The sensitivities in detection of RF (IgM,IgA,IgG)AKA, APF,and anti-CCP were 71.1 %,44.7% , 28.9%,42.1%,48.7%and 68.4%, respectively and the specificities were 78.9% ,85.9% ,89.1% ,89.8% ,914% and 93.8% respectively. The sensitivity and specificitiy of combined detection of RF-IgM,IgA and IgG were 27.6 % and 92.2%,that of combined detection of RF-IgM,IgA,IgG and AKA were 19.7% and 94.5%%,that combined detection of RF- IgM,IgA,IgG and APF were 23.7% and 96.1%%,that of combined detection of RF-IgM,IgA,IgG and anti-CCP were 26.3% and 96.1% , that of combined detection of RF-IgM,IgA,IgG ,AKA and APF were 18.4% and 97.7% ,that of combined detection of RF-IgM,IgA,IgG,AKA and anti-CCP were 15.8% and 99.2%,that of combined detection of RF-IgM,IgA,IgG,APF and anti-CCP were 15.8% and 99.2% ,and that of combined detection of RF-IgM ,IgA,IgG,AKA,APF and anti-CCP were 13.2% and 100%. Conclusion In comaprison of detection of six antibodies,the sensitivity is the highest in detection of RF-IgM,with the lowest specificity; The specificity in detection of CCP is the highest,possessing diagnostic value and the most valuable. Combined detection of the six auto-antibodies will improve the specificity in early daignosis of RA.%目的 比较类风湿因子(RF-IgM,IgA,IgG)、抗角蛋白抗体(AKA)、抗核周因子(APF)、抗环胍氨酸肽抗体(anti-CCP)诊断类风湿性关节炎(RA)的敏感性及特异性,并探讨6种

  5. Diagnostic value analysis of anti-CCP antibodies combined RF on elderly patients with rheumatoid arthritis%抗环瓜氨酸肽抗体联合类风湿因子对老年类风湿关节炎的诊断价值分析

    Institute of Scientific and Technical Information of China (English)

    陶蕾; 薛建峰; 翟乾勋; 薛夫营; 翟荣慧

    2015-01-01

    Objective To investigate the diagnostic value of anti-cyclic citrullinated peptides ( CCP ) antibodies combined rheumatoid factors (RF) on elderly patients with rheumatoid arthritis.Methods From January 2012 to December 2014, 29 cases of elder patients in our hospital with rheumatoid arthritis (elder RA group, age >60 year), 47 cases of elderly health control group (elder RA group, age≥60), and 48 cases of elder patients without rheumatoid arthritis (non-elder RA group, age<60 year) were selected.The anti-CCP antibodies and rheumatoid factor (RF) levels of three groups were detected, and the significance of anti-CCP antibody combined RF on the diagnosis of elderly rheumatoid arthritis was analyzed.Results Diagnostic positive rate of anti-CCP antibodies +RF was significantly higher than that of anti-CCP antibodies, and the difference was significant (χ2 =7.632, P =0.006).Diagnostic positive rate of anti-CCP antibodies +RF was higher than that of RF, but the difference was not statistically significant (χ2 =3.107, P=0.078).The diagnostic positive rate of anti-CCP antibodies, RF, and anti-CCP antibodies +RF for diagnosis of elderly rheumatoid arthritis had no statistically difference with that of non-elderly RA group.The sensitivity and negative predictive value of anti-CCP antibodies +RF was higher than that of only anti-CCP antibodies and RF.The area under the ROC curve of detecting anti-CCP +RF was 0.786, which was higher than that of anti-CCP antibodies (0.699) and RF (0.663), indicated that the reliability of anti-CCP antibodies +RF was higher than that of anti-CCP antibodies and RF.Conclusion The anti-CCP antibodies and RF can diagnose elderly rheumatoid arthritis, and anti-CCP antibodies combined RF has more clinical significance.%目的:探讨抗环瓜氨酸肽( cyclic citrullinated peptides,CCP)抗体联合类风湿因子( rheumatoid factors,RF)对老年类风湿性关节炎的诊断价值。方法选取2012年1月~2014年12月间泰山

  6. Autoanticorpos na artrite reumatoide inicial: coorte Brasília - resultados de uma análise seriada de três anos Autoantibodies in early rheumatoid arthritis: Brasília cohort - results of a three-year serial analysis

    Directory of Open Access Journals (Sweden)

    Licia Maria Henrique da Mota

    2011-12-01

    Full Text Available O valor diagnóstico e prognóstico da análise seriada dos anticorpos como fator reumatoide (FR, anticorpos antipeptídeos citrulinados cíclicos (anti-CCP e antivimentina citrulinada (anti-Sa não está definido nos pacientes com artrite reumatoide inicial (ERA. OBJETIVOS: Avaliar de forma prospectiva a presença de FR, anti-CCP e anti-Sa em pacientes com ERA. PACIENTES E MÉTODOS: Quarenta pacientes da coorte Brasília de ERA (menos de 12 meses foram avaliados e monitorados durante três anos. Os dados clínicos e demográficos foram registrados, além dos resultados (ELISA para FR (IgM, IgG e IgA, anti-CCP (CCP2, CCP3 e CCP3.1 e anti-Sa na avaliação inicial e aos 3, 6, 12, 18, 24 e 36 meses de acompanhamento. Comparações pelos testes t de Student e t pareado. RESULTADOS: A idade média foi de 45 anos, 90% dos pacientes do gênero feminino. No momento do diagnóstico, FR foi observado em 50% dos casos (FR IgA 42%, FR IgG 30% e FR IgM 50%, anti-CCP em 52,5% (não houve diferença entre CCP2, CCP3 e CCP3.1 e anti-Sa em 10%. Após três anos, não houve diferença na prevalência de FR e anti-CCP, mas a de anti-Sa aumentou para 17,5% (P = 0,001. CONCLUSÃO: A análise repetida do FR e anti-CCP, incluindo aqui diferentes isotipos, durante três anos de acompanhamento, não mostrou mudanças significativas. A terceira geração do anti-CCP não aumentou o valor diagnóstico dos testes de segunda geração.The diagnostic and prognostic value of the serial measurement of antibodies, such as rheumatoid factor (RF, anti-cyclic citrullinated peptide (anti-CCP, and anti-citrullinated vimentin (anti-Sa antibodies, has not been defined in early rheumatoid arthritis (ERA. OBJECTIVES: To prospectively assess the presence of RF, anti-CCP, and anti-Sa in ERA patients. PATIENTS AND METHODS: Forty ERA (less than 12 months patients of the Brasília cohort were evaluated and followed up for three years. Both clinical and demographic data were recorded, in

  7. Savings in Public Services after the Crisis: A Multilevel Analysis of Public Preferences in the EU27 (Working Paper 8)

    NARCIS (Netherlands)

    S.G.J. Van de Walle (Steven); S.R. Jilke (Sebastian)

    2012-01-01

    textabstractPolicy responses to the financial crisis can be divided into cyclical and anti-cyclical approaches. The former advocates reducing public spending in times of financial constraints. The latter approach advocates public spending to boost the economy. Using multinomial multilevel analysis o

  8. 英文摘要

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    Anti-cyclical Enterprise COVER STORY With the prosperity of the solar and wind power industry in China, a number of enterprises have emerged via taking advantage of the cheap labor and strong policy support (or facilitative policies). However, the positioning of these firms is problematic, thereby giving rise to a fragile industry with "both ends are outer".

  9. High-performance liquid chromatography method with radiochemical detection for measurement of nitric oxide synthase, arginase, and arginine decarboxylase activities

    DEFF Research Database (Denmark)

    Volke, A; Wegener, Gregers; Vasar, E

    2006-01-01

    regulate NOS activity. We aimed to develop a HPLC-based method to measure simultaneously the products of these three enzymes. Traditionally, the separation of amino acids and related compounds with HPLC has been carried out with precolumn derivatization and reverse phase chromatography. We describe here...... a simple and fast HPLC method with radiochemical detection to separate radiolabeled L-arginine, L-citrulline, L-ornithine, and agmatine. 3H-labeled L-arginine, L-citrulline, agmatine, and 14C-labeled L-citrulline were used as standards. These compounds were separated in the normal phase column (Allure...

  10. 粪肠球菌SK32.001精氨酸脱亚胺酶的分离纯化及酶学性质研究%Purification and characterization of an arginine deiminase from Enterococcus faecalis SK32.001 producing citrulline

    Institute of Scientific and Technical Information of China (English)

    刘昕; 帅玉英; 张涛; 江波; 缪铭; 沐万孟

    2015-01-01

    对Enterococcus faecalis SK32.001所产的精氨酸脱亚胺酶(ADI)进行分离纯化并对其酶学性质进行研究.实验结果表明,通过细胞破碎,硫酸铵沉淀,HiPrep Q FF 16/10阴离子交换层析,Sephadex G-75等纯化方法获得电泳纯精氨酸脱亚胺酶,分子量约为42ku,催化最适温度和pH分别为50℃和6.5,在30~40℃和pH5.5~7.5时较稳定.不同浓度的Zn2+对酶活性影响较大.1 mmol/L的Zn2+和10mmol/L的Co2+、Ca2+、Mg2+对酶活有较大的促进作用,10mmol/L的Cu2+对酶的抑制作用最强.精氨酸脱亚胺酶在最适反应条件测定其米氏常数为1.33mmol/L,最大反应速度为2.41 μmol/min.

  11. 类风湿因子和抗环瓜氨酸多肽抗体联合检测在类风湿关节炎诊断中的意义%Diagnostic significance of combined detection of rheumatoid factor and anticyclic citrullinated peptide antibodies in rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    穆荣; 孙晓云; 栗占国

    2005-01-01

    目的:评估抗聚丝蛋白抗体群(AFAs)抗体与类风湿因子(RF)联合检测在类风湿关节炎(RA)诊断中的意义. 方法:分别检测266例RA患者和186例对照者血清中的RF和抗角蛋白抗体(AKA)、抗核周因子(APF)、抗环瓜氨酸多肽(CCP)抗体等AFAs.以乳凝法检测RF-IgM,酶联免疫吸附法检测RF-IgG、IgA及抗CCP抗体,间接免疫荧光染色法检测AKA、APF,并分析上述抗体在RA诊断中的意义. 结果:与单独检测RF相比,联合检测RF和抗CCP抗体可使敏感度由65.8%提高至86.5%,二者特异度相当,分别为80.6%和81.8%.在RF阴性的91例RA患者中,64.8%的患者至少1项AFAs阳性,其中抗CCP阳性者占59.3%.AKA和APF特异性很高,但敏感性低. 结论:AFAs与RF联合检测可显著提高RA的诊断率,尤其在RF阴性的RA患者中更具有意义.但以目前的检测方法,AKA和APF的敏感性太低.临床上,以RF和抗CCP抗体联合测定更为实用.

  12. 联合检测类风湿因子、抗角蛋白抗体及抗环瓜氨酸多肽抗体对类风湿性关节炎的诊断价值%Diagnostic value of combined detection of rheumatoid factor,antikeratin antibody and cyclic citrullinated peptide antibody in rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    张家明; 卓少贤; 林伊萍; 黎阳

    2009-01-01

    目的 探讨类风湿因子(RF)、抗角蛋白抗体(AKA)及抗环瓜氨酸多肽(CCP)抗体联合检测对类风湿性关节炎(RA)的临床诊断价值.方法 对83例RA和106例非RA患者用速率散射比浊法检测RF,间接免疫荧光染色法检测AKA,酶联免疫吸附法检测抗CCP抗体,并对3种指标检测进行比较分析.结果 3种抗体单独检测对RA诊断的敏感性、特异性分别是:RF为71.1%、74.5%,AKA为49.4%、95.3%,抗CCP抗体为65.1%、94.3%;不同方式联合检测对RA诊断的敏感性、特异性分别是RF+AKA为34.9%、97.2%,RF+抗CCP抗体为45.8%、98.1%,RF+AKA+抗CCP抗体为28.9%、100%;RF在AKA、抗CCP抗体分别阴性的RA患者中检出率分别为28.6%和34.5%;AKA和抗CCP抗体在RF阴性的RA患者中分别有45.8%和62.5%的阳性率.结论 单独检测RF对RA诊断的敏感性最高,特异性最高的是AKA,抗CCP抗体有较高的的敏感性及特异性,3种指标各有优点,可互为补充,联合检测RF、AKA及抗CCP抗体可提高对RA诊断的特异性,有助于早期RA的诊断.

  13. 未分化关节炎162例抗CCP抗体检测及3年随访分析%A three year follow up study of anti-CCP (cyclic citrullinated peptide) antibody determination of 162 patients with undifferentiated arthritis

    Institute of Scientific and Technical Information of China (English)

    李中青; 李莉; 李从力; 霍毓平

    2014-01-01

    目的:了解未分化关节炎(undifferentiated arthritis,UA)的抗CCP检测情况及发展规律。方法分析162例UA患者抗CCP检测情况及3年随访结果。结果①首诊检测抗CCP抗体阳性率为4.3%;②病程中双手近端指间及足腕关节疼痛最多见;③3年随访结果:42例仍为UA,58例症状消失;另外62例转归为类风湿关节炎(RA)、骨性关节炎(OA)、强直性脊柱炎(AS)、系统性红斑狼疮(SLE);④3年内抗CCP检测阳性率上升明显,3年后上升为14.8%;⑤3年中抗CCP抗体阳性患者全部确诊RA,RA患者抗CCP抗体阳性率52.2%。结论 UA是一组常见的关节炎,部分患者可进展为RA、OA、AS及SLE等其他疾病。对UA患者应定期进行抗CCP抗体检测,有助于类风湿关节炎的早期诊断。%Objective To investigate the determination of anti-CCP and the law of development of undifferentiated arthritis (UA). Methods 162 UA patients were registered in rheumatology outpatient clinic of Jincheng People's Hospital. The determination results of anti-CCP and 3-year follow-up data of them were collected and analyzed. Results ①4.3%were anti-CCP positive in the initial diagnosis.②The chief symptoms of 162 UA patients were hands proximal interphalangeal pain and foot wrist pain. ③In three years 162 cases developed to 46 cases rheumatoid arthritis(RA),8 osteoarthritis(OA),5 ankylosing spondylitis(AS),3 systemic lupus erythematosus(SLE),42 UA,58 cases with symptomatic disappeared.④In 3 years the positive rates of anti-CCP had dramatically increased, and reached to 14.8%after 3-year follow-up. ⑤In three years, the anti-CCP positive patients all have been confirmed RA, and the positive rates of anti-CCP of RA was 52.2%. Conclusion UA were a group of a variety of arthritis, some patients can progress to RA, OA, AS and SLE, and other rheumatism. Close follow-up on the patients, especially anti-CCP positive patients, and regular anti-CCP determination conduce to early diagnosis of RA.

  14. Neo-Epitopes—Fragments of Cartilage and Connective Tissue Degradation in Early Rheumatoid Arthritis and Unclassified Arthritis

    DEFF Research Database (Denmark)

    Maijer, Karen I; Gudmann, Natasja Stæhr; Karsdal, Morten Asser

    2016-01-01

    Objective: Tissue destruction in rheumatoid arthritis (RA) is predominantly mediated by matrix metalloproteinases (MMPs), thereby generating protein fragments. Previous studies have revealed that these fragments include MMP-mediated collagen type I, II, and III degradation, citrullinated and MMP...

  15. Amino acid residues important for substrate specificity of the amino acid permeases Can I p and Gnp I p in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Regenberg, Birgitte; Kielland-Brandt, M.C.

    2001-01-01

    Deletion of the general amino acid permease gene GAP1 abolishes uptake of L-citrulline in Saccharomyces cerevisiae, resulting in the inability to grow on L-citrulline as sole nitrogen source. Selection for suppressor mutants that restored growth on L-citrulline led to isolation of 21 mutations...... in the arginine permease gene CAN1. One similar mutation was found in the glutamine-asparagine permease gene GNP1. L-[C-14]citrulline uptake measurements confirmed that suppressor mutations in CAN1 conferred uptake of this amino acid, while none of the mutant permeases had lost the ability to transport L-[C-14......]arginine. Substrate specificity seemed to remain narrow in most cases, and broad substrate specificity was only observed in the cases where mutations affect two proline residues (P148 and P313) that are both conserved in the amino acid-polyamine-choline (APC) transporter superfamily. We found mutations...

  16. Periodontitis and Rheumatoid Arthritis : What Do We Know?

    NARCIS (Netherlands)

    de Smit, Menke J.; Westra, Johanna; Brouwer, Elisabeth; Janssen, Koen M. J.; Vissink, Arjan; van Winkelhoff, Arie Jan

    2015-01-01

    Background: Currently, in the field of rheumatology, there is much attention given towards the possible causality between periodontitis and rheumatoid arthritis (RA), specifically regarding the role of Porphyromonas gingivalis (Pg). This bacterium is unique, having a citrullinating enzyme. Antibodie

  17. How Is It Treated?

    Science.gov (United States)

    ... erythrocyte sedimentation rate (ESR), described below. Anticyclic citrullinated peptide (anti-CCP) antibodies. Anti-CCP antibodies may be ... children, juvenile arthritis is characterized by periods of remission punctuated by flares. Immune-response modifiers. A relatively ...

  18. Pancreatic cancer cell lines deficient in argininosuccinate synthetase are sensitive to arginine deprivation by arginine deiminase

    OpenAIRE

    Bowles, Tawnya L.; Kim, Randie; Galante, Joseph; Parsons, Colin M.; Virudachalam, Subbulakshmi; Kung, Hsing-Jien; Bold, Richard J.

    2008-01-01

    Eukaryotic cells can synthesize the non-essential amino acid arginine from aspartate and citrulline using the enzyme argininosuccinate synthetase (ASS). It has been observed that ASS is under-expressed in various types of cancers ASS, for which arginine become auxotrophic. Arginine deiminase (ADI) is a prokaryotic enzyme that metabolizes arginine to citrulline and has been found to inhibit melanoma and hepatoma cancer cells deficient of ASS. We tested the hypothesis that pancreatic cancers ha...

  19. Arginine catabolism in Lactobacillus sake isolated from meat.

    OpenAIRE

    Montel, M C; Champomier, M C

    1987-01-01

    Lactobacillus sake isolated from meat can hydrolyze arginine via the arginine deiminase pathway. Two enzymes, arginine deiminase and ornithine transcarbamylase, have been revealed by detection of their reaction products, citrulline and ornithine, respectively. The production of citrulline depends on the concentration of glucose in a synthetic medium; it does not occur when the concentration of glucose is 27.5 mM or higher.

  20. Potential protein targets of the peptidylarginine deiminase 2 and peptidylarginine deiminase 4 enzymes in rheumatoid synovial tissue and its possible meaning

    Science.gov (United States)

    Badillo-Soto, Martha Adriana; Rodríguez-Rodríguez, Mayra; Pérez-Pérez, María Elena; Daza-Benitez, Leonel; Bollain-y-Goytia, Juan José; Carrillo-Jiménez, Miguel Angel; Avalos-Díaz, Esperanza; Herrera-Esparza, Rafael

    2016-01-01

    Objective The molecular mechanism of citrullination involves the calcium-dependent peptidylarginine deiminase (PAD) family of enzymes. These enzymes induce a stereochemical modification of normal proteins and transform them into autoantigens, which in rheumatoid arthritis trigger a complex cascade of joint inflammatory events followed by chronic synovitis, pannus formation, and finally, cartilage destruction. By hypothesizing that PAD2 and PAD4 enzymes produce autoantigens, we investigated five possible synovial protein targets of PAD enzymes. Material and Methods We measured PAD2, PAD4, and citrullinated proteins in 10 rheumatoid and 10 osteoarthritis synovial biopsies and then assessed the post-translational modifications of fibrinogen, cytokeratin, tubulin, IgG, and vimentin proteins using a double-fluorescence assay with specific antibodies and an affinity-purified anti-citrullinated peptide (CCP) antibody. The degree of co-localization was analyzed, and statistical significance was determined by ANOVA, Fisher’s exact test, and regression analysis. Results The principal results of this study demonstrated that citrullinated proteins, such as fibrinogen, IgG, and other probed proteins, were targets of PAD2 and PAD4 activity in rheumatoid synovial biopsies, whereas osteoarthritis biopsies were negative for this enzyme (p<0.0001). An analysis of citrullination sites using the UniProtKB/Swiss-Prot data bank predicts that the secondary structure of the analyzed proteins displays most of the sites for citrullination; a discussion regarding its possible meaning in terms of pathogenesis is made. Conclusion Our results support the conclusion that the synovial citrullination of proteins is PAD2 and PAD4 dependent. Furthermore, there is a collection of candidate proteins that can be citrullinated. PMID:27708970

  1. Enteral Glutamine Administration in Critically Ill Nonseptic Patients Does Not Trigger Arginine Synthesis

    Science.gov (United States)

    Vermeulen, Mechteld A. R.; Brinkmann, Saskia J. H.; Buijs, Nikki; Beishuizen, Albertus; Bet, Pierre M.; Houdijk, Alexander P. J.; van Goudoever, Johannes B.; van Leeuwen, Paul A. M.

    2016-01-01

    Glutamine supplementation in specific groups of critically ill patients results in favourable clinical outcome. Enhancement of citrulline and arginine synthesis by glutamine could serve as a potential mechanism. However, while receiving optimal enteral nutrition, uptake and enteral metabolism of glutamine in critically ill patients remain unknown. Therefore we investigated the effect of a therapeutically relevant dose of L-glutamine on synthesis of L-citrulline and subsequent L-arginine in this group. Ten versus ten critically ill patients receiving full enteral nutrition, or isocaloric isonitrogenous enteral nutrition including 0.5 g/kg L-alanyl-L-glutamine, were studied using stable isotopes. A cross-over design using intravenous and enteral tracers enabled splanchnic extraction (SE) calculations. Endogenous rate of appearance and SE of glutamine citrulline and arginine was not different (SE controls versus alanyl-glutamine: glutamine 48 and 48%, citrulline 33 versus 45%, and arginine 45 versus 42%). Turnover from glutamine to citrulline and arginine was not higher in glutamine-administered patients. In critically ill nonseptic patients receiving adequate nutrition and a relevant dose of glutamine there was no extra citrulline or arginine synthesis and glutamine SE was not increased. This suggests that for arginine synthesis enhancement there is no need for an additional dose of glutamine when this population is adequately fed. This trial is registered with NTR2285. PMID:27200186

  2. Enteral Glutamine Administration in Critically Ill Nonseptic Patients Does Not Trigger Arginine Synthesis

    Directory of Open Access Journals (Sweden)

    Mechteld A. R. Vermeulen

    2016-01-01

    Full Text Available Glutamine supplementation in specific groups of critically ill patients results in favourable clinical outcome. Enhancement of citrulline and arginine synthesis by glutamine could serve as a potential mechanism. However, while receiving optimal enteral nutrition, uptake and enteral metabolism of glutamine in critically ill patients remain unknown. Therefore we investigated the effect of a therapeutically relevant dose of L-glutamine on synthesis of L-citrulline and subsequent L-arginine in this group. Ten versus ten critically ill patients receiving full enteral nutrition, or isocaloric isonitrogenous enteral nutrition including 0.5 g/kg L-alanyl-L-glutamine, were studied using stable isotopes. A cross-over design using intravenous and enteral tracers enabled splanchnic extraction (SE calculations. Endogenous rate of appearance and SE of glutamine citrulline and arginine was not different (SE controls versus alanyl-glutamine: glutamine 48 and 48%, citrulline 33 versus 45%, and arginine 45 versus 42%. Turnover from glutamine to citrulline and arginine was not higher in glutamine-administered patients. In critically ill nonseptic patients receiving adequate nutrition and a relevant dose of glutamine there was no extra citrulline or arginine synthesis and glutamine SE was not increased. This suggests that for arginine synthesis enhancement there is no need for an additional dose of glutamine when this population is adequately fed. This trial is registered with NTR2285.

  3. Enteral Glutamine Administration in Critically Ill Nonseptic Patients Does Not Trigger Arginine Synthesis.

    Science.gov (United States)

    Vermeulen, Mechteld A R; Brinkmann, Saskia J H; Buijs, Nikki; Beishuizen, Albertus; Bet, Pierre M; Houdijk, Alexander P J; van Goudoever, Johannes B; van Leeuwen, Paul A M

    2016-01-01

    Glutamine supplementation in specific groups of critically ill patients results in favourable clinical outcome. Enhancement of citrulline and arginine synthesis by glutamine could serve as a potential mechanism. However, while receiving optimal enteral nutrition, uptake and enteral metabolism of glutamine in critically ill patients remain unknown. Therefore we investigated the effect of a therapeutically relevant dose of L-glutamine on synthesis of L-citrulline and subsequent L-arginine in this group. Ten versus ten critically ill patients receiving full enteral nutrition, or isocaloric isonitrogenous enteral nutrition including 0.5 g/kg L-alanyl-L-glutamine, were studied using stable isotopes. A cross-over design using intravenous and enteral tracers enabled splanchnic extraction (SE) calculations. Endogenous rate of appearance and SE of glutamine citrulline and arginine was not different (SE controls versus alanyl-glutamine: glutamine 48 and 48%, citrulline 33 versus 45%, and arginine 45 versus 42%). Turnover from glutamine to citrulline and arginine was not higher in glutamine-administered patients. In critically ill nonseptic patients receiving adequate nutrition and a relevant dose of glutamine there was no extra citrulline or arginine synthesis and glutamine SE was not increased. This suggests that for arginine synthesis enhancement there is no need for an additional dose of glutamine when this population is adequately fed. This trial is registered with NTR2285.

  4. Estimating simple fiscal policy reaction functions for the euro area countries

    OpenAIRE

    2014-01-01

    We formulate and estimate a simple fiscal policy reaction function for the euro area and individual euro area countries. Our reaction function allows for primary surpluses to feature three components: an anti-cyclical response of primary surpluses to the output gap, a response to the debt-GDP ratio, and an exogenous fiscal policy shifter. In line with the cyclical adjustment literature and in contrast with much of the previous time-series literature, we find a consistently strong anti-cyclica...

  5. Risk Factors, Clinical and Radiographic Characteristics of Rheumatoid Arthritis Associated Interstitial Lung Disease%类风湿关节炎相关肺间质病变的危险因素、临床和影像学特点

    Institute of Scientific and Technical Information of China (English)

    赵颖; 李菁; 吴庆军; 唐福林

    2012-01-01

    -citrullinaLed peptide/protein antihodies ( ACPA ) ( including anti-cyclic citrullinated peptide, anti-perinuclear factor, and anti-keratin antihody ) ( all P < 0. 05 ). RA-ILD manifesLed as cough, progressive exertional dyspnea, and cracles at both lung fields clinically. The findings on high-resolution computed Lomography ( 11RCT ) wore fiberoLic lines/reLiculaLion ( 68.75%, 33/48 ), exudalivo infikration/ consolidation ( 21/48, 43.75% ), ground glass opackies ( 15/48, 31.25% ), honeycombing ( 11/48, 22.92% ), and ploural effusion ( 5/48, 10.42% ). Pulmonary funcLion tests ( PFT ) were done in 37 pationts with RA-ILD and 75. 68% of these pationLs were abnormal. DLCO( diffusion oapaoity for carbon monoxide of the lung) was decreased in all 28 pationts, complicated with restrictive vontilation impairment in 7 paLionLs, and 4 pationLs vviLh mixed vonLilaLion disLurbance. Conclusions RA-ILD is an important feature of RA. IL is relaLed vviLh age, course of disease, smoking, serum level of rheumaLoid facLor, positivo ACPA, and disease severiLy. RA-ILD is noL relaLed Lo disease acLiviLy. IIRCT and PFT are valuable examinations for oarly diagnosis and appropriaLed Lhorapy of RA-ILD.

  6. 类风湿关节炎并发肺间质纤维化的相关因素研究%Related Factors of Rheumatoid Arthritis Complicated with Interstitial Pulmonary Fibrosis

    Institute of Scientific and Technical Information of China (English)

    李宗英; 王俊祥

    2013-01-01

    groups. Results Among these 345 HA patients, IPF was identified in 60 patients ( 17. 39% ). Compared with the non - IPF group, the RA - IPF group had significantly more males and smokers; Were significantly older; Had significantly higher levels of rheumatoid factor ( HF ), anti - cyclic citrullinated antibody ( anti - CCP ), and C - reactive protein ( CHP ) ( all P 0.05 ). Comparison of the OR values showed that male gender, smoking history, bone destruction, older age ( ≥60 yrs ), onset age ( ≥50 yrs ), long disease duration (≥5 yrs ), high CHP level ( ≥ 24 mg/L ), high RF titer ( ≥60 U/ml ) and high anti -CCP antibody level (≥75 RU/ml) were independent risk factors of RA - IPF. Conclusion IPF is a common complication of RA, with male gender, old age, smoking, high levels of CRP and high titer of RF or anti - CCP being its independent risk factors. HHCT provides a useful tool for early diagnosis and treatment.

  7. 5例抗丙氨酰 tRNA 合成酶抗体阳性患者临床特征%Clinical Characters of Anti-alanyl-tRNA Synthetase Antibody

    Institute of Scientific and Technical Information of China (English)

    吴庆军; 张文; 李永哲; 田新平; 张; 赵岩; 曾小峰; 张奉春; 唐福林

    2014-01-01

    Objective The purpose of this study was to examine the clinical profile of patients with anti-alanyl-tRNA synthetase (anti-PL-1 2)antibody.Methods Five patients with anti-PL-1 2 antibody admitted into Peking Union Medical College Hospital were presented.The major clinical,serological,and radiographic data were analyzed.Results All 5 patients with anti-PL-1 2 antibody had evidence of interstitial lung disease (ILD)by clinical examination,imaging and pulmonary function tests.Clinical features presented were dry cough,gradual dyspnea,and crackles at lung bases.Lung function test showed a restrictive pulmonary dysfunction pattern and impaired gas exchange.High-resolution computed tomography scan revealed (predominantly basilar)reticular and ground-glass opacities,accompanied by a loss of lung volume,traction bronchiectasis,and scattered (usually peribronchovascular)areas of consolidation.This distinct pattern was highly suggestive of antisynthetase syndrome-related ILD.Four of 5 anti-PL-12 positive patients had underlying connective tissue disease,including dermatomyositis (2 cases),Sjoegren’s syndrome/rheumatoid arthritis (1 case),and systemic sclerosis (1 case).Only one of five anti-PL-12 positive patients demonstrated clinical myositis,including symmetrical proximal muscle weakness,increased serum creatine phosphokinase,myogenic damage on electromyography,and positive results on biopsy.Two patients had typical rash of dermatomyositis (DM).Mechanic hands occurred in 2 patients,fever in 1 patient,Raynaud’ s phenomenon in 1 patient,and inflammatory polyarthritis with anti-cyclic citrullinated polypeptide antibody in 1 patient.Four patients demonstrated a cytoplasmic pattern when tested for antinuclear antibodies by immunofluorescent assay.Four patients had positive anti-Ro-52 antibodies.Four of 5 patients received high-dose glucocorticosteroid (prednisone 0.8 ~1.5 mg·kg -1 ·d -1 )plus cyclophosphamide (100 mg·d -1 ) therapy.Response was favorable with recovery

  8. Systemic Sclerosis Combined with Rheumatoid Arthritis:Report of Three Cases and Literature Review%系统性硬化症合并类风湿关节炎三例并文献复习

    Institute of Scientific and Technical Information of China (English)

    鲁芙爱; 王慧; 王永福

    2014-01-01

    Objective Toexploretheclinicalfeaturesandlaboratorytestsofpatientswithsystemicsclerosis(SSc) combinedwithrheumatoidarthritis(RA),toimprovetheunderstandingofoverlapsyndrome(OS).Methods Theclinical manifestations,laboratory results and X-ray examinations of the hands of 3 patients with SSc combined with RA were analyzed andliteraturesbothdomesticandabroadreviewed.Results Allpatientswerefemale,startingwithSSc,withtypicalSScclini-cal manifestations,including Raynaud′s phenomenon,mask -like face,limitation of mouth opening,skin sclerosis of finger tips,both-hand contracture deformity,etc. and combined with interstitial lung disease,hypertensive pulmonary vascular dis-ease. None of patients had obvious arthritis manifestations but all or part of rheumatoid factors( RF) were positive;patient 1 had positive anti-perinuclear factor( APF),patient 2 had positive anti-cyclic citrullinated peptide( CCP)antibody,patient 3 had positive APF,anti-CCP antibody,anti-keratin antibody( AKA) and anti-RA33 antibody. The patients′hand X-ray suggested that there were different degrees of narrow or even disappeared joint space in metacarpophalangeal joints or carpal joints,part sclerotin being cystic-degenerated and destructed. Three patients were discharged after treatment of glucocorticoids andcyclophosphamide.Conclusion InOS,SSccombinedwithRAisrare.Patientsmayhavenotypicalarthritismanifesta-tions when SSc combined with RA. Screening RF antibody,anti-CCP antibody,AKA,APF,anti-RA33 antibody and hand X-ray help its diagnoses,to carry out standard treatment and improve patients′outcomes.%目的:探讨系统性硬化症( SSc)合并类风湿关节炎( RA)患者的临床特征和实验室检查特点,提高临床医生对重叠综合征的认识。方法对我科近年收治的3例SSc合并RA患者的临床表现、实验室检查结果及双手X线检查结果进行分析,并结合国内外文献进行复习。结果3例患者均为女性,以SSc起病,有典型的SSc

  9. ASSOCIATION OF BLOOD GENE EXPRESSIONS IN RHEUMATOID ARTHRITIS PATIENTS WITH CLINICAL AND LABORATORY PARAMETERS BEFORE AND AFTER METHOTREXATE THERAPY

    Directory of Open Access Journals (Sweden)

    E. V. Chetina

    2016-01-01

    Full Text Available The genes, the high basic expression of which indicates the efficiency of methotrexate (MTX therapy in relieving joint inflammation and destruction in patients with rheumatoid arthritis (RA, have been defined.Objective: to find an association between the initial expression of the genes: mTOR (mammalian target of rapamycin, a major regulator of cell growth and proliferation; ULK1 (an autophagy marker 1; p21 (a cyclin-dependent kinase inhibitor; kaspase-3 (an apoptosis activity indicator; MMP-9 (matrix metalloproteinase 9, and cathepsin K, which are involved in joint destruction, and the cytokines: TNF-α (tumor necrosis factor-α, TGFβ1 (transforming growth factor β1 and Runx2 (Runt-related transcription factor 2 in the blood of RA patients with disease activity and joint destruction before and after MTX therapy during 24 months.Subjects and methods. Forty patients (mean age, 47.5 years with RA lasting < 2 years and 26 healthy donors (mean age, 45.1 years were examined. All the patients took MTX for 2 years. A clinical response was assessed with disease activity score (DAS28; erythrocyte sedimentation rate and the serum levels of anti-cyclic citrullinated peptide antibodies (ACCPA, C-reactive protein (CRP, and rheumatoid factor (RF were also estimated. Joint destructive changes were assessed by radiography. Furthermore, blood and knee articular cartilage samples from 21 patients (mean age, 50.4 years with late-stage RA and cartilage samples from 25 healthy individuals were investigated. Gene expression in the cells of peripheral blood and cartilage was determined by real-time reverse transcriptase polymerase chain reaction.Results and discussion. MTX therapy considerably reduced disease activity assessed by DAS28, CRP levels, stiffness, tender and swollen joint counts (TJC and SJC; however, joint space (JS narrowing (JSN substantially increased compared with the baseline values. The expression of the ULK1, p21, MMP-9, cathepsin K genes, and

  10. 广西壮族类风湿关节炎患者HLA -DR基因表达及其与临床指标的相关性研究%HLA-DR Gene Expression of Zhuang Ethnic Patients With Rheumatoid Arthritis and Its Correlation With Clinical Indicators

    Institute of Scientific and Technical Information of China (English)

    揭旭日; 王小超; 陆翔; 黄丹; 吕丽娜; 李红文

    2015-01-01

    目的:了解广西壮族类风湿关节炎( RA)患者HLA-DR基因的表达情况,探讨RA患者HLA-DR基因的表达与抗环瓜氨酸肽( CCP)抗体、类风湿因子( RF)、 C反应蛋白( CRP)的相关性。方法选取2008年1月—2013年2月右江民族医学院附属医院风湿科收治的广西壮族RA患者49例为RA组,另选取同时期本院体检健康的广西壮族成年人54例为对照组,采用序列特异性引物-聚合酶链式反应( SSP-PCR)法检测HLA-DR基因表达,双抗体夹心酶联免疫吸附试验( ELISA)法检测抗CCP抗体,免疫比浊法检测RF、 CRP水平。结果 RA组抗CCP抗体阳性率、 RF、 CRP水平高于对照组( P<0.05)。两组均可检测出DRB1*03、 DRB1*04、 DRB1*08~DRB1*17、DRB3*01、 DRB4*01、 DRB5*01亚型; RA组DRB1*10、 DRB4*01阳性表达率均高于对照组( P<0.05);两组其余13个亚型阳性表达率比较,差异均无统计学意义(P>0.05)。 DRB1*10阳性RA患者与DRB1*10阴性RA患者、DRB3*01阳性RA患者与DRB3*01阴性RA患者、 DRB4*01阳性RA患者与DRB4*01阴性RA患者、 DRB5*01阳性RA患者与DRB5*01阴性RA患者抗CCP抗体阳性率、 RF、 CRP水平比较,差异均无统计学意义( P>0.05)。结论广西壮族RA患者HLA-DR基因DRB1*10、 DRB4*01亚型可能为易患基因,但DRB1*10、 DRB3*01、 DRB4*01、 DRB5*01的阳性表达均与抗CCP抗体、 RF、 CRP无相关性。%Objective To explore the HLA-DR gene expression of Zhuang ethnic patients with rheumatoid arthritis ( RA) and investigate its correlation with anti-cyclic citrullinated peptide ( CCP) antibody, rheumatoid factor ( RF) and C-reactive protein ( CRP) .Methods 49 Zhuang ethnic patients with RA who received treatment in the Department of Rheumatism of the Affiliated Hospital of Youjiang Medical University for Nationalities from January 2008 to February 2013 as the RA group.And another 54 Zhuang ethnic healthy adults who

  11. 抗鼠科肉瘤病毒癌基因同源物B1抗体的检测及其在类风湿关节炎诊断中的意义%Significance of the detection of anti-v-raf murine sarcoma viral oncogene homologue B1 antibodies in the diagnostic practice of rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    张霞; 赵金霞; 孙琳; 李茹; 刘湘源; 栗占国

    2012-01-01

    Objective: To clarify the clinical significance of the antibody against v-raf murine sarcoma viral oncogene homologue Bl ( BRAF) in the diagnostic practice of rheumatoid arthritis (RA). Methods: In the study, 112 patients with RA, 112 patients with other rheumatic diseases,and 73 healthy individuals were recruited . With recombinant human BRAF protein as antigen, we examined the level of anti-BRAF antibody in all the patients by enzyme-linked immunosorbent assay ( ELISA) , The clinical data of the RA patients were collected simultaneously, and analysed statistically by using SPSS 13. 0. Results: The positive rate of anti-BRAF antibody was 53. 6% in the RA patients, which was significantly higher than that of the normal control group(4. 1% ,P <0. 01 ) and other rheumatic diseases groups (P all <0. 01) except osteoarthritis group. The titer of anti-BRAF antibody was also notably higher in the patients with RA than in other rheumatic diseases and normal control groups(P all <0. 01). The diagnostic sensitivity and specificity of anti-BRAF antibody for RA were 53. 6% and 84. 3% respectively. The positive rate of anti-BRAF antibody in rheumatoid factor, anti-cyclic citrullinated peptide antibody, antikera-tin antibody,antiperinuclear factor negative groups were 52. 6% ,38. 2% , 30. 3% and 31.0% respectively. It showed significant negative correlation between the titer of anti-BRAF antibody and patient' s age, disease duration and the level of CRP. Conclusion: The anti-BRAF antibody contributes to the diagnosis of RA, and may act as a supplement of other autoantibodies.%目的:了解抗鼠科肉瘤病毒癌基因同源物B1( v-raf murine sarcoma viral oncogene homologue B1,BRAF)抗体在类风湿关节炎( rheumatoid arthritis,RA)诊断中的临床意义.方法:纳入RA患者112例、健康对照73例、其他风湿病患者112例,以重组人BRAF蛋白为抗原,采用酶联免疫吸附法(enzyme-linked immunosorbent assays,ELISA)检测患者血清中的抗BRAF抗体水

  12. Serum levels of sTREM-1 and IL-17 in patients with rheumatoid arthritis%类风湿关节炎患者血清可溶性髓样细胞触发受体-1、白介素-17水平分析

    Institute of Scientific and Technical Information of China (English)

    吴志明; 郭健; 黄清水

    2012-01-01

    Rheumatoid arthritis (RA) is an inflammatory autoimmune disease of unknown etiology. Many cytokines have been found to be associated with RA pathogenesis. This study aims to investigate the role of soluble triggering receptors expressed on myeloid cells-1 (sTREM-1) and interleukin 17 (IL-17) in RA. sTREM-1 and IL-17 serum levels were determined in serum samples of 114 RA patients (RA group), 39 other antoimmune disease patients (NO RA group), and 32 healthy subjects (HS group) by enzyme-linked immunosorbent assay (ELISA). Anti-cyclic citrullinated peptide (anti-CCP) antibodies, Rheumatoid factor (RHF), C reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) were measured by routine methods. Disease activity was evaluated using the DAS28 score. Patients were subgrouped according to disease activity and years of disease evolution. Statistical analysis was carried out by SPSS 13.0. Inter-group comparison showed increased levels of sTREM-1 and IL-17 in RA patients versus HS (P = 0.03,0.02); in the RA group, the levels of sTREM-1 was higher in active RA patients than stable RA patients (P = 0.02), and sTREM-1 serum levels positively correlated with IL-17 (r = 0.97, P = 0.001), CRP (r = 0.255, P = 0.006) and ESR (r = 0.442, P = 0.001). Moreover, the serum levels of sTREM-1 and IL-17 were not found to be associated with years of RA evolution (P= 0.64, 0.50); there was no significant difference in the sTREM-1 and IL-17 serum levels between RA group and NO RA group (P = 0.39,0.09). These results suggest that serum sTREM-1 and IL-17 levels are positively correlated in RA, they may play a synergistic effect in RA pathogenesis. Furthermore, sTREM-1 may be associated with RA pathogenesis and disease activity, which could be a potent serum marker for clinical activity of rheumatoid arthritis.%目的 检测类风湿关节炎血清可溶性髓样细胞触发受体1 (soluble triggering receptors expressed on myeloid cells-1,sTREM-1)与白介素-17(interleukin-17,IL-17

  13. INVESTIGATION OF CANDIDATE GENE POLYMORPHISMS IN AN IMMUNE RESPONSE AS MARKERS FOR THE RISK OF DEVELOPING RHEUMATOID ARTHRITIS AND PRODUCING AUTOANTIBODIES

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    I. A. Guseva

    2016-01-01

    Full Text Available Objective: to investigate the distribution of the genotypes and alleles of the PTPN22, TNFAIP3, CTLA4, TNFA, IL6, IL6R, IL10, MCP1, and ICAM1 genes in patients with rheumatoid arthritis (RA and in the control group of healthy individuals, to estimate their significance as molecular genetic markers for predisposition to RA; and to analyze the correlation between the gene polymorphisms included in the study and the production of anti-cyclic citrullinated peptide antibodies (ACCPA and IgM rheumatoid factor (RF.Subjects and methods. The investigation was conducted within the framework of the «Early arthritis: Diagnosis, outcome, criteria, active treatment program». The prospective follow-up study included 122 patients with RA fulfilling the 1987 American College of Rheumatology (ACR criteria; with disease duration of ≤ 2 years. 73 (59.8% patients were included during the first 6 months after the onset of the disease. 74 (60.7% and 81 (66.5% patients were found to be positive for ACCPA and IgM RF, respectively. 314 healthy blood donors served as a control group. A real-time polymerase chain reaction was used in the patients and control individuals to study the distribution of the polymorphic variants of PTPN22 (+1858 C >T, rs2476601, TNFAIP3 (rs675520, rs6920220, rs10499194, CTLA4 (+49A>G, rs231775 , TNFА (-308A>G, rs1800629, IL6 (-174G>C, rs1800795, IL6R (+358A>C, rs8192284, IL10 (-592A>C, rs1800872, -1082 A>G, rs1800896, MCP1/CCL2 (+2518A>G, rs1024611, and ICAM1 (721G>A, rs1799969 genes. Results and discussion. This analysis revealed an association of PTPN22 (+1858 C >T, rs2476601 and TNFAIP3 (rs675520, rs10499194 polymorphisms with the risk of RA (odds ratio (OR, 1.5; 95% confidence interval (CI, 1.0–2.3; p = 0.05; OR, 1.5; 95% CI, 1.1–2.0; p = 0.02; OR, 0.5; 95% CI, 0.4–0.8; p = 0.01, respectively. Further, there was a tendency towards a positive association of TNFAIP3 (rs6920220 and IL6R (rs8192284 polymorphisms with a predisposition

  14. The clinical predictive value analysis of multi-autoantibodies detection in the transformation from undifferentiated arthritis to rheumatoid arthritis%自身抗体阳性的未分化关节炎向类风湿关节炎转化的预测价值

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    陈竹; 杨宇峰; 王彩虹; 贾捷婷; 张琳; 张震; 靳志勇; 安广文; 李小峰

    2009-01-01

    Objective To investigate the clinical predictive value of rheumatoid factor (RF), anti-keratin antibodies (AKA), anti-cyclic citrullinated peptide (anti-CCP) antibody and anti-perinuclear factor (APF) in the transition from undifferentiated arthritis (UA) to rheumatoid arthritis (RA), and to analyze the clinical relevant factors. Methods 271 patients with UA who were followed up for a year were enrolled into the investigation. RF was measured by the rate scatting immunity method. APF and AKA were detected by immuniofluorescence method(IFA). Anti-CCP was measured by ELISA. Erythrocyte sedimentation rate (ESR) was analyzed by Wilcoxon method. The duration of morning stiffness, the numbers of swelling and tender joints, tender joints involved and DAS28 score were recorded and analyzed. Results 99% patients who had four-antibody-positive finally convetted from UA to RA. The conversation rate for those who had two or more than two antibody-positive was 83.0% and 65.9% respectively. The sensitivity and specificity of RF and anti-CCP antibody-positive in those who converted from UA to RA was 77.8% and 80.5% respectively. The percentage of polyarticular swelling in antibody-negative, one-antibody-positive, two-antibody-positive, three-antibody- positive and four-antibody-positive was 48%, 57%, 59%, 70% and 70% respectively. Meanwhile, the percentage of multi-small-joint involvement was 71%, 71%, 72%, 76% and 83% respectively. The proportion of elbow involvement in antibody-negative patients was 72%, which was the highest among all joint area involvement. The conversion differences of the group with more than 3 swelling joints or more than 3 small joints involvement ranked the first and second in frequency. Conclusion The combined detection of these autoantibodies could increase the specificity of early diagnosis of RA. The more positive antibodies present, the more likely the concersion form UA to RA. The sensitivity and specificity of RF and anti-CCP-positive is high, so

  15. Clinical value of combined detection of three serum indicators in patients with rheumatoid arthritis%血清3项指标联合检测在类风湿关节炎诊疗中的临床价值

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    杨晏; 吴军伟

    2012-01-01

    目的 探讨抗环瓜氨酸肽抗体(抗CCP)、类风湿因子(RF)和超敏C反应蛋白(hs-CRP)联合检测在类风湿关节炎(RA)诊疗中的临床价值.方法 以53例RA患者、30例非RA患者和25例健康者为研究对象,检测并比较血清抗CCP、RF和hs-CRP水平和阳性率;采用四格表计算抗CCP、RF和hs-CRP不同组合结果的诊断效率.结果 RA患者血清3项指标检测水平和阳性率均显著高于非RA患者和健康者(P<0.01).RA患者血清抗CCP、RF和hs-CRP阳性率分别为84.9%、86.8%和81.1%,非RA患者血清RF和hs-CRP阳性率分别为23.3%和36.7%.3项指标单独检测对RA的诊断性能的优势依次为抗CCP、RF、hs-CRP;抗CCP和RF联合检测的敏感性、特异性和诊断符合率分别为92.5%、81.1%和87.0%;三者联合检测的敏感性、阴性预报率和诊断符合率分别为94.3%、93.3%和85.2%.结论 检测抗CCP诊断RA具有较高的敏感性和特异性,RF和hs-CRP特异性较差;抗CCP和RF联合检测可作为RA患者的筛查指标,有利于早期诊断,hs-CRP对RA病情严重程度的判断及指导治疗具有重要临床价值.%Objective To investigate the clinical value of combined detection of anti-cyclic citrullinated pep tide antibodies (anti-CC P ) , rheum atoid factor(R F ) and high-sensitivity C -reactive protein (hs-C RP ) for the diagnosis and treatm ent of rheum atoid ar-thritis(RA ) .M eihods Serum concentration and positive rate of anti-CCP , RF and hs-CRP were detected and com pared in 53 cases of patients w ith R A ,30 cases of patients w ithout R A and 25 cases of healthy controls . D iagnosis efficiency w ere calculated by m a-trix decision m ethod .Results Serum level and positive rate of the three detected indicators were significantly elevated in patients w ith R A , com pared w ith in patients w ithout R A and in healthy controls ( P<0 .01). T he positive rates of anti-CC P , R F and hs-CRP in patients with R A were 84 .9% ,86.8% and 81.1% ,respectively , while in

  16. Diagnostic Value of Combined Determination of anti-CCP AKA in Patients with Rheumatoid Arthritis%类风湿性关节炎患者类风湿因子抗环瓜氨酸抗体抗角蛋白抗体联合检测的临床意义

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    耿学丽; 张秀琴; 陈向华; 宗春光; 肖丽君; 宋鸿儒

    2015-01-01

    目的:探讨类风湿因子( RF)、抗环瓜氨酸肽抗体(抗CCP 抗体)、抗角蛋白抗体( AKA)联合检测对类风湿性关节炎( RA)的诊断价值,及IgG、IgA、IgM、C3、C4在类风湿性关节炎中的意义。方法:采用免疫散射比浊法检测RF、IgG、IgA、IgM、C3、C4,采用ELISA法检测抗CCP抗体,间接免疫荧光法检测AKA的水平,并对结果进行统计学分析。结果:RA患者组RF、抗CCP 抗体、AKA、IgG、IgA、IgM、C3、C4的水平均高于健康对照组,差异具有统计学意义( P<0.05);RF、抗CCP 抗体、AKA在RA诊断中的敏感度为95%、83.3%、68.3%,特异度为81.2%、96.9%、100%;RF、抗CCP 抗体、AKA联合检测串联实验的敏感性为58.3%,特异性为100%;RF、抗CCP抗体、AKA联合检测并联实验的敏感性为98.3%,特异性为78.1%。结论:以上指标对类风湿性关节炎的诊断具有参考价值;联合检测在一定程度上避免了抗CCP抗体跟AKA的敏感度低,以及RF的特异性低而造成的漏诊,为临床早期诊断断提供依据。%Objective:To evaluate the diagnostic value of combined determination of rheumatoid factor (RF), anti-cyclic citrulline peptide (anti-CCP) antibody, and antikeratin antibody (AKA) in patients with rheumatoid arthritis ( RA ) , and significance of IgG, IgA, IgM, C3 and C4 in rheumatoid arthritis. Method:Scattering method adopts immune turbidimetry was used to detect the level of RF, IgG, IgA, IgM, C3, C4 and measured the levels of anti–CCP by ELISA and measured the levels of AKA indirect immuno-fluorescence method , and the results were analyzed statisticy.Result:The level of RF, anti-CCP antibody , AKA, IgG, IgA, IgM, C3 and C4 in the serum of RA patients was higher than the normal control group, and the difference was statistically significant ( P<0.05) , the diagnostic sensitivity of The RF, anti-CCP an-tibody, AKA were 95%, 83.3%, 68

  17. 4项血清学指标联合检测在类风湿关节炎中的诊断价值%Diagnostic value of combined detection of four serum indicators in patients with rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    张彬; 苏建蓉

    2015-01-01

    Objective To investigate the clinical value of combined detection of anti-cyclic citrullinated peptide antibody(anti-CCP antibody),rheumatoid factor(RF),C-reactive protein(CRP)and erythrocyte sedimentation rate(ESR)in the diagnosis of rheu-matoid arthritis(RA).Methods The detection results of the four serum indicators of 290 cases of patients with RA(RA group), 286 cases of patients with non-RA autoimmune diseases(non-RA group)and 1 50 cases of healthy individuals(control group),from March 2013 to August 2014 in this hospital,were retrospectively analysed.Results The serum levels of the four indicators have significant differences among the three groups,between the RA group and non-RA group,and between the RA group and control group(P =0.000).Between non-RA group and control group,there was significant difference of serum levels of anti-CCP antibodies (P =0.013),while the other three serum indicators had no significant differences (P >0.05).The sensitivity of combined detection of anti-CCP antibody and RF,combined detection of anti-CCP antibody,RF and CRP,combined detection of anti-CCP antibody,RF and ESR,and combined detection of anti-CCP antibody,RF,CRP and ESR for RA diagnosis have statistically significant differences (P 0.05 ).The area under a receiver operating characteristic (ROC) curve of anti-CCP antibody,RF,CRP and ESR were 0.873,0.893,0.678 and 0.747,respectively. Conclusion Combined detection of anti-CCP antibody and RF has good specificity and sensitivity,which could improve the clinical diagnosis of RA.Combined detection of CRP and ESR could improve the detection rate of RA.%目的:探讨抗环瓜氨酸肽抗体(抗-CCP 抗体)、类风湿因子(RF)、C 反应蛋白(CRP)及红细胞沉降率(ESR)联合检测在诊断类风湿关节炎(RA)的临床价值。方法回顾性分析2013年3月至2014年8月该院290例 RA 患者(RA 组)、286例非RA 的自身免疫疾病患者(非 RA 组)及150例体检健康者(对照组)的4项血清

  18. 化痰祛瘀蠲痹方治疗类风湿关节炎的随机对照研究%Effects of Wenhua Juanbi Rescription on TNF- α and IL- 1β in Peripheral Blood of Rheumatoid Arthritis Patients

    Institute of Scientific and Technical Information of China (English)

    韩树利; 宋亚微

    2011-01-01

    Objective: To observe the clinical effect on promoting doses decrease of western medicine and stabilizing patients' condition of Wenhua Juanbi Rescription in treating rheumatoid arthritis( RA). To study the effects of Wenhua Juanbi Prescription on TNF -α,IL - 1β and anti - cyclic citrullinated peptide( CCP) antibody in peripheral blood of RA patients,and to explore the mechanism of Wenhua Juanbi Prescription treating RA preliminary. Methods;One hundred patients with RA were randomly divided into 2 groups,50 in each group:the control group were treated with oral administration of methotrexate (MTX,7.5mg,qw) ,sulfasalazine(0.5g,tid) ,meloxicam( Mobic,7.5mg,bid). The Chinese herbs treatment group were treated with Wenhua Juanbi Prescription and western medicine. The therapeutic course for both groups was 3 months. Clinical effect after treatment,changes of symptoms and physical signs before treatment,the doses of western medicine and the changes of laboratory indexes in 2 groups before and after treatment, and relapse of patients'condition after 3 months in the end of treatment were observed. Results:The total effective rate in the Chinese herbs treatment group was superior to that in the western medicine control group( P <0.05). The improvement in aspects of integral scoring of symptoms and physical signs,including joint swelling, joint activity,joint pain,joint pressing pain,morning stiff, griping,and number of joint swelling in the Chinese herbs treatment group after treatment were sinificantly different from those before treatment and those in the western medicine control group ( P < 0. 05 or P < 0. 01). Comparing with the western medicine control group, doses of MTX and meloxicam, the rate of relapse of patients' condition in the Chinese herbs treatment group decreased significantly( P <0.05 or P <0.01). Compared with before treatment, laboratory indexes in 2 groups including TNF -α,IL - 1β,anti - CCP antibody, RF,ESR,CRP,PLT and Ig were improved sinificantly

  19. 类风湿关节炎患者抑郁症发生的相关因素分析%Analysis on depression and the related factors in patients with rheumatoid arthritis

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    陈晓; 杨敏; 王天; 付睿; 曾小峰

    2013-01-01

    as having depression in this study.There were no significant differences in gender,age,marital status,rheumatoid factor (RF),anti-cyclic citrullinated peptide (Anti-CCP)positive,using of DMARDs and Prednisone dose between the depression and the non-depression group (P > 0.05).There were statistically significant differences in working conditions,cultural degree,annual household income,DAS28,HAQ score between the two groups (P < 0.05).Logistic regression analysis showed that annual household income,disease duration,DAS28,HAQ score were risk factors of depression.Conclusions Depression were frequently seen in RA patients,and were related to high disease activity,more disability and low income.Identifying associated predictors of depression in patients with RA can help diagnosis of depressive symptoms earlier as well as guide targeting treatment.

  20. Consenso da Sociedade Brasileira de Reumatologia 2011 para o diagnóstico e avaliação inicial da artrite reumatoide 2011 Consensus of the Brazilian Society of Rheumatology for diagnosis and early assessment of rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Licia Maria Henrique da Mota

    2011-06-01

    of RA Committee members of the Brazilian Society of Rheumatology. RESULTS AND CONCLUSIONS: The following ten reccommendations were established: 1 RA diagnosis should be established considering clinical findings and complementary test results; 2 Special attention should be given to the differential diagnosis of arthritis; 3 Rheumatoid factor (RF is an important diagnostic test, but has limited sensitivity and specificity, mainly in early RA; 4 Anti-CCP (anti-cyclic citrullinated peptide antibody is a marker with sensitivity similar to that of the RF, but with higher specificity, mainly in the initial phase of disease; 5 Although unspecific, acute-phase reactants should be measured in patients with clinical suspicion of RA; 6 Conventional radiography should be performed for diagnostic and prognostic assessment of the disease. When necessary and available, ultrasound and magnetic resonance may be used; 7 Rheumatoid arthritis classification criteria (ACR/EULAR 2010, although not yet validated, may be used as a guide to aid in diagnosing patients with early RA; 8 One of the combined disease activity indices should be used to assess disease activity; 9 At least one of the functional capacity assessment instruments, such as mHAQ or HAQ-DI, should be regularly used; 10 At the early assessment of the disease, the presence of worse prognostic factors, such as polyarticular involvement, high titers of RF and/or anti-CCP, and early joint erosion, should be investigated.

  1. 临床缓解类风湿关节炎患者的超声评估%Ultrasound assessment of rheumatoid arthritis patients with clinically remission

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    张斌; 张珠凤; 顾娟芳; 王宏智

    2016-01-01

    ,acromioclavicular joint,shoulder joint,elbow joint,wrist joint,1-5 metacarpophalangeal joints and the interphalangeal joint of the thumb,the 2-5 proximal interphalangeal joints,the 2-5 distal interphalangeal joints,hip,knee joint,ankle joint,tarsus joint,the 1-5 metatarsophalangeal joint,1-5 toeinterphalangeal joints.Analysis for the correlation between PD,GS score and gender,age,course of disease and clinical disease activity index were conducted.The pain visual analogue scale (VAS),time of morning stiffness,swollen joint count (SJC) and tender joint count (TJC),health assessment questionnaire (HAQ) score,erythrocyte sedimentation rate (ESR),and C-reactive protein (CRP) and rheumatoid factor (RF),anti cyclic citrullinated peptide (anti CCP) antibody,simplified disease activity index (SDAI),DAS28-CRP,DAS28-ESR were compared.Using Pearson and Spearman to analyze ultrasonic joint synovitis index score and clinical indexes,Student's t-test was employed to assess the significance of difference between two independent sample.Results Twenty-six patients reached/European League against Rheumatism (ACR/EULAR) 2011 remission,19 patients achieved ACR remission,and 3 patients achieved ultrasound remission.There was correlation between GS score and the course of disease and the number of swollen joints (r=0.602,0.470,P<0.01).There was a positive correlation between ultrasound PD score and the patient's pain score,the total score of patients,ACR/EULAR2011,DAS28-ESR,DAS28-CRP (r=0.323,0.337,0.329,0.360,0.343,P<0.05).The ultrasound PD score also had a positive correlation with CRP,ESR,time of morning stiffness (r=0.474,0.490,0.415,P<0.01).Conclusion The subclinical arthrosynovitis can be detected by high frequency ultrasound in most rheumatoid arthritis patients at clinical remission.The PD ultrasound has advantage in evaluating RA activity over GS ultrasound.

  2. The application of matrix metalloproteinase-3 and 7 joints ultrasonic score in assessment of disease activity in patients with rheumatoid arthritis%血清基质金属蛋白酶-3和7个关节超声评分在类风湿关节炎病情活动性评估中的应用

    Institute of Scientific and Technical Information of China (English)

    周凌; 宋婧; 陈凌; 徐沪济

    2016-01-01

    anti-cyclic citrullinated peptide (CCP) antibody,health assessment questionnaire (HAQ) and disease activity score 28 (DAS28) were measured.The level of disease activity is interpreted as remission(DAS28 <2.6),low(DAS 28≥2.6-<3.2),moderate(DAS 28≥3.2-<5.1),high(DAS28≥5.1).The discriminating validity of MMP-3 and US7 score in disease was evaluated using receiver operating characteristic (ROC) curve analysis with DAS28 as the reference standard.Results Compared with that in healthy controls [35.20(25.90,48.90) μg/L] and remission patients[33.40(22.60,678.40) μg/L],the MMP-3 level in moderate [105.1 (61.70,172.70) μg/L] and high [363.1 (161.50,475.90) μg/L]groups increased dramatically.US7 score in patients with high disease activity was significantly higher than that in other groups.The level of MMP-3 was significantly correlated with DAS28,HAQ,US7 score,yet did not have correlation with anti-CCP antibody.Serum level of MMP-3 was positively correlated with US7 score (r =0.566,P < 0.001).In evaluating the disease activity,US7 score combined with MMP-3 (AUC 0.863 2) was not superior to MMP-3 alone (AUC 0.854 3),but significantly better than single US7 score (AUC 0.7643,P < 0.05).Conclusions MMP-3 is an effective and simple index in evaluating RA disease activity.The combination of MMP-3 and US7 score does not further improve the efficacy to evaluate disease activity than MMP-3 alone in patients with RA.

  3. Expression and significance of survivin in rheumatoid arthritis synovium%存活素在类风湿关节炎滑膜组织中的表达及意义

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    马莎; 林俊; 杨慧; 晋松; 李芹; 郑红梅; 王静; 杨永红

    2014-01-01

    ,age,course of disease,erythrocyte sedimentation rate (ESR),C reactive protein (CRP),rheumatoid factor (RF),anti-cyclic citrullinated peptide antibodies (CCP) and DAS28 score.Comparison of means of above parameters in multiple groups was conducted with variance analysis.Pair-wise comparisons among groups were conducted with one-way ANOVA.The expression of survivin was examined and compared among the three groups,the relationship between survivin and the clinical pathological features of the active group of RA were analyzed.The likelihood ratio chi-square test or Pearson chi-square test was used in the comparison of rates,Spearman's correlation analysis was used among parameters in the study.Results ① The expression of survivin in synovial tissue of patients with RA was significantly higher than that in OA group and normal control group (P=0.001).② The expression of survivin in synovial tissue of active RA group was significantly higher than in the remission group (x2=41.62,P=0.001).③ The survivin expression level was positively correlated with ESR,CRP,DAS28 score (r=0.297,0.411,0.416 respectively,P<0.05),but not correlated with anti-CCP,RF,sex,patients' age and course of disease in RA patients (r=0.004,-0.1 14.,-0.074,-0.035,-0.188 respectively,P>0.05).Conclusion The increased expression of survivin in RA synovial tissue has shown that the synovial fibroblast abnormal apoptosis is associated with survivin,and the increasing of survivin is involved in the pathogenesis of RA.Detection of survivin level is helpful for evaluation of RA disease activity.

  4. Studyon Anxiety and Depression of 604 Patients with Rheumatoid Arthritis%604例类风湿关节炎患者的焦虑抑郁情绪及相关性研究

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    孙玥; 刘健; 方利; 朱福兵; 谈冰; 章平衡

    2016-01-01

    (Treg)and B and T lymphocyte attenuator (BTLA),and to made a determination of indexes of erythrocyte sedimentation rate(ESR),immunoglobulin G (IgG),immunoglobulin M(IgM),C- reactive protein(CRP),rheumatoid factor(RF)and anti cyclic citrullinated peptide(CCP)antibody,calculating the disease activity score(DAS28).Results:①Compared with the healthy control group,more than 70% patients in the RA group had HAQ,SDS and SAS integral anomaly:the higher scores of HAQ,SDS and SAS,the higher inflammatory indexes of ESR and CRP and the decrease of expression frequency of BTLA and Treg.② Correlation analysis showed that in the RA group the HAQ scores were positively correlated with ESR,RF,IgG,BTLA and Treg;SDS scores were negatively correlated with ESR,CRP,RF,IgG,BTLA,and Treg and positively correlated with anti CCP antibody and IgM;and SAS scores were positively correlated with ESR and IgG and negatively correlated with anti CCP antibody,BTLA and Treg.Conclusion:Many RA patients have anxiety and depression associated with disease activity and disorder of immune function,which is a concrete manifestation of RA.

  5. Protein arginine deiminase 4 inhibition is sufficient for the amelioration of collagen-induced arthritis.

    Science.gov (United States)

    Willis, V C; Banda, N K; Cordova, K N; Chandra, P E; Robinson, W H; Cooper, D C; Lugo, D; Mehta, G; Taylor, S; Tak, P P; Prinjha, R K; Lewis, H D; Holers, V M

    2017-01-27

    Citrullination of joint proteins by the protein arginine deiminase (PAD) family of enzymes is recognized increasingly as a key process in the pathogenesis of rheumatoid arthritis. This present study was undertaken to explore the efficacy of a novel PAD4-selective inhibitor, GSK199, in the murine collagen-induced arthritis model of rheumatoid arthritis. Mice were dosed daily from the time of collagen immunization with GSK199. Efficacy was assessed against a wide range of end-points, including clinical disease scores, joint histology and immunohistochemistry, serum and joint citrulline levels and quantification of synovial autoantibodies using a proteomic array containing joint peptides. Administration of GSK199 at 30 mg/kg led to significant effects on arthritis, assessed both by global clinical disease activity and by histological analyses of synovial inflammation, pannus formation and damage to cartilage and bone. In addition, significant decreases in complement C3 deposition in both synovium and cartilage were observed robustly with GSK199 at 10 mg/kg. Neither the total levels of citrulline measurable in joint and serum, nor levels of circulating collagen antibodies, were affected significantly by treatment with GSK199 at any dose level. In contrast, a subset of serum antibodies reactive against citrullinated and non-citrullinated joint peptides were reduced with GSK199 treatment. These data extend our previous demonstration of efficacy with the pan-PAD inhibitor Cl-amidine and demonstrate robustly that PAD4 inhibition alone is sufficient to block murine arthritis clinical and histopathological end-points.

  6. GAP1, a novel selection and counter-selection marker for multiple gene disruptions in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Regenberg, Birgitte; Hansen, J.

    2000-01-01

    We report on the use of a new homologous marker for use in multiple gene deletions in S, cerevisiae, the general amino acid permease gene (GAP1), A GAP1 strain can utilize L-citrulline as the sole nitrogen source but cannot grow in the presence of the toxic amino acid D-histidine, L-citrulline as......We report on the use of a new homologous marker for use in multiple gene deletions in S, cerevisiae, the general amino acid permease gene (GAP1), A GAP1 strain can utilize L-citrulline as the sole nitrogen source but cannot grow in the presence of the toxic amino acid D-histidine, L......-citrulline as well as D-histidine uptake is mediated solely by the general amino acid permease, and a gap1 strain is therefore able to grow in the presence of D-histidine but cannot utilize L-citrulline, Gene disruption is effected by transforming a gap1 strain with a gene cassette generated by PCR, containing GAP1...... the GAP1 gene. This is caused by recombination between two Salmonella typuimurium hisG direct repeats embracing GAP1, and will result in a sub-population of gap1 cells. Such cells are selected on a medium containing D-histidine, and may subsequently be used for a second gene disruption. Hence, multiple...

  7. Posttranslational Protein Modification in the Salivary Glands of Sjögren's Syndrome Patients.

    Science.gov (United States)

    Herrera-Esparza, Rafael; Rodríguez-Rodríguez, Mayra; Pérez-Pérez, María Elena; Badillo-Soto, Martha Adriana; Torres-Del-Muro, Felipe; Bollain-Y-Goytia, Juan José; Pacheco-Tovar, Deyanira; Avalos-Díaz, Esperanza

    2013-01-01

    The present study investigated posttranslational reactions in the salivary glands of patients with Sjögren's syndrome. We analysed the biopsies of primary Sjögren's patients using immunohistochemistry and a tag-purified anticyclic citrullinated protein (CCP) antibody to detect citrullinated peptides, and the presence of peptidylarginine deiminase 2 (PAD2) was assessed simultaneously. The present work demonstrated the weak presence of the PAD2 enzyme in some normal salivary glands, although PAD2 expression was increased considerably in Sjögren's patients. The presence of citrullinated proteins was also detected in the salivary tissues of Sjögren's patients, which strongly supports the in situ posttranslational modification of proteins in this setting. Furthermore, the mutual expression of CCP and PAD2 suggests that this posttranslational modification is enzyme dependent. In conclusion, patients with Sjögren's syndrome expressed the catalytic machinery to produce posttranslational reactions that may result in autoantigen triggering.

  8. The nitric oxide synthase of mouse spermatozoa.

    Science.gov (United States)

    Herrero, M B; Goin, J C; Boquet, M; Canteros, M G; Franchi, A M; Perez Martinez, S; Polak, J M; Viggiano, J M; Gimeno, M A

    1997-07-01

    Nitric oxide synthase (NOS) was evidenced in mature mouse spermatozoa by means of biochemical techniques and Western blot. During 120 min of incubation, 10(7) spermatozoa synthesized 7 +/- 2 pmol of L-[14C]citrulline. Besides, L-citrulline formation depended on the incubation time and on the concentration of L-arginine present in the incubation medium. Different concentrations of N(G)-nitro-L-arginine methyl ester (L-NAME) but not aminoguanidine, inhibited L-[14C]citrulline formation. Western-blot analysis of solubilized sperm proteins revealed a unique band of M(r)=140 kDa with the neural, endothelial and inducible NOS antisera tested. These results provide evidence that mature mouse sperm contains a NOS isoform and that spermatozoa have the potential ability to synthesize NO, suggesting a role for endogenous NO on mammalian sperm function.

  9. Arginine synthesis from enteral glutamine in healthy adults in the fed state.

    Science.gov (United States)

    Tomlinson, Chris; Rafii, Mahroukh; Ball, Ronald O; Pencharz, Paul

    2011-08-01

    Recent studies have documented transfer of labeled nitrogen from [2-(15)N]glutamine to citrulline and arginine in fasting human adults. Conversely, in neonates and piglets we have shown no synthesis of arginine from [2-(15)N]glutamate, and others have shown in mice that glutamine is a nitrogen, but not a carbon donor, for arginine synthesis. Therefore, we performed a multitracer study to determine whether glutamine is a nitrogen and/or carbon donor for arginine in healthy adult men. Two glutamine tracers, 2-(15)N and 1-(13)C, were given enterally to five healthy men fed a standardized milkshake diet. There was no difference in plasma enrichments between the two glutamine tracers. 1-(13)C isotopomers of citrulline and arginine were synthesized from [1-(13)C]glutamine. Three isotopomers each of citrulline and arginine were synthesized from the [2-(15)N]glutamine tracer: 2-(15)N, 5-(15)N, and 2,5-(15)N(2). Significantly greater enrichment was found of both [5-(15)N]arginine (0.75%) and citrulline (3.98%) compared with [2-(15)N]arginine (0.44%) and [2-(15)N]citrulline (2.62%), indicating the amino NH(2) from glutamine is mostly transferred to arginine and citrulline by transamination. Similarly, the enrichment of the 1-(13)C isotopomers was significantly less than the 2-(15)N isotopomers, suggesting rapid formation of α-ketoglutarate and recycling of the nitrogen label. Our results show that the carbon for 50% of newly synthesized arginine comes from dietary glutamine but that glutamine acts primarily as a nitrogen donor for arginine synthesis. Hence, studies using [2-(15)N]glutamine will overestimate arginine synthesis rates.

  10. Peptidylarginine Deiminase 3 (PAD3 Is Upregulated by Prolactin Stimulation of CID-9 Cells and Expressed in the Lactating Mouse Mammary Gland.

    Directory of Open Access Journals (Sweden)

    Guangyuan Li

    Full Text Available Peptidylarginine deiminases (PADs post-translationally convert arginine into neutral citrulline residues. Our past work shows that PADs are expressed in the canine and murine mammary glands; however, the mechanisms regulating PAD expression and the function of citrullination in the normal mammary gland are unclear. Therefore, the first objective herein was to investigate regulation of PAD expression in mammary epithelial cells. We first examined PAD levels in CID-9 cells, which were derived from the mammary gland of mid-pregnant mice. PAD3 expression is significantly higher than all other PAD isoforms and mediates protein citrullination in CID-9 cells. We next hypothesized that prolactin regulates PAD3 expression. To test this, CID-9 cells were stimulated with 5 μg/mL of prolactin for 48 hours which significantly increases PAD3 mRNA and protein expression. Use of a JAK2 inhibitor and a dominant negative (DN-STAT5 adenovirus indicate that prolactin stimulation of PAD3 expression is mediated by the JAK2/STAT5 signaling pathway in CID-9 cells. In addition, the human PAD3 gene promoter is prolactin responsive in CID-9 cells. Our second objective was to investigate the expression and activity of PAD3 in the lactating mouse mammary gland. PAD3 expression in the mammary gland is highest on lactation day 9 and coincident with citrullinated proteins such as histones. Use of the PAD3 specific inhibitor, Cl4-amidine, indicates that PAD3, in part, can citrullinate proteins in L9 mammary glands. Collectively, our results show that upregulation of PAD3 is mediated by prolactin induction of the JAK2/STAT5 signaling pathway, and that PAD3 appears to citrullinate proteins during lactation.

  11. Identification of a linear epitope recognized by a monoclonal antibody directed to the heterogeneous nucleoriboprotein A2

    DEFF Research Database (Denmark)

    Tronstrøm, Julie; Dragborg, Anette H.; Hansen, Paul Robert;

    2014-01-01

    Rheumatoid arthritis (RA) is a chronic autoimmune disorder, characterized by progressive joint destruction and disability. Classical autoantibodies of RA are rheumatoid factors and citrulline antibodies. Patients positive for these autoantibodies are usually associated with a progressive disease...... to as RA33. In the absence of citrulline antibodies, RA33 antibodies have been suggested to be associated with a milder disease course. In this study we screened the reactivity of a monoclonal antibody to RA33-derived peptides by modified enzyme-linked immunosorbent assays (ELISA). Terminally truncated...

  12. 类风湿关节炎患者血清抗鼠科肉瘤病毒癌基因同源物B1抗体检测及临床意义探讨%Detection of serum anti v-raf murine sarcoma viral oncogene homologue B1 antibodies in patients with rheumatoid arthritis and the assessment of its clinical significance

    Institute of Scientific and Technical Information of China (English)

    李扬; 竺红

    2014-01-01

    Objective To investigate the serum levels of anti-BRAF antibody in patients with rheumatoid arthritis (RA) and its clinical significance.Methods Blood samples from 129 patients with RA,71 patients with other rheumatic diseases and 68 healthy controls were measured by enzyme-linked immunosorbent assays (ELISA).The serum levels of anti-BRAF antibody in patients with RA were divided into high,medium and low groups,each group had 43 cases.The clinical symptoms,immunological findings and related imaging data of all cases were recorded.We investigated the relationship between the serum levels of anti-BRAF antibody and the clinical symptoms,immunological findings and related imaging changes of the RA group.Chi-square test,Mann-Whitney U test,Spearman's correlation test were used for statistical analysis.Results ① The serum levels of anti-BRAF antibody were significantly higher in RA group [A:1.093 (0.150-3.210)] than in other rheumatic diseases group [A:0.278 (0.093-0.455)] and healthy controls [A:0.202 (0.121-0.443)] (Z=-11.223,P=0.021 ; Z=-7.839,P=0.008 7).The serum levels of anti-BRAF antibody was not significantly different between patients with other rheumatic diseases group and healthy controls (Z=-0.905,P=0.445).② The difference in positive rate of rheumatoid factor (RF) in different groups of anti-BRAF antibody levels was statistically significant (λx2=10.14,P=0.006),namely the positive rate was significantlyhigher in the low-level group (88%) than in the high-level group (58%) (x2=10.03,P=0.002).Thepositive rate of anti-cyclic citrullinated peptide antibody and anti-keratin antibody of the three groups was not significantly different (x2=0.721,P=0.697; x2=1.735,P=0.188).③ There was significant negative correlation between the levels of anti-BRAF antibody and the course of disease (r=-0.233,P=0.047),RF(r=-2.84,P=0.039),IgM (r=-0.234,P=0.038),and hemoglobin (r=-0.287,P=0.032).There was no significant correlation between the level of anti-BRAF antibody

  13. The Euro crisis. Causes and Symptoms

    Directory of Open Access Journals (Sweden)

    Christoph S. Weber

    2015-06-01

    Full Text Available The Euro crisis is mainly a consequence of the international financial crisis of 2008. Thereby, the term Euro crisis is misleading as there is no currency crisis. First, the article shows some of the birth defects of the Euro. Second, it shows that the increase in public debt was caused by rescue measures for banks and anti-cyclical fiscal policy. Third, we argue that the Euro crisis is not just one crisis (a sovereign debt crisis but it is a combination of several macroeconomic crises including a growth crisis, a labour market crisis, a public debt crisis, and a current account crisis.

  14. The microbiome, intestinal function, and arginine metabolism of healthy Indian women are different from those of American and Jamaican women

    Science.gov (United States)

    Indian women have slower arginine flux during pregnancy compared with American and Jamaican women. Arginine is a semi-essential amino acid that becomes essential during periods of rapid lean tissue deposition. It is synthesized only from citrulline, a nondietary amino acid produced mainly in the gut...

  15. Metabolomic profiling identifies potential pathways involved in the interaction of iron homeostasis with glucose metabolism

    Directory of Open Access Journals (Sweden)

    Lars Stechemesser

    2017-01-01

    Conclusions: Our data suggest that high serum ferritin concentrations are linked to impaired glucose homeostasis in subjects with the MetS. Iron excess is associated to distinct changes in the serum concentrations of phosphatidylcholine subsets. A pathway involving sarcosine and citrulline also may be involved in iron-induced impairment of glucose metabolism.

  16. Left ventricular deformation at 2-year follow-up in treatment-naive rheumatoid arthritis patients is associated with high inflammation parameters

    DEFF Research Database (Denmark)

    Logstrup, B. B.; Masic, D.; Laurbjerg, T. B.;

    2015-01-01

    Introduction: Patients with rheumatoid arthritis (RA) are at increased risk of cardiovascular disease (CVD). The role of autoimmunity and especially citrullination in the pathogenesis of the increased risk of CVD and the time-course of left ventricular (LV) dysfunction are unknown. Hypothesis: To...

  17. Combining a Laboratory Practical Class with a Computer Simulation: Studies on the Synthesis of Urea in Isolated Hepatocytes.

    Science.gov (United States)

    Bender, David A.

    1986-01-01

    Describes how a computer simulation is used with a laboratory experiment on the synthesis of urea in isolated hepatocytes. The simulation calculates the amount of urea formed and the amount of ammonium remaining as the concentrations of ornithine, citrulline, argininosuccinate, arginine, and aspartate are altered. (JN)

  18. Fine Mapping Seronegative and Seropositive Rheumatoid Arthritis to Shared and Distinct HLA Alleles by Adjusting for the Effects of Heterogeneity

    NARCIS (Netherlands)

    Han, Buhm; Diogo, Dorothee; Eyre, Steve; Kallberg, Henrik; Zhernakova, Alexandra; Bowes, John; Padyukov, Leonid; Okada, Yukinori; Gonzalez-Gay, Miguel A.; Rantapaa-Dahlqvist, Solbritt; Martin, Javier; Huizinga, Tom W. J.; Plenge, Robert M.; Worthington, Jane; Gregersen, Peter K.; Klareskog, Lars; de Bakker, Paul I. W.; Raychaudhuri, Soumya

    2014-01-01

    Despite progress in defining human leukocyte antigen (HLA) alleles for anti-citrullinated-protein-autoantibody-positive (ACPA(+)) rheumatoid arthritis (RA), identifying HLA alleles for ACPA-negative (ACPA(-)) RA has been challenging because of clinical heterogeneity within clinical cohorts. We imput

  19. Neutrophil extracellular traps - the dark side of neutrophils

    DEFF Research Database (Denmark)

    Sørensen, Ole E; Borregaard, Niels

    2016-01-01

    originally described in vitro. Citrullination of histones by peptidyl arginine deiminase 4 (PAD4) is central for NET formation in vivo. NETs may spur formation of autoantibodies and may also serve as scaffolds for thrombosis, thereby providing a link among infection, autoimmunity, and thrombosis...

  20. Porphyromonas gingivalis facilitates the development and progression of destructive arthritis through its unique bacterial peptidylarginine deiminase (PAD.

    Directory of Open Access Journals (Sweden)

    Katarzyna J Maresz

    2013-09-01

    Full Text Available Rheumatoid arthritis and periodontitis are two prevalent chronic inflammatory diseases in humans and are associated with each other both clinically and epidemiologically. Recent findings suggest a causative link between periodontal infection and rheumatoid arthritis via bacteria-dependent induction of a pathogenic autoimmune response to citrullinated epitopes. Here we showed that infection with viable periodontal pathogen Porphyromonas gingivalis strain W83 exacerbated collagen-induced arthritis (CIA in a mouse model, as manifested by earlier onset, accelerated progression and enhanced severity of the disease, including significantly increased bone and cartilage destruction. The ability of P. gingivalis to augment CIA was dependent on the expression of a unique P. gingivalis peptidylarginine deiminase (PPAD, which converts arginine residues in proteins to citrulline. Infection with wild type P. gingivalis was responsible for significantly increased levels of autoantibodies to collagen type II and citrullinated epitopes as a PPAD-null mutant did not elicit similar host response. High level of citrullinated proteins was also detected at the site of infection with wild-type P. gingivalis. Together, these results suggest bacterial PAD as the mechanistic link between P. gingivalis periodontal infection and rheumatoid arthritis.

  1. Inflammatory response to mucosal barrier injury after myeloablative therapy in allogeneic stem cell transplant recipients.

    NARCIS (Netherlands)

    Blijlevens, N.M.A.; Donnelly, J.P.; Pauw, B.E. de

    2005-01-01

    We noted a significant increase of interleukin-8 (IL-8), LBP and CRP mirroring the pattern of mucosal barrier injury as measured by gut integrity (lactulose/rhamnose ratio), daily mucositis score (DMS) and serum citrulline concentrations of 32 haematopoietic stem cell transplant (HSCT) recipients fo

  2. Pre-treatment antinuclear antibody positivity, therapeutic efficacy and persistence of biologics in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Codreanu Cătălin

    2016-06-01

    Full Text Available Introduction: Rheumatoid factor (RF and anti-citrullinated protein antibodies (ACPA are poor prognostic factors in rheumatoid arthritis (RA. The therapeutic implication of antinuclear antibody (ANA positivity in RA is still debated. The study aims to evaluate ANA positivity as a prognostic factor for the therapeutic response to biologics in RA.

  3. Plasma amino acid levels are elevated in young, healthy low birth weight men exposed to short-term high-fat overfeeding

    DEFF Research Database (Denmark)

    Ribel-Madsen, Amalie; Hellgren, Lars; Brøns, Charlotte;

    2016-01-01

    and after a 5‐day high‐fat, high‐calorie diet. We demonstrated that LBW and NBW men increased plasma alanine levels and decreased valine and leucine/isoleucine levels in response to overfeeding. Also, LBW men had higher alanine, proline, methionine, citrulline, and total amino acid levels after overfeeding...

  4. High Protein Diet and Huntington's Disease.

    Directory of Open Access Journals (Sweden)

    Chiung-Mei Chen

    Full Text Available Huntington's disease (HD is a neurodegenerative disorder caused by the huntingtin (HTT gene with expanded CAG repeats. In addition to the apparent brain abnormalities, impairments also occur in peripheral tissues. We previously reported that mutant Huntingtin (mHTT exists in the liver and causes urea cycle deficiency. A low protein diet (17% restores urea cycle activity and ameliorates symptoms in HD model mice. It remains unknown whether the dietary protein content should be monitored closely in HD patients because the normal protein consumption is lower in humans (~15% of total calories than in mice (~22%. We assessed whether dietary protein content affects the urea cycle in HD patients. Thirty HD patients were hospitalized and received a standard protein diet (13.7% protein for 5 days, followed by a high protein diet (HPD, 26.3% protein for another 5 days. Urea cycle deficiency was monitored by the blood levels of citrulline and ammonia. HD progression was determined by the Unified Huntington's Disease Rating Scale (UHDRS. The HPD increased blood citrulline concentration from 15.19 μmol/l to 16.30 μmol/l (p = 0.0378 in HD patients but did not change blood ammonia concentration. A 2-year pilot study of 14 HD patients found no significant correlation between blood citrulline concentration and HD progression. Our results indicated a short period of the HPD did not markedly compromise urea cycle function. Blood citrulline concentration is not a reliable biomarker of HD progression.

  5. In palindromic rheumatism, hand joint involvement and positive anti-CCP antibodies predict RA development after 1 year of follow-up

    NARCIS (Netherlands)

    Emad, Yasser; Anbar, Ashraf; Abo-Elyoun, Ihab; El-Shaarawy, Nashwa; Al-Hanafi, Hadeel; Darwish, Hatem; Gamil, Mona; Rasker, Johannes J.

    2014-01-01

    This study aimed to determine the frequency of rheumatoid factor (RF) and cyclic citrullinated peptide (CCP) antibodies in a cohort of patients with palindromic rheumatism (PR) and to find determinants for progression to rheumatoid arthritis (RA). All new cases of PR (n = 90) were included prospecti

  6. Four weeks of treatment with liraglutide reduces insulin dose without loss of glycemic control in type 1 diabetic patients with and without residual beta-cell function

    DEFF Research Database (Denmark)

    Kielgast, Urd; Holst, Jens Juul; Madsbad, Sten

    2011-01-01

    OBJECTIVE To investigate the effect of 4 weeks of treatment with liraglutide on insulin dose and glycemic control in type 1 diabetic patients with and without residual ß-cell function. RESEARCH DESIGN AND METHODS Ten type 1 diabetic patients with residual ß-cell function (C-peptide positive) and 19.......1]; P type 1 diabetic patients reduces insulin dose with improved or unaltered glycemic control.......-peptide-positive patients and from 0.72 ± 0.08 to 0.59 ± 0.06 units/kg per day (P correlated with ß...

  7. Perioperative glutamine supplementation restores disturbed renal arginine synthesis after open aortic surgery: a randomized controlled clinical trial.

    Science.gov (United States)

    Brinkmann, Saskia J H; Buijs, Nikki; Vermeulen, Mechteld A R; Oosterink, Efraim; Schierbeek, Henk; Beishuizen, Albertus; de Vries, Jean-Paul P M; Wisselink, Willem; van Leeuwen, Paul A M

    2016-09-01

    Postoperative renal failure is a common complication after open repair of an abdominal aortic aneurysm. The amino acid arginine is formed in the kidneys from its precursor citrulline, and citrulline is formed from glutamine in the intestines. Arginine enhances the function of the immune and cardiovascular systems, which is important for recovery after surgery. We hypothesized that renal arginine production is diminished after ischemia-reperfusion injury caused by clamping of the aorta during open abdominal aortic surgery and that parenteral glutamine supplementation might compensate for this impaired arginine synthesis. This open-label clinical trial randomized patients who underwent clamping of the aorta during open abdominal aortic surgery to receive a perioperative supplement of intravenous alanyl-glutamine (0.5 g·kg(-1)·day(-1); group A, n = 5) or no supplement (group B, n = 5). One day after surgery, stable isotopes and tracer methods were used to analyze the metabolism and conversion of glutamine, citrulline, and arginine. Whole body plasma flux of glutamine, citrulline, and arginine was significantly higher in group A than in group B (glutamine: 391 ± 34 vs. 258 ± 19 μmol·kg(-1)·h(-1), citrulline: 5.7 ± 0.4 vs. 2.8 ± 0.4 μmol·kg(-1)·h(-1), and arginine: 50 ± 4 vs. 26 ± 2 μmol·kg(-1)·h(-1), P glutamine (4.8 ± 0.7 vs. 1.6 ± 0.3 μmol·kg(-1)·h(-1)), citrulline from arginine (2.3 ± 0.3 vs. 0.96 ± 0.1 μmol·kg(-1)·h(-1)), and arginine from glutamine (7.7 ± 0.4 vs. 2.8 ± 0.2 μmol·kg(-1)·h(-1)), respectively (P arginine is severely reduced after clamping during aortic surgery. This study shows that an intravenous supplement of glutamine increases the production of citrulline and arginine and compensates for the inhibitory effect of ischemia-reperfusion injury.

  8. Peptidyl arginine deiminase from Porphyromonas gingivalis abolishes anaphylatoxin C5a activity.

    Science.gov (United States)

    Bielecka, Ewa; Scavenius, Carsten; Kantyka, Tomasz; Jusko, Monika; Mizgalska, Danuta; Szmigielski, Borys; Potempa, Barbara; Enghild, Jan J; Prossnitz, Eric R; Blom, Anna M; Potempa, Jan

    2014-11-21

    Evasion of killing by the complement system, a crucial part of innate immunity, is a key evolutionary strategy of many human pathogens. A major etiological agent of chronic periodontitis, the Gram-negative bacterium Porphyromonas gingivalis, produces a vast arsenal of virulence factors that compromise human defense mechanisms. One of these is peptidylarginine deiminase (PPAD), an enzyme unique to P. gingivalis among bacteria, which converts Arg residues in polypeptide chains into citrulline. Here, we report that PPAD citrullination of a critical C-terminal arginine of the anaphylatoxin C5a disabled the protein function. Treatment of C5a with PPAD in vitro resulted in decreased chemotaxis of human neutrophils and diminished calcium signaling in monocytic cell line U937 transfected with the C5a receptor (C5aR) and loaded with a fluorescent intracellular calcium probe: Fura-2 AM. Moreover, a low degree of citrullination of internal arginine residues by PPAD was also detected using mass spectrometry. Further, after treatment of C5 with outer membrane vesicles naturally shed by P. gingivalis, we observed generation of C5a totally citrullinated at the C-terminal Arg-74 residue (Arg74Cit). In stark contrast, only native C5a was detected after treatment with PPAD-null outer membrane vesicles. Our study suggests reduced antibacterial and proinflammatory capacity of citrullinated C5a, achieved via lower level of chemotactic potential of the modified molecule, and weaker cell activation. In the context of previous studies, which showed crosstalk between C5aR and Toll-like receptors, as well as enhanced arthritis development in mice infected with PPAD-expressing P. gingivalis, our findings support a crucial role of PPAD in the virulence of P. gingivalis.

  9. DOMETI FISKALNE POLITIKE U PODSTICANJU PRIVREDNOG RASTA

    Directory of Open Access Journals (Sweden)

    Predrag Mlinarević

    2013-01-01

    Full Text Available The issue of use of expansive fiscal instruments in order to encourage the growth has produced in the past as it does today, a significant division among economists. This division is reflected in the doctrinal and practical aspects. Doctrinal aspect touches different approaches to state interventionism. While its supporters within Keynesian teachings believe that the recession could become a permanent condition if the state does not reach for anti-cyclical policies, the supporters of the infallibility of the market believe that it would result in inflation without affecting growth. This paper presents, with inevitable reference to the genesis of bipolar thinking, the results of empirical studies and our own research on the value of the relevant fiscal multipliers as realistic measures of effectualization of fiscal stimulus to economic growth. Conferring a direct connection between appropriate fiscal stimulus packages with the growth of economic activity will give an answer to the issue about the effectiveness of cyclic measures. It turned out that the results are different for developed countries compared to those who belong to the group of developing countries. It has been proved that for developing countries it is much more useful to rely on public investment in relation to the growth of public spending. It should serve as a guide to the holders of economic power in composing the measures that will form the anti-cyclical economic policies during the current crisis.

  10. Struktura rizikových přirážek vlastníků dle citlivosti odvětví na hospodářský cyklus

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    Zdeněk Konečný

    2013-10-01

    Full Text Available Purpose of the article: All national economies go through their economic cycle and partial sectors of these economies go through their market life cycle, too. But the course of the market life cycle doesn’t have to ever be the same as in the case of the economic cycle. So, there exist sectors with different sensitivities to economic cycle. The sector sensitivity can considerably influence many financial quantities, especially quantities describing the entrepreneurial risk, which can be expressed in form of cost of capital. The main aim of this article is to find out the structure of cost of equity, which is required in sectors with different sensitivity to the economic cycle. Methodology/methods: There are used and analyzed secondary data for periods from I. 2007 to II. 2011, gotten from materials published by the Czech Statistical Office and the Czech Ministry of Industry and Trade. The sector sensitivity is measured according to the correlation between gross domestic product (GDP, used for considering the economic cycle, and amount of sales reached on the sector, used for identifying the market life cycle. The structure of owner’s risk rewards is calculated with the use of the constructional model by the Czech Ministry of Industry and Trade. Scientific aim: There is selected one cyclical, one neutral and one anti-cyclical, ever with the extreme value of the coefficient of correlation. By each of these three sectors there is calculated the structure of cost of equity to know shares of partial owner’s risk rewards. Findings: Highest values of all risk rewards are reached in the anti-cyclical sector. On the contrary there is reached the lowest value of risk reward to the size of the company (rLA in the cyclical sector and of the risk reward to entrepreneurial risk (rPOD in the neutral sector. The risk reward to financial stability (rFINSTAB and to financial structure (rFINSTRU were required in both sectors approximately on the same level

  11. Evolution of watermelon fruit physicochemical and phytochemical composition during ripening as affected by grafting.

    Science.gov (United States)

    Soteriou, G A; Kyriacou, M C; Siomos, A S; Gerasopoulos, D

    2014-12-15

    Flesh reflectance colorimetry, mechanical texture analysis, pH, titratable acidity (TA), and soluble solid (SS), soluble carbohydrate, lycopene and citrulline content of watermelon fruit were assessed throughout ripening (30-50 days post-anthesis; dpa) in grafted and self-rooted plants. Grafting increased firmness, TA, and lycopene content though it delayed its peak. Lycopene content was mostly ripening-dependant, highly correlated and synchronous with changes in pulp chroma (C) and colour a. The sweetness was affected only by ripening. However, total sugars and SS peaked later in fruit of grafted plants than in non-grafted ones, and significant interaction of ripening with grafting was observed. Citrulline content increased with ripening in fruit of grafted plants, reaching a peak at 45 dpa; whereas in non-grafted ones it was unchanged between 30 and 45 dpa and declined at 50 dpa. As ripening overall was retarded by grafting, fruit quality of grafted watermelon may benefit from belated harvest.

  12. Associations between gastrointestinal toxicity, micro RNA and cytokine production in patients undergoing myeloablative allogeneic stem cell transplantation

    DEFF Research Database (Denmark)

    Pontoppidan, Peter Erik Lotko; Jordan, Karina Kwi Im; Carlsen, Anting Liu

    2015-01-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is a procedure with a high risk of treatment related mortality. The primary aim of the present study was to examine associations between markers of gastrointestinal toxicity, markers of systemic inflammation, and plasma levels of microRNA...... (miRNA) -155 and -146a during the first month after HSCT. The secondary aim was to characterize the impact of the toxic-inflammatory response on the function of circulating leukocytes during immune recovery. Thirty HSCT patients were included. Gastrointestinal injury was monitored by toxicity scores......, lactulose-mannitol test and plasma citrulline, as a measure of the enterocyte population. Nadir of citrulline and maximum of oral toxicity scores, intestinal permeability, CRP and plasma levels of IL-6 and IL-10 was seen at day +7 post-HSCT. miRNA-155 and mi-RNA-146a showed an inverse relation...

  13. Arginine deprivation and metabolomics: important aspects of intermediary metabolism in relation to the differential sensitivity of normal and tumour cells.

    Science.gov (United States)

    Wheatley, Denys N

    2005-08-01

    Arginine deprivation causes many types of tumour cells to die, often because they cannot recover or convert urea cycle intermediates into arginine. The powerful homeostatic mechanisms that kicks in to restore arginine levels in vivo are lacking in vitro, where there is no supply of citrulline. Comparison between cells deprived of arginine by direct elimination methods or indirectly via arginine degrading enzymes should show differences depending on their ability to handle alternative intermediates (ornithine, citrulline and argininosuccinate) of the urea cycle. The internal state of cells that can, versus those that cannot, use intermediates will metabolically be quite different. These differences should provide clear indicators regarding the sensitivity (susceptibility) of cells to arginine deprivation, from which we will be in a much better position to judge which tumours to treat, and possibly how to design the best treatment to eliminate them.

  14. The association between rheumatoid arthritis and periodontitis.

    Science.gov (United States)

    Leech, Michelle T; Bartold, P M

    2015-04-01

    The relationship between rheumatoid arthritis and poor oral health has been recognised for many decades. The association between periodontal infection and the risk of developing RA has been the subject of epidemiological, clinical and basic science research in recent times. Converging and reproducible evidence now makes a clear case for the role of specific periodontal infective pathogens in initiating, amplifying and perpetuating rheumatoid arthritis. The unique enzymatic properties of the periodontal pathogen Porphyromonas gingivalis and its contribution to the burden of citrullinated peptides is now well established. The impact of localized infection such as periodontitis in shaping specific anti-citrullinated peptide immune responses highlights a key area for treatment, prevention and risk assessment in rheumatoid arthritis.

  15. Larger differences in utilization of rarely requested tests in primary care in Spain

    OpenAIRE

    Salinas, Maria; López-Garrigós, Maite; Flores, Emilio; Uris, Joaquín; Leiva-Salinas, Carlos

    2015-01-01

    Introduction: The study was performed to compare and analyze the inter-departmental variability in the request of rarely requested laboratory tests in primary care, as opposed to other more common and highly requested tests. Materials and methods: Data from production statistics for the year 2012 from 76 Spanish laboratories was used. The number of antinuclear antibodies, antistreptolysin O, creatinine, cyclic citrullinated peptide antibodies, deaminated peptide gliadine IgA antibodies, g...

  16. Biomolecules from HCN

    Science.gov (United States)

    Ferris, J. P.; Wos, J. D.; Ryan, T. J.; Lobo, A. P.; Donner, D. B.

    1974-01-01

    It has been suggested by Sanchez et al. (1967) that HCN might have been one of the more important precursors of biological molecules on the primitive earth. Studies were conducted to determine the mechanisms involved in HCN oligomerizations in dilute aqueous solutions and to identify the compounds which are produced in these oligomerization mixtures. Indirect evidence for the formation of cyanate was obtained along with direct evidence for the formation of citrulline, aspartic acid, and orotic acid.

  17. Involvement of nitric oxide in myotoxicity produced by diisopropylphosphorofluoridate (DFP)-induced muscle hyperactivity

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, Ramesh C. [Toxicology Department, Breathitt Veterinary Center, Murray State University, PO Box 2000, Hopkinsville, KY 42240 (United States); Milatovic, Dejan [Department of Pathology, Medical Center North, Vanderbilt University, Nashville, Tennessee (United States); Dettbarn, Wolf-D. [Department of Pharmacology, Vanderbilt University, Nashville, Tennessee (United States)

    2002-12-01

    Oxidative stress, as determined by increased lipid peroxidation, has been implicated in the pathology of myotoxicity. As a model system to study the response of muscle to oxidative insults, we have studied the effects of diisopropylphosphorofluoridate (DFP)-induced muscle hyperactivity on levels of nitric oxide (NO) and energy metabolites in rat skeletal muscles. In in vivo experiments, citrulline levels as indicators of NO and NO synthase (NOS), and ATP and phosphocreatine (PCr) as indicators of mitochondrial dysfunction, were determined using HPLC methods 15 min, 30 min, 60 min, 2 h, and 24 h after intoxication. Within 15 min of DFP exposure, with onset of fasciculations, citrulline levels were significantly elevated in all three muscles [soleus, extensor digitorum longus (EDL), and diaphragm]. Maximum increases in citrulline (272-288%) were noted 60 min after DFP injection. At this time point, acetylcholinesterase activity was reduced by 90-96% (soleus < diaphragm < EDL). The levels of ATP and PCr were maximally reduced (30-43%), and total adenine nucleotides, and total creatine compounds showed declines. The findings revealed that the increase in NOS activity and NO was greater than the decrease of ATP and PCr. Since memantine (MEM) has been shown to reduce nerve and muscle hyperactivity, we have studied the possible protective effect of MEM on the DFP-induced biochemical changes. Pretreatment with MEM (18 mg/kg s.c.) and atropine sulfate (16 mg/kg s.c.), 60 min and 15 min, respectively, before DFP injection prevented the increase in citrulline and muscle hyperactivity and the decrease in ATP and PCr. These data suggest that free radical reactions by depleting high-energy phosphates may be initiating the cascade of events leading to myotoxicity during DFP-induced muscle hyperactivity. (orig.)

  18. TBI Endpoints Development

    Science.gov (United States)

    2015-10-01

    Research Program/ Stuart Hoffman (VA), Scientific Program Manager for the Brain Injury Portfolio 810 Vermont Avenue, NW, Washington, DC 20420... class of brain proteins that undergo TBI-induced citrullination (2). Development of Assays for TBI Biomarkers. Immunoassays will be developed for...hours) x x x Head CT scan or imaging completed x x x ? ? ? Negative x x Positive x x Acuity for testing (hearing/eye) x x x x Speak English or

  19. ГЕНЕРАЛІЗОВАНИЙ ПАРОДОНТИТ І РЕВМАТОЇДНИЙ АРТРИТ: ІМУНОЛОГІЧНІ АСПЕКТИ ВЗАЄМООБТЯЖЕННЯ

    OpenAIRE

    S. I. Smiyan; Mazur, I.P.; Bilozetskyi, I. I.

    2014-01-01

    Aim. The combination of rheumatoid arthritis and periodontitis may have an adverse prognostic significance for both diseases. Methods and results. In order to study the relationships between generalized periodontitis course and tumor necrosis factor alpha (TNF-α) level 60 patients with rheumatoid arthritis were examined. Conclusion. It was established that markers of activity and aggression of rheumatoid arthritis, such as the presence of rheumatoid factor, antibodies to cyclic citrullinated ...

  20. Prevalence of Periodontitis in Patients with Established Rheumatoid Arthritis: A Swedish Population Based Case-Control Study

    OpenAIRE

    Kaja Eriksson; Lena Nise; Anna Kats; Elin Luttropp; Anca Irinel Catrina; Johan Askling; Leif Jansson; Lars Alfredsson; Lars Klareskog; Karin Lundberg; Tülay Yucel-Lindberg

    2016-01-01

    Introduction The possible hypothesis of a link between periodontitis and rheumatoid arthritis (RA), specifically anti-citrullinated protein antibody (ACPA) positive RA, prompted us to investigate the prevalence of periodontitis in the Swedish Epidemiological Investigation of RA (EIRA), a well-characterised population-based RA case-control cohort. Methods Periodontal status of 2,740 RA cases and 3,942 matched controls was retrieved through linking EIRA with the National Dental Health Registry ...

  1. Route of administration (enteral or parenteral) affects the contribution of L-glutamine to de novo L-arginine synthesis in mice: a stable-isotope study.

    Science.gov (United States)

    Boelens, Petra G; Melis, Gerdien C; van Leeuwen, Paul A; ten Have, Gabrie A; Deutz, Nicolaas E

    2006-10-01

    A pathway from enteral L-glutamine as substrate for L-arginine synthesis is suggested by previous studies. L-Glutamine and L-glutamine dipeptides exhibit numerous beneficial effects in experimental and clinical studies. In trauma patients, enteral L-glutamine supply increased plasma L-arginine. The present study was designed to quantify the contribution of L-glutamine to the de novo L-citrulline and L-arginine synthesis in mice when L-glutamine is administered in a high dose of labeled L-glutamine or L-alanyl-L-glutamine by the enteral or parenteral route. For this purpose, male Swiss mice (n = 43) underwent a laparotomy, and catheters were inserted for sampling and infusion. A primed, constant, and continuous infusion of L-alanyl-L-[2-(15)N]glutamine (dipeptide groups) or L-[2-(15)N]glutamine (free L-glutamine groups), simultaneously with L-[ureido-(13)C,(2)H(2)]citrulline and L-[guanidino-(15)N(2),(2)H(2)]arginine, was given (steady-state model). Mice received the L-glutamine tracers intravenously (jugular vein) or enterally (duodenum). Enrichments of metabolites were measured by LC-MS. Arterial L-glutamine concentrations were the highest in the intravenous dipeptide group. L-Glutamine was converted to L-citrulline and L-arginine when L-[2-(15)N]glutamine and L-alanyl-L-[2-(15)N]glutamine were given by enteral or parenteral route. The contribution of L-glutamine to the de novo synthesis of L-citrulline and L-arginine was higher in the enteral groups when compared with the intravenous groups (P glutamine, provided as free molecule or dipeptide, to the de novo synthesis of L-arginine in mice.

  2. Influence of phenolic compounds on the growth and arginine deiminase system in a wine lactic acid bacterium

    OpenAIRE

    Alberto, María R.; Manca de Nadra,María C.; Arena, Mario E.

    2012-01-01

    The influence of seven phenolic compounds, normally present in wine, on the growth and arginine deiminase system (ADI) of Lactobacillus hilgardii X1B, a wine lactic acid bacterium, was established. This system provides energy for bacterial growth and produces citrulline that reacts with ethanol forming the carcinogen ethyl carbamate (EC), found in some wines. The influence of phenolic compounds on bacterial growth was compound dependent. Growth and final pH values increased in presence of arg...

  3. Metformin Effect on Nontargeted Metabolite Profiles in Patients With Type 2 Diabetes and in Multiple Murine Tissues.

    Science.gov (United States)

    Adam, Jonathan; Brandmaier, Stefan; Leonhardt, Jörn; Scheerer, Markus F; Mohney, Robert P; Xu, Tao; Bi, Jie; Rotter, Markus; Troll, Martina; Chi, Shen; Heier, Margit; Herder, Christian; Rathmann, Wolfgang; Giani, Guido; Adamski, Jerzy; Illig, Thomas; Strauch, Konstantin; Li, Yixue; Gieger, Christian; Peters, Annette; Suhre, Karsten; Ankerst, Donna; Meitinger, Thomas; Hrabĕ de Angelis, Martin; Roden, Michael; Neschen, Susanne; Kastenmüller, Gabi; Wang-Sattler, Rui

    2016-12-01

    Metformin is the first-line oral medication to increase insulin sensitivity in patients with type 2 diabetes (T2D). Our aim was to investigate the pleiotropic effect of metformin using a nontargeted metabolomics approach. We analyzed 353 metabolites in fasting serum samples of the population-based human KORA (Cooperative Health Research in the Region of Augsburg) follow-up survey 4 cohort. To compare T2D patients treated with metformin (mt-T2D, n = 74) and those without antidiabetes medication (ndt-T2D, n = 115), we used multivariable linear regression models in a cross-sectional study. We applied a generalized estimating equation to confirm the initial findings in longitudinal samples of 683 KORA participants. In a translational approach, we used murine plasma, liver, skeletal muscle, and epididymal adipose tissue samples from metformin-treated db/db mice to further corroborate our findings from the human study. We identified two metabolites significantly (P < 1.42E-04) associated with metformin treatment. Citrulline showed lower relative concentrations and an unknown metabolite X-21365 showed higher relative concentrations in human serum when comparing mt-T2D with ndt-T2D. Citrulline was confirmed to be significantly (P < 2.96E-04) decreased at 7-year follow-up in patients who started metformin treatment. In mice, we validated significantly (P < 4.52E-07) lower citrulline values in plasma, skeletal muscle, and adipose tissue of metformin-treated animals but not in their liver. The lowered values of citrulline we observed by using a nontargeted approach most likely resulted from the pleiotropic effect of metformin on the interlocked urea and nitric oxide cycle. The translational data derived from multiple murine tissues corroborated and complemented the findings from the human cohort.

  4. A Biophysical Model of the Mitochondrial ATP-Mg/Pi Carrier

    OpenAIRE

    2012-01-01

    Mitochondrial adenine nucleotide (AdN) content is regulated through the Ca2+-activated, electroneutral ATP-Mg/Pi carrier (APC). The APC is a protein in the mitochondrial carrier super family that localizes to the inner mitochondrial membrane (IMM). It is known to modulate a number of processes that depend on mitochondrial AdN content, such as gluconeogenesis, protein synthesis, and citrulline synthesis. Despite this critical role, a kinetic model of the underlying mechanism has not been devel...

  5. Proceedings of the 2016 Childhood Arthritis and Rheumatology Research Alliance (CARRA) Scientific Meeting: Toronto, Canada. 14-17 April 2016

    OpenAIRE

    Fotis, Lampros; Shaikh, Nur; Baszis, Kevin; French, Anthony; Tarr, Phillip; Grevich, Sriharsha; Lee, Peggy; Ringold, Sarah; Leroux, Brian; Leahey, Hannah; Yuasa, Megan; Foster, Jessica; Sokolove, Jeremy; Lahey, Lauren; Robinson, William

    2016-01-01

    Table of Contents P1 Serologic evidence of gut-driven systemic inflammation in juvenile idiopathic arthritis Lampros Fotis, Nur Shaikh, Kevin Baszis, Anthony French, Phillip Tarr P2 Oral health and anti-citrullinated peptide antibodies (ACPA) in juvenile idiopathic arthritis Sriharsha Grevich, Peggy Lee, Sarah Ringold, Brian Leroux, Hannah Leahey, Megan Yuasa, Jessica Foster, Jeremy Sokolove, Lauren Lahey, William Robinson, Joshua Newsom, Anne Stevens P3 Novel autoantigens for endothelial cel...

  6. Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation

    Science.gov (United States)

    Lewis, Huw D.; Liddle, John; Coote, Jim E.; Atkinson, Stephen J.; Barker, Michael D.; Bax, Benjamin, D.; Bicker, Kevin L.; Bingham, Ryan P.; Campbell, Matthew; Chen, Yu Hua; Chung, Chun-wa; Craggs, Peter D.; Davis, Rob P.; Eberhard, Dirk; Joberty, Gerard; Lind, Kenneth E.; Locke, Kelly; Maller, Claire; Martinod, Kimberly; Patten, Chris; Polyakova, Oxana; Rise, Cecil E.; Rüdiger, Martin; Sheppard, Robert J.; Slade, Daniel J.; Thomas, Pamela; Thorpe, Jim; Yao, Gang; Drewes, Gerard; Wagner, Denisa D.; Thompson, Paul R.; Prinjha, Rab K.; Wilson, David M.

    2015-01-01

    PAD4 has been strongly implicated in the pathogenesis of autoimmune, cardiovascular and oncological diseases, through clinical genetics and gene disruption in mice. Novel, selective PAD4 inhibitors binding to a calcium-deficient form of the PAD4 enzyme have, for the first time, validated the critical enzymatic role of human and mouse PAD4 in both histone citrullination and neutrophil extracellular trap formation. The therapeutic potential of PAD4 inhibitors can now be explored. PMID:25622091

  7. Comparison of Watermelon and Carbohydrate Beverage on Exercise-Induced Alterations in Systemic Inflammation, Immune Dysfunction, and Plasma Antioxidant Capacity

    Directory of Open Access Journals (Sweden)

    R. Andrew Shanely

    2016-08-01

    Full Text Available Consuming carbohydrate- and antioxidant-rich fruits during exercise as a means of supporting and enhancing both performance and health is of interest to endurance athletes. Watermelon (WM contains carbohydrate, lycopene, l-citrulline, and l-arginine. WM may support exercise performance, augment antioxidant capacity, and act as a countermeasure to exercise-induced inflammation and innate immune changes. Trained cyclists (n = 20, 48 ± 2 years participated in a randomized, placebo controlled, crossover study. Subjects completed two 75 km cycling time trials after either 2 weeks ingestion of 980 mL/day WM puree or no treatment. Subjects drank either WM puree containing 0.2 gm/kg carbohydrate or a 6% carbohydrate beverage every 15 min during the time trials. Blood samples were taken pre-study and pre-, post-, 1 h post-exercise. WM ingestion versus no treatment for 2-weeks increased plasma l-citrulline and l-arginine concentrations (p < 0.0125. Exercise performance did not differ between WM puree or carbohydrate beverage trials (p > 0.05, however, the rating of perceived exertion was greater during the WM trial (p > 0.05. WM puree versus carbohydrate beverage resulted in a similar pattern of increase in blood glucose, and greater increases in post-exercise plasma antioxidant capacity, l-citrulline, l-arginine, and total nitrate (all p < 0.05, but without differences in systemic markers of inflammation or innate immune function. Daily WM puree consumption fully supported the energy demands of exercise, and increased post-exercise blood levels of WM nutritional components (l-citrulline and l-arginine, antioxidant capacity, and total nitrate, but without an influence on post-exercise inflammation and changes in innate immune function.

  8. HPLC-MS/MS investigation of biochemical markers for the disclosure of erythropoietin abuse in sports

    Science.gov (United States)

    Appolonova, S. A.; Dikunets, M. A.; Rodchenkov, G. M.

    2009-04-01

    The polypeptide hormone erythropoietin (EPO), which is a forbidden doping drug, was determined by high-performance liquid chromatography combined with tandem mass spectrometry (HPLC-MS/MS). The hypothesis about the influence of EPO on the asymmetric dimethylarginine (ADMA)-dimethylargininedime-thylaminohydrolase (DDAH)-NO-synthase system was verified. Changes in this system can serve as indirect biochemical markers of the presence of the forbidden EPO drug in the organism. In the test group, the concentrations of biochemical markers varied from 10 to 40 μg/ml for ADMA and symmetrical DMA (SDMA) and from 0.5 to 10 μg/ml for arginine and citrulline. A single intravenous administration of r-HuEPO (Epocrin, 2000 ME/day) for two volunteers reliably increased ADMA, SDMA, arginine, and citrulline concentrations to 40-270 μg/ml, 40-240μg/ml, 10-60 μg/ml, and 12-140 μg/ml, respectively, with respect to the reference values. The simultaneous increase in arginine, methylarginines, and citrulline contents could be an indirect marker of EPO abuse. The method is recommended for fast screening analysis.

  9. ABAP: antibody-based assay for peptidylarginine deiminase activity.

    Science.gov (United States)

    Zendman, Albert J W; Raijmakers, Reinout; Nijenhuis, Suzanne; Vossenaar, Erik R; Tillaart, Marloes van den; Chirivi, Renato G S; Raats, Jos M H; van Venrooij, Walther J; Drijfhout, Jan W; Pruijn, Ger J M

    2007-10-15

    Members of the family of peptidylarginine deiminases (PADs, EC 3.5.3.15) catalyze the posttranslational modification of peptidylarginine into peptidylcitrulline. Citrulline-containing epitopes have been shown to be major and specific targets of autoantibodies produced by rheumatoid arthritis patients. Recently, the citrullination of histone proteins by PAD enzyme was reported to influence gene expression levels. These findings greatly increase the interest in the PAD enzymes and their activities. A few procedures to monitor PAD activity in biological samples have been described previously. However, these assays either have low sensitivity or are rather laborious. Here we describe a reliable and reproducible method for the determination of PAD activity in both purified and crude samples. The method is based on the quantification of PAD-dependent citrullination of peptides, immobilized in microtiter plates, using antibodies that are exclusively reactive with the reaction product(s). Our results demonstrate that this antibody-based assay for PAD activity, called ABAP, is very sensitive and can be applied to monitor PAD activity in biological samples.

  10. Inhibition of insulin fibrillation by osmolytes: Mechanistic Insights

    Science.gov (United States)

    Choudhary, Sinjan; Kishore, Nand; Hosur, Ramakrishna V.

    2015-11-01

    We have studied here using a number of biophysical tools the effects of osmolytes, betaine, citrulline, proline and sorbitol which differ significantly in terms of their physical characteristics such as, charge distribution, polarity, H-bonding abilities etc, on the fibrillation of insulin. Among these, betaine, citrulline, and proline are very effective in decreasing the extent of fibrillation. Proline also causes a substantial delay in the onset of fibrillation in the concentration range (50-250 mM) whereas such an effect is seen for citrulline only at 250 mM, and in case of betaine this effect is not seen at all in the whole concentration range. The enthalpies of interaction at various stages of fibrillation process have suggested that the preferential exclusion of the osmolyte and its polar interaction with the protein are important in inhibition. The results indicate that the osmolytes are most effective when added prior to the elongation stage of fibrillation. These observations have significant biological implications, since insulin fibrillation is known to cause injection amyloidosis and our data may help in designing lead drug molecules and development of potential therapeutic strategies.

  11. Biochemical abnormalities in Pearson syndrome.

    Science.gov (United States)

    Crippa, Beatrice Letizia; Leon, Eyby; Calhoun, Amy; Lowichik, Amy; Pasquali, Marzia; Longo, Nicola

    2015-03-01

    Pearson marrow-pancreas syndrome is a multisystem mitochondrial disorder characterized by bone marrow failure and pancreatic insufficiency. Children who survive the severe bone marrow dysfunction in childhood develop Kearns-Sayre syndrome later in life. Here we report on four new cases with this condition and define their biochemical abnormalities. Three out of four patients presented with failure to thrive, with most of them having normal development and head size. All patients had evidence of bone marrow involvement that spontaneously improved in three out of four patients. Unique findings in our patients were acute pancreatitis (one out of four), renal Fanconi syndrome (present in all patients, but symptomatic only in one), and an unusual organic aciduria with 3-hydroxyisobutyric aciduria in one patient. Biochemical analysis indicated low levels of plasma citrulline and arginine, despite low-normal ammonia levels. Regression analysis indicated a significant correlation between each intermediate of the urea cycle and the next, except between ornithine and citrulline. This suggested that the reaction catalyzed by ornithine transcarbamylase (that converts ornithine to citrulline) might not be very efficient in patients with Pearson syndrome. In view of low-normal ammonia levels, we hypothesize that ammonia and carbamylphosphate could be diverted from the urea cycle to the synthesis of nucleotides in patients with Pearson syndrome and possibly other mitochondrial disorders.

  12. A novel method for simultaneous measurement of concentration and enrichment of NO synthesis-specific amino acids in human plasma using stable isotopes and LC/MS ion trap analysis.

    Science.gov (United States)

    Oosterink, J Efraim; Buijs, Nikki; van Goudoever, Johannes B; Schierbeek, Henk

    2014-05-01

    Stable isotope studies offer the opportunity to study the in-depth metabolic pathway of glutamine, citrulline, and arginine amino acids involved in NO synthesis. The use of multiple stable isotopes can be used to elucidate the exact transformation of glutamine to citrulline and arginine de novo synthesis. This novel method provides a purification step using cation exchange resin in combination with a rapid and easy derivatization procedure for a precise and robust measurement of the concentration and isotopic enrichments of NO synthesis-specific amino acids using a liquid chromatography mass spectrometry (LC/MS) ion trap system with high sensitivity and selectivity. The ethyl chloroformate derivatization procedure is beneficial in terms of robustness, velocity, simplicity, and derivative stability. In addition, the ethyl chloroformate derivatization can be performed at room temperature in an aqueous environment without incubation and the isolation of the derivatives from the reaction mixture also serves as a purification step. The concentration and enrichment of NO synthesis-specific amino acids as well as phenylalanine and tyrosine to determine protein turnover, were measured with good inter-day precision for the concentration (glutamine-citrulline-arginine pathway by using stable isotope studies.

  13. The arginine deiminase pathway of Lactobacillus fermentum IMDO 130101 responds to growth under stress conditions of both temperature and salt.

    Science.gov (United States)

    Vrancken, G; Rimaux, T; Wouters, D; Leroy, F; De Vuyst, L

    2009-10-01

    The arginine deiminase (ADI) pathway is a means by which certain sourdough lactic acid bacteria (LAB) convert arginine into ornithine via citrulline while producing ammonia and ATP, thereby coping with acid stress and gaining an energetic advantage. Lactobacillus fermentum IMDO 130101, an isolate from a spontaneous laboratory rye sourdough, possesses an ADI pathway which is modulated by environmental pH. In the present study, a broader view of the activity of the ADI pathway in response to growth under two other commonly encountered stress factors, temperature and added salt, was obtained. In both cases, an increase in ornithine production was observed as a response to growth under both temperature and salt stress conditions. Biokinetic parameters were obtained to describe the kinetics of the ADI pathway as a function of temperature and added salt. The arginine conversion rate increased as a function of added NaCl concentrations but was hardly affected by temperature. In addition, arginine-into-citrulline conversion rate was not affected by temperature but increased with increasing NaCl concentrations. Citrulline-into-ornithine conversion rate increased with increasing temperature, while it dropped to zero with added salt. These findings suggest a more pronounced adaptation of the strain through the ADI pathway to added salt, as compared with different constant temperatures. Furthermore, these results suggest that the ADI pathway in L. fermentum IMDO 130101 is active in adapting to non-optimal growth conditions.

  14. Posttranslational Protein Modification in the Salivary Glands of Sjögren’s Syndrome Patients

    Directory of Open Access Journals (Sweden)

    Rafael Herrera-Esparza

    2013-01-01

    Full Text Available The present study investigated posttranslational reactions in the salivary glands of patients with Sjögren’s syndrome. We analysed the biopsies of primary Sjögren’s patients using immunohistochemistry and a tag-purified anticyclic citrullinated protein (CCP antibody to detect citrullinated peptides, and the presence of peptidylarginine deiminase 2 (PAD2 was assessed simultaneously. The present work demonstrated the weak presence of the PAD2 enzyme in some normal salivary glands, although PAD2 expression was increased considerably in Sjögren’s patients. The presence of citrullinated proteins was also detected in the salivary tissues of Sjögren’s patients, which strongly supports the in situ posttranslational modification of proteins in this setting. Furthermore, the mutual expression of CCP and PAD2 suggests that this posttranslational modification is enzyme dependent. In conclusion, patients with Sjögren’s syndrome expressed the catalytic machinery to produce posttranslational reactions that may result in autoantigen triggering.

  15. Development of an optofluidic SERS-based biomedical sensor

    Science.gov (United States)

    Walton, Brian; Huang, Po-Jung; Kameoka, Jun; Deutz, Nicolaas; Coté, Gerard L.

    2016-03-01

    Rapid assessment of radiation exposure to sensitive organs like the gut is extremely important for large populations exposed to ionized radiation, for instance during warfare. Recent results have shown that plasma citrulline levels appear to track gut function after irradiation levels in mice and humans. The current ways to monitor blood citrulline levels are bulky, laborious, time-consuming and expensive methods. Therefore, an optofludic point-of-care (POC) system using surface enhanced Raman spectroscopy to measure plasma citrulline as a marker for radiation exposure that overcomes the above issues is being developed. As a first step toward development of this system four colloidal nanoparticles, spherical gold, silver cubes, silica-gold nanoshells, and silver-gold nanocages have been analyzed for use in the POC system. Transmission electron microscopy (TEM) images have been taken of each nanoparticle to visualize the morphology of the nanoparticles, which is vital for SERS. Ultraviolet-visible (UV/Vis) spectroscopy was also collected to verify the extinction spectra for each nanoparticle was in resonance with the excitation wavelength. The nanoparticles were functionalized with mercaptobenzoic acid (MBA), a Raman reporter molecule, and SERS spectra were collected to determine which has better utility in a novel micro-to-nanochannel. The data showed that the silver nanocubes have a larger enhancement factor than the gold nanospheres, nanoshells, or nanocages. Currently, these nanocubes are being functionalized with the citulline for assessing the concentration sensitivity and dynamic range for ultimate use as a marker for radiation.

  16. A non-synonymous single-nucleotide polymorphism in the gene encoding Toll-like Receptor 3 (TLR3) is associated with sero-negative Rheumatoid Arthritis (RA) in a Danish population

    DEFF Research Database (Denmark)

    Laska, Magdalena Janina; Hansen, Bettina; Troldborg, Anne;

    2014-01-01

    BACKGROUND: It has been suggested that polymorphisms in Toll-like Receptors (TLRs) are associated with Rheumatoid Arthritis (RA), but the implicated alleles have differed between studies. The aim of this investigation was to explore whether polymorphisms of TLR genes are associated with RA...... according to IgM rheumatoid factor (RF) and anti-cyclic citrinullated peptide (CCP) status suggested a significant association of sero-negative RA with the rs3775291 A allele and disease activity in this subset. CONCLUSION: These observations on a RA population of Danish ancestry suggest that variations...... in the TLR3 locus may be implicated in the pathogenesis of sero-negative RA. Since this TLR3 SNP has previously been associated with systemic lupus erythematous (SLE), the present findings support the notion that TLR3 genetic variants may represent a common risk factor in different chronic inflammatory...

  17. An ephemeral project on private regulation of viticulture in Mendoza (Argentina in a crisis context: Mendoza’s Viticulture Society, 1916-1919

    Directory of Open Access Journals (Sweden)

    Patricia Elena Barrio

    2015-01-01

    Full Text Available In early 1917, a company that gathered all of Mendoza’s wine producers was founded. This was the last anti-cyclical strategy promoted by the State with the goal of dealing with a long lasting economical crisis. It aimed to set wine and grape prices in a monopolistic fashion, and to establish wine marketing quotas. The limited amount of bibliography on this topic is what motivated this study, based on 3 aspects: how it was created, who it benefitted and how it was dissolved. Lack of official documentation forced its story to be rebuilt with information gathered from newspapers and public and private memoirs. It was concluded that the ideas this experiment was based on were misguided, since wine is a dispensable and replaceable asset. It was also concluded that it benefitted wine growers and that its dissolution process was longer and more complex than it foreseen.

  18. Enriching Peptide Libraries for Binding Affinity and Specificity Through Computationally Directed Library Design.

    Science.gov (United States)

    Foight, Glenna Wink; Chen, T Scott; Richman, Daniel; Keating, Amy E

    2017-01-01

    Peptide reagents with high affinity or specificity for their target protein interaction partner are of utility for many important applications. Optimization of peptide binding by screening large libraries is a proven and powerful approach. Libraries designed to be enriched in peptide sequences that are predicted to have desired affinity or specificity characteristics are more likely to yield success than random mutagenesis. We present a library optimization method in which the choice of amino acids to encode at each peptide position can be guided by available experimental data or structure-based predictions. We discuss how to use analysis of predicted library performance to inform rounds of library design. Finally, we include protocols for more complex library design procedures that consider the chemical diversity of the amino acids at each peptide position and optimize a library score based on a user-specified input model.

  19. Maturity-onset diabetes of the young with end-stage nephropathy

    DEFF Research Database (Denmark)

    Saudek, Frantisek; Pruhová, Stepánka; Boucek, Peter;

    2004-01-01

    -onset diabetes of the young (MODY). SPK was performed in a 47-year old man who has MODY3 because of a Arg272His mutation in the hepatocyte nuclear factor-1alphagene. He developed overt diabetes mellitus at 19 years and end-stage diabetic nephropathy 26 years thereafter. Before SPK, the patient had measurable....... CONCLUSION: Identification of MODY3 among all C-peptide-positive patients with advanced diabetic nephropathy might help to select a specific group profiting from SPK....

  20. Metabolism via arginase or nitric oxide synthase: two competing arginine pathways in macrophages

    Directory of Open Access Journals (Sweden)

    Meera eRath

    2014-10-01

    Full Text Available Macrophages play a major role in the immune system, both as antimicrobial effector cells and as immunoregulatory cells, which induce, suppress or modulate adaptive immune responses. These key aspects of macrophage biology are fundamentally driven by the phenotype of macrophage arginine metabolism that is prevalent in an evolving or ongoing immune response. M1 macrophages express the enzyme nitric oxide synthase (NOS, which metabolizes arginine to nitric oxide (NO and citrulline. NO can be metabolized to further downstream reactive nitrogen species, while citrulline might be reused for efficient NO synthesis via the citrulline-NO cycle. M2 macrophages are characterized by expression of the enzyme arginase, which hydrolyzes arginine to ornithine and urea. The arginase pathway limits arginine availability for NO synthesis and ornithine itself can further feed into the important downstream pathways of polyamine and proline syntheses, which are important for cellular proliferation and tissue repair. M1 versus M2 polarization leads to opposing outcomes of inflammatory reactions, but depending on the context, M1 and M2 macrophages can be both pro- and antiinflammatory. Notably, M1/M2 macrophage polarization can be driven by microbial infection or innate danger signals without any influence of adaptive immune cells, secondarily driving the T helper (Th1/Th2 polarization of the evolving adaptive immune response. Since both arginine metabolic pathways cross-inhibit each other on the level of the respective arginine break-down products and Th1 and Th2 lymphocytes can drive or amplify macrophage M1/M2 dichotomy via cytokine activation, this forms the basis of a self-sustaining M1/M2 polarization of the whole immune response. Understanding the arginine metabolism of M1/M2 macrophage phenotypes is therefore central to find new possibilities to manipulate immune responses in infection, autoimmune diseases, chronic inflammatory conditions and cancer.

  1. Down-regulation of Hepatic Urea Synthesis by Oxypurines

    Science.gov (United States)

    Nissim, Itzhak; Horyn, Oksana; Nissim, Ilana; Daikhin, Yevgeny; Caldovic, Ljubica; Barcelona, Belen; Cervera, Javier; Tuchman, Mendel; Yudkoff, Marc

    2011-01-01

    We previously reported that isobutylmethylxanthine (IBMX), a derivative of oxypurine, inhibits citrulline synthesis by an as yet unknown mechanism. Here, we demonstrate that IBMX and other oxypurines containing a 2,6-dione group interfere with the binding of glutamate to the active site of N-acetylglutamate synthetase (NAGS), thereby decreasing synthesis of N-acetylglutamate, the obligatory activator of carbamoyl phosphate synthase-1 (CPS1). The result is reduction of citrulline and urea synthesis. Experiments were performed with 15N-labeled substrates, purified hepatic CPS1, and recombinant mouse NAGS as well as isolated mitochondria. We also used isolated hepatocytes to examine the action of various oxypurines on ureagenesis and to assess the ameliorating affect of N-carbamylglutamate and/or l-arginine on NAGS inhibition. Among various oxypurines tested, only IBMX, xanthine, or uric acid significantly increased the apparent Km for glutamate and decreased velocity of NAGS, with little effect on CPS1. The inhibition of NAGS is time- and dose-dependent and leads to decreased formation of the CPS1-N-acetylglutamate complex and consequent inhibition of citrulline and urea synthesis. However, such inhibition was reversed by supplementation with N-carbamylglutamate. The data demonstrate that xanthine and uric acid, both physiologically occurring oxypurines, inhibit the hepatic synthesis of N-acetylglutamate. An important and novel concept emerging from this study is that xanthine and/or uric acid may have a role in the regulation of ureagenesis and, thus, nitrogen homeostasis in normal and disease states. PMID:21540182

  2. Down-regulation of hepatic urea synthesis by oxypurines: xanthine and uric acid inhibit N-acetylglutamate synthase.

    Science.gov (United States)

    Nissim, Itzhak; Horyn, Oksana; Nissim, Ilana; Daikhin, Yevgeny; Caldovic, Ljubica; Barcelona, Belen; Cervera, Javier; Tuchman, Mendel; Yudkoff, Marc

    2011-06-24

    We previously reported that isobutylmethylxanthine (IBMX), a derivative of oxypurine, inhibits citrulline synthesis by an as yet unknown mechanism. Here, we demonstrate that IBMX and other oxypurines containing a 2,6-dione group interfere with the binding of glutamate to the active site of N-acetylglutamate synthetase (NAGS), thereby decreasing synthesis of N-acetylglutamate, the obligatory activator of carbamoyl phosphate synthase-1 (CPS1). The result is reduction of citrulline and urea synthesis. Experiments were performed with (15)N-labeled substrates, purified hepatic CPS1, and recombinant mouse NAGS as well as isolated mitochondria. We also used isolated hepatocytes to examine the action of various oxypurines on ureagenesis and to assess the ameliorating affect of N-carbamylglutamate and/or l-arginine on NAGS inhibition. Among various oxypurines tested, only IBMX, xanthine, or uric acid significantly increased the apparent K(m) for glutamate and decreased velocity of NAGS, with little effect on CPS1. The inhibition of NAGS is time- and dose-dependent and leads to decreased formation of the CPS1-N-acetylglutamate complex and consequent inhibition of citrulline and urea synthesis. However, such inhibition was reversed by supplementation with N-carbamylglutamate. The data demonstrate that xanthine and uric acid, both physiologically occurring oxypurines, inhibit the hepatic synthesis of N-acetylglutamate. An important and novel concept emerging from this study is that xanthine and/or uric acid may have a role in the regulation of ureagenesis and, thus, nitrogen homeostasis in normal and disease states.

  3. A prospective comparison of acute intestinal toxicity following whole pelvic versus small field intensity-modulated radiotherapy for prostate cancer

    Directory of Open Access Journals (Sweden)

    Kim YJ

    2016-03-01

    Full Text Available Yeon Joo Kim, Jin-hong Park, In-Ha Yun, Young Seok KimDepartment of Radiation Oncology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of KoreaPurpose: To compare the acute intestinal toxicity of whole pelvic (WP and small field (SF intensity-modulated radiotherapy (IMRT for prostate cancer using dosimetric and metabolic parameters as well as clinical findings.Methods: Patients who received IMRT in either a definitive or postoperative setting were prospectively enrolled. Target volume and organs at risk including intestinal cavity (IC were delineated in every patient by a single physician. The IC volume that received a 10–50 Gy dose at 5-Gy intervals (V10–V50 and the percentage of irradiated volume as a fraction of total IC volume were calculated. Plasma citrulline levels, as an objective biological marker, were checked at three time points: baseline and after exposure to 30 Gy and 60 Gy.Results: Of the 41 patients, only six experienced grade 1 acute intestinal toxicity. Although all dose–volume parameters were significantly worse following WP than SF IMRT, there was no statistically significant relationship between these dosimetric parameters and clinical symptoms. Plasma citrulline levels did not show a serial decrease by radiotherapy volume difference (WP versus SF and were not relevant to the irradiated doses.Conclusion: Given that WP had comparable acute intestinal toxicities to those associated with SF, WP IMRT appears to be a feasible approach for the treatment of prostate cancer despite dosimetric disadvantages.Keywords: prostate cancer, intensity-modulated radiotherapy, intestinal toxicity, citrulline

  4. Associations between gastrointestinal toxicity, micro RNA and cytokine production in patients undergoing myeloablative allogeneic stem cell transplantation.

    Science.gov (United States)

    Pontoppidan, Peter L; Jordan, Karina; Carlsen, Anting Liu; Uhlving, Hilde Hylland; Kielsen, Katrine; Christensen, Mette; Ifversen, Marianne; Nielsen, Claus Henrik; Sangild, Per; Heegaard, Niels Henrik Helweg; Heilmann, Carsten; Sengeløv, Henrik; Müller, Klaus

    2015-03-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is a procedure with a high risk of treatment related mortality. The primary aim of the present study was to examine associations between markers of gastrointestinal toxicity, markers of systemic inflammation, and plasma levels of microRNA (miRNA) -155 and -146a during the first month after HSCT. The secondary aim was to characterize the impact of the toxic-inflammatory response on the function of circulating leukocytes during immune recovery. Thirty HSCT patients were included. Gastrointestinal injury was monitored by toxicity scores, lactulose-mannitol test and plasma citrulline, as a measure of the enterocyte population. Nadir of citrulline and maximum of oral toxicity scores, intestinal permeability, CRP and plasma levels of IL-6 and IL-10 was seen at day +7 post-HSCT. miRNA-155 and mi-RNA-146a showed an inverse relation with significantly elevated miRNA-155 and decreased miRNA-146a levels, from day 0 to day +28 compared with pre-conditioning levels. Citrulline levels below the median at day +7 were associated with higher spontaneous production of IL-6 and TNF-α as well as higher in vitro stimulated production of IL-17A at day +21. This study is the first to demonstrate that toxic responses to chemotherapy are accompanied by differential regulation of miRNAs with opposing effects on immune regulation. We find that a proinflammatory miRNA profile is sustained during the first three weeks after the transplantation, indicating that these miRNAs may play a role in the regulation of the inflammatory environment during immune reconstitution after HSCT.

  5. Arginine consumption by the intestinal parasite Giardia intestinalis reduces proliferation of intestinal epithelial cells.

    Directory of Open Access Journals (Sweden)

    Britta Stadelmann

    Full Text Available In the field of infectious diseases the multifaceted amino acid arginine has reached special attention as substrate for the hosts production of the antimicrobial agent nitric oxide (NO. A variety of infectious organisms interfere with this part of the host immune response by reducing the availability of arginine. This prompted us to further investigate additional roles of arginine during pathogen infections. As a model we used the intestinal parasite Giardia intestinalis that actively consumes arginine as main energy source and secretes an arginine-consuming enzyme, arginine deiminase (ADI. Reduced intestinal epithelial cell (IEC proliferation is a common theme during bacterial and viral intestinal infections, but it has never been connected to arginine-consumption. Our specific question was thereby, whether the arginine-consumption by Giardia leads to reduced IEC proliferation, in addition to NO reduction. In vitro cultivation of human IEC lines in arginine-free or arginine/citrulline-complemented medium, as well as in interaction with different G. intestinalis isolates, were used to study effects on host cell replication by MTT assay. IEC proliferation was further analyzed by DNA content analysis, polyamine measurements and expressional analysis of cell cycle regulatory genes. IEC proliferation was reduced upon arginine-withdrawal and also in an arginine-dependent manner upon interaction with G. intestinalis or addition of Giardia ADI. We show that arginine-withdrawal by intestinal pathogens leads to a halt in the cell cycle in IECs through reduced polyamine levels and upregulated cell cycle inhibitory genes. This is of importance with regards to intestinal tissue homeostasis that is affected through reduced cell proliferation. Thus, the slower epithelial cell turnover helps the pathogen to maintain a more stable niche for colonization. This study also shows why supplementation therapy of diarrhea patients with arginine/citrulline is helpful

  6. Potential role for PAD2 in gene regulation in breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Brian D Cherrington

    Full Text Available The peptidylarginine deiminase (PAD family of enzymes post-translationally convert positively charged arginine residues in substrate proteins to the neutral, non-standard residue citrulline. PAD family members 1, 2, 3, and 6 have previously been localized to the cell cytoplasm and, thus, their potential to regulate gene activity has not been described. We recently demonstrated that PAD2 is expressed in the canine mammary gland epithelium and that levels of histone citrullination in this tissue correlate with PAD2 expression. Given these observations, we decided to test whether PAD2 might localize to the nuclear compartment of the human mammary epithelium and regulate gene activity in these cells. Here we show, for the first time, that PAD2 is specifically expressed in human mammary gland epithelial cells and that a portion of PAD2 associates with chromatin in MCF-7 breast cancer cells. We investigated a potential nuclear function for PAD2 by microarray, qPCR, and chromatin immunoprecipitation analysis. Results show that the expression of a unique subset of genes is disregulated following depletion of PAD2 from MCF-7 cells. Further, ChIP analysis of two of the most highly up- and down-regulated genes (PTN and MAGEA12, respectively found that PAD2 binds directly to these gene promoters and that the likely mechanism by which PAD2 regulates expression of these genes is via citrullination of arginine residues 2-8-17 on histone H3 tails. Thus, our findings define a novel role for PAD2 in gene expression in human mammary epithelial cells.

  7. Arginine depletion by arginine deiminase does not affect whole protein metabolism or muscle fractional protein synthesis rate in mice.

    Directory of Open Access Journals (Sweden)

    Juan C Marini

    Full Text Available Due to the absolute need for arginine that certain cancer cells have, arginine depletion is a therapy in clinical trials to treat several types of cancers. Arginine is an amino acids utilized not only as a precursor for other important molecules, but also for protein synthesis. Because arginine depletion can potentially exacerbate the progressive loss of body weight, and especially lean body mass, in cancer patients we determined the effect of arginine depletion by pegylated arginine deiminase (ADI-PEG 20 on whole body protein synthesis and fractional protein synthesis rate in multiple tissues of mice. ADI-PEG 20 successfully depleted circulating arginine (<1 μmol/L, and increased citrulline concentration more than tenfold. Body weight and body composition, however, were not affected by ADI-PEG 20. Despite the depletion of arginine, whole body protein synthesis and breakdown were maintained in the ADI-PEG 20 treated mice. The fractional protein synthesis rate of muscle was also not affected by arginine depletion. Most tissues (liver, kidney, spleen, heart, lungs, stomach, small and large intestine, pancreas were able to maintain their fractional protein synthesis rate; however, the fractional protein synthesis rate of brain, thymus and testicles was reduced due to the ADI-PEG 20 treatment. Furthermore, these results were confirmed by the incorporation of ureido [14C]citrulline, which indicate the local conversion into arginine, into protein. In conclusion, the intracellular recycling pathway of citrulline is able to provide enough arginine to maintain protein synthesis rate and prevent the loss of lean body mass and body weight.

  8. Arginine consumption by the intestinal parasite Giardia intestinalis reduces proliferation of intestinal epithelial cells.

    Science.gov (United States)

    Stadelmann, Britta; Merino, María C; Persson, Lo; Svärd, Staffan G

    2012-01-01

    In the field of infectious diseases the multifaceted amino acid arginine has reached special attention as substrate for the hosts production of the antimicrobial agent nitric oxide (NO). A variety of infectious organisms interfere with this part of the host immune response by reducing the availability of arginine. This prompted us to further investigate additional roles of arginine during pathogen infections. As a model we used the intestinal parasite Giardia intestinalis that actively consumes arginine as main energy source and secretes an arginine-consuming enzyme, arginine deiminase (ADI). Reduced intestinal epithelial cell (IEC) proliferation is a common theme during bacterial and viral intestinal infections, but it has never been connected to arginine-consumption. Our specific question was thereby, whether the arginine-consumption by Giardia leads to reduced IEC proliferation, in addition to NO reduction. In vitro cultivation of human IEC lines in arginine-free or arginine/citrulline-complemented medium, as well as in interaction with different G. intestinalis isolates, were used to study effects on host cell replication by MTT assay. IEC proliferation was further analyzed by DNA content analysis, polyamine measurements and expressional analysis of cell cycle regulatory genes. IEC proliferation was reduced upon arginine-withdrawal and also in an arginine-dependent manner upon interaction with G. intestinalis or addition of Giardia ADI. We show that arginine-withdrawal by intestinal pathogens leads to a halt in the cell cycle in IECs through reduced polyamine levels and upregulated cell cycle inhibitory genes. This is of importance with regards to intestinal tissue homeostasis that is affected through reduced cell proliferation. Thus, the slower epithelial cell turnover helps the pathogen to maintain a more stable niche for colonization. This study also shows why supplementation therapy of diarrhea patients with arginine/citrulline is helpful and that

  9. Increased erythrocytes by-products of arginine catabolism are associated with hyperglycemia and could be involved in the pathogenesis of type 2 diabetes mellitus.

    Science.gov (United States)

    Ramírez-Zamora, Serafín; Méndez-Rodríguez, Miguel L; Olguín-Martínez, Marisela; Sánchez-Sevilla, Lourdes; Quintana-Quintana, Miguel; García-García, Norberto; Hernández-Muñoz, Rolando

    2013-01-01

    Diabetes mellitus (DM) is a worldwide disease characterized by metabolic disturbances, frequently associated with high risk of atherosclerosis and renal and nervous system damage. Here, we assessed whether metabolites reflecting oxidative redox state, arginine and nitric oxide metabolism, are differentially distributed between serum and red blood cells (RBC), and whether significant metabolism of arginine exists in RBC. In 90 patients with type 2 DM without regular treatment for diabetes and 90 healthy controls, paired by age and gender, we measured serum and RBC levels of malondialdehyde (MDA), nitrites, ornithine, citrulline, and urea. In isolated RBC, metabolism of L-[(14)C]-arginine was also determined. In both groups, nitrites were equally distributed in serum and RBC; citrulline predominated in serum, whereas urea, arginine, and ornithine were found mainly in RBC. DM patients showed hyperglycemia and increased blood HbA1C, and increased levels of these metabolites, except for arginine, significantly correlating with blood glucose levels. RBC were observed to be capable of catabolizing arginine to ornithine, citrulline and urea, which was increased in RBC from DM patients, and correlated with an increased affinity for arginine in the activities of putative RBC arginase (Km = 0.23±0.06 vs. 0.50±0.13 mM, in controls) and nitric oxide synthase (Km = 0.28±0.06 vs. 0.43±0.09 mM, in controls). In conclusion, our results suggest that DM alters metabolite distribution between serum and RBC, demonstrating that RBC regulate serum levels of metabolites which affect nitrogen metabolism, not only by transporting them but also by metabolizing amino acids such as arginine. Moreover, we confirmed that urea can be produced also by human RBC besides hepatocytes, being much more evident in RBC from patients with type 2 DM. These events are probably involved in the specific physiopathology of this disease, i.e., endothelial damage and dysfunction.

  10. Cytotoxicity and cellular uptake of ZnS:Mn nanocrystals biofunctionalized with chitosan and aminoacids

    Science.gov (United States)

    Sajimol Augustine, M.; Anas, Abdulaziz; Das, Ani V.; Sreekanth, S.; Jayalekshmi, S.

    2015-02-01

    Highly luminescent, manganese doped, zinc sulphide (ZnS:Mn) nanocrystals biofunctionalized with chitosan and various aminoacids such as L-citrulline, L-lysine, L-arginine, L-serine, L-histidine and glycine were synthesized by chemical capping co-precipitation method at room temperature, which is a simple and cost effective technique. The synthesized nanocrystals were structurally characterized by TEM, XRD, EDXS and FT-IR spectroscopy techniques. They possess high colloidal stability with strong orange red photoluminescence emission at 598 nm. The intensity of orange red emission has been observed to be maximum in L-citrulline capped ZnS:Mn nanocrystals in which the emission at 420 nm is effectively quenched by surface passivation due to capping. Taking into consideration the prospects of these highly luminescent, bio-compatible ZnS:Mn nanocrystals in bio-imaging applications, cytotoxicity studies were conducted to identify the capping combination which would accomplish minimum toxic effects. ZnS:Mn nanocrystals biofunctionalized with chitosan, L-citrulline, glycine, L-artginine, L-serine and L-histidine showed least toxicity up to 10 nM concentrations in mouse fibroblast L929 cells, which further confirms their cytocompatibility. Also the ZnS:Mn nanocrystals biofunctionalized with L-arginine showed maximum uptake in in vitro studies carried out in human embryonic kidney cells, HEK-293T, which shows the significant role of this particular amino acid in fetoplacental nutrition. The present study highlights the suitability of aminoacid conjugated ZnS:Mn nanocrystals, as promising candidates for biomedical applications.

  11. Depletion of regulatory T cells leads to an exacerbation of delayedtype hypersensitivity arthritis in C57BL/6 mice that can be counteracted by IL-17 blockade

    DEFF Research Database (Denmark)

    Atkinson, Sara Marie; Hoffmann, Ute; Bach, Emil

    2016-01-01

    bone remodelling and increased production of inflammatory mediators, as well as increased production of anti-citrullinated protein antibodies. Anti-IL-17 mAb treatment demonstrated that IL-17 is important for disease severity in both the presence and absence of Tregs, and that IL-17 blockade is able...... to rescue mice from the exacerbated disease caused by Treg depletion and caused a reduction in RANKL, IL-6 and the number of neutrophils. We show that Tregs are important for the containment of inflammation and bone remodelling in DTHA. To our knowledge, this is the first study using the Foxp3-DTR...

  12. N-acetylglutamate synthetase deficiency: diagnosis, management and follow-up of a rare disorder of ammonia detoxication.

    Science.gov (United States)

    Schubiger, G; Bachmann, C; Barben, P; Colombo, J P; Tönz, O; Schüpbach, D

    1991-03-01

    We report the 9-year follow-up of a patient suffering from N-acetylglutamate synthetase deficiency, an urea cycle disorder leading to severe neonatal hyperammonaemia. Hitherto two patients from two families with this inborn error of metabolism had been observed. Our management consisted mainly of a protein-restricted diet and oral treatment with N-carbamylglutamate, an activator of carbamylphosphate synthetase, together with arginine or citrulline. The somatic development was normal whereas a moderate psychomotor retardation was diagnosed. The patient died after an episode of coma and prolonged generalized convulsions at the age of 9.5 years.

  13. Post-translational modifications of the extracellular matrix are key events in cancer progression: opportunities for biochemical marker development

    DEFF Research Database (Denmark)

    Leeming, D J; Bay-Jensen, A C; Vassiliadis, E;

    2011-01-01

    The aim of this review is to discuss the potential usefulness of a novel class of biochemical markers, designated neoepitopes. Neoepitopes are post-translational modifications (PTMs) of proteins and are derived by processes, such as protease cleavage, citrullination, nitrosylation, glycosylation...... and isomerization. Each PTM results from a specific local physiological or pathobiological process. Identification of each modification to a tissue-specific protein may reveal a unique disease-specific biochemical marker. During cancer metastasis, the host tissue is extensively degraded and replaced by cancer...

  14. Oxidative and other posttranslational modifications in extracellular vesicle biology.

    Science.gov (United States)

    Szabó-Taylor, Katalin; Ryan, Brent; Osteikoetxea, Xabier; Szabó, Tamás G; Sódar, Barbara; Holub, Marcsilla; Németh, Andrea; Pálóczi, Krisztina; Pállinger, Éva; Winyard, Paul; Buzás, Edit I

    2015-04-01

    Extracellular vesicles including exosomes, microvesicles and apoptotic vesicles, are phospholipid bilayer surrounded structures secreted by cells universally, in an evolutionarily conserved fashion. Posttranslational modifications such as oxidation, citrullination, phosphorylation and glycosylation play diverse roles in extracellular vesicle biology. Posttranslational modifications orchestrate the biogenesis of extracellular vesicles. The signals extracellular vesicles transmit between cells also often function via modulating posttranslational modifications of target molecules, given that extracellular vesicles are carriers of several active enzymes catalysing posttranslational modifications. Posttranslational modifications of extracellular vesicles can also contribute to disease pathology by e.g. amplifying inflammation, generating neoepitopes or carrying neoepitopes themselves.

  15. Glucagon-like peptide-2 (GLP-2) increases net amino acid utilization by the portal-drained viscera of ruminating calves

    DEFF Research Database (Denmark)

    Taylor-Edwards, C C; Burrin, D G; Kristensen, N B;

    2012-01-01

    , potentially by increased small intestinal epithelial growth and thus energy and amino acid requirements of this tissue. Increased PDV extraction of glutamine and alterations in PDV metabolism of arginine, ornithine and citrulline support the concept that GLP-2 influences intestine-specific amino acid...... periods: baseline (saline infusion), treatment (infusion of bovine serum albumin or 3.76 μg/kg BW per h GLP-2) and recovery (saline infusion). Arterial concentrations and net PDV, hepatic and total splanchnic fluxes of glucose, lactate, glutamate, glutamine, β-hydroxybutyrate and urea-N were measured...

  16. Raw bovine milk improves gut responses to feeding relative to infant formula in preterm piglets

    DEFF Research Database (Denmark)

    Li, Yang; Lykke, Mikkel; Chatterton, D E W

    2014-01-01

    height) and function (increased nutrient absorption and enzyme activities, decreased gut permeability, nutrient fermentation, and NEC severity). BC further improved these effects relative to BM (lactase activity, lactose absorption, plasma citrulline, and tissue interleukin-8). WMP induced similar...... effects as BM, except for lactase activity and lactose absorption. In conclusion, the maturational and protective effects on the immature intestine decreased in the order BC>BM>WMP, but all three intact bovine milk diets were markedly better than IF. The stage of lactation (colostrum vs. mature milk...

  17. Arginine Deiminase Enzyme Evolving As A Potential Antitumor Agent.

    Science.gov (United States)

    Somani, Rakesh; Chaskar, Pratip K

    2016-08-17

    Some melanomas and hepatocellular carcinomas have been shown to be auxotrophic for arginine. Arginine deiminase (ADI), an arginine degrading enzyme isolated from Mycoplasma, can inhibit the growth of these tumors. It is a catabolizing enzyme which catabolizes arginine to citrulline. Tumor cells do not express an enzyme called arginosuccinate synthetase (ASS) and hence, these cells becomes auxotrophic for arginine. It is found that ADI is specific for arginine and did not degrade other amino acid. This review covers various aspects of ADIs like origin, properties and chemical modifications for better antitumor activity.

  18. Peptidomimetics as protein arginine deiminase 4 (PAD4) inhibitors.

    Science.gov (United States)

    Trabocchi, Andrea; Pala, Nicolino; Krimmelbein, Ilga; Menchi, Gloria; Guarna, Antonio; Sechi, Mario; Dreker, Tobias; Scozzafava, Andrea; Supuran, Claudiu T; Carta, Fabrizio

    2015-06-01

    The protein arginine deiminase 4 (PAD4) is a calcium-dependent enzyme, which catalyses the irreversible conversion of peptidyl-arginines into peptidyl-citrullines and plays an important role in several diseases such as in the rheumatoid arthritis, multiple sclerosis, Alzheimer's disease, Creutzfeldt-Jacob's disease and cancer. In this study, we report the inhibition profiles and computational docking toward the PAD4 enzyme of a series of 1,2,3-triazole peptidomimetic-based derivatives incorporating the β-phenylalanine and guanidine scaffolds. Several effective, low micromolar PAD4 inhibitors are reported in this study.

  19. Smoking and polymorphisms of genes encoding mannose-binding lectin and surfactant protein-D in patients with rheumatoid arthritis

    DEFF Research Database (Denmark)

    Kristiansen, Malthe; Frisch, Morten; Madsen, Hans Ole;

    2014-01-01

    To investigate whether polymorphisms in genes coding for mannose-binding lectin (MBL) and surfactant protein-D (SP-D) are associated directly or by interaction with smoking with rheumatoid arthritis (RA), anti-citrullinated peptide antibody (ACPA) positive RA, and erosive RA. MBL2 genotypes, SFTPD...... genotype at codon 11, and HLA-shared epitope were determined in 456 patients with rheumatoid arthritis and 533 sex- and age-matched controls. Patients were grouped according to the presence of ACPA antibodies and RA-associated bone erosions and sub-stratified according to smoking status as never or ever...

  20. 中国上市企业R&D投入的周期性特征研究——来自深圳中小板2008年金融危机期间的证据%Study on Cyclicality of R&D of the Listed Company in China: Evidence from Shenzhen Stock Market in Financial Crisis in 2008

    Institute of Scientific and Technical Information of China (English)

    关勇军; 洪开荣

    2012-01-01

    This paper reviews theory of the cyclicality of R&D, considers the effect of financial crisis on Chinese economy, takes 216 small-medium enterprise of Shenzhen stock market for sample, checks the R&D investment strategy and its affecting factors chosen by the listed company in China and draws the following conclusions: (1) only 22% of sample chosen the strategy of reducing R&D investment (pro-cyclicality behaviors) and back the theo- ry of opportunity cost;(2) the company with rich cash flow would choose the anti-cyclicality behaviors;(3) the com- pany with taking part in R&D coloration would choose the anti-cyclicality behaviors;(4) the high-tech company with high R&D intensity would choose the anti-cyclicality behaviors;(5) the company under high product competi- tive pressure would choose the pro-cyclicality behaviors.%在对研发投资周期性特征相关理论综述的基础上,结合2008年金融危机对中国经济的影响,以2006--2009年深圳中小板的216家企业为样本,考察了我国上市企业在金融危机期间所采取的研发投资策略及其影响因素。得出以下结论:(1)深圳中小板上市公司在金融危机期间仅有22%的企业采取了减少研发投资(顺周期)的策略,这支持了机会成本效应理论;(2)现金流量比较充裕的企业在金融危机期间会采取研发投入的逆周期行为;(3)参与研发合作的企业在金融危机期间会采取研发投入的逆周期行为;(4)研发强度大的高新技术企业在金融危机期间会采取研发投入的逆周期行为;(5)产品竞争激烈的企业在金融危机期间会采取研发投入的顺周期行为。

  1. Metabolic profiling of presymptomatic Huntington’s disease sheep reveals novel biomarkers

    Science.gov (United States)

    Skene, Debra J.; Middleton, Benita; Fraser, Cara K.; Pennings, Jeroen L. A.; Kuchel, Timothy R.; Rudiger, Skye R.; Bawden, C. Simon; Morton, A. Jennifer

    2017-01-01

    The pronounced cachexia (unexplained wasting) seen in Huntington’s disease (HD) patients suggests that metabolic dysregulation plays a role in HD pathogenesis, although evidence of metabolic abnormalities in HD patients is inconsistent. We performed metabolic profiling of plasma from presymptomatic HD transgenic and control sheep. Metabolites were quantified in sequential plasma samples taken over a 25 h period using a targeted LC/MS metabolomics approach. Significant changes with respect to genotype were observed in 89/130 identified metabolites, including sphingolipids, biogenic amines, amino acids and urea. Citrulline and arginine increased significantly in HD compared to control sheep. Ten other amino acids decreased in presymptomatic HD sheep, including branched chain amino acids (isoleucine, leucine and valine) that have been identified previously as potential biomarkers of HD. Significant increases in urea, arginine, citrulline, asymmetric and symmetric dimethylarginine, alongside decreases in sphingolipids, indicate that both the urea cycle and nitric oxide pathways are dysregulated at early stages in HD. Logistic prediction modelling identified a set of 8 biomarkers that can identify 80% of the presymptomatic HD sheep as transgenic, with 90% confidence. This level of sensitivity, using minimally invasive methods, offers novel opportunities for monitoring disease progression in HD patients. PMID:28223686

  2. Urea Cycle Defects: Early-Onset Disease Associated with A208T Mutation in OTC Gene—Expanding the Clinical Phenotype

    Science.gov (United States)

    Sánchez, Ana Isabel; Rincón, Alejandra; García, Mary

    2017-01-01

    Ornithine transcarbamylase deficiency (OMIM: 311250) is the most common disorder of urea cycle disorders, accounting for nearly 50% of all cases. We report a case of a two-month- old male patient, who attends our medical genetics consultation because of low citrulline levels and elevated glutamine to citrulline ratio detected by expanded newborn screening with tandem mass spectrometry. He is an asymptomatic male with a normal physical examination and appropriate neurodevelopmental milestones. The patient has a family history of one older brother who died at 18 months old from severe and sudden hyperammonemia and a maternal aunt who suddenly died at two years old. He had high plasma ammonium concentration and a confirmed OTC mutation (p.A208T). Usually, this mutation causes OTC deficiency of late onset in adult males. However, this report raises awareness about mutations previously described as a late-onset causing disease, which can cause severe hyperammonemia and high risk of dying at an early age. PMID:28261508

  3. Mutation of Glu-361 in Human Endothelial Nitric-oxide Synthase Selectively Abolishes L-Arginine Binding without Perturbing the Behavior of Heme and Other Redox Centers

    Science.gov (United States)

    Chen, Pei-Feng; Tsai, Ah-Lim; Berka, Vladimir; Wu, Kenneth K.

    2010-01-01

    Nitric oxide (NO) and L-citrulline are formed from the oxidation of L-arginine by three different isoforms of NO synthase (NOS). Defining amino acid residues responsible for L-arginine binding and oxidation is a primary step toward a detailed understanding of the NOS reaction mechanisms and designing strategies for the selective inhibition of the individual isoform. We have altered Glu-361 in human endothelial NOS to Gln or Leu by site-directed mutagenesis and found that these mutations resulted in a complete loss of L-citrulline formation without disruption of the cytochrome c reductase and NADPH oxidase activities. Optical and EPR spectroscopic studies demonstrated that the Glu-361 mutants had similar spectra either in resting state or reduced CO-complex as the wild type. The heme ligand, imidazole, could induce a low spin state in both wild-type and Glu-361 mutants. However, unlike the wild-type enzyme, the low spin imidazole complex of Glu-361 mutants was not reversed to a high spin state by addition of either L-arginine, acetylguanidine, or 2-aminothiazole. Direct L-arginine binding could not be detected in the mutants either. These results strongly indicate that Glu-361 in human endothelial NOS is specifically involved in the interaction with L-arginine. Mutation of this residue abolished the L-arginine binding without disruption of other functional characteristics. PMID:9045621

  4. [Pathophysiology of rheumatoid arthritis].

    Science.gov (United States)

    Lequerré, Thierry; Richez, Christophe

    2012-10-01

    These last years were especially marked by the best understanding of the physiopathological mechanisms at the onset of rheumatoid arthritis (RA) and in the processes of joint inflammation and joint destruction. RA is more and more considered as a syndrome with at least two clinical entities with different phenotype and profiles: seronegative RA and seropositive RA. In RA with ACPA, it is the process of immunization, that is the immunological reaction against citrullinated peptides, that leads to the disease. The peptide citrullination is directly favored by environmental factors such as tobacco, infection to Porphyromonas gingivalis and alcohol. The immunization supposes a genetic predisposition including approximately 22 genetic factors including the molecules of the major histocompatibility complex (MHC) and PTPN22. Finally, joint damage result at the same time from an excess of destruction (RANK/RANKL, TNFalpha) and from a defect of bone reparation by the way Wnt/Frizzled. It is thanks to the best understanding of RA physiopathology that leads to development of targeted treatments and specially processing for this disease.

  5. Urinary Metabolomic Approach Provides New Insights into Distinct Metabolic Profiles of Glutamine and N-Carbamylglutamate Supplementation in Rats.

    Science.gov (United States)

    Liu, Guangmang; Cao, Wei; Fang, Tingting; Jia, Gang; Zhao, Hua; Chen, Xiaoling; Wu, Caimei; Wang, Jing

    2016-08-04

    Glutamine and N-carbamylglutamate can enhance growth performance and health in animals, but the underlying mechanisms are not yet elucidated. This study aimed to investigate the effect of glutamine and N-carbamylglutamate supplementation in rat metabolism. Thirty rats were fed a control, glutamine, or N-carbamylglutamate diet for four weeks. Urine samples were analyzed by nuclear magnetic resonance (NMR)-based metabolomics, specifically high-resolution ¹H NMR metabolic profiling combined with multivariate data analysis. Glutamine significantly increased the urine levels of acetamide, acetate, citrulline, creatinine, and methymalonate, and decreased the urine levels of ethanol and formate (p carbamylglutamate significantly increased the urine levels of creatinine, ethanol, indoxyl sulfate, lactate, methymalonate, acetoacetate, m-hydroxyphenylacetate, and sarcosine, and decreased the urine levels of acetamide, acetate, citrulline, creatine, glycine, hippurate, homogentisate, N-acetylglutamate, phenylacetyglycine, acetone, and p-hydroxyphenylacetate (p carbamylglutamate could modify urinary metabolome related to nitrogen metabolism and gut microbiota metabolism. Moreover, N-carbamylglutamate could alter energy and lipid metabolism. These findings indicate that different arginine precursors may lead to differences in the biofluid profile in rats.

  6. A prospective comparison of acute intestinal toxicity following whole pelvic versus small field intensity-modulated radiotherapy for prostate cancer

    Science.gov (United States)

    Kim, Yeon Joo; Park, Jin-hong; Yun, In-Ha; Kim, Young Seok

    2016-01-01

    Purpose To compare the acute intestinal toxicity of whole pelvic (WP) and small field (SF) intensity-modulated radiotherapy (IMRT) for prostate cancer using dosimetric and metabolic parameters as well as clinical findings. Methods Patients who received IMRT in either a definitive or postoperative setting were prospectively enrolled. Target volume and organs at risk including intestinal cavity (IC) were delineated in every patient by a single physician. The IC volume that received a 10–50 Gy dose at 5-Gy intervals (V10–V50) and the percentage of irradiated volume as a fraction of total IC volume were calculated. Plasma citrulline levels, as an objective biological marker, were checked at three time points: baseline and after exposure to 30 Gy and 60 Gy. Results Of the 41 patients, only six experienced grade 1 acute intestinal toxicity. Although all dose–volume parameters were significantly worse following WP than SF IMRT, there was no statistically significant relationship between these dosimetric parameters and clinical symptoms. Plasma citrulline levels did not show a serial decrease by radiotherapy volume difference (WP versus SF) and were not relevant to the irradiated doses. Conclusion Given that WP had comparable acute intestinal toxicities to those associated with SF, WP IMRT appears to be a feasible approach for the treatment of prostate cancer despite dosimetric disadvantages. PMID:27022287

  7. Vitamin C: A Novel Regulator of Neutrophil Extracellular Trap Formation

    Directory of Open Access Journals (Sweden)

    Ramesh Natarajan

    2013-08-01

    Full Text Available Introduction: Neutrophil extracellular trap (NET formation was recently identified as a novel mechanism to kill pathogens. However, excessive NET formation in sepsis can injure host tissues. We have recently shown that parenteral vitamin C (VitC is protective in sepsis. Whether VitC alters NETosis is unknown. Methods: We used Gulo−/− mice as they lack the ability to synthesize VitC. Sepsis was induced by intraperitoneal infusion of a fecal stem solution (abdominal peritonitis, FIP. Some VitC deficient Gulo−/− mice received an infusion of ascorbic acid (AscA, 200 mg/kg 30 min after induction of FIP. NETosis was assessed histologically and by quantification for circulating free DNA (cf-DNA in serum. Autophagy, histone citrullination, endoplasmic reticulum (ER stress, NFκB activation and apoptosis were investigated in peritoneal PMNs. Results: Sepsis produced significant NETs in the lungs of VitC deficient Gulo−/− mice and increased circulating cf-DNA. This was attenuated in the VitC sufficient Gulo−/− mice and in VitC deficient Gulo−/− mice infused with AscA. Polymorphonuclear neutrophils (PMNs from VitC deficient Gulo−/− mice demonstrated increased activation of ER stress, autophagy, histone citrullination, and NFκB activation, while apoptosis was inhibited. VitC also significantly attenuated PMA induced NETosis in PMNs from healthy human volunteers.

  8. Influence of phenolic compounds on the growth and arginine deiminase system in a wine lactic acid bacterium

    Directory of Open Access Journals (Sweden)

    María R. Alberto

    2012-03-01

    Full Text Available The influence of seven phenolic compounds, normally present in wine, on the growth and arginine deiminase system (ADI of Lactobacillus hilgardii X1B, a wine lactic acid bacterium, was established. This system provides energy for bacterial growth and produces citrulline that reacts with ethanol forming the carcinogen ethyl carbamate (EC, found in some wines. The influence of phenolic compounds on bacterial growth was compound dependent. Growth and final pH values increased in presence of arginine. Arginine consumption decreased in presence of protocatechuic and gallic acids (31 and 17%, respectively and increased in presence of quercetin, rutin, catechin and the caffeic and vanillic phenolic acids (between 10 and 13%, respectively. ADI enzyme activities varied in presence of phenolic compounds. Rutin, quercetin and caffeic and vanillic acids stimulated the enzyme arginine deiminase about 37-40%. Amounts of 200 mg/L gallic and protocatechuic acids inhibited the arginine deiminase enzyme between 53 and 100%, respectively. Ornithine transcarbamylase activity was not modified at all concentrations of phenolic compounds. As gallic and protocatechuic acids inhibited the arginine deiminase enzyme that produces citrulline, precursor of EC, these results are important considering the formation of toxic compounds.

  9. Anti-CCP Antibody Levels Are Not Associated with MS: Results from a Case-Control Study

    Directory of Open Access Journals (Sweden)

    Mahmut Alpayci

    2015-01-01

    Full Text Available Citrullinated proteins have been suggested to play a critical role in the pathogenesis of multiple sclerosis (MS. Anticyclic citrullinated peptide (anti-CCP antibody is used in the early diagnosis of rheumatoid arthritis (RA. The objective of this study was to investigate the presence of anti-CCP antibody in patients with MS compared to RA patients and healthy controls. Fifty patients with MS (38 females, 12 males; mean age 36.72 ± 8.82 years, 52 patients with RA (40 females, 12 males; mean age 40.87 ± 10.17 years, and 50 healthy controls (32 females, 18 males; mean age 38.22 ± 11.59 years were included in this study. The levels of serum anti-CCP antibody were measured using an enzyme-linked immunosorbent assay (ELISA. The results of the study showed that anti-CCP antibody levels were significantly higher in RA patients versus MS or healthy controls (P<0.001. Moreover, anti-CCP antibody was positive in 43 (83% patients with RA, while it was negative in all MS patients as well as in all healthy controls. Also, no significant correlation was found between the anti-CCP levels and EDSS scores (r=-0.250. In conclusion, the results of this study did not support a positive association between serum anti-CCP antibody and MS.

  10. Comparative aspects of tissue glutamine and proline metabolism.

    Science.gov (United States)

    Bertolo, Robert F; Burrin, Douglas G

    2008-10-01

    The cellular metabolism of glutamine and proline are closely interrelated, because they can be interconverted with glutamate and ornithine via the mitochondrial pathway involving pyrroline-5-carboxylate (P5C). In adults, glutamine and proline are converted via P5C to citrulline in the gut, then citrulline is converted to arginine in the kidney. In neonates, arginine is a semiindispensable amino acid and is synthesized from proline completely in the gut; because of low P5C synthase activity, glutamine is not an important precursor for neonatal arginine synthesis. Thus, splanchnic metabolism of glutamine and proline is important, because both amino acids serve as key precursors for arginine synthesis with some developmental differences. Studies investigating splanchnic extraction demonstrate that about two-thirds of dietary glutamine and almost all dietary glutamate are extracted on first pass and the vast majority is oxidized in the gut. This capacity to extract glutamine and glutamate appears to be very large, so diets high in glutamine or glutamate probably have little impact on circulating concentrations and consequent potential toxicity. In contrast, it appears that very little proline is extracted by the gut and liver, at least in the neonate, which may result in hyperprolinemia and potential toxicity. Therefore, the upper limits of safe dietary intake for glutamine and proline, and other amino acids, appear to be substantially different depending on the extent of first-pass splanchnic extraction and irreversible catabolism.

  11. The role for neutrophil extracellular traps in cystic fibrosis autoimmunity

    Science.gov (United States)

    Skopelja, Sladjana; Hamilton, B. JoNell; Jones, Jonathan D.; Yang, Mei-Ling; Mamula, Mark; Ashare, Alix; Gifford, Alex H.; Rigby, William F.C.

    2016-01-01

    While respiratory failure in cystic fibrosis (CF) frequently associates with chronic infection by Pseudomonas aeruginosa, no single factor predicts the extent of lung damage in CF. To elucidate other causes, we studied the autoantibody profile in CF and rheumatoid arthritis (RA) patients, given the similar association of airway inflammation and autoimmunity in RA. Even though we observed that bactericidal permeability-increasing protein (BPI), carbamylated proteins, and citrullinated proteins all localized to the neutrophil extracellular traps (NETs), which are implicated in the development of autoimmunity, our study demonstrates striking autoantibody specificity in CF. Particularly, CF patients developed anti-BPI autoantibodies but hardly any anti-citrullinated protein autoantibodies (ACPA). In contrast, ACPA-positive RA patients exhibited no reactivity with BPI. Interestingly, anti-carbamylated protein autoantibodies (ACarPA) were found in both cohorts but did not cross-react with BPI. Contrary to ACPA and ACarPA, anti-BPI autoantibodies recognized the BPI C-terminus in the absence of posttranslational modifications. In fact, we discovered that P. aeruginosa–mediated NET formation results in BPI cleavage by P. aeruginosa elastase, which suggests a novel mechanism in the development of autoimmunity to BPI. In accordance with this model, autoantibodies associated with presence of P. aeruginosa on sputum culture. Finally, our results provide a role for autoimmunity in CF disease severity, as autoantibody levels associate with diminished lung function. PMID:27777975

  12. Proteome Analysis of Rheumatoid Arthritis Gut Mucosa.

    Science.gov (United States)

    Bennike, Tue Bjerg; Ellingsen, Torkell; Glerup, Henning; Bonderup, Ole Kristian; Carlsen, Thomas Gelsing; Meyer, Michael Kruse; Bøgsted, Martin; Christiansen, Gunna; Birkelund, Svend; Andersen, Vibeke; Stensballe, Allan

    2017-01-06

    Rheumatoid arthritis (RA) is an inflammatory joint disease leading to cartilage damage and ultimately impaired joint function. To gain new insight into the systemic immune manifestations of RA, we characterized the colon mucosa proteome from 11 RA-patients and 10 healthy controls. The biopsies were extracted by colonoscopy and analyzed by label-free quantitative proteomics, enabling the quantitation of 5366 proteins. The abundance of dihydrofolate reductase (DHFR) was statistically significantly increased in RA-patient biopsies compared with controls and correlated with the administered dosage of methotrexate (MTX), the most frequently prescribed immunosuppressive drug for RA. Additionally, our data suggest that treatment with Leflunomide, a common alternative to MTX, increases DHFR. The findings were supported by immunohistochemistry with confocal microscopy, which furthermore demonstrated that DHFR was located in the cytosol of the intestinal epithelial and interstitial cells. Finally, we identified 223 citrullinated peptides from 121 proteins. Three of the peptides were unique to RA. The list of citrullinated proteins was enriched in extracellular and membrane proteins and included known targets of anticitrullinated protein antibodies (ACPAs). Our findings support that the colon mucosa could trigger the production of ACPAs, which could contribute to the onset of RA. The MS data have been deposited to ProteomeXchange with identifiers PXD001608 and PXD003082.

  13. Effects of microalgae chlorella species crude extracts on intestinal adaptation in experimental short bowel syndrome

    Institute of Scientific and Technical Information of China (English)

    Mustafa Kerem; Bulent Salman; Hatice Pasaoglu; Abdulkadir Bedirli; Murat Alper; Hikmet Katircioglu; Tahir Atici; E Ferda Pertoin; Ebru Ofluoglu

    2008-01-01

    AIM: To evaluate the effects of chlorella crude extract (CCE) on intestinal adaptation in rats subjected to short bowel syndrome (SBS).METHODS: Wistar rats weighing 230-260 g were used in the study. After anesthesia a 75% small bowel resection was performed. Rats were randomized and divided into groups. Control group (n = 10): where 5% dextrose was given through a gastrostomy tube, Enteral nutrition (EN) group (n = 10): Isocaloric and isonitrogen EN (Alitraq, Abbott, USA), study group (/7 = 10): CCE was administrated through a gastrostomy tube. Rats were sacrificed on the fifteenth postoperative day and blood and tissue samples were taken. Histopathologic evaluation, intestinal mucosal protein and DNA levels,intestinal proliferation and apoptosis were determined in intestinal tissues, and total protein, albumin and citrulline levels in blood were studied.RESULTS: In rats receiving CCE, villus lengthening,crypt depth, mucosal DNA and protein levels, intestinal proliferation, and serum citrulline, protein and albumin levels were found to be significantly higher than those in control group. Apoptosis in CCE treated rats was significantly reduced when compared to EN group rats.CONCLUSION: CCE has beneficial effects on intestinala daptation in experimental SBS.

  14. Enzymatic Modification of Soluble Cyanophycin Using the Type II Peptidyl Arginine Deiminase from Oryctolagus cuniculus.

    Science.gov (United States)

    Wiefel, Lars; Steinbüchel, Alexander

    2016-07-01

    An increased structural variety expands the number of putative applications for cyanophycin (multi-l-arginyl-poly-[l-aspartic acid], CGP). Therefore, structural modifications of CGP are of major interest; these are commonly obtained by modification and optimization of the bacterial producing strain or by chemical modification. In this study, an enzymatic modification of arginine side chains from lysine-rich CGP is demonstrated using the peptidyl arginine deiminase from Oryctolagus cuniculus, purified from Escherichia coli after heterologous expression. About 10% of the arginine side chains are converted to citrulline which corresponds to 4% of the polymer's total side chains. An inhibition of the reaction in the presence of small amounts of l-citrulline is observed, thereby explaining the low conversion rate. CGP dipeptides can be modified with about 7.5 mol% of the Asp-Arg dipeptides being converted to Asp-Cit. These results show that the enzymatic modification of CGP is feasible, opening up a whole new area of possible CGP modifications for further research.

  15. Convergent evolution of the arginine deiminase pathway: the ArcD and ArcE arginine/ornithine exchangers.

    Science.gov (United States)

    Noens, Elke E E; Lolkema, Juke S

    2017-02-01

    The arginine deiminase (ADI) pathway converts L-arginine into L-ornithine and yields 1 mol of ATP per mol of L-arginine consumed. The L-arginine/L-ornithine exchanger in the pathway takes up L-arginine and excretes L-ornithine from the cytoplasm. Analysis of the genomes of 1281 bacterial species revealed the presence of 124 arc gene clusters encoding the pathway. About half of the clusters contained the gene encoding the well-studied L-arginine/L-ornithine exchanger ArcD, while the other half contained a gene, termed here arcE, encoding a membrane protein that is not a homolog of ArcD. The arcE gene product of Streptococcus pneumoniae was shown to take up L-arginine and L-ornithine with affinities of 0.6 and 1 μmol/L, respectively, and to catalyze metabolic energy-independent, electroneutral exchange. ArcE of S. pneumoniae could replace ArcD in the ADI pathway of Lactococcus lactis and provided the cells with a growth advantage. In contrast to ArcD, ArcE catalyzed translocation of the pathway intermediate L-citrulline with high efficiency. A short version of the ADI pathway is proposed for L-citrulline catabolism and the presence of the evolutionary unrelated arcD and arcE genes in different organisms is discussed in the context of the evolution of the ADI pathway.

  16. Influence of phenolic compounds on the growth and arginine deiminase system in a wine lactic acid bacterium.

    Science.gov (United States)

    Alberto, María R; de Nadra, María C Manca; Arena, Mario E

    2012-01-01

    The influence of seven phenolic compounds, normally present in wine, on the growth and arginine deiminase system (ADI) of Lactobacillus hilgardii X1B, a wine lactic acid bacterium, was established. This system provides energy for bacterial growth and produces citrulline that reacts with ethanol forming the carcinogen ethyl carbamate (EC), found in some wines. The influence of phenolic compounds on bacterial growth was compound dependent. Growth and final pH values increased in presence of arginine. Arginine consumption decreased in presence of protocatechuic and gallic acids (31 and 17%, respectively) and increased in presence of quercetin, rutin, catechin and the caffeic and vanillic phenolic acids (between 10 and 13%, respectively). ADI enzyme activities varied in presence of phenolic compounds. Rutin, quercetin and caffeic and vanillic acids stimulated the enzyme arginine deiminase about 37-40%. Amounts of 200 mg/L gallic and protocatechuic acids inhibited the arginine deiminase enzyme between 53 and 100%, respectively. Ornithine transcarbamylase activity was not modified at all concentrations of phenolic compounds. As gallic and protocatechuic acids inhibited the arginine deiminase enzyme that produces citrulline, precursor of EC, these results are important considering the formation of toxic compounds.

  17. The kinetics of the arginine deiminase pathway in the meat starter culture Lactobacillus sakei CTC 494 are pH-dependent.

    Science.gov (United States)

    Rimaux, T; Vrancken, G; Pothakos, V; Maes, D; De Vuyst, L; Leroy, F

    2011-05-01

    Lactobacillus sakei is frequently present as the dominant lactic acid bacterium in spontaneously fermented meat products, demonstrating its competitiveness in and adaptation to the meat environment. Since meat is generally low in carbohydrate content, the ability to utilize other energy sources to generate ATP, such as arginine via the arginine deiminase (ADI) pathway, represents a competitive benefit. In this study, the kinetics of growth and arginine conversion capabilities of Lb. sakei CTC 494 were analyzed, and a model was set up to describe the influence of pH on growth and arginine conversion. A series of in vitro batch fermentations using reconstituted MRS medium at different constant pH values (pH 4.50-pH 7.75) was performed. Arginine conversion through the ADI pathway, which was activated from the stationary growth phase on, resulted in the production of both citrulline and ornithine for all pH conditions tested. However, the pattern and the ratio of the end-products of the ADI pathway were influenced by pH. For certain pH values (between pH 5.0 and 6.5), a further conversion of citrulline into ornithine was found when all arginine was depleted. Characterization of responses of the ADI pathway in Lb. sakei CTC 494 to environmental conditions will allow a better understanding and control of this important starter culture in meat fermentations.

  18. Arginine depletion by arginine deiminase does not affect whole protein metabolism or muscle fractional protein synthesis rate in mice.

    Science.gov (United States)

    Marini, Juan C; Didelija, Inka Cajo

    2015-01-01

    Due to the absolute need for arginine that certain cancer cells have, arginine depletion is a therapy in clinical trials to treat several types of cancers. Arginine is an amino acids utilized not only as a precursor for other important molecules, but also for protein synthesis. Because arginine depletion can potentially exacerbate the progressive loss of body weight, and especially lean body mass, in cancer patients we determined the effect of arginine depletion by pegylated arginine deiminase (ADI-PEG 20) on whole body protein synthesis and fractional protein synthesis rate in multiple tissues of mice. ADI-PEG 20 successfully depleted circulating arginine (arginine, whole body protein synthesis and breakdown were maintained in the ADI-PEG 20 treated mice. The fractional protein synthesis rate of muscle was also not affected by arginine depletion. Most tissues (liver, kidney, spleen, heart, lungs, stomach, small and large intestine, pancreas) were able to maintain their fractional protein synthesis rate; however, the fractional protein synthesis rate of brain, thymus and testicles was reduced due to the ADI-PEG 20 treatment. Furthermore, these results were confirmed by the incorporation of ureido [14C]citrulline, which indicate the local conversion into arginine, into protein. In conclusion, the intracellular recycling pathway of citrulline is able to provide enough arginine to maintain protein synthesis rate and prevent the loss of lean body mass and body weight.

  19. Rheumatoid Arthritis-Associated Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis: Shared Mechanistic and Phenotypic Traits Suggest Overlapping Disease Mechanisms.

    Science.gov (United States)

    Paulin, Francisco; Doyle, Tracy J; Fletcher, Elaine A; Ascherman, Dana P; Rosas, Ivan O

    2015-01-01

    The prevalence of clinically evident interstitial lung disease in patients with rheumatoid arthritis is approximately 10%. An additional 33% of undiagnosed patients have interstitial lung abnormalities that can be detected with high-resolution computed tomography. Rheumatoid arthritis-interstitial lung disease patients have three times the risk of death compared to those with rheumatoid arthritis occurring in the absence of interstitial lung disease, and the mortality related to interstitial lung disease is rising. Rheumatoid arthritis-interstitial lung disease is most commonly classified as the usual interstitial pneumonia pattern, overlapping mechanistically and phenotypically with idiopathic pulmonary fibrosis, but can occur in a non-usual interstitial pneumonia pattern, mainly nonspecific interstitial pneumonia. Based on this, we propose two possible pathways to explain the coexistence of rheumatoid arthritis and interstitial lung disease: (i) Rheumatoid arthritis-interstitial lung disease with a non-usual interstitial pneumonia pattern may come about when an immune response against citrullinated peptides taking place in another site (e.g. the joints) subsequently affects the lungs; (ii) Rheumatoid arthritis-interstitial lung disease with a usual interstitial pneumonia pattern may represent a disease process in which idiopathic pulmonary fibrosis-like pathology triggers an immune response against citrullinated proteins that promotes articular disease indicative of rheumatoid arthritis. More studies focused on elucidating the basic mechanisms leading to different sub-phenotypes of rheumatoid arthritis-interstitial lung disease and the overlap with idiopathic pulmonary fibrosis are necessary to improve our understanding of the disease process and to define new therapeutic targets.

  20. Markers of Perioperative Bowel Complications in Colorectal Surgery Patients

    Directory of Open Access Journals (Sweden)

    Radomír Hyšpler

    2015-01-01

    Full Text Available Colorectal cancer is a clinical condition whose treatment often involves intestinal resection. Such treatment frequently results in two major gastrointestinal complications after surgery: anastomotic leakage and prolonged ileus. Anastomotic leakage is a serious complication which, more often than not, is diagnosed late; to date, C-reactive protein is the only available diagnostic marker. A monocentric, prospective, open case-control study was performed in patients (n=117 undergoing colorectal surgery. Intestinal fatty acid binding protein (i-FABP, citrulline, D-lactate, exhaled hydrogen, Escherichia coli genomic DNA, and ischemia modified albumin (IMA were determined preoperatively, postoperatively, and on the following four consecutive days. Bacterial DNA was not detected in any sample, and i-FABP and D-lactate lacked any distinct potential to detect postoperative bowel complications. Exhaled breath hydrogen content showed unacceptably low sensitivity. However, citrulline turned out to be a specific marker for prolonged ileus on postoperative days 3-4. Using a cut-off value of 20 μmol/L, a sensitivity and specificity of ~75% was achieved on postoperative day 4. IMA was found to be an efficient predictor of anastomosis leak by calculating the difference between preoperative and postoperative values. This test had 100% sensitivity and 80% specificity and 100% negative and 20% positive predictive value.

  1. Aloe vera affects changes induced in pulmonary tissue of mice caused by cigarette smoke inhalation.

    Science.gov (United States)

    Koul, Ashwani; Bala, Shashi; Yasmeen; Arora, Neha

    2015-09-01

    This study was undertaken to determine the influence of Aloe vera (AV) on changes induced in pulmonary tissue of cigarette smoke (CS) inhaling mice. CS inhalation for 4 weeks caused pulmonary damage as evident by histoarchitectural alterations and enhanced serum and tissue lactate dehydrogenase (LDH) activities. CS inhalation also led to increased mucin production as revealed by mucicarmine and Alcian Blue-Periodic Acid Schiff (AB-PAS) staining. Studies on bronchoalveolar lavage fluid (balf) of CS exposed animals revealed structural changes in phospholipids and increase in surface tension when compared with control counterparts. These changes were accompanied by enhanced nitric oxide (NO) levels, citrulline levels, peroxidative damage, and differential modulation of antioxidant defense system. AV administration (seven weeks, 500 mg/kg b.w. daily) to CS inhaling mice led to modulation of CS induced pulmonary changes as revealed by lesser degree of histoarchitectural alterations, lesser mucin production, decreased NO levels, citrulline levels, peroxidative damage, and serum LDH activity. AV treatment to CS inhaling mice was associated with varying response to antioxidant defense system, however balf of CS + AV treated animals did not exhibit appreciable changes when compared with that of CS exposed animals. These observations suggest that AV has the potential to modulate CS induced changes in the pulmonary tissue which could have implications in management of CS associated pulmonary diseases, however, further investigations are required to explore its complete mechanism of action.

  2. Inducible nitric oxide synthase is expressed in synovial fluid granulocytes.

    Science.gov (United States)

    Cedergren, J; Forslund, T; Sundqvist, T; Skogh, T

    2002-10-01

    The objective of the study was to evaluate the NO-producing potential of synovial fluid (SF) cells. SF from 15 patients with arthritis was compared with blood from the same individuals and with blood from 10 healthy controls. Cellular expression of inducible nitric oxide synthase (iNOS) was analysed by flow cytometry. High-performance liquid chromatography was used to measure l-arginine and l-citrulline. Nitrite and nitrate were measured colourimetrically utilizing the Griess' reaction. Compared to whole blood granulocytes in patients with chronic arthritis, a prominent iNOS expression was observed in SF granulocytes (P < 0.001). A slight, but statistically significant, increase in iNOS expression was also recorded in lymphocytes and monocytes from SF. l-arginine was elevated in SF compared to serum (257 +/- 78 versus 176 +/- 65 micro mol/l, P = 0.008), whereas a slight increase in l-citrulline (33 +/- 11 versus 26 +/- 9 micro mol/l), did not reach statistical significance. Great variations but no significant differences were observed comparing serum and SF levels of nitrite and nitrate, respectively, although the sum of nitrite and nitrate tended to be elevated in SF (19.2 +/- 20.7 versus 8.6 +/- 6.5 micro mol/l, P = 0.054). Synovial fluid leucocytes, in particular granulocytes, express iNOS and may thus contribute to intra-articular NO production in arthritis.

  3. Importance of post-translational modifications on the function of key haemostatic proteins.

    Science.gov (United States)

    Karlaftis, Vasiliki; Perera, Sachin; Monagle, Paul; Ignjatovic, Vera

    2016-01-01

    Post-translational modifications (PTMs) such as glycosylation and phosphorylation play an important role on the function of haemostatic proteins and are critical in the setting of disease. Such secondary level changes to haemostatic proteins have wide ranging effects on their ability to interact with other proteins. This review aimed to summarize the knowledge of the common PTMs associated with haemostatic proteins and the implications of such modifications on protein function. Haemostatic proteins that represent the main focus for studies specific to PTMs are von Willebrand factor, tissue factor, factor VIII, antithrombin and fibrinogen. These proteins are susceptible to PTMs by glycosylation, phosphorylation, sulphation, citrullination and nitration, respectively, with a significant impact on their function. During synthesis, vWF must undergo extensive PTMs, with N-linked glycosylation being the most common. Increased phosphorylation of tissue factor results in increased affinity for platelets to the vessel endothelium. Citrullination of antithrombin leads to an increased anticoagulant function of this protein and therefore an anticoagulant state that inhibits clot formation. On the contrary, nitration of fibrinogen has been shown to result in a prothrombotic state, whilst sulphation is required for the normal function of Factor VIII. From this review, it is evident that PTMs of haemostatic proteins as a change in protein structure at a secondary level greatly influences the behaviour of the protein at a tertiary level.

  4. A Comparative Metabolomic Evaluation of Behcet's Disease with Arthritis and Seronegative Arthritis Using Synovial Fluid.

    Science.gov (United States)

    Ahn, Joong Kyong; Kim, Sooah; Kim, Jungyeon; Hwang, Jiwon; Kim, Kyoung Heon; Cha, Hoon-Suk

    2015-01-01

    Behcet's disease (BD) with arthritis is often confused with seronegative arthritis (SNA) because of shared clinical symptoms and the lack of definitive biomarkers for BD. To investigate possible metabolic patterns and potential biomarkers of BD with arthritis, metabolomic profiling of synovial fluid (SF) from 6 patients with BD with arthritis and 18 patients with SNA was performed using gas chromatography/time-of-flight mass spectrometry in conjunction with univariate and multivariate statistical analyses. A total of 123 metabolites were identified from samples. Orthogonal partial least square-discriminant analysis showed clear discrimination between BD with arthritis and SNA. A set of 11 metabolites were identified as potential biomarkers for BD using variable importance for projection values and the Wilcoxon-Mann-Whitney test. Compared with SNA, BD with arthritis exhibited relatively high levels of glutamate, valine, citramalate, leucine, methionine sulfoxide, glycerate, phosphate, lysine, isoleucine, urea, and citrulline. There were two markers identified, elevated methionine sulfoxide and citrulline, that were associated with increased oxidative stress, providing a potential link to BD-associated neutrophil hyperactivity. Glutamate, citramalate, and valine were selected and validated as putative biomarkers for BD with arthritis (sensitivity, 100%; specificity, 61.1%). This is the first report to present potential biomarkers from SF for discriminating BD with arthritis from SNA. The metabolomics of SF may be helpful in searching for potential biomarkers and elucidating the clinicopathogenesis of BD with arthritis.

  5. The T1405N carbamoyl phosphate synthetase polymorphism does not affect plasma arginine concentrations in preterm infants.

    Directory of Open Access Journals (Sweden)

    Rob M J Moonen

    Full Text Available BACKGROUND: A C-to-A nucleotide transversion (T1405N in the gene that encodes carbamoyl-phosphate synthetase 1 (CPS1 has been associated with changes in plasma concentrations of L-arginine in term and near term infants but not in adults. In preterm infants homozygosity for the CPS1 Thr1405 variant (CC genotype was associated with an increased risk of having necrotizing enterocolitis (NEC. Plasma L-arginine concentrations are decreased in preterm infants with NEC. AIM: To examine the putative association between the CPS1 T1405N polymorphism and plasma arginine concentrations in preterm infants. METHODS: Prospective multicenter cohort study. Plasma and DNA samples were collected from 128 preterm infants (<30 weeks between 6 and 12 hours after birth. Plasma amino acid and CPS1 T1405N polymorphism analysis were performed. RESULTS: Distribution of genotypes did not differ between the preterm (CC:CA:AA = 55.5%:33.6%:10.9%, n = 128 and term infants (CC:CA:AA = 54.2%:35.4%:10.4%, n = 96. There was no association between the CPS1 genotype and plasma L-arginine or L-citrulline concentration, or the ornithine to citrulline ratio, which varies inversely with CPS1 activity. Also the levels of asymmetric dimethylarginine, and symmetric dimethylarginine were not significantly different among the three genotypes. CONCLUSIONS: The present study in preterm infants did not confirm the earlier reported association between CPS1 genotype and L-arginine levels in term infants.

  6. Aroclor 1254 treatment and fasting influences on rat liver mitochondrial carbamoyl phosphate synthesis with ADP and ATP.

    Science.gov (United States)

    Ebner, K; Couri, D

    1988-10-01

    Previous studies have shown that the polychlorinated biphenyl mixture, Aroclor 1254 (ARO), -induced wasting in male rats is associated with increased permeability of hepatic mitochondria. This was correlated with hyperuremia and stimulated urea synthesis, hypoglycemia and suppressed glucogenesis after an ammonium acetate injection, and decreased retention of assimilated nitrogen and food intake. For ARO-toxic rats (100 mg/kg, ip, for 1, 2, and 4 days) versus Tween 80-treated, ad libitum-fed controls, mitochondrial carbamoyl phosphate (CP) formation (the initial step in urea synthesis from NH4+) was progressively stimulated for the duration of treatment from NH4+ and ATP but not from NH4+ and ADP. ARO maximal stimulation of CP formation also correlated with significant loss in body weight. Mitochondrial ornithine transcarbamoylase synthesis of citrulline from ornithine and carbamoyl phosphate was also stimulated. In comparison to fasted rats (24 hr), mitochondrial CP synthesis from NH4+ was enhanced with ADP but not with ATP. This ARO uncoupling of mitochondrial NH4+ metabolism and stimulation of CP formation with exogenous ATP and citrulline synthesis may have resulted from increased availability of substrates and cofactors in the matrix space, leakage of enzymes from the matrix, or a combination of these effects. These results are consistent with an increased inner membrane permeability and fragility during isolation and assays. In agreement with our previous studies, the data show that ARO exposure poises hepatic mitochondria toward the synthesis of urea intermediates.

  7. Inhibition of peptidyl-arginine deiminases reverses protein-hypercitrullination and disease in mouse models of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Mario A. Moscarello

    2013-03-01

    Multiple sclerosis (MS is the most common CNS-demyelinating disease of humans, showing clinical and pathological heterogeneity and a general resistance to therapy. We first discovered that abnormal myelin hypercitrullination, even in normal-appearing white matter, by peptidylarginine deiminases (PADs correlates strongly with disease severity and might have an important role in MS progression. Hypercitrullination is known to promote focal demyelination through reduced myelin compaction. Here we report that 2-chloroacetamidine (2CA, a small-molecule, PAD active-site inhibitor, dramatically attenuates disease at any stage in independent neurodegenerative as well as autoimmune MS mouse models. 2CA reduced PAD activity and protein citrullination to pre-disease status. In the autoimmune models, disease induction uniformly induced spontaneous hypercitrullination with citrulline+