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Sample records for antibody induced autoimmunity

  1. Characterization of Polyclonal Antibody Induced by Autoantibody TPO (Thyroidperoxidase) From Autoimmune Thyroid Disease (AITD) Serum with ELISA and Western Blotting

    OpenAIRE

    Maulidya Aulia Fiqriyana; Aulanni'am Aulanni'am; Anna Roosdiana

    2013-01-01

    Autoantibody TPO is a potential marker for early detection of autoimmune thyroid disease (AITD). Autoantibody TPO has a specifity and a sensitivity ranging from 82% to100% in comparison to other AITD serology markers. Concentration of autoantibody TPO in sera had a positive correlation with activities of chronic AITD. This research have been conducted to investigate the characteristic of polyclonal antibody TPO induced by autoantibody TPO from serum of AITD patients. The autoantibody TPO was ...

  2. Progranulin antibodies in autoimmune diseases.

    Science.gov (United States)

    Thurner, Lorenz; Preuss, Klaus-Dieter; Fadle, Natalie; Regitz, Evi; Klemm, Philipp; Zaks, Marina; Kemele, Maria; Hasenfus, Andrea; Csernok, Elena; Gross, Wolfgang L; Pasquali, Jean-Louis; Martin, Thierry; Bohle, Rainer Maria; Pfreundschuh, Michael

    2013-05-01

    Systemic vasculitides constitute a heterogeneous group of diseases. Autoimmunity mediated by B lymphocytes and their humoral effector mechanisms play a major role in ANCA-associated vasculitis (AAV) as well as in non-ANCA associated primary systemic vasculitides and in the different types of autoimmune connective tissue disorders and rheumatoid arthritis. In order to detect autoantibodies in systemic vasculitides, we screened protein macroarrays of human cDNA expression libraries with sera from patients with ANCA-associated and ANCA-negative primary systemic vasculitides. This approach led to the identification of antibodies against progranulin, a 88 kDA secreted glycoprotein with strong anti-inflammatory activity in the course of disease of giant-cell arteritis/polymyalgia rheumatica (14/65), Takayasu's arteritis (4/13), classical panarteritis nodosa (4/10), Behcet's disease (2/6) and in the course of disease in granulomatosis with polyangiitis (31/75), Churg-Strauss syndrome (7/23) and in microscopic polyangiitis (7/19). In extended screenings the progranulin antibodies were also detected in other autoimmune diseases such as systemic lupus erythematosus (39/91) and rheumatoid arthritis (16/44). Progranulin antibodies were detected only in 1 of 97 healthy controls. Anti-progranulin positive patients with systemic vasculitides, systemic lupus erythematosus or rheumatoid arthritis had significant lower progranulin plasma levels, indicating a neutralizing effect. In light of the anti-inflammatory effects of progranulin, progranulin antibodies might exert pro-inflammatory effects thus contributing to the pathogenesis of the respective autoimmune diseases and might serve as a marker for disease activity. This hypothesis is supported by the fact that a positive progranulin antibody status was associated with active disease in granulomatosis with polyangiitis. PMID:23149338

  3. MuSK induced experimental autoimmune myasthenia gravis does not require IgG1 antibody to MuSK.

    Science.gov (United States)

    Küçükerden, Melike; Huda, Ruksana; Tüzün, Erdem; Yılmaz, Abdullah; Skriapa, Lamprini; Trakas, Nikos; Strait, Richard T; Finkelman, Fred D; Kabadayı, Sevil; Zisimopoulou, Paraskevi; Tzartos, Socrates; Christadoss, Premkumar

    2016-06-15

    Sera of myasthenia gravis (MG) patients with muscle-specific receptor kinase-antibody (MuSK-Ab) predominantly display the non-complement fixing IgG4 isotype. Similarly, mouse IgG1, which is the analog of human IgG4, is the predominant isotype in mice with experimental autoimmune myasthenia gravis (EAMG) induced by MuSK immunization. The present study was performed to determine whether IgG1 anti-MuSK antibody is required for immunized mice to develop EAMG. Results demonstrated a significant correlation between clinical severity of EAMG and levels of MuSK-binding IgG1+, IgG2+ and IgG3+ peripheral blood B cells in MuSK-immunized wild-type (WT) mice. Moreover, MuSK-immunized IgG1 knockout (KO) and WT mice showed similar EAMG severity, serum MuSK-Ab levels, muscle acetylcholine receptor concentrations, neuromuscular junction immunoglobulin and complement deposit ratios. IgG1 and IgG3 were the predominant anti-MuSK isotypes in WT and IgG1 KO mice, respectively. These observations demonstrate that non-IgG1 isotypes can mediate MuSK-EAMG pathogenesis. PMID:27235354

  4. Antinuclear antibodies defining autoimmunity pathways

    OpenAIRE

    Tan, Eng M.

    2014-01-01

    Immunofluorescent imaging has been a powerful technique in helping to identify intracellular nuclear and cytoplasmic molecules which are target antigens of autoantibodies in systemic autoimmune disorders. Patterns of staining can be correlated with molecules engaged in specific cellular functions and distributed in distinct cellular domains. Different autoimmune disorders have different profiles of autoantibodies, and immunodiagnostics has become an important adjunct in differential diagnosis...

  5. Drug-Induced Bullous Sweet Syndrome with Multiple Autoimmune Features

    OpenAIRE

    2010-01-01

    Sweet syndrome (SS) (Acute Febrile Neutrophilic Dermatosis) has been reported in association with autoimmune phenomena including relapsing polychondritis, drug-induced lupus, and the development of antineutrophil cytoplasmic antibodies (ANCAs). However, a combination of these autoimmune features has not been reported. Herein, we report a case of drug-induced bullous SS with ocular and mucosal involvement, glomerulonephritis, and multiple autoimmune features including clinical polychondritis w...

  6. Drug-Induced Bullous Sweet Syndrome with Multiple Autoimmune Features

    Directory of Open Access Journals (Sweden)

    Jared J. Lund

    2010-01-01

    Full Text Available Sweet syndrome (SS (Acute Febrile Neutrophilic Dermatosis has been reported in association with autoimmune phenomena including relapsing polychondritis, drug-induced lupus, and the development of antineutrophil cytoplasmic antibodies (ANCAs. However, a combination of these autoimmune features has not been reported. Herein, we report a case of drug-induced bullous SS with ocular and mucosal involvement, glomerulonephritis, and multiple autoimmune features including clinical polychondritis with antitype II collagen antibodies, ANCAs, antinuclear (HEp-2, and antihistone antibodies in a patient on hydralazine and carbamazepine.

  7. The Effect of CD3-Specific Monoclonal Antibody on Treating Experimental Autoimmune Myasthenia Gravis

    Institute of Scientific and Technical Information of China (English)

    Ruonan Xu; Jianan Wang; Guojiang Chen; Gencheng Han; Renxi Wang; Beffen Shen; Yan Li

    2005-01-01

    CD3-specific monoclonal antibody was the first one used for clinical practice in field of transplantation. Recently,renewed interests have elicited in its capacity to prevent autoimmune diabetes by inducing immune tolerance. In this study, we tested whether this antibody can also be used to treat another kind of autoimmune disease myasthenia gravis (MG) and explored the possible mechanisms. MG is caused by an autoimmune damage mediated by antibody- and complement-mediated destruction of AChR at the neuromuscular junction. We found that administration of CD3-specific antibody (Fab)2 to an animal model with experimental autoimmune myasthenia gravis (EAMG) (B6 mice received 3 times of AChR/CFA immunization) could not significantly improve the clinical signs and clinical score. When the possible mechanisms were tested, we found that CD3 antibody treatment slightly down-regulated the T-cell response to AChR, modestly up-regulation the muscle strength. And no significant difference in the titers of IgG2b was found between CD3 antibody treated and control groups. These data indicated that CD3-specific antibody was not suitable for treating MG, an antibody- and complementmediated autoimmune disease, after this disease has been established. The role of CD3-specific antibody in treating this kind of disease remains to be determined.

  8. Familial autoimmune myasthenia gravis with different pathogenetic antibodies.

    OpenAIRE

    C. Provenzano; Arancio, O; Evoli, A; Rocca, B.; Bartoccioni, E; De Grandis, D; Tonali, P.

    1988-01-01

    Two cases of familial myasthenia gravis are reported. One patient is a typical case of autoimmune myasthenia with positive anti acetylcholine receptor antibodies, while in the second patient the impairment of neuromuscular transmission is likely to be due to antibodies directed against determinants other than the acetylcholine receptors.

  9. [Autoimmune hepatitis induced by isotretionine].

    Science.gov (United States)

    Guzman Rojas, Patricia; Gallegos Lopez, Roxana; Ciliotta Chehade, Alessandra; Scavino, Yolanda; Morales, Alejandro; Tagle, Martín

    2016-01-01

    We describe a case of a teenage patient with the diagnosis of drug induced autoimmune hepatitis. The patient is a 16 years old female, with the past medical history of Hashimoto’s hypothyroidism controlled with levothyroxine, who started treatment with Isotretionin (®Accutane) 20 mg q/12 hours for a total of 3 months for the treatment of severe acne. The physical examination was within normal limits and the results of the laboratory exams are: Baseline values of ALT 28 U/L, AST 28 U/L. Three months later: AST 756 U/L, ALT 1199U/L, alkaline phosphatase 114 U/L, with normal bilirrubin levels throughout the process. The serology studies were negative for all viral hepatitis; ANA titers were positive (1/160) and igG levels were also elevated. A liver biopsy was performed, and was compatible with the diagnosis of autoimmune hepatitis. Corticosteroid therapy was started with Prednisone 40 mg per day one week after stopping the treatment with isotretionin, observing an improvement in the laboratory values. We describe this case and review the world literature since there are no reported cases of Isotretinoin-induced autoimmune hepatitis. PMID:27131947

  10. Propylthiouracil-induced autoimmune disease

    Directory of Open Access Journals (Sweden)

    Santosh Paiaulla

    2015-01-01

    Full Text Available Hyperthyroidism is a condition characterized by excessive production of thyroid hormones. Propylthiouracil (PTU is commonly used as first line drug in the management of hyperthyroidism. This is a case report of 24-year-old female, a known case of hyperthyroidism since 4 years, who came with a history of fever and myalgia since 3 days and dyspnea with coughing out of blood since 1 day. Patient was taking PTU (100 mg per day since 4 years for hyperthyroidism. Patient was immediately intubated for type-II respiratory failure. Diagnosed to be having PTU-induced autoimmune disease. PTU was stopped and treated with methylprednisolone and cyclophosphamide. Clinical features improved over a period of 8 days and discharged home successfully. Having a high suspicion for the onset of autoimmune disease in hyperthyroidism patients who are on PTU therapy and timely treatment with immunosuppressants and supportive care along with the withdrawal of the drug can make a difference in morbidity and mortality.

  11. Antilipide antibodies cofactor in syphilis, Lyme borreliosis and autoimmune diseases

    OpenAIRE

    B Voicechovskaya; J Zabek

    2003-01-01

    Objective. To study (32 glycoprotein 1 contribution to frequency of aCL in pts with autoimmune and some infectious diseases. Methods. Antibodies to different phospholipids were tested by immune-enzyme method (IEM) in serum of 92 pts: 20 of them had systemic lupus erythematosus (SLE), 15 Sjogren’s disease (SD), 20 rheumatoid arthritis (RA), 20 syphilis and 17 Lyme disease (LD). Pts with syphilis and LD did not have clinical signs of autoimmune disease. Stimulation of aCL test in IEM was perfor...

  12. Antibody-Mediated Autoimmune Encephalopathies and Immunotherapies.

    Science.gov (United States)

    Gastaldi, Matteo; Thouin, Anaïs; Vincent, Angela

    2016-01-01

    Over the last 15 years it has become clear that rare but highly recognizable diseases of the central nervous system (CNS), including newly identified forms of limbic encephalitis and other encephalopathies, are likely to be mediated by antibodies (Abs) to CNS proteins. The Abs are directed against membrane receptors and ion channel-associated proteins that are expressed on the surface of neurons in the CNS, such as N-methyl D-aspartate receptors and leucine-rich, glioma inactivated 1 protein and contactin-associated protein like 2, that are associated with voltage-gated potassium channels. The diseases are not invariably cancer-related and are therefore different from the classical paraneoplastic neurological diseases that are associated with, but not caused by, Abs to intracellular proteins. Most importantly, the new antibody-associated diseases almost invariably respond to immunotherapies with considerable and sometimes complete recovery, and there is convincing evidence of their pathogenicity in the relatively limited studies performed so far. Treatments include first-line steroids, intravenous immunoglobulins, and plasma exchange, and second-line rituximab and cyclophosphamide, followed in many cases by steroid-sparing agents in the long-term. This review focuses mainly on N-methyl D-aspartate receptor- and voltage-gated potassium channel complex-related Abs in adults, the clinical phenotypes, and treatment responses. Pediatric cases are referred to but not reviewed in detail. As there have been very few prospective studies, the conclusions regarding immunotherapies are based on retrospective studies. PMID:26692392

  13. [Autoimmunization induced by interferon alpha therapy in chronic hepatitis C].

    Science.gov (United States)

    Rocca, Pierre; Codes, Liana; Chevallier, Michèle; Trépo, Christian; Zoulim, Fabien

    2004-11-01

    We report the case of a 56 year-old woman with post-transfusion chronic hepatitis C who presented with a severe ALT flare up associated with a rapid progression of liver fibrosis during interferon alpha 2b therapy. Several hypotheses were considered to explain the etiology of this ALT flare: there was no viral super infection by other hepatotropic viruses, no toxic hepatitis, no metabolic disease, and no other specific liver diseases could be identified. HLA typing showed a specific profile A1 B8 DR3 (risk factor of auto-immunization during interferon alpha therapy) with antinuclear antibodies and anti smooth muscle antibodies. This case suggests that auto-immunization induced by interferon alpha should be investigated in case of ALT flare that is not followed by an HCV breakthrough. PMID:15657545

  14. Non-HLA antibodies against endothelial targets bridging allo- and autoimmunity.

    Science.gov (United States)

    Dragun, Duska; Catar, Rusan; Philippe, Aurélie

    2016-08-01

    Detrimental actions of donor-specific antibodies (DSAs) directed against both major histocompatibility antigens (human leukocyte antigen [HLA]) and specific non-HLA antigens expressed on the allograft endothelium are a flourishing research area in kidney transplantation. Newly developed solid-phase assays enabling detection of functional non-HLA antibodies targeting G protein-coupled receptors such as angiotensin type I receptor and endothelin type A receptor were instrumental in providing long-awaited confirmation of their broad clinical relevance. Numerous recent clinical studies implicate angiotensin type I receptor and endothelin type A receptor antibodies as prognostic biomarkers for earlier occurrence and severity of acute and chronic immunologic complications in solid organ transplantation, stem cell transplantation, and systemic autoimmune vascular disease. Angiotensin type 1 receptor and endothelin type A receptor antibodies exert their pathophysiologic effects alone and in synergy with HLA-DSA. Recently identified antiperlecan antibodies are also implicated in accelerated allograft vascular pathology. In parallel, protein array technology platforms enabled recognition of new endothelial surface antigens implicated in endothelial cell activation. Upon target antigen recognition, non-HLA antibodies act as powerful inducers of phenotypic perturbations in endothelial cells via activation of distinct intracellular cell-signaling cascades. Comprehensive diagnostic assessment strategies focusing on both HLA-DSA and non-HLA antibody responses could substantially improve immunologic risk stratification before transplantation, help to better define subphenotypes of antibody-mediated rejection, and lead to timely initiation of targeted therapies. Better understanding of similarities and dissimilarities in HLA-DSA and distinct non-HLA antibody-related mechanisms of endothelial damage should facilitate discovery of common downstream signaling targets and pave the

  15. Azathioprine-induced fever in autoimmune hepatitis

    OpenAIRE

    Tawfik Khoury; Ollech, Jacob E; Shmuel Chen; Meir Mizrahi; Meir Shalit

    2013-01-01

    Underdiagnosis of drug-induced fever leads to extensive investigation and prolongation of hospitalization, and may lead to multiple unnecessary invasive procedures and a wrong diagnosis. Azathioprine is a widely used immunosuppressive drug. We report a case of a 53-year-old female patient diagnosed with autoimmune hepatitis treated with azathioprine, who presented to the emergency room with a 6-wk history of fever and chills without other associated symptoms. Since the patient’s fever ...

  16. Requirements for innate immune pathways in environmentally induced autoimmunity.

    Science.gov (United States)

    Pollard, Kenneth Michael; Kono, Dwight H

    2013-01-01

    There is substantial evidence that environmental triggers in combination with genetic and stochastic factors play an important role in spontaneous autoimmune disease. Although the specific environmental agents and how they promote autoimmunity remain largely unknown, in part because of diverse etiologies, environmentally induced autoimmune models can provide insights into potential mechanisms. Studies of idiopathic and environmentally induced systemic autoimmunity show that they are mediated by common adaptive immune response genes. By contrast, although the innate immune system is indispensable for autoimmunity, there are clear differences in the molecular and cellular innate components that mediate specific systemic autoimmune diseases, suggesting distinct autoimmune-promoting pathways. Some of these differences may be related to the bifurcation of toll-like receptor signaling that distinguishes interferon regulatory factor 7-mediated type I interferon production from nuclear factor-κB-driven proinflammatory cytokine expression. Accordingly, idiopathic and pristane-induced systemic autoimmunity require both type I interferon and proinflammatory cytokines whereas the less aggressive mercury-induced autoimmunity, although dependent on nucleic acid-binding toll-like receptors, does not require type I interferon but needs proinflammatory cytokines. Scavenger receptors and the inflammasome may contribute to silica-induced autoimmunity. Greater understanding of the innate mechanisms responsible for idiopathic and environmentally induced autoimmunity should yield new information into the processes that instigate and drive systemic autoimmunity. PMID:23557436

  17. "Clickable" LNA/DNA probes for fluorescence sensing of nucleic acids and autoimmune antibodies

    DEFF Research Database (Denmark)

    Jørgensen, Anna S; Gupta, Pankaj; Wengel, Jesper; Astakhova, I Kira

    2013-01-01

    Herein we describe fluorescent oligonucleotides prepared by click chemistry between novel alkyne-modified locked nucleic acid (LNA) strands and a series of fluorescent azides for homogeneous (all-in-solution) detection of nucleic acids and autoimmune antibodies.......Herein we describe fluorescent oligonucleotides prepared by click chemistry between novel alkyne-modified locked nucleic acid (LNA) strands and a series of fluorescent azides for homogeneous (all-in-solution) detection of nucleic acids and autoimmune antibodies....

  18. Expression of anti-SRP19 antibody in muscle tissues from patients with autoimmune necrotizing myopathy.

    Science.gov (United States)

    Wang, Q; Duan, F; Liu, P; Wang, P F; Wang, M X

    2016-01-01

    This study aimed to investigate the role of anti-SRP19 antibody in muscle tissues of patients with autoimmune necrotizing myopathy. Immunohistochemistry staining was used to determine the expression of anti-SRP19 antibodies in muscle tissues of autoimmune necrotizing myopathy patients. Results demonstrated that anti-SRP19 antibody was expressed in 71.4% (20/28) of muscle tissue specimens from patients with autoimmune necrotizing myopathy. Anti-SRP19 antibody expression was mainly localized in cytoplasm of necrotic muscle fibers surrounding the small blood vessels and interstitial cells. There were no significant differences in the age, course of disease, muscle, and creatine kinase levels between patients with positive or negative expression of anti-SRP19 antibodies. The expression levels of anti-SRP19, serum anti-nuclear antibodies, as well as anti-Ro-52, anti- SSA, anti-Sm, and anti-Jo-1 antibodies were not significantly different among groups. This study demonstrates that anti-SRP19 antibody is highly expressed in muscle tissues of patients with autoimmune necrotizing myopathy, and suggests that this protein may be involved in the origin and progression of the disease. PMID:27525944

  19. Immunization of mice with purified U1 small nuclear ribonucleoprotein (RNP) induces a pattern of antibody specificities characteristic of the anti-Sm and anti-RNP autoimmune response of patients with lupus erythematosus, as measured by monoclonal antibodies.

    OpenAIRE

    Reuter, R; Lührmann, R

    1986-01-01

    Sera of patients with systemic lupus erythematosus and related autoimmune diseases often possess anti-Sm and anti-ribonucleoprotein (RNP) autoantibodies that recognize antigenic sites on small nuclear (sn) RNPs containing the snRNAs U1, U2, U4, U5, and U6. Although the major immunoreactive Sm polypeptides B', B, and D are present in snRNPs U1-U6, the RNP-antigenic proteins termed 70 kDa, A, and C are found only in U1 snRNP particles. We have immunized genetically nonautoimmune C57BL/6 mice wi...

  20. Auto-antibodies to vascular endothelial cadherin in humans: association with autoimmune diseases.

    Science.gov (United States)

    Bouillet, L; Baudet, A E; Deroux, A; Sidibé, A; Dumestre-Perard, C; Mannic, T; Treillard, B; Arboleas, M A; Chiquet, C A; Gulino-Debrac, D G; Vilgrain, I Y

    2013-11-01

    To identify patients with autoimmune diseases who are at high risk of developing vascular cell dysfunction, early biomarkers must be identified. This study was designed to detect and characterize circulating autoantibodies to VE-cadherin (AAVEs) in patients with early-stage autoimmune diseases. An enzyme-linked immunosorbent assay (ELISA) was developed to capture autoantibodies, using a recombinant human VE-cadherin fragment covering the extracellular domains as a target antigen. AAVEs specificity for the target antigen was confirmed by western blotting. Basal AAVEs levels were determined for healthy donors (n=75). Sera from patients (n=100) with various autoimmune diseases, including rheumatoid arthritis (n=23), systemic lupus erythematosus (SLE, n=31), systemic sclerosis (n=30), and Behçet's disease (BD, n=16) were also tested. Levels of AAVEs were significantly higher in rheumatoid arthritis (PPP<0.05) populations than in healthy subjects. Purified immunoglobulin G (IgG) from a BD patient with exceptionally high AAVEs levels recognized the EC1-4 fragment in western blots. Further characterization of the epitopes recognized by AAVEs showed that BD patients had antibodies specific for the EC3 and EC4 domains, whereas SLE patients preferentially recognized the EC1 fragment. This suggests that distinct epitopes of human VE-cadherin might be recognized in different immune diseases. Purified IgG from BD patients was found to induce endothelial cell retraction, redistribution of VE-cadherin, and cause the formation of numerous intercellular gaps. Altogether, these data demonstrate a potential pathogenic effect of AAVEs isolated from patients with dysimmune disease. This is the first description of AAVEs in humans. Because regions EC1 and EC3-4 have been shown to be involved in homophilic VE-cadherin interactions, AAVEs produced in the course of dysimmune diseases might be specific biomarkers for endothelial injury, which is part of the early pathogenicity of these

  1. Multiple autoimmune antibody limbic encephalitis: a case in a pregnant woman

    Directory of Open Access Journals (Sweden)

    Meha Goyal

    2015-03-01

    Full Text Available Autoimmune limbic encephalitis is most commonly associated with antibodies against the N-methyl-D-aspartate receptor (NMDAR, among other neuronal cell surface receptors. Here, a case of a pregnant female with limbic encephalitis in the presence of multiple additional autoimmune antibodies is described. The patient was a 36-year-old female who presented with 4 days of confusion, hallucinations, hypersexuality, disinhibition, and pressured speech. The patient's work-up detected the presence of anti-NMDAR antibodies, anti-glutamic acid decarboxylase antibodies, and a yet uncharacterized neuronal autoantibody. The patient was also found to be pregnant. No evidence of ovarian or other pelvic malignancy was discovered. Symptomatic control was achieved with plasma exchange.

  2. Synthesis of Phospholipid-Protein Conjugates as New Antigens for Autoimmune Antibodies

    Directory of Open Access Journals (Sweden)

    Arindam Maity

    2015-06-01

    Full Text Available Copper(I-catalyzed azide-alkyne cycloaddition, or CuAAC click chemistry, is an efficient method for bioconjugation aiming at chemical and biological applications. Herein, we demonstrate how the CuAAC method can provide novel phospholipid-protein conjugates with a high potential for the diagnostics and therapy of autoimmune conditions. In doing this, we, for the first time, covalently bind via 1,2,3-triazole linker biologically complementary molecules, namely phosphoethanol amine with human β2-glycoprotein I and prothrombin. The resulting phospholipid-protein conjugates show high binding affinity and specificity for the autoimmune antibodies against autoimmune complexes. Thus, the development of this work might become a milestone in further diagnostics and therapy of autoimmune diseases that involve the production of autoantibodies against the aforementioned phospholipids and proteins, such as antiphospholipid syndrome and systemic lupus erythematosus.

  3. Autoimmune thyroiditis in antinuclear antibody positive children without rheumatologic disease

    Directory of Open Access Journals (Sweden)

    Arkachaisri Thaschawee

    2010-05-01

    Full Text Available Abstract Background Children are commonly referred to a pediatric rheumatology center for the laboratory finding of an Anti-nuclear antibody (ANA of undetermined significance. Previous studies regarding adult rheumatology patients have supported an association between ANA and anti-thyroid antibodies, with the prevalence of thyroid antibodies being significantly higher in patients referred to a rheumatology center for an ANA without evidence of connective tissue disease compared to the general population. The purpose of the present study was to determine the frequency of thyroid antibodies in children referred to a pediatric rheumatology center for a positive ANA without evidence of a connective tissue disease. Methods A retrospective chart review was performed on children who were referred to our pediatric rheumatology center between August 2003 and March 2007 for positive ANA with concurrent thyroid antibody and thyroid function tests performed who did not fulfill criteria for a specific connective tissue disease. Laboratory and clinical features were recorded and analyzed. Mean and standard deviation were used to describe continuous data. Chi-square or Fisher's exact tests were used to compare proportions between variables. Results One-hundred and four ANA-positive patients with concurrent thyroid studies were evaluated (88% female, 93% Caucasian, mean age 11.9 ± 4.0 years. Half of patients had an ANA titer ≥ 1:320. The ANA pattern was speckled in 60% of the patients. Thyroid antibodies were detected in 30% of the patients. Anti-Thyroglobulin (ATG was detected in 29% and Anti-thyroid peroxidase (ATPO in 21% of the patients; of these children, 14% had hypothyroidism. ANA pattern and titer were not associated with anti-thyroid antibody positivity. Conclusion Thyroid antibodies associated with chronic lymphocytic thyroiditis, ATG and ATPO, were detected significantly higher in ANA-positive children without a rheumatologic condition (30% as

  4. Activation-Induced Cell Death in T Cells and Autoimmunity

    Institute of Scientific and Technical Information of China (English)

    JianZhang; XuemeiXu; YongLiu

    2004-01-01

    Activation-induced cell death (AICD), which results from the interaction between Fas and Fas ligand, is responsible for maintaining tolerance to self-antigen. A defect in AICD may lead to development of autoimmunity. During the last several years, much progress has been made in understanding the mechanism(s) of AICD and its potential role in the pathogenesis of autoimmune diseases. In this review, we summarize the most recent progress on the regulation of the susceptibility of T cells to AICD and its possible involvement in autoimmune diseases.

  5. Novel Phospholipid-Protein Conjugates Allow Improved Detection of Antibodies in Patients with Autoimmune Diseases

    DEFF Research Database (Denmark)

    Samuelsen, Simone V; Maity, Arindam; Nybo, Mads;

    2016-01-01

    Reliable measurement of clinically relevant autoimmune antibodies toward phospholipid-protein conjugates is highly desirable in research and clinical assays. To date, the development in this field has been limited to the use of natural heterogeneous antigens. However, this approach does not take ...... correlation of detected autoantibodies with disease activity and manifestations. This confirms the crucial importance of antigens' composition on research and diagnostic assays, and opens up exciting perspectives for synthetic antigens in future studies of autoimmunity.......Reliable measurement of clinically relevant autoimmune antibodies toward phospholipid-protein conjugates is highly desirable in research and clinical assays. To date, the development in this field has been limited to the use of natural heterogeneous antigens. However, this approach does not take...... structural features of biologically active antigens into account and leads to low reliability and poor scientific test value. Here we describe novel phospholipid-protein conjugates for specific detection of human autoimmune antibodies. Our synthetic approach includes mild oxidation of synthetic phospholipid...

  6. Hypoxia-inducible factor 1 in autoimmune diseases.

    Science.gov (United States)

    Deng, Wei; Feng, Xuebing; Li, Xia; Wang, Dandan; Sun, Lingyun

    2016-05-01

    Autoimmune disorders are a complicated and varied group of diseases arising from inappropriate immune responses. Recent studies have demonstrated that ongoing inflammatory and immune responses are associated with increased oxygen consumption, a process resulting in localized tissue hypoxia within inflammatory lesions ("inflammatory hypoxia"), in which hypoxia-inducible factor 1 (HIF-1), an oxygen-sensitive transcription factor that allows adaptation to hypoxia environments, has been shown to play an important function. HIF-1 is a regulator of angiogenesis and immune system. Besides, HIF-1-mediated metabolic shift and fibrosis may also play crucial roles in some autoimmune disorders. Firstly, we briefly summarize the role of HIF-1 in angiogenesis, immune responses and fibrosis. Secondly, we will show the major recent findings demonstrating a role for HIF-1 signaling in autoimmune disorders, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, systemic sclerosis and multiple sclerosis. The growing evidences may prompt HIF-1 to be a new target for treatment of autoimmune diseases. PMID:27071377

  7. Burkitt Lymphoma Preceded by Autoimmune Hemolytic Anemia due to Anti-D Antibody.

    Science.gov (United States)

    Mizuno, Yoshimi; Shimura, Yuji; Horiike, Shigeo; Takimoto, Tomoko; Maegawa, Saori; Tanba, Kazuna; Matsumura-Kimoto, Yayoi; Sumida, Yukari; Tatekawa, Shotaro; Tsukamoto, Taku; Chinen, Yoshiaki; Mizutani, Shinsuke; Nagoshi, Hisao; Yamamoto-Sugitani, Mio; Matsumoto, Yosuke; Kobayashi, Tsutomu; Kuroda, Junya; Taniwaki, Masafumi

    2016-01-01

    We herein report a rare case of Burkitt lymphoma (BL) preceded by autoimmune hemolytic anemia (AIHA) caused by autoantibodies against D antigen. After a partial response to AIHA with prednisolone (PSL) treatment for 7 months, the patient developed BL with a t(8;22)(q24;q11.2) chromosomal translocation. Intensive immunochemotherapy, including rituximab, led to a complete response (CR) of BL; however, anti-D antibody remained detectable in the plasma and antibody-dissociated solution from erythrocytes, thus continuous therapy with PSL was necessary even after achievement of the CR. BL with AIHA is extremely rare, with only one previously reported case in the literature. PMID:27523004

  8. Pulse labeling of small nuclear ribonucleoproteins in vivo reveals distinct patterns of antigen recognition by human autoimmune antibodies.

    OpenAIRE

    Fisher, D E; Reeves, W H; Conner, G E; Blobel, G; Kunkel, H. G.

    1984-01-01

    Antibodies directed against small nuclear ribonucleoprotein ( snRNP ) particles are found in the Sm and RNP autoimmune sera from numerous patients with systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). These two reactivities differ in disease distribution as well as antigen specificity. Although sera from both of these autoimmune syndromes contain snRNP reactive antibodies, distinction in antigen binding specificity have been difficult to define because of the par...

  9. A therapeutic anti-CD4 monoclonal antibody inhibits T cell receptor signal transduction in mouse autoimmune cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    WANG Zhao-hui; LIAO Yu-hua; YUAN Jing; ZHANG Li; WANG Min; ZHANG Jing-hui; LIU Zhong-ping; DONG Ji-hua

    2007-01-01

    Background T cell immune abnormalities in patients with dilated cardiomyopathy (DCM) has been intensively studied over the past 10 years. Our previous study has suggested that immunization of mice with the peptides derived from human adenine nucleotide translocator (ANT) result in the production of autoantibodies against the ANT and histopathological changes similar to those in human DCM. The ANT peptides can induce autoimmune cardiomyopathy like DCM in Balb/c mice. In this study we aimed to focus on the molecular mechanism of T cells in the autoimmune cardiomyopathy mouse model by detecting the expression of the two T cell signaling molecules.Methods The ANT peptides were used to cause autoimmune cardiomyopathy in Balb/c mice. Anti-L3T4 or rat anti-mouse IgG was administered to the mice (n=6 in each group) simultaneously immunized with ANT. ELISA analysis was used to detect autoantibodies against the ANT peptides and the percentages of interferon-Y and interleukin-4 producing cells among splenic CD4+ lymphocytes was determined by using flow cytometry analysis. The expression of CD45 in spleen T cells was determined by immunohistochemistry and the mRNAs of T cell signaling molecules were detected by real-time PCR.Results Treatment of ANT immunized Balb/c mice with anti-CD4 mAb caused a reduction in the gene expression of P56lck and Zap-70 and a lower level of CD45 expression by spleen T cells. Aiso, a reverse of the Th1/Th2 ratio that results in the reduced production of antibodies against ANT was found in the anti-CD4 monoclonal antibodies (mAb)group. Whereas irrelevant antibody (rat anti-mouse IgG) did not suppress T cell signaling molecules nor inhibit CD45 expression, and control-antibody mice did not show any significant differences compared with the DCM group.Conclusion The results show that anti-CD4 mAb is a powerful inhibitor of the early initiating events of T cell receptor(TCR) signal transduction in mouse autoimmune dilated cardiomyopathy.

  10. A region of the insulin receptor important for ligand binding (residues 450-601) is recognized by patients' autoimmune antibodies and inhibitory monoclonal antibodies.

    OpenAIRE

    Zhang, B; Roth, R A

    1991-01-01

    Chimeric receptors containing different portions of the homologous human insulin receptor, insulin-like growth factor I receptor, and insulin receptor-related receptor were utilized to identify the epitopes recognized by various anti-insulin receptor antibodies. The antibodies studied included 12 monoclonal antibodies to the extracellular domain of the human insulin receptor as well as 15 patients' sera with autoimmune anti-insulin receptor antibodies. All of the patients' sera and all 8 mono...

  11. Autoimmunity in connection with a metal implant: a case of autoimmune/autoinflammatory syndrome induced by adjuvants.

    Science.gov (United States)

    Loyo, Esthela; Jara, Luis J; López, Persio David; Puig, Ana Carolina

    2013-04-01

    Autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA) has been recently proposed by Shoenfeld and Agmon-Levin as a new entity that comprises several conditions: the macrophagic-myofasciitis syndrome, the Gulf War syndrome, silicosis and post-vaccination phenomena, autoimmunity related to infectious fragments, hormones, aluminum, silicone, squalene oil, and pristane. We report the case of a 23-year-old woman who developed serial episodes of high fever, extreme fatigue, transient thrombocytopenia, multiple cervical adenopathies, hepatosplenomegaly, anemia, neutropenia, severe proteinuria and urine sediment abnormalities, elevated serum ferritin levels, and transient low positive antinuclear antibodies 1 year after she had a nickel-titanium chin implant for cosmetic reasons. The clinical picture simulated a variety of probable diseases: systemic lupus erythematosus, Kikuchi-Fujimoto syndrome, adult onset Still's disease, antiphospholipid syndrome, and hemophagocytic syndrome, among others, so she underwent an extensive medical investigation including two lymph node biopsies. She received treatment accordingly with steroids, methotrexate, and mofetil mycophenolate, with initial improvement of her symptoms, which recurred every time the dose was reduced. Two and a half years later the patient decided to retire the chin implant and afterwards all her systemic symptoms have disappeared. She remains in good health, without recurrence of any symptom and off medications until today. Albeit this patient fulfills proposed major ASIA criteria, to our knowledge it would be the first description of systemic features of autoinflammation in connection with a metal implant. PMID:26000140

  12. Novel Phospholipid-Protein Conjugates Allow Improved Detection of Antibodies in Patients with Autoimmune Diseases

    Science.gov (United States)

    Nybo, Mads; Macaubas, Claudia; Lønstrup, Lars; Balboni, Imelda M.; Mellins, Elizabeth D.; Astakhova, Kira

    2016-01-01

    Reliable measurement of clinically relevant autoimmune antibodies toward phospholipid-protein conjugates is highly desirable in research and clinical assays. To date, the development in this field has been limited to the use of natural heterogeneous antigens. However, this approach does not take structural features of biologically active antigens into account and leads to low reliability and poor scientific test value. Here we describe novel phospholipid-protein conjugates for specific detection of human autoimmune antibodies. Our synthetic approach includes mild oxidation of synthetic phospholipid cardiolipin, and as the last step, coupling of the product with azide-containing linker and copper-catalyzed click chemistry with β2-glycoprotein I and prothrombin. To prove utility of the product antigens, we used enzyme-linked immunosorbent assay and three cohorts of samples obtained from patients in Denmark (n = 34) and the USA (n = 27 and n = 14). Afterwards we analyzed correlation of the obtained autoantibody titers with clinical parameters for each patient. Our results prove that using novel antigens clinically relevant autoantibodies can be detected with high repeatability, sensitivity and specificity. Unlike previously used antigens the obtained autoantibody titers strongly correlate with high disease activity and in particular, with arthritis, renal involvement, anti-Smith antibodies and high lymphocyte count. Importantly, chemical composition of antigens has a strong influence on the correlation of detected autoantibodies with disease activity and manifestations. This confirms the crucial importance of antigens’ composition on research and diagnostic assays, and opens up exciting perspectives for synthetic antigens in future studies of autoimmunity. PMID:27257889

  13. Acute exacerbation of autoimmune hepatitis induced by Twinrix

    Institute of Scientific and Technical Information of China (English)

    Antal Csepregi; Gerhard Treiber; Christoph R(o)cken; Peter Malfertheiner

    2005-01-01

    We report on a 26-year-old man who presented with severe jaundice and elevated serum liver enzyme activities after having received a dose of Twinrix(○R). In his past medical history, jaundice or abnormal liver function tests were never recorded. Following admission, an elevated immunoglobulin G level and antinuclear antibodies at a titer of 320 with a homogenous pattern were found. Histology of a liver biopsy showed marked bridging liver fibrosis and a chronic inflammation, compatible with autoimmune hepatitis. Treatment was started with budesonide and ursodeoxycholic acid,and led to complete normalization of the pathological liver function tests. We believe that Twinrix(○R) led to an acute exacerbation of an unrecognized autoimmune hepatitis in our patient. The pathogenesis remains to be clarified. It is tempting to speculate that inactivated hepatitis A virus and/or recombinant surface antigen of the hepatitis B virus -as seen in patients with chronic hepatitis C and unrecognized autoimmune hepatitis who were treated with interferon alpha-might have been responsible for disease exacerbation.

  14. Antibodies to nuclear antigens in polymyositis: relationship to autoimmune 'overlap syndromes' and carcinoma.

    OpenAIRE

    Venables, P.J.; Mumford, P A; Maini, R N

    1981-01-01

    Thirty-two patients with polymyositis were categorised into 4 groups: (1) 'pure' polymyositis, (2) dermatomyositis, (3) myositis associated with autoimmune 'overlap syndrome', and (4) those with associated malignancy. Serum from each patient was examined for a range of antinuclear antibodies. Seventeen patients had ANA detected by immunofluorescence, 18 patients had raised DNA binding (greater than 25 U/ml), of whom eight had levels greater than 50 U/ml (SI conversion: U/l = U/ml x 10(3)). An...

  15. Antibodies to soluble liver antigen and alpha-enolase in patients with autoimmune hepatitis.

    OpenAIRE

    Bogdanos, Dimitrios-Petrou; Gilbert, Daniele; Bianchi, Ilaria; Leoni, Simona; Mitry, Ragai; Ma, Yun; Mieli-vergani, Giorgina; Vergani, Diego

    2004-01-01

    BACKGROUND: Antibodies to a cytosolic soluble liver antigen (SLA) are specifically detected in patients with autoimmune hepatitis (AIH). The target of anti-SLA has been identified as a ~50 kDa UGA serine tRNA-associated protein complex (tRNP(Ser)Sec), through the screening of cDNA libraries. A recent report questioned the identity of tRNP(Ser)Sec as the real SLA antigen. The latter study identified alpha-enolase as a major anti-SLA target, through proteomic analysis. METHODS: In an attempt to...

  16. Exploration of high-density protein microarrays for antibody validation and autoimmunity profiling.

    Science.gov (United States)

    Sjöberg, Ronald; Mattsson, Cecilia; Andersson, Eni; Hellström, Cecilia; Uhlen, Mathias; Schwenk, Jochen M; Ayoglu, Burcu; Nilsson, Peter

    2016-09-25

    High-density protein microarrays of recombinant human protein fragments, representing 12,412 unique Ensembl Gene IDs, have here been produced and explored. These protein microarrays were used to analyse antibody off-target interactions, as well as for profiling the human autoantibody repertoire in plasma against the antigens represented by the protein fragments. Affinity-purified polyclonal antibodies produced within the Human Protein Atlas (HPA) were analysed on microarrays of three different sizes, ranging from 384 antigens to 21,120 antigens, for evaluation of the antibody validation criteria in the HPA. Plasma samples from secondary progressive multiple sclerosis patients were also screened in order to explore the feasibility of these arrays for broad-scale profiling of autoantibody reactivity. Furthermore, analysis on these near proteome-wide microarrays was complemented with analysis on HuProt™ Human Proteome protein microarrays. The HPA recombinant protein microarray with 21,120 antigens and the HuProt™ Human Proteome protein microarray are currently the largest protein microarray platforms available to date. The results on these arrays show that the Human Protein Atlas antibodies have few off-target interactions if the antibody validation criteria are kept stringent and demonstrate that the HPA-produced high-density recombinant protein fragment microarrays allow for a high-throughput analysis of plasma for identification of possible autoantibody targets in the context of various autoimmune conditions. PMID:26417875

  17. Antibodies to Lactobacilli and Bifidobacteria in Young Children with Different Propensity to Develop Islet Autoimmunity

    Directory of Open Access Journals (Sweden)

    Ija Talja

    2014-01-01

    Full Text Available The intestinal microbiota is essential to the maturation and homeostasis of the immune system. Immunoblot assays were used to establish the prevalence of serum IgG, IgM, and IgA antibodies specific for Bifidobacterium adolescentis, Bifidobacterium longum, and Lactobacillus rhamnosus GG proteins in young children presenting with or without type 1 diabetes (T1D. We demonstrated that children between the ages of 6 and 12 months had a substantial increase in the frequency of IgG antibodies specific for L. rhamnosus GG proteins. We measured IgG, IgM, and IgA class antibody reactivity against B. adolescentis DSM 20083, B. adolescentis DSM 20086, and B. longum DSM 20088 proteins demonstrating significantly higher IgA responses against B. adolescentis DSM 20083 strain proteins in children who developed islet autoimmunity and T1D later in life. B. adolescentis strains showed more IgM type antibodies in children who developed T1D later in life, but the difference was not statistically significant. B. longum proteins were recognized by IgG and IgA antibodies to a higher extent compared to other bacteria studied. These results confirm that differences in immune reactivity against some commensal strains in young children may represent a different risk factor for developing T1D.

  18. Antibodies to Lactobacilli and Bifidobacteria in young children with different propensity to develop islet autoimmunity.

    Science.gov (United States)

    Talja, Ija; Kubo, Anna-Liisa; Veijola, Riitta; Knip, Mikael; Simell, Olli; Ilonen, Jorma; Vähä-Mäkilä, Mari; Sepp, Epp; Mikelsaar, Marika; Utt, Meeme; Uibo, Raivo

    2014-01-01

    The intestinal microbiota is essential to the maturation and homeostasis of the immune system. Immunoblot assays were used to establish the prevalence of serum IgG, IgM, and IgA antibodies specific for Bifidobacterium adolescentis, Bifidobacterium longum, and Lactobacillus rhamnosus GG proteins in young children presenting with or without type 1 diabetes (T1D). We demonstrated that children between the ages of 6 and 12 months had a substantial increase in the frequency of IgG antibodies specific for L. rhamnosus GG proteins. We measured IgG, IgM, and IgA class antibody reactivity against B. adolescentis DSM 20083, B. adolescentis DSM 20086, and B. longum DSM 20088 proteins demonstrating significantly higher IgA responses against B. adolescentis DSM 20083 strain proteins in children who developed islet autoimmunity and T1D later in life. B. adolescentis strains showed more IgM type antibodies in children who developed T1D later in life, but the difference was not statistically significant. B. longum proteins were recognized by IgG and IgA antibodies to a higher extent compared to other bacteria studied. These results confirm that differences in immune reactivity against some commensal strains in young children may represent a different risk factor for developing T1D. PMID:24741589

  19. Use of monoclonal antibodies for the characterization of novel DNA- binding proteins recognized by human autoimmune sera

    OpenAIRE

    1985-01-01

    Autoantibodies to a DNA-binding heterodimer consisting of 70,000 and 80,000 dalton subunits were identified in 30-50% of human autoimmune sera from patients with systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), and scleroderma. Three murine monoclonal antibodies (mAb) against the heterodimer were produced in BALB/c mice by immunizing with isolated human B cell nuclei. By immunofluorescence, the mAb and autoimmune sera demonstrated both speckled nucleoplasmic stainin...

  20. Pendrin and NIS antibodies are absent in healthy individuals and are rare in autoimmune thyroid disease

    DEFF Research Database (Denmark)

    Brix, Thomas H; Hegedüs, Laszlo; Weetman, Anthony P;

    2014-01-01

    OBJECTIVE: Antibodies against thyroglobulin, thyroid peroxidase and the TSH receptor are accepted as pathophysiological and diagnostic biomarkers in autoimmune thyroid disease (AITD). In contrast, the prevalence, aetiology and clinical relevance of autoantibodies against the human sodium-iodine s......OBJECTIVE: Antibodies against thyroglobulin, thyroid peroxidase and the TSH receptor are accepted as pathophysiological and diagnostic biomarkers in autoimmune thyroid disease (AITD). In contrast, the prevalence, aetiology and clinical relevance of autoantibodies against the human sodium......-iodine symporter (NISAb) and pendrin (PenAb) remain unclear. The objectives of the study were to investigate the presence of NISAb and PenAb in Danish twins, with and without AITD, to study whether the published variations in NISAb and PenAb frequencies were related to differences in methodology or study...... populations, and to evaluate whether the presence of NISAb or PenAb most likely results from genetic or nongenetic factors. METHODS: Sera from 93 patients with AITD and 230 healthy controls were evaluated for NISAb and PenAb using radioligand binding assays (RBA). RESULTS: Patients with AITD had a higher...

  1. Heparin-Induced Thrombocytopenia Antibody Test

    Science.gov (United States)

    ... Thrombocytopenia Platelet Factor 4 Antibody Related tests: Complete Blood Count , Platelet Count , Serotonin Release Assay, Heparin-induced Platelet Aggregation All content on Lab Tests Online has been ...

  2. Diagnosis of autoimmune neutropenia by neutrophil-bound IgG and IgM antibodies.

    Science.gov (United States)

    Ito, Taichi; Taniuchi, Shoichiro; Tsuji, Shoji; Iharada, Anna; Hasui, Masafumi; Kaneko, Kazunari

    2011-10-01

    Autoimmune neutropenia (AIN) in infancy is caused by antineutrophil (granulocyte-specific) autoantibodies. These antibodies are rarely found in circulation because their serum levels are extremely low. We hypothesized that a direct granulocyte immunofluorescence test (D-GIFT) that enables us to detect neutrophil-bound autoantibodies consisting of both immunoglobulin (Ig) G and IgM has better diagnostic value than the detection of circulating autoantibodies. Whole blood (100 μL) was obtained from 50 infants with AIN, 12 infants with transient neutropenia, and 37 control infants. D-GIFT was performed using both fluorescein isothiocyanate-conjugated antihuman IgG Fc portion monoclonal antibodies and fluorescein isothiocyanate antihuman IgM monoclonal antibodies. Results were assessed as relative fluorescence intensity (RFI). The RFIs of antineutrophil IgG-bound and antineutrophil IgM-bound cells in patients with AIN were significantly higher than those in patients with transient neutropenia and in controls. Positive results, as assessed by RFI scores of more than 1.81 in either antineutrophil IgG-bound or antineutrophil IgM-bound cells, showed the sensitivity and specificity of D-GIFT, and the areas under the receiver operating characteristic curve (0.98, 0.98, and 0.997, respectively) in the diagnosis of AIN. D-GIFT detecting both neutrophil-bound IgG autoantibodies and IgM autoantibodies has discriminatory power for identifying patients with AIN and, therefore, can be a useful diagnostic test. PMID:21941149

  3. Synthetic LNA/DNA nano-scaffolds for highly efficient diagnostics of nucleic acids and autoimmune antibodies

    DEFF Research Database (Denmark)

    Astakhova, Irina Kira

    2014-01-01

    Herein novel fluorescent oligonucleotides for homogeneous (all-in-solution) detection of nucleic acids and autoimmune antibodies (autoantibodies) are described. The probes are prepared by highly efficient copper-catalyzed click chemistry between novel alkyne-modified locked nucleic acid (LNA) str...

  4. Identification of antigenic proteins associated with trichloroethylene-induced autoimmune disease by serological proteome analysis

    International Nuclear Information System (INIS)

    Although many studies indicated that trichloroethylene (TCE) could induce autoimmune diseases and some protein adducts were detected, the proteins were not identified and mechanisms remain unknown. To screen and identify autoantigens which might be involved in TCE-induced autoimmune diseases, three groups of sera were collected from healthy donors (I), patients suffering from TCE-induced exfoliative dermatitis (ED) (II), and the healed ones (III). Serological proteome analysis (SERPA) was performed with total proteins of TCE-treated L-02 liver cells as antigen sources and immunoglobins of the above sera as probes. Highly immunogenic spots (2-fold or above increase compared with group I) in group II and III were submitted to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and tandem mass spectrometry sequencing. Western blot analysis was followed using commercial antibodies and individual serum. Six proteins were identified. Among them, Enoyl Coenzyme A hydratase peroxisoma 1 and lactate dehydrogenase B only showed stronger immunogenicity for group II sera, while Purine nucleoside phosphorylase, ribosomal protein P0 and proteasome activator subunit1 isoform1 also showed stronger immunogenicity for group III sera. Noteworthy, NM23 reacted only with group II sera. Western blot analysis of NM23 expression indicated that all of the individual serum of group II showed immune activity, which confirmed the validity of SERPA result. These findings revealed that there exist autoantibodies in group II and III sera. Besides, autoantibodies of the two stages of disease course were different. These autoantigens might serve as biomarkers to elucidate mechanisms underlying TCE toxicity and are helpful for diagnosis, therapy and prognosis of TCE-induced autoimmune diseases.

  5. Drug-induced hepatitis superimposed on the presence of anti-SLA antibody: a case report

    Directory of Open Access Journals (Sweden)

    Etxagibel Aitziber

    2008-01-01

    Full Text Available Abstract Introduction Autoimmune hepatitis is a necroinflammatory disorder of unknown etiology characterized by the presence of circulating antibodies, hypergammaglobulinemia, and response to immunosuppression. It has the histological features of chronic hepatitis. The onset is usually insidious, but in some patients the presentation may be acute and occasionally severe. Certain drugs can induce chronic hepatitis mimicking autoimmune hepatitis. Different autoantibodies have been associated with this process but they are not detectable after drug withdrawal and clinical resolution. Case presentation We describe a case of drug-induced acute hepatitis associated with antinuclear, antisoluble liver-pancreas and anti-smooth muscle autoantibodies in a 66-year-old woman. Abnormal clinical and biochemical parameters resolved after drug withdrawal, but six months later anti-soluble liver-pancreas antibodies remained positive and liver biopsy showed chronic hepatitis and septal fibrosis. Furthermore, our patient has a HLA genotype associated with autoimmune hepatitis. Conclusion Patient follow-up will disclose whether our patient suffers from an autoimmune disease and if the presence of anti-soluble liver antigens could precede the development of an autoimmune hepatitis, as the presence of antimitochondrial antibodies can precede primary biliary cirrhosis.

  6. Azathioprine Induced Pancreatitis in a Patient with Co-Existing Autoimmune Pancreatitis and Hepatitis

    Directory of Open Access Journals (Sweden)

    Preethi GK Venkatesh

    2011-05-01

    Full Text Available Context Azathioprine induced pancreatitis usually runs a benign self limited course with rapid disappearance of signs and symptoms upon with drawl of the drug. Azathioprine is used in treating relapses in patients with autoimmune pancreatitis and maintenance of remission in autoimmune hepatitis. Acute pancreatitis complicated by symptomatic pseudocysts requiring drainage is not usually associated with drug induced pancreatitis. The risk of azathioprine use in patients with underlying disease of pancreas including autoimmune pancreatitis is unclear. Case report We report here a case of an African American patient with co-existing autoimmune pancreatitis and autoimmune hepatitis who developed azathioprine induced acute pancreatitis complicated by a large symptomatic pseudocyst compressing the duodenum requiring a cystoduodenostomy. Conclusions Future studies to investigate the risk of azathioprine induced pancreatitis in the presence of underlying disease of the pancreas including autoimmune pancreatitis are required to further understand the safety of azathioprine in this sub group of patients.

  7. Endogenous interleukin (IL)-17A promotes pristane-induced systemic autoimmunity and lupus nephritis induced by pristane.

    Science.gov (United States)

    Summers, S A; Odobasic, D; Khouri, M B; Steinmetz, O M; Yang, Y; Holdsworth, S R; Kitching, A R

    2014-06-01

    Interleukin (IL)-17A is increased both in serum and in kidney biopsies from patients with lupus nephritis, but direct evidence of pathogenicity is less well established. Administration of pristane to genetically intact mice results in the production of autoantibodies and proliferative glomerulonephritis, resembling human lupus nephritis. These studies sought to define the role of IL-17A in experimental lupus induced by pristane administration. Pristane was administered to wild-type (WT) and IL-17A(-/-) mice. Local and systemic immune responses were assessed after 6 days and 8 weeks, and autoimmunity, glomerular inflammation and renal injury were measured at 7 months. IL-17A production increased significantly 6 days after pristane injection, with innate immune cells, neutrophils (Ly6G(+)) and macrophages (F4/80(+)) being the predominant source of IL-17A. After 8 weeks, while systemic IL-17A was still readily detected in WT mice, the levels of proinflammatory cytokines, interferon (IFN)-γ and tumour necrosis factor (TNF) were diminished in the absence of endogenous IL-17A. Seven months after pristane treatment humoral autoimmunity was diminished in the absence of IL-17A, with decreased levels of immunoglobulin (Ig)G and anti-dsDNA antibodies. Renal inflammation and injury was less in the absence of IL-17A. Compared to WT mice, glomerular IgG, complement deposition, glomerular CD4(+) T cells and intrarenal expression of T helper type 1 (Th1)-associated proinflammatory mediators were decreased in IL-17A(-/-) mice. WT mice developed progressive proteinuria, but functional and histological renal injury was attenuated in the absence of IL-17A. Therefore, IL-17A is required for the full development of autoimmunity and lupus nephritis in experimental SLE, and early in the development of autoimmunity, innate immune cells produce IL-17A. PMID:24528105

  8. The Roles of the TSH Receptor Antibodies in Autoimmune Thyroid Diseases

    International Nuclear Information System (INIS)

    To evaluate the clinical and pathogenetic roles of TSH receptor antibodies in autoimmune thyroid diseases, TBII were measured by TSH-radioreceptor assay methods in 352 patients with Graves disease, 108 patients with other thyroid diseases and 69 normal persons. The normal range of TBII activity was less than 15%. The frequencies of detectable TBIl in 169 patients with untreated Graves disease, 31 patients with hyperthyroidism under treatment and 70 patients with euthyroidism under treatment were 92.4%, 87.1% and 54.3% respectively. However 12 (21.8%) out of 55 patients who have been in remission more than one year after discontinuation of antithyroid drugs treatment had detectable TBII activities in their sera. In 196 patients with untreated Graves disease, the frequency of TBII increased by increasing size of goiter and the frequency of proptosis was significantly high in patients whose TBII activities were more than 60%. TBll activities were roughly correlated with total T3,T4 and free T4, index but low γ2 value(less than 0.1). In 67 patients with Graves' disease who were positive TB1I before antithyroid drugs treatment, TBII activities began to decrease from the third months and it was converted to negative in 35.8% of patients at 12 months after treatment. There were no significant differences of the declining and disappearing rates of TBII activities between high dose and conventional dose groups. TBII activities were significantly increased initially (2-4 months) and then began to decrease from 5-9 months after 131I treatment. There were two groups, one whose TBII activities decreased gradually and the other did not change until 12 months after subtotal thyroidectomy. Although preoperative clinical and laboratory findings of both groups were not different, TBII activities of non-decreasing group were significantly higher than those of decreasing group(74.6+18.6% vs 39.2+15.2%; P(0.01). Thirty three(55.9%) out of 59 patients with Graves disease relapsed

  9. A role for plasma cell targeting agents in immune tolerance induction in autoimmune disease and antibody responses to therapeutic proteins.

    Science.gov (United States)

    Rosenberg, A S; Pariser, A R; Diamond, B; Yao, L; Turka, L A; Lacana, E; Kishnani, P S

    2016-04-01

    Antibody responses to life saving therapeutic protein products, such as enzyme replacement therapies (ERT) in the setting of lysosomal storage diseases, have nullified product efficacy and caused clinical deterioration and death despite treatment with immune-suppressive therapies. Moreover, in some autoimmune diseases, pathology is mediated by a robust antibody response to endogenous proteins such as is the case in pulmonary alveolar proteinosis, mediated by antibodies to Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF). In this work, we make the case that in such settings, when the antibody response is high titered, sustained, and refractory to immune suppressive treatments, the antibody response is mediated by long-lived plasma cells which are relatively unperturbed by immune suppressants including rituximab. However, long-lived plasma cells can be targeted by proteasome inhibitors such as bortezomib. Recent reports of successful reversal of antibody responses with bortezomib in the settings of ERT and Thrombotic Thrombocytopenic Purpura (TTP) argue that the safety and efficacy of such plasma cell targeting agents should be evaluated in larger scale clinical trials to delineate the risks and benefits of such therapies in the settings of antibody-mediated adverse effects to therapeutic proteins and autoantibody mediated pathology. PMID:26928739

  10. Regulation of Adenosine Deaminase on Induced Mouse Experimental Autoimmune Uveitis.

    Science.gov (United States)

    Liang, Dongchun; Zuo, Aijun; Zhao, Ronglan; Shao, Hui; Kaplan, Henry J; Sun, Deming

    2016-03-15

    Adenosine is an important regulator of the immune response, and adenosine deaminase (ADA) inhibits this regulatory effect by converting adenosine into functionally inactive molecules. Studies showed that adenosine receptor agonists can be anti- or proinflammatory. Clarification of the mechanisms that cause these opposing effects should provide a better guide for therapeutic intervention. In this study, we investigated the effect of ADA on the development of experimental autoimmune uveitis (EAU) induced by immunizing EAU-prone mice with a known uveitogenic peptide, IRBP1-20. Our results showed that the effective time to administer a single dose of ADA to suppress induction of EAU was 8-14 d postimmunization, shortly before EAU expression; however, ADA treatment at other time points exacerbated disease. ADA preferentially inhibited Th17 responses, and this effect was γδ T cell dependent. Our results demonstrated that the existing immune status strongly influences the anti- or proinflammatory effects of ADA. Our observations should help to improve the design of ADA- and adenosine receptor-targeted therapies. PMID:26856700

  11. Azathioprine Induced Pancreatitis in a Patient with Co-Existing Autoimmune Pancreatitis and Hepatitis

    OpenAIRE

    Preethi GK Venkatesh; Udayakumar Navaneethan

    2011-01-01

    Context Azathioprine induced pancreatitis usually runs a benign self limited course with rapid disappearance of signs and symptoms upon with drawl of the drug. Azathioprine is used in treating relapses in patients with autoimmune pancreatitis and maintenance of remission in autoimmune hepatitis. Acute pancreatitis complicated by symptomatic pseudocysts requiring drainage is not usually associated with drug induced pancreatitis. The risk of azathioprine use in patients with underlying disease ...

  12. Repulsive Guidance Molecule-a Is Involved in Th17-Cell-Induced Neurodegeneration in Autoimmune Encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Shogo Tanabe

    2014-11-01

    Full Text Available Multiple sclerosis (MS is a chronic autoimmune disease characterized by inflammation, demyelination, and neurodegeneration in the CNS. Although it is important to prevent neurodegeneration for alleviating neurological disability, the molecular mechanism of neurodegeneration remains largely unknown. Here, we report that repulsive guidance molecule-a (RGMa, known to regulate axonal growth, is associated with neurodegeneration in experimental autoimmune encephalomyelitis (EAE, a mouse model of MS. RGMa is highly expressed in interleukin-17-producing CD4+ T cells (Th17 cells. We induced EAE by adoptive transfer of myelin oligodendrocyte glycoprotein (MOG-specific Th17 cells and then inhibited RGMa with a neutralizing antibody. Inhibition of RGMa improves EAE scores and reduces neuronal degeneration without altering immune or glial responses. Th17 cells induce cultured cortical neuron death through RGMa-neogenin and Akt dephosphorylation. Our results demonstrate that RGMa is involved in Th17-cell-mediated neurodegeneration and that RGMa-specific antibody may have a therapeutic effect in MS.

  13. Autoimmune antibodies and recurrence-free interval in melanoma patients treated with adjuvant interferon

    DEFF Research Database (Denmark)

    Bouwhuis, Marna G; Suciu, Stefan; Collette, Sandra;

    2009-01-01

    BACKGROUND: Appearance of autoantibodies and clinical manifestations of autoimmunity in melanoma patients treated with adjuvant interferon (IFN)-alpha2b was reported to be associated with improved prognosis. We assessed the association of the appearance of autoantibodies after initiation of treat......BACKGROUND: Appearance of autoantibodies and clinical manifestations of autoimmunity in melanoma patients treated with adjuvant interferon (IFN)-alpha2b was reported to be associated with improved prognosis. We assessed the association of the appearance of autoantibodies after initiation...

  14. Simultaneous measurements of auto-immune and infectious disease specific antibodies using a high throughput multiplexing tool.

    Directory of Open Access Journals (Sweden)

    Atul Asati

    Full Text Available Considering importance of ganglioside antibodies as biomarkers in various immune-mediated neuropathies and neurological disorders, we developed a high throughput multiplexing tool for the assessment of gangliosides-specific antibodies based on Biolpex/Luminex platform. In this report, we demonstrate that the ganglioside high throughput multiplexing tool is robust, highly specific and demonstrating ∼100-fold higher concentration sensitivity for IgG detection than ELISA. In addition to the ganglioside-coated array, the high throughput multiplexing tool contains beads coated with influenza hemagglutinins derived from H1N1 A/Brisbane/59/07 and H1N1 A/California/07/09 strains. Influenza beads provided an added advantage of simultaneous detection of ganglioside- and influenza-specific antibodies, a capacity important for the assay of both infectious antigen-specific and autoimmune antibodies following vaccination or disease. Taken together, these results support the potential adoption of the ganglioside high throughput multiplexing tool for measuring ganglioside antibodies in various neuropathic and neurological disorders.

  15. Autosomal Recessive Chronic Granulomatous Disease, IgA Deficiency and Refractory Autoimmune Thrombocytopenia Responding to Anti-CD20 Monoclonal Antibody

    Directory of Open Access Journals (Sweden)

    Shahin Shamsian Bibi

    2008-09-01

    Full Text Available Immunodeficiency and autoimmune disease may occur concomitantly in the same individual. Some of the immunodeficiency syndromes, especially humoral defects are associated with autoimmune disorders. Hematological manifestations such as thrombocytopenia and hemolytic anemia are the most common presentations. Persistent antigen stimulation due to an inherent defect in the ability of the immune system to eradicate pathogens is the primary cause leading to autoimmunity in patients with primary immunodeficiency states.We describe a 10 year old Iranian girl with chronic granulomatous disease -the autosomal recessive type with mutation of NCF1 gene P47- associated with selective IgA deficiency, refractory immune thrombocytopenia that showed an excellent response to Rituximab (Anti-CD20 monoclonal antibody.Patients with primary immunodeficiencies may have variable autoimmune manifestations. So for early detection and appropriate treatment, autoimmune diseases should always be suspected in such patients.

  16. Autoimmune hepatitis type 2 associated with an unexpected and transient presence of primary biliary cirrhosis-specific antimitochondrial antibodies: a case study and review of the literature

    OpenAIRE

    Invernizzi Pietro; Alessio Maria; Smyk Daniel S; Lleo Ana; Sonzogni Aurelio; Fabris Luca; Candusso Manila; Bogdanos Dimitrios P; Iorio Raffaele; Torre Giuliano

    2012-01-01

    Abstract Background Unlike other autoimmune liver diseases, primary biliary cirrhosis (PBC) has never been reported in early childhood, while type 2 autoimmune hepatitis (AIH) is eminently a paediatric disease. Case presentation We describe a case of type 2 AIH with serological positivity for PBC-specific anti-mitochondrial antibodies (AMA) in a 3-year old girl. We found this observation intriguing as AMA and indeed an overlap with PBC are virtually absent in Type 2 AIH, a pediatric form of A...

  17. Voltage gated potassium channel antibodies positive autoimmune encephalopathy in a child: A case report and literature review of an under-recognized condition

    Directory of Open Access Journals (Sweden)

    Subramanian Ganesan

    2013-01-01

    Full Text Available Autoimmune limbic encephalitis (LE associated with voltage gated potassium channel antibodies (VGKC-Abs in children is more common than previously thought and is not always paraneoplastic. Non-neoplastic, autoimmune LE associated with VGKC-Abs has been described recently. However, only few case reports in children as the disease is predominantly described in the adult population. It is likely that this type of autoimmune encephalitis is currently under-diagnosed and hence, under-treated, especially in children. We present a 13-year-old previously fit and healthy African girl diagnosed with LE and we reviewed the literature for its current management.

  18. Extraction of Ku antigen and anti-Ku antibody assay in various autoimmune connective tissue diseases

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To extract Ku antigen and to detect anti-Ku antibody in connective tissue diseases (CTDs). Methods: Ku antigen was prepared from rabbit thymus acetone powder. Anti-Ku antibodies were tested in 50 normal controls and 438 patients

  19. Clinical implications of a new TSH-receptor-antibody-assay (DYNOtest trademark TRAKhuman) in autoimmune thyroid diseases

    International Nuclear Information System (INIS)

    Aim: Conventional radioreceptor-antibody-assays (RAAs) fail in the detection of TSH-receptor antibodies (TRAKs) in 10-30% of patients with Graves' disease (GD). The aim of this study was the evaluation of the diagnostic and clinical impact of a new RRA (DYNOtest trademark TRAKhuman) which uses the human recombinant TSH-Receptor in the diagnosis of autoimmune thyroid disease. Methods: Sera from 142 consecutive patients (GD: n=50, autoimmune thyroiditis/AIT: n=92) and from 55 controls (31 patients without any thyroid disease and 14 with euthyroid goiter) were evaluated both with the DYNOtest trademark TRAKhuman-assay and a conventional RRA (TRAK-Assay trademark). Thyroid in vitro parameters and thyroid sonography were performed in all patients. Results: The DYNOtest trademark TRAK-assay was significantly superior to the conventional RRA in the diagnosis of GD (ptrademark as well as in the DYNOtest trademark TRAKhuman-Assay. Therefore the specifity of the DYNOtest trademark TRAKhuman was not inferior compared with the conventional assay. Conclusion: The DYNOtest trademark TRAK-assay is superior in the diagnostic work up of Graves' disease compared with a conventional TRAK-assay and offers an equal specifity. (orig.)

  20. Autoimmune hemolytic anemia induced by anti-PD-1 therapy in metastatic melanoma.

    Science.gov (United States)

    Kong, Benjamin Y; Micklethwaite, Kenneth P; Swaminathan, Sanjay; Kefford, Richard F; Carlino, Matteo S

    2016-04-01

    We report the occurrence of autoimmune hemolytic anemia in a patient receiving the anti-PD-1 monoclonal antibody, nivolumab, for metastatic melanoma in the presence of known red cell alloantibodies, despite having received prior ipilimumab without evidence of hemolysis. The patient had a history of multiple red cell alloantibodies and a positive direct antiglobulin test, identified at the time of a prior transfusion, which occurred before treatment with ipilimumab. The patient developed symptomatic warm autoimmune hemolytic anemia after four cycles of treatment with nivolumab. Clinical improvement was noted following cessation of the drug and treatment with corticosteroids. Given that there was no prior history of hemolysis, even during treatment with ipilimumab, we hypothesize that anti-PD-1 therapy disrupted peripheral tolerance, unmasking an underlying autoimmune predisposition. PMID:26795275

  1. A strong association between thyrotropin receptor-blocking antibody-positive atrophic autoimmune thyroiditis and HLA-DR8 and HLA-DQB1 0302 in Koreans

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Bo Youn; Chung, Jae Hoon; Lee, Hong Kyu; Koh, Chang-Soon; Lee, Jung-Bin (Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)); Shong, Young Kee (Univ. of Ulsan College of Medicine Ulsan (Korea, Republic of)); Han, Hoon (Catholic Univ. Medical College, Seoul (Korea, Republic of)); Chang, Youn Bok (Hallym Univ. College of Medicine, Seoul (Korea, Republic of))

    1993-09-01

    The authors investigated whether the associations between HLA alleles of patients with autoimmune hypothyroidism varied according to the presence or absence of TSH receptor-blocking antibody (TRBab). They analyzed the HLA-A, -B, -C, and -DR antigens by serotyping and the DQA1 and DQB1 genes using both enzymatic DNA amplification and sequence-specific oligonucleotide hybridizations. The patient population consisted of 47 Korean patients with atrophic autoimmune thyroiditis and 62 patients with goitrous autoimmune thyroiditis. The antigen frequency of HLA-DR8 was significantly increased in 23 atrophic autoimmune thyroiditis patients that were positive for TSH binding inhibitor immunoglobulin (TBII) compared to 136 controls [52% vs. 16%; x[sup 2] = 13.1; Pc (corrected P value) = 0.003]. This relative risk was 5.7; the etiological fraction was 0.43. HLA-DQB1*0302 was also increased in patients with TBII-positive atrophic autoimmune thyroiditis (24% vs. 7%; x[sup 2] = 11.2; Pc = 0.012; relative risk = 4.4; etiological fraction = 0.19). No specific DR antigens or DQB1 alleles were increased in either TBII-negative atrophic autoimmune thyroidities or goitrous autoimmune thyroiditis. A significant decrease in the frequency of HLA-DR6 antigen was observed in both TBII-positive atrophic antoimmune thyroiditis (0% vs. 32%; x[sup 2] = 8.4; Pc = 0.03) and goitrous autoimmune thyroiditis (0% vs. 32%; x[sup 2] = 23.2; Pc < 0.001) patients. The frequency of the HLC-Cwl antigen was significantly increased in all patient groups. The authors conclude that TRBab-positive atrophic autoimmune thyroiditis is immunogenetically different from both goitrous autoimmune thyroiditis and TRBab-negative atrophic autoimmune thyroiditis. It is possible that HLA-DR8 and/or DQB1*0302 may be related to the susceptibility genes involved in the production of TRBab in Koreans. 32 refs., 5 tabs.

  2. [Autoimmune encephalitis].

    Science.gov (United States)

    Davydovskaya, M V; Boyko, A N; Beliaeva, I A; Martynov, M Yu; Gusev, E I

    2015-01-01

    The authors consider the issues related to pathogenesis, clinical features, diagnosis and treatment of autoimmune encephalitis. It has been demonstrated that the development of autoimmune encephalitis can be associated with the oncologic process or be of idiopathic character. The pathogenesis of autoimmune encephalitis is caused by the production of antibodies that directly or indirectly (via T-cell mechanism) damage exo-and/or endocellular structures of the nerve cells. The presence of antobodies to endocellular structures of neurons in the cerebrospinal fluid of patients with autoimmune encephalitis in the vast majority of cases (> 95%) indicates the concomitant oncologic process, the presence of antibodies to membranes or neuronal synapses can be not associated with the oncologic process. Along with complex examination, including neuroimaging, EEG, cerebrospinal fluid and antibodies, the diagnostic algorithm in autoimmune encephalitis should include the search for the nidus of cancer. The treatment algorithm in autoimmune encephalitis included the combined immunosupressive therapy, plasmapheresis, immunoglobulines, cytostatics as well as treatment of the oncologic process. PMID:26322363

  3. Human adjuvant disease: remission of silicone induced autoimmune disease after explanation of breast augmentation.

    OpenAIRE

    Kaiser, W; Biesenbach, G; Stuby, U; Grafinger, P; Zazgornik, J.

    1990-01-01

    Autoimmune diseases following silicone or paraffin implantation are rarely encountered complications of plastic surgery. A 42 year old woman is presented who developed clinical and immunological features of systemic lupus erythematosus 11 years after silicone augmentation. After explanation antinuclear antibody titres decreased from 1/1280 to 1/160, C4 complement fraction and the previously raised angiotensin converting enzyme normalised in step with clinical improvement. It is important that...

  4. Autoimmune disease

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    2005164 Optimal cut-point of glutamic acid decar-boxylase antibody (GAD-Ab) for differentiating two subtypes of latent autoimmune diabetes in adults (LADA). LI Xia(李霞), et al. Dept Endocrinol, 2nd Xiangya Hosp, Central South Univ, Changsha, 410011. Chin J Diabetes, 2005;13(1) :34-38. Objective: To investigate the optimal cut-point of glutamate decarboxylase antibody (GAD-Ab) for differentiating two subtypes of latent autoimmune diabetes in adults (I. ADA). Methods: The frequency

  5. Selective loss of Purkinje cells in a patient with anti-gliadin-antibody-positive autoimmune cerebellar ataxia

    Directory of Open Access Journals (Sweden)

    Hasegawa Akira

    2011-02-01

    Full Text Available Abstract The patient was an 84-year-old woman who had the onset of truncal ataxia at age 77 and a history of Basedow's disease. Her ataxic gait gradually deteriorated. She could not walk without support at age 81 and she was admitted to our hospital at age 83. Gaze-evoked nystagmus and dysarthria were observed. Mild ataxia was observed in all limbs. Her deep tendon reflex and sense of position were normal. IgA anti-gliadin antibody, IgG anti-gliadin antibody, anti-SS-A/Ro antibody, anti-SS-B/La antibody and anti-TPO antibody were positive. A conventional brain MRI did not show obvious cerebellar atrophy. However, MRI voxel based morphometry (VBM and SPECT-eZIS revealed cortical cerebellar atrophy and reduced cerebellar blood flow. IVIg treatment was performed and was moderately effective. After her death at age 85, the patient was autopsied. Neuropathological findings were as follows: selective loss of Purkinje cells; no apparent degenerative change in the efferent pathways, such as the dentate nuclei or vestibular nuclei; no prominent inflammatory reaction. From these findings, we diagnosed this case as autoimmune cerebellar atrophy associated with gluten ataxia. All 3 autopsies previously reported on gluten ataxia have noted infiltration of inflammatory cells in the cerebellum. In this case, we postulated that the infiltration of inflammatory cells was not found because the patient's condition was based on humoral immunity. The clinical conditions of gluten ataxia have not yet been properly elucidated, but are expected to be revealed as the number of autopsied cases increases.

  6. Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) 2013: Unveiling the pathogenic, clinical and diagnostic aspects.

    Science.gov (United States)

    Perricone, Carlo; Colafrancesco, Serena; Mazor, Roei D; Soriano, Alessandra; Agmon-Levin, Nancy; Shoenfeld, Yehuda

    2013-12-01

    In 2011 a new syndrome termed 'ASIA Autoimmune/Inflammatory Syndrome Induced by Adjuvants' was defined pointing to summarize for the first time the spectrum of immune-mediated diseases triggered by an adjuvant stimulus such as chronic exposure to silicone, tetramethylpentadecane, pristane, aluminum and other adjuvants, as well as infectious components, that also may have an adjuvant effect. All these environmental factors have been found to induce autoimmunity by themselves both in animal models and in humans: for instance, silicone was associated with siliconosis, aluminum hydroxide with post-vaccination phenomena and macrophagic myofasciitis syndrome. Several mechanisms have been hypothesized to be involved in the onset of adjuvant-induced autoimmunity; a genetic favorable background plays a key role in the appearance on such vaccine-related diseases and also justifies the rarity of these phenomena. This paper will focus on protean facets which are part of ASIA, focusing on the roles and mechanisms of action of different adjuvants which lead to the autoimmune/inflammatory response. The data herein illustrate the critical role of environmental factors in the induction of autoimmunity. Indeed, it is the interplay of genetic susceptibility and environment that is the major player for the initiation of breach of tolerance. PMID:24238833

  7. Review on Autoimmune Reactions in Female Infertility: Antibodies to Follicle Stimulating Hormone

    OpenAIRE

    Raivo Uibo; Kadri Haller-Kikkatalo; Andres Salumets

    2012-01-01

    Female fertility can be affected by diseases or dysfunctions of reproductive tract, neuroendocrine system, and immune system. Reproductive autoimmune failure can be associated with overall activation of immune system or with immune system reactions specifically directed against ovarian antigens. Majority of the antiovarian autoantibodies are directed against β -subunit of follicle stimulating hormone (anti-FSH). This paper summarizes a current clinical classification of female infertility in ...

  8. Induced Foxp3+ regulatory T cells: a potential new weapon to treat autoimmune and inflammatory diseases?

    Institute of Scientific and Technical Information of China (English)

    Qin Lan; Huimin Fan; Valerie Quesniaux; Bernhard Ryffel; Zhongmin Liu; Song Guo Zheng

    2012-01-01

    Foxp3+ T regulatory cells (Tregs) consisting of natural and induced Treg subsets play a crucial role in the maintenance of immune homeostasis against self-antigen.The actions designed to correct defects in numbers or functions of Tregs may be therapeutic in the treatment of autoimmune diseases.While recent studies demonstrated that natural Tregs are instable and dysfunctional in the inflammatory condition,induced Tregs (iTregs) may have a different feature.Here we review the progress of iTregs,particularly focus on their stability and function in the established autoimmune diseases.The advantage of iTregs as therapeutics used under inflammatory conditions is highlighted.Proper generation and manipulation of iTregs used for cellular therapy may provide a promise for the treatment of many autoimmune and inflammatory diseases.

  9. Study on serum thyroid peroxidase antibody levels in autoimmune thyroid disease

    International Nuclear Information System (INIS)

    Objective: To investigate the clinical significance of changes of serum thyroid peroxidase antibody (TPO-Ab) in patients with hyperthyroidism, hypothyroidism and simple goiter. Methods: Serum TPO-Ab, TMA,TGA and FT3, FT4, TSH levels were measured with radioimmunoassay(RIA) in 69 patients with hyperthyroidism, 53 patients with hypothyroidism, 45 patients with simple goiter and 20 controls. Results: The positive rate of thyroid peroxidase antibody (TPO-Ab) (82%-92.5%) was higher than that of thyroidglobulim antibody(TGA) (44.2%) and thyroid microsome antibody(TMA) (60.4-69.8%) in all patients with AICD. Conclusion: TPO-Ab could be taken as an important indicator in assessment of treatment and prognosis in patients with auto- immune thyroid diseases. (authors)

  10. Antibodies against Ku protein in sera from patients with autoimmune diseases.

    Science.gov (United States)

    Yaneva, M; Arnett, F C

    1989-01-01

    Immunoaffinity-purified Ku protein was used to screen sera from patients with systemic lupus erythematosus (SLE), scleroderma, myositis and Sjögren's syndrome for anti-Ku antibodies in a quantitative immunoblot assay. Sixteen percent of the 159 studied sera were reactive with the Ku protein; significantly increased frequencies of anti-Ku antibodies were found in SLE (19%) and scleroderma (14%) sera. Patients with myositis and Sjögren's syndrome showed similar frequencies. All positive sera had antibodies to the 86 kD subunit of Ku protein; only one serum did not react with 70 kD subunit. Frequencies of other autoantibodies were compared in anti-Ku positive and negative patients. Only anti-Sm antibodies, especially in the absence of anti-nRNP, appear to be associated with the presence of anti-Ku antibodies. A strong correlation between anti-Ku antibodies and the class II HLA antigen DQw1 (89% of the positive sera) was observed, suggesting participation of MHC genes in the mounting of the anti-Ku immune response. Images Fig. 1 Fig. 2 PMID:2665976

  11. Role of Peritoneal Macrophages in Cytomegalovirus-induced Acceleration of Autoimmune Diabetes in BB-rats

    Directory of Open Access Journals (Sweden)

    Jan-Luuk Hillebrands

    2003-01-01

    Full Text Available Background: As one of the natural perturbants, infection with cytomegalovirus (CMV is believed to play a role in the development of Type I diabetes. Using the DP-BB rat model for autoimmune diabetes, we here report about possible mechanisms responsible for R(atCMV-induced accelerated onset of diabetes.

  12. Activation-induced cytidine deaminase deficiency causes organ-specific autoimmune disease.

    Directory of Open Access Journals (Sweden)

    Koji Hase

    Full Text Available Activation-induced cytidine deaminase (AID expressed by germinal center B cells is a central regulator of somatic hypermutation (SHM and class switch recombination (CSR. Humans with AID mutations develop not only the autosomal recessive form of hyper-IgM syndrome (HIGM2 associated with B cell hyperplasia, but also autoimmune disorders by unknown mechanisms. We report here that AID-/- mice spontaneously develop tertiary lymphoid organs (TLOs in non-lymphoid tissues including the stomach at around 6 months of age. At a later stage, AID-/- mice develop a severe gastritis characterized by loss of gastric glands and epithelial hyperplasia. The disease development was not attenuated even under germ-free (GF conditions. Gastric autoantigen -specific serum IgM was elevated in AID-/- mice, and the serum levels correlated with the gastritis pathological score. Adoptive transfer experiments suggest that autoimmune CD4+ T cells mediate gastritis development as terminal effector cells. These results suggest that abnormal B-cell expansion due to AID deficiency can drive B-cell autoimmunity, and in turn promote TLO formation, which ultimately leads to the propagation of organ-specific autoimmune effector CD4+ T cells. Thus, AID plays an important role in the containment of autoimmune diseases by negative regulation of autoreactive B cells.

  13. Antiplatelet antibodies in oxaliplatin-induced immune thrombocytopenia

    Science.gov (United States)

    McNamara, Michael J; Curtis, Brian R; McCrae, Keith R

    2014-01-01

    Lesson Drug-induced immune thrombocytopenia may be potentially fatal; here we report the development of severe thrombocytopenia with strong oxaliplatin-dependent antiplatelet antibodies. PMID:25057402

  14. THE RELATIONSHIP BETWEEN AUTOIMMUNE ANTIBODIES AND HCG TREATMENT 1N HABITUAL ABORTION

    Institute of Scientific and Technical Information of China (English)

    TANGPei-Zhong; WUJin-Zhi; BAOChun-De; CHENShun-Le

    1989-01-01

    The antibodies to cardiolipin (aCL), double stranded DNA (aDNA) and to nuclear axttigcns(Sm, SSA, SSB, Ribonucleoprotein) were prospe, ctivcly investigated in 86 patients of habitual abortion without abilormaiity in their reprodutive system and karyotypes. All

  15. Detection of GAD65 antibodies in diabetes and other autoimmune diseases using a simple radioligand assay.

    Science.gov (United States)

    Petersen, J S; Hejnaes, K R; Moody, A; Karlsen, A E; Marshall, M O; Høier-Madsen, M; Boel, E; Michelsen, B K; Dyrberg, T

    1994-03-01

    Autoantibodies to glutamic acid decarboxylase (GAD) are frequent at or before the onset of insulin-dependent diabetes mellitus (IDDM). We have developed a simple, reproducible, and quantitative immunoprecipitation radioligand assay using as antigen in vitro transcribed and translated [35S]methionine-labeled human islet GAD65. By using this assay, 77% (77 of 100) of serum samples from recent-onset IDDM patients were positive for GAD65 antibodies compared with 4% (4 of 100) of serum samples from healthy control subjects. In competition analysis with unlabeled purified recombinant human islet GAD65, binding to tracer was inhibited in 74% (74 of 100) of the GAD65-positive IDDM serum samples compared with 2% of the control samples. The levels of GAD antibodies expressed as an index value relative to a standard serum, analyzed with or without competition, were almost identical (r = 0.991). The intra- and interassay variations of a positive control serum sample were 2.9 and 7.6%, respectively (n = 4). The frequency of GAD antibodies was significantly higher with IDDM onset before the age of 30 (80%, 59 of 74) than after the age of 30 (48%, 10 of 21) (P DNA autoantibodies (8% [2 of 25] and 4% [1 of 25] in competition analysis) or rheuma factor autoantibodies [12% (4 of 35) and 3% (1 of 35) in competition analysis] was not different from that in control samples. In contrast, in sera positive for ribonucleoprotein antibodies the frequency of GAD antibodies was significantly increased (73% [51 of 70] and 10% [7 of 70] in competition analysis [P history of IDDM for the presence of this marker. PMID:8314020

  16. Frequency-specific association of antibodies against heat shock proteins 60 and 70 with noise-induced hearing loss in Chinese workers

    OpenAIRE

    Yang, Miao; Zheng, Jianru; Yang, Qiaoling; Yao, Huiling; Chen, Yongwen; Tan, Hao; Jiang, Changzheng; Wang, Feng; He, Meian; Chen, Sheng; Wei, Qingyi; Tanguay, Robert M.; Wu, Tangchun

    2004-01-01

    Noise exposure may result in production of auto-antibodies against heat shock proteins (Hsps), which might be of significance in the pathogenesis or prognosis (or both) of auto-immune ear diseases. However, it is not known whether these antibodies are associated with noise-induced hearing loss (NIHL) in workers exposed to noise in occupational settings. Using immunoblotting with human recombinant Hsps, audiological assessment, and multivariate logistic regression models, we investigated the p...

  17. Intrathecal-specific glutamic acid decarboxylase antibodies at low titers in autoimmune neurological disorders.

    Science.gov (United States)

    Sunwoo, Jun-Sang; Chu, Kon; Byun, Jung-Ick; Moon, Jangsup; Lim, Jung-Ah; Kim, Tae-Joon; Lee, Soon-Tae; Jung, Keun-Hwa; Park, Kyung-Il; Jeon, Daejong; Jung, Ki-Young; Kim, Manho; Lee, Sang Kun

    2016-01-15

    Autoantibodies to glutamic acid decarboxylase (Gad-Abs) are implicated in various neurological syndromes. The present study aims to identify intrathecal-specific GAD-Abs and to determine clinical manifestations and treatment outcomes. Nineteen patients had GAD-Abs in cerebrospinal fluid but not in paired serum samples. Neurological syndromes included limbic encephalitis, temporal lobe epilepsy, cerebellar ataxia, autonomic dysfunction, and stiff-person syndrome. Immunotherapy had beneficial effects in 57.1% of patients, and the patients with limbic encephalitis responded especially well to immunotherapy. Intrathecal-specific antibodies to GAD at low titers may appear as nonspecific markers of immune activation within the central nervous system rather than pathogenic antibodies causing neuronal dysfunction. PMID:26711563

  18. The role of anti-phospholipid antibodies in autoimmune reproductive failure.

    Science.gov (United States)

    Pantham, Priyadarshini; Abrahams, Vikki M; Chamley, Lawrence W

    2016-05-01

    Anti-phospholipid antibodies (aPL) are autoantibodies that are associated with thrombosis and a range of pregnancy complications including recurrent pregnancy loss and pre-eclampsia. The three clinically relevant, well-characterized aPL are anti-cardiolipin antibodies, lupus anticoagulant and anti-beta-2-glycoprotein I (β2GPI) antibodies. aPL do not bind directly to phospholipids but instead bind to a plasma-binding 'cofactor'. The most extensively studied cofactor is β2GPI, whose role in pregnancy is not fully elucidated. Although the pathogenicity of aPL in recurrent pregnancy loss is well established in humans and animal models, the association of aPL with infertility does not appear to be causative. aPL may exert their detrimental effects during pregnancy by directly binding trophoblast cells of the placenta, altering trophoblast signalling, proliferation, invasion and secretion of hormones and cytokines, and by increasing apoptosis. Heparin is commonly used to treat pregnant women with aPL; however, as thrombotic events do not occur in the placentae of all women with aPL, it may exert a protective effect by preventing the binding of aPL to β2GPI or by acting through non-thrombotic pathways. The aim of this review is to present evidence summarizing the current understanding of this field. PMID:26884418

  19. Interferin with thyroid scintigraphy: the effects of interferon alpha induced thyroid gland autoimmunity and dysfunction upon thyroid scintigraphy in patients with the hepatitis C virus

    International Nuclear Information System (INIS)

    Full text: The incidence of hepatitis C virus (HCV) infection is increasing. Interferon alpha therapy is often used to treat patients who are HCV positive. Thyroid gland autoimmunity and dysfunction has been reported to occur with variable frequency during INF-alpha therapy in patients with the HCV. This study reviews the scintigraphic findings of thyroid scans in such patients in order to assess for the effects on thyroid scintigraphy. To our knowledge, there has been no comprehensive study of this important occurrence to date. There were a number of patients with the HCV being treated at our institution between 23/09/1996 and 09/08/2000. Some of them received INF-alpha therapy, certain were subsequently diagnosed with thyroid gland autoimmunity and/or dysfunction. Eight were imaged with thyroid scintigraphy and reviewed. The scintigraphic findings in the 8 patients fell into two broad categories; 4 demonstrated changes of Graves' disease, and 3 changes of thyroiditis (1 of these was sub-acute). One hypothyroid patient with anti-thyroglobulin antibodies had normal thyroid scintigraphy. Six patients were found to have antithyroid antibodies. One patient with thyroiditis tested negative to antithyroid antibodies. One patient was not tested for antithyroid antibodies. Interferon alpha induced thyroid gland autoimmunity and/or dysfunction can markedly affect the thyroid scintigraphic findings of patients with the hepatitis C virus. This hitherto undescribed occurrence on thyroid scintigraphy has important practical implications of which Nuclear Medicine Specialists need to be aware in order to correctly interpret thyroid scintigraphy studies in such patients. The clinical presentation and effects on imaging appearances are varied. The Nuclear Medicine Specialist can play a central role in establishing the causal link. Awareness of this occurrence enables the Nuclear Medicine Specialist to add value to the referral. This occurrence will become an increasingly common

  20. Long-Term Follow-Up of a Child with Autoimmune Thyroiditis and Recurrent Hyperthyroidism in the Absence of TSH Receptor Antibodies

    OpenAIRE

    Dunne, Christopher; De Luca, Francesco

    2014-01-01

    Hashitoxicosis is an initial, transient, hyperthyroid phase that rarely affects patients with Hashimoto thyroiditis. We present here an unusual case of a child with Hashimoto thyroiditis and recurrent hyperthyroidism. A 4 yr 6/12 old male was diagnosed by us with autoimmune subclinical hypothyroidism (normal free T4, slightly elevated TSH, and elevated TG antibody titer). Two years and 6/12 later he experienced increased appetite and poor weight gain; a laboratory evaluation revealed suppress...

  1. N-type calcium channel antibody-mediated autoimmune encephalitis: An unlikely cause of a common presentation ☆ ☆☆ ★

    OpenAIRE

    Finkel, Leslie; Koh, Sookyong

    2013-01-01

    We report, to our knowledge, the only known pediatric case with encephalopathy and significantly elevated titers of N-type voltage-gated calcium channel antibody (N-type VGCC). The patient, an 8th grader, was previously healthy and presented with a one-week history of confusion, aphasia, transient fever, headaches, and dizziness. An underlying autoimmune process was suspected because of inflammatory changes in the brain MRI and multiple focal electrographic seizures captured in the EEG in the...

  2. Population of antithyroid autoantibodies as a source of antibodies of various levels of specificity and functionality: the clinical importance of a phenomenon of combination theory at monitoring of patients with autoimmune diseases of a thyroid gland

    Directory of Open Access Journals (Sweden)

    A V Andreeva

    2011-06-01

    Full Text Available The review of literature is dedicated to comparative analysis of pathogenetic and clinicodiagnostic significance of antithyroid autoantibodies (autoAB differing in their specificity (АB to thyroglobulin (anti-TG and АB to thyroid peroxidase (anti-TPO, anti-TGPO, and functionality TG- and TPO-antibodies, namely antibodies-proteases in pathogenesis autoimmune diseases thyroid gland and possibility of their use in modern diagnostics of autoimmune thyroid diseases.

  3. Two Japanese cases of dermatitis herpetiformis associated each with lung cancer and autoimmune pancreatitis but showing no intestinal symptom or circulating immunoglobulin A antibodies to any known antigens.

    Science.gov (United States)

    Shigeta, Mika; Saiki, Minoru; Tsuruta, Daisuke; Ohata, Chika; Ishii, Norito; Ono, Fumitake; Hamada, Takahiro; Dainichi, Teruki; Furumura, Minao; Zone, John J; Karpati, Sarolta; Sitaru, Cassian; Hashimoto, Takashi

    2012-12-01

    Dermatitis herpetiformis (DH) is common in some Caucasian populations but extremely rare in Japanese, probably because of different immunogenetic backgrounds. We report two Japanese DH cases with typical clinical, histological and direct immunofluorescence features. However, no symptom of gluten-sensitive enteropathy was shown. The diagnosis was confirmed by eliminating other autoimmune blistering diseases by indirect immunofluorescence, enzyme-linked immunosorbent assays and immunoblotting. However, circulating immunoglobulin (Ig)A anti-endomysium, reticulin and gliadin antibodies were not detected. IgA antibodies to tissue and epidermal transglutaminases were also negative. One case was associated with lung cancer and the other one with autoimmune pancreatitis. On review of 17 cases of DH reported in Japan over the previous 10 years, including our cases, one case was associated with gluten-sensitive enteropathy, four with malignant neoplasms, two with autoimmune systemic disorders and one with psoriasis. Although our cases were typical of DH in clinical, histopathological and IgA deposit features, they showed different human leukocyte antigen haplotypes, no gluten-sensitive enteropathy and no DH-specific IgA antibodies, including those to epidermal and tissue transglutaminases. These results suggest that studies of unique characteristics in Japanese DH patients should facilitate further understanding of pathogenesis in DH. PMID:22963165

  4. Promoting tolerance to proteolipid protein-induced experimental autoimmune encephalomyelitis through targeting dendritic cells

    OpenAIRE

    Stern, Joel N. H.; Keskin, Derin B.; Kato, Zenichiro; Waldner, Hanspeter; Schallenberg, Sonja; Anderson, Ana; von Boehmer, Harald; Kretschmer, Karsten; Strominger, Jack L.

    2010-01-01

    In T cell-mediated autoimmune diseases, self-reactive T cells with known antigen specificity appear to be particularly promising targets for antigen-specific induction of tolerance without compromising desired protective host immune responses. Several lines of evidence suggest that delivery of antigens to antigen-presenting dendritic cells (DCs) in the steady state (i.e., to immature DCs) may represent a suitable approach to induce antigen-specific T-cell tolerance peripherally. Here, we repo...

  5. The paracrine effect of mesenchymal human stem cells restored hearing in β-tubulin induced autoimmune sensorineural hearing loss.

    Science.gov (United States)

    Yoo, T J; Du, Xiaoping; Zhou, Bin

    2015-12-01

    The aim of this study was to examine the activities of hASCs (Human Adipose tissue Derived Stem Cells) on experimental autoimmune hearing loss (EAHL) and how human stem cells regenerated mouse cochlea cells. We have restored hearing in 19 years old white female with autoimmune hearing loss with autologous adipose tissue derived stem cells and we wish to understand the mechanism of restoration of hearing in animal model. BALB/c mice underwent to develop EAHL; mice with EAHL were given hASCs intraperitoneally once a week for 6 consecutive weeks. ABR were examined over time. The helper type 1 autoreactive responses and T-reg cells were examined. H&E staining or immunostaining with APC conjugated anti-HLA-ABC antibody were conducted. The organ of Corti, stria vascularis, spira ligament and spiral ganglion in stem cell group are normal. In control group, without receiving stem cells, the organ of Corti is replaced by a single layer of cells, atrophy of stria vascularis. Systemic infusion of hASCs significantly improved hearing function and protected hair cells in established EAHL. The hASCs decreased the proliferation of antigen specific Th1/Th17 cells and induced the production of anti-inflammatory cytokine interleukin10 in splenocytes. They also induced the generation of antigen specific CD4(+)CD25(+)Foxp3(+)T-reg cells. The experiment showed the restoration is due to the paracrine activities of human stem cells, since there are newly regenerated mice spiral ganglion cells, not human mesenchymal stem cells derived tissue given by intraperitoneally. PMID:26235980

  6. Human parvovirus B19 and autoimmune diseases. Review of the literature and pathophysiological hypotheses.

    Science.gov (United States)

    Page, Cyril; François, Catherine; Goëb, Vincent; Duverlie, Gilles

    2015-11-01

    A number of arguments support the role played by PVB19 in autoimmunity, in the broad sense of the term essentially derived from numerous clinical case reports and/or small series over the past 20-30 years in the medical literature. PVB19 can induce a very broad spectrum of autoantibody production, especially including: anti-soluble nuclear antigen antibodies, antiphospholipid antibodies anti-native DNA antibodies, antilymphocyte antibody, anticardiolipin antibodies, antinuclear antibodies and rheumatoid factor. Notably acute PVB19 infection can mimic or stimulate autoimmune systemic diseases as rheumatoid arthritis or systemic lupus erythematosus. However, at the present time, there is no formal scientific evidence demonstrating a direct role of PVB19 in autoimmunity, bearing in mind that there are also no formal arguments against it. Further large studies are needed to understand the eventual role of PVB19 in autoimmune diseases. PMID:26433772

  7. High Prevalence of Neutrophil Cytoplasmic Autoantibodies in Infants with Food Protein-Induced Proctitis/Proctocolitis: Autoimmunity Involvement?

    Directory of Open Access Journals (Sweden)

    Alena Sekerkova

    2015-01-01

    Full Text Available Background. Food protein-induced proctitis/proctocolitis (FPIP is the most common noninfectious colitis in children in the first year of life. Along with the overall clinical symptoms, diarrhoea and rectal bleeding are the main manifestations of the disease. There is no routine noninvasive test that would be specific for this type of colitis. The aim of our study was to find a noninvasive laboratory test or tests that may be helpful in differential diagnosis of food protein-induced proctitis/proctocolitis. Methods. ANA, ANCA, ASCA, a-EMA, a-tTg, specific IgE, total IgE, IgG, IgA, IgM, and concentration of serum calprotectin were measured in a group of 25 patients with colitis and 18 children with other diagnoses. Results. Atypical-pANCA antibodies of IgG isotype were detected in the sera of 24 patients by the method of indirect immunofluorescence, and 5 patients showed also the positivity of IgA isotype. In control samples these autoantibodies were not detected. Other autoantibodies were not demonstrated in either patient or control group. Conclusions. Of the parameters tested in noninfectious colitis, atypical-pANCA on ethanol-fixed granulocytes appears to be a suitable serological marker of food protein-induced proctitis/proctocolitis and suggests a possible involvement of an autoimmune mechanisms in the pathogenesis of this disease.

  8. Autoimmune Encephalitis

    OpenAIRE

    Leypoldt, Frank; Wandinger, Klaus-Peter; Bien, Christian G; Dalmau, Josep

    2013-01-01

    The term autoimmune encephalitis is used to describe a group of disorders characterised by symptoms of limbic and extra-limbic dysfunction occurring in association with antibodies against synaptic antigens and proteins localised on the neuronal cell surface. In recent years there has been a rapidly expanding knowledge of these syndromes resulting in a shift in clinical paradigms and new insights into pathogenic mechanisms. Since many patients respond well to immunosuppressive treatment, the r...

  9. Thyroid dysfunction: an autoimmune aspect.

    Science.gov (United States)

    Khan, Farah Aziz; Al-Jameil, Noura; Khan, Mohammad Fareed; Al-Rashid, May; Tabassum, Hajera

    2015-01-01

    Auto immune thyroid disease (AITD) is the common organ specific autoimmune disorder, Hashimoto thyroiditis (HT) and Grave's disease (GD) are its well-known sequelae. It occurs due to loss of tolerance to autoantigens thyroid peroxidase (TPO), thyroglobulin (Tg), thyroid stimulating hormone receptor (TSH-R) which leads to the infiltration of the gland. T cells in chronic autoimmune thyroiditis (cAIT) induce apoptosis in thyroid follicular cells and cause destruction of the gland. Presences of TPO antibodies are common in HT and GD, while Tg has been reported as an independent predictor of thyroid malignancy. Cytokines are small proteins play an important role in autoimmunity, by stimulating B and T cells. Various cytokines IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-14, TNF-α and IFN-γ are found in thyroid follicular cells which enhance inflammatory response with nitric oxide (NO) and prostaglandins. PMID:26221205

  10. Celiac anti-type 2 transglutaminase antibodies induce phosphoproteome modification in intestinal epithelial Caco-2 cells.

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    Gaetana Paolella

    Full Text Available BACKGROUND: Celiac disease is an inflammatory condition of the small intestine that affects genetically predisposed individuals after dietary wheat gliadin ingestion. Type 2-transglutaminase (TG2 activity seems to be responsible for a strong autoimmune response in celiac disease, TG2 being the main autoantigen. Several studies support the concept that celiac anti-TG2 antibodies may contribute to disease pathogenesis. Our recent findings on the ability of anti-TG2 antibodies to induce a rapid intracellular mobilization of calcium ions, as well as extracellular signal-regulated kinase phosphorylation, suggest that they potentially act as signaling molecules. In line with this concept, we have investigated whether anti-TG2 antibodies can induce phosphoproteome modification in an intestinal epithelial cell line. METHODS AND PRINCIPAL FINDINGS: We studied phosphoproteome modification in Caco-2 cells treated with recombinant celiac anti-TG2 antibodies. We performed a two-dimensional electrophoresis followed by specific staining of phosphoproteins and mass spectrometry analysis of differentially phosphorylated proteins. Of 14 identified proteins (excluding two uncharacterized proteins, three were hypophosphorylated and nine were hyperphosphorylated. Bioinformatics analyses confirmed the presence of phosphorylation sites in all the identified proteins and highlighted their involvement in several fundamental biological processes, such as cell cycle progression, cell stress response, cytoskeletal organization and apoptosis. CONCLUSIONS: Identification of differentially phosphorylated proteins downstream of TG2-antibody stimulation suggests that in Caco-2 cells these antibodies perturb cell homeostasis by behaving as signaling molecules. We hypothesize that anti-TG2 autoantibodies may destabilize the integrity of the intestinal mucosa in celiac individuals, thus contributing to celiac disease establishment and progression. Since several proteins here

  11. Respuesta autoinmune sistémica en pacientes con aterosclerosis coronaria Autoimmunity, antinuclear antibodies, coronary heart disease, atherosclerosis

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    Flor de la C. Heres Álvarez

    2005-04-01

    Full Text Available Se ha sugerido la existencia de un papel de la autoinmunidad en la aterosclerosis. Se realizó este trabajo para determinar si una respuesta autoinmune sistémica, caracterizada por la presencia de anticuerpos antinucleares (ANA, factor reumatoideo (FR y alteraciones de las inmunoglobulinas séricas (Igs está asociada con la aterosclerosis coronaria. Se estudió el suero de 2 grupos de pacientes; 41 sujetos con al menos 50 % de estenosis en las 3 arterias coronarias principales (EAC y 26 sujetos sin evidencia de lesiones coronarias (NEAC determinada mediante angiografía coronaria. Se determinaron los ANA mediante inmunofluorescencia en secciones criostáticas de hígado de rata; el FR por fijación en látex y la cuantificación de IgG, IgA e IgM por inmunoturbidimetría. Se halló que la frecuencia de autoanticuerpos detectados en el grupo EAC resultó muy similar a la del grupo NEAC (ANA: 17 % vs. 15 %, p = 0,856; FR: 7 % vs. 4 %, p = 0,559. Se comprobó que las diferencias de los valores promedio de las inmunoglobulinas séricas entre ambos grupos de pacientes no fueron estadísticamente significativas (IgG: 12,4 g/L vs. 13,0 g/L; IgA: 3,6 g/L vs. 3,6 g/L; IgM: 1,2 g/L vs. 1,4 g/L; p = 0,328, p = 0,946, p = 0.157, respectivamente.Se concluyó que según los resultados, la presencia de ANA, FR y concentraciones anormales de Igs séricas carecen de utilidad para identificar sujetos con aterosclerosis avanzada.It has been suggested that autoimmunity plays a role in atherosclerosis. The aim of this paper was to determine wether a systemic autoimmune response, characterized by the presence of antinuclear antibodies (ANA, rheumatoid factor (RF and alterations of serum immunglobulins (Igs, is associated with coronary atherosclerosis. The serum of 2 groups of patients was studied; 41 subjects with at least 50 % of stenosis in the 3 main coronary arteries (SCA and 26 subjects with no evidence of coronary injuries (NECI determined by coronary

  12. Anti-asialo GM1 antibodies prevents guanethidine-induced sympathectomy in athymic rats

    DEFF Research Database (Denmark)

    Thygesen, P; Hougen, H P; Christensen, H B; Rygaard, J; Svendsen, O; Juul, P

    Guanethidine sulphate induces destruction of peripheral sympathetic neurons and infiltration of mononuclear cells in rat sympathetic ganglia. The effect of guanethidine is believed to be an autoimmune reaction. In order to determine the effect of anti-asialo GM1, an antibody that binds to the...... glycolipid asialo GM1 expressed on rodent natural killer cells, athymic Lewis rats received guanethidine 40 mg/kg i.p. daily from day 1 to 14 and anti-asialo GM1 i.p. 1 mg/rat on day -2, 0, 2, 6, and 10 in the study period. Saline and anti-asialo GM1 were given alone in the same doses as control. The number...... of neurons in the sympathetic ganglia were counted and the ganglionic volume determined. The presence of natural killer cells in the ganglia were determined by immunohistochemical methods. Our results shows that anti-asialo GM1 can prevent guanethidine-induced reduction of sympathetic neurons, but...

  13. Aberrant O-glycosylation and anti-glycan antibodies in an autoimmune disease IgA nephropathy and breast adenocarcinoma

    DEFF Research Database (Denmark)

    Stuchlová Horynová, Milada; Raška, Milan; Clausen, Henrik;

    2013-01-01

    Glycosylation abnormalities have been observed in autoimmune diseases and cancer. Here, we compare mechanisms of aberrant O-glycosylation, i.e., formation of Tn and sialyl-Tn structures, on MUC1 in breast cancer, and on IgA1 in an autoimmune disease, IgA nephropathy. The pathways of aberrant O...

  14. Blockade of Extracellular ATP Effect by Oxidized ATP Effectively Mitigated Induced Mouse Experimental Autoimmune Uveitis (EAU)

    Science.gov (United States)

    Zhao, Ronglan; Liang, Dongchun; Sun, Deming

    2016-01-01

    Various pathological conditions are accompanied by ATP release from the intracellular to the extracellular compartment. Extracellular ATP (eATP) functions as a signaling molecule by activating purinergic P2 purine receptors. The key P2 receptor involved in inflammation was identified as P2X7R. Recent studies have shown that P2X7R signaling is required to trigger the Th1/Th17 immune response, and oxidized ATP (oxATP) effectively blocks P2X7R activation. In this study we investigated the effect of oxATP on mouse experimental autoimmune uveitis (EAU). Our results demonstrated that induced EAU in B6 mice was almost completely abolished by the administration of small doses of oxATP, and the Th17 response, but not the Th1 response, was significantly weakened in the treated mice. Mechanistic studies showed that the therapeutic effects involve the functional change of a number of immune cells, including dendritic cells (DCs), T cells, and regulatory T cells. OxATP not only directly inhibits the T cell response; it also suppresses T cell activation by altering the function of DCs and Foxp3+ T cell. Our results demonstrated that inhibition of P2X7R activation effectively exempts excessive autoimmune inflammation, which may indicate a possible therapeutic use in the treatment of autoimmune diseases. PMID:27196432

  15. Induced autoimmunity against gonadal proteins affects gonadal development in juvenile zebrafish.

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    Christopher Presslauer

    Full Text Available A method to mitigate or possibly eliminate reproduction in farmed fish is highly demanded. The existing approaches have certain applicative limitations. So far, no immunization strategies affecting gonadal development in juvenile animals have been developed. We hypothesized that autoimmune mechanisms, occurring spontaneously in a number of diseases, could be induced by targeted immunization. We have asked whether the immunization against specific targets in a juvenile zebrafish gonad will produce an autoimmune response, and, consequently, disturbance in gonadal development. Gonadal soma-derived factor (Gsdf, growth differentiation factor (Gdf9, and lymphocyte antigen 75 (Cd205/Ly75, all essential for early gonad development, were targeted with 5 immunization tests. Zebrafish (n = 329 were injected at 6 weeks post fertilization, a booster injection was applied 15 days later, and fish were sampled at 30 days. We localized transcripts encoding targeted proteins by in situ hybridization, quantified expression of immune-, apoptosis-, and gonad-related genes with quantitative real-time PCR, and performed gonadal histology and whole-mount immunohistochemistry for Bcl2-interacting-killer (Bik pro-apoptotic protein. The treatments resulted in an autoimmune reaction, gonad developmental retardation, intensive apoptosis, cell atresia, and disturbed transcript production. Testes were remarkably underdeveloped after anti-Gsdf treatments. Anti-Gdf9 treatments promoted apoptosis in testes and abnormal development of ovaries. Anti-Cd205 treatment stimulated a strong immune response in both sexes, resulting in oocyte atresia and strong apoptosis in supporting somatic cells. The effect of immunization was FSH-independent. Furthermore, immunization against germ cell proteins disturbed somatic supporting cell development. This is the first report to demonstrate that targeted autoimmunity can disturb gonadal development in a juvenile fish. It shows a

  16. Induced Autoimmunity against Gonadal Proteins Affects Gonadal Development in Juvenile Zebrafish

    Science.gov (United States)

    Presslauer, Christopher; Nagasawa, Kazue; Dahle, Dalia; Babiak, Joanna; Fernandes, Jorge M. O.; Babiak, Igor

    2014-01-01

    A method to mitigate or possibly eliminate reproduction in farmed fish is highly demanded. The existing approaches have certain applicative limitations. So far, no immunization strategies affecting gonadal development in juvenile animals have been developed. We hypothesized that autoimmune mechanisms, occurring spontaneously in a number of diseases, could be induced by targeted immunization. We have asked whether the immunization against specific targets in a juvenile zebrafish gonad will produce an autoimmune response, and, consequently, disturbance in gonadal development. Gonadal soma-derived factor (Gsdf), growth differentiation factor (Gdf9), and lymphocyte antigen 75 (Cd205/Ly75), all essential for early gonad development, were targeted with 5 immunization tests. Zebrafish (n = 329) were injected at 6 weeks post fertilization, a booster injection was applied 15 days later, and fish were sampled at 30 days. We localized transcripts encoding targeted proteins by in situ hybridization, quantified expression of immune-, apoptosis-, and gonad-related genes with quantitative real-time PCR, and performed gonadal histology and whole-mount immunohistochemistry for Bcl2-interacting-killer (Bik) pro-apoptotic protein. The treatments resulted in an autoimmune reaction, gonad developmental retardation, intensive apoptosis, cell atresia, and disturbed transcript production. Testes were remarkably underdeveloped after anti-Gsdf treatments. Anti-Gdf9 treatments promoted apoptosis in testes and abnormal development of ovaries. Anti-Cd205 treatment stimulated a strong immune response in both sexes, resulting in oocyte atresia and strong apoptosis in supporting somatic cells. The effect of immunization was FSH-independent. Furthermore, immunization against germ cell proteins disturbed somatic supporting cell development. This is the first report to demonstrate that targeted autoimmunity can disturb gonadal development in a juvenile fish. It shows a straightforward potential

  17. Oxidative and nitrosative stress in trichloroethene-mediated autoimmune response

    International Nuclear Information System (INIS)

    Reactive oxygen and nitrogen species (RONS) are implicated in the pathogenesis of several autoimmune diseases. Also, increased lipid peroxidation and protein nitration are reported in systemic autoimmune diseases. Lipid peroxidation-derived aldehydes (LPDAs) such as malondialdehyde (MDA) and 4-hydroxynonenal (HNE) are highly reactive and bind proteins covalently, but their potential to elicit an autoimmune response and contribution to disease pathogenesis remain unclear. Similarly, nitration of protein could also contribute to disease pathogenesis. To assess the status of lipid peroxidation and/or RONS, autoimmune-prone female MRL+/+ mice (5-week old) were treated with trichloroethene (TCE), an environmental contaminant known to induce autoimmune response, for 48 weeks (0.5 mg/ml via drinking water), and formation of antibodies to LPDA-protein adducts was followed in the sera of control and TCE-treated mice. TCE treatment led to greater formation of both anti-MDA- and -HNE-protein adduct antibodies and higher serum iNOS and nitrotyrosine levels. The increase in TCE-induced oxidative stress was associated with increases in anti-nuclear-, anti-ssDNA- and anti-dsDNA-antibodies. These findings suggest that TCE exposure not only leads to oxidative/nitrosative stress, but is also associated with induction/exacerbation of autoimmune response in MRL+/+ mice. Further interventional studies are needed to establish a causal role of RONS in TCE-mediated autoimmunity

  18. [Autoimmune Associated Encephalitis and Dementia].

    Science.gov (United States)

    Watanabe, Osamu

    2016-04-01

    Antibodies against various neural surface antigens induce cognitive impairments. Anti-VGKC (voltage gated potassium channel) complex antibodies are well known as one of the causative autoantibodies. An anti-VGKC antibody was identified as the autoantibody in acquired neuromyotonia (Isaacs' syndrome), which causes muscle cramps and difficulty in opening the palm of the hands. However, this antibody also tests positive in autoimmune limbic encephalitis, which has a subacute progress and causes poor memory or epilepsy attacks. Typical cases have a distinctive adult-onset, frequent, brief dystonic seizure semiology that predominantly affects the arms and ipsilateral face. It has now been termed faciobrachial dystonic seizures. In recent years, the true target antigens of the anti-VGKC antibody of this VGKC limbic encephalitis have been recognized as leucine rich glioma inactivated protein (LGI)-1 and others. These antibodies to amnesia-related LGI-1 in limbic encephalitis neutralize the LGI-1-ADAM22 (an anchor protein) interaction and reduce synaptic AMPA receptors. There have been reports of limbic encephalitis associated with anti-VGKC complex antibodies mimicking Creutzfeldt-Jakob disease (CJD). Less than 2% of the patients with sporadic CJD (sCJD) develop serum anti-VGKC complex antibodies and, when positive, only at low titres. Low titres of these antibodies occur only rarely in suspected patients with sCJD, and when present, should be interpreted with caution. PMID:27056852

  19. Time-Dependent Progression of Demyelination and Axonal Pathology in MP4-Induced Experimental Autoimmune Encephalomyelitis.

    Directory of Open Access Journals (Sweden)

    Johanna Prinz

    Full Text Available Multiple sclerosis (MS is an autoimmune disease of the central nervous system (CNS characterized by inflammation, demyelination and axonal pathology. Myelin basic protein/proteolipid protein (MBP-PLP fusion protein MP4 is capable of inducing chronic experimental autoimmune encephalomyelitis (EAE in susceptible mouse strains mirroring diverse histopathological and immunological hallmarks of MS. Lack of human tissue underscores the importance of animal models to study the pathology of MS.Twenty-two female C57BL/6 (B6 mice were immunized with MP4 and the clinical development of experimental autoimmune encephalomyelitis (EAE was observed. Methylene blue-stained semi-thin and ultra-thin sections of the lumbar spinal cord were assessed at the peak of acute EAE, three months (chronic EAE and six months after onset of EAE (long-term EAE. The extent of lesional area and inflammation were analyzed in semi-thin sections on a light microscopic level. The magnitude of demyelination and axonal damage were determined using electron microscopy. Emphasis was put on the ventrolateral tract (VLT of the spinal cord.B6 mice demonstrated increasing demyelination and severe axonal pathology in the course of MP4-induced EAE. Additionally, mitochondrial swelling and a decrease in the nearest neighbor neurofilament distance (NNND as early signs of axonal damage were evident with the onset of EAE. In semi-thin sections we observed the maximum of lesional area in the chronic state of EAE while inflammation was found to a similar extent in acute and chronic EAE. In contrast to the well-established myelin oligodendrocyte glycoprotein (MOG model, disease stages of MP4-induced EAE could not be distinguished by assessing the extent of parenchymal edema or the grade of inflammation.Our results complement our previous ultrastructural studies of B6 EAE models and suggest that B6 mice immunized with different antigens constitute useful instruments to study the diverse

  20. Nuclear antigen expression by ultraviolet light irradiation - a contribution to the UV-induced autoimmunity

    International Nuclear Information System (INIS)

    A review is given about nuclear antigen expression due to UVB, UVA, and PUVA. UVB alters DNA resulting in strong immunogenic UVDNA and complementary antibodies. Antibodies to UVDNA cross react with double-stranded DNA. UVDNA plays a (hypothetical) role in the induction of cutaneous lesions in lupus erythematosus (LE). Investigations about SS-A/Ro expression due to UVB seem to be more important under this view. Antibodies against SS-A/Ro are related to an increased photosensitivity in LE. PUVA and UVA are able to induce antinuclear antibodies of unknown specificity. It is likely that PUVA enhances SS-A/Ro expression in vitro. The results are discussed in sense of LE photobiology and unwanted side effects of photo(chemo)therapy in psoriasis. (author)

  1. Coombs-negative Autoimmune Hemolytic Anemia Followed by Anti-erythropoetin Receptor Antibody-associated Pure Red Cell Aplasia: A Case Report and Review of Literature.

    Science.gov (United States)

    Yoshimi, Mayumi; Kadowaki, Yutaka; Kikuchi, Yuji; Takahashi, Tsuyoshi

    2016-01-01

    A 76-year-old woman was referred to our hospital because of anemia. The laboratory findings revealed hemolysis. Although a direct Coombs test was negative, a high titer of RBC-bound IgG was detected, and a diagnosis of Coombs-negative autoimmune hemolytic anemia was made. She was successfully treated with prednisolone. One year and five months later, she again presented anemia and was diagnosed with pure red cell aplasia. Anti-erythropoietin receptor antibody was detected in the serum. She was treated with cyclosporine and obtained prompt recovery. We herein report this rare case and review the pertinent literature. PMID:26935373

  2. Importance of the dense fine speckled pattern on HEp-2 cells and anti-DFS70 antibodies for the diagnosis of systemic autoimmune diseases.

    Science.gov (United States)

    Mahler, Michael; Hanly, John G; Fritzler, Marvin J

    2012-07-01

    The presence of anti-nuclear antibodies (ANA) is a hallmark of systemic autoimmune rheumatic diseases (SARD). The indirect immunofluorescence (IIF) assay on HEp-2 cells is a commonly used test for the detection of ANA and was recently recommended as the screening test of choice by a task force of the American College of Rheumatology. However, up to 20% of serum samples from healthy individuals (HI) have been reported to have a positive ANA test, the majority of which are directed to the dense fine speckles 70 (DFS70) antigen. Even more important, the DFS IIF pattern has been reported in 33% of ANA positive HI, but not in ANA positive SARD sera. Since the intended use of the ANA HEp-2 test is to aid in the diagnosis of SARD, the reporting of anti-DFS70 antibodies and their associated pattern (DFS) as a positive test, significantly reduces the specificity and the positive likelihood of the ANA test. This has significant implications for diagnostic algorithms involving the detection of ANA. We summarize the current knowledge of anti-DFS70 antibodies and their impact on ANA testing. We also suggest a test algorithm which considers the DFS pattern and the presence of anti-DFS70 antibodies. In addition, we describe a novel method based on immunoadsorption of anti-DFS70 antibodies, which increases the specificity of the ANA HEp-2 test for SARD and which has the potential to overcome a significant limitation of the ANA HEp-2 assay. PMID:22100330

  3. Measurement of anti-DFS70 antibodies in patients with ANA-associated autoimmune rheumatic diseases suspicion is cost-effective.

    Science.gov (United States)

    Gundín, Simón; Irure-Ventura, Juan; Asensio, Esther; Ramos, David; Mahler, Michael; Martínez-Taboada, Victor; López-Hoyos, Marcos

    2016-12-01

    The presence of antinuclear antibodies (ANA) is associated with a wide range of ANA-associated autoimmune rheumatic diseases (AARD). The most commonly method used for the detection of ANA is indirect immunofluorescence (IIF) on HEp-2 cells. This method is very sensitive but unspecific. As a consequence, ANA testing on HEp-2 substrates outside a proper clinical specialist framework may lead to inappropriate referrals to tertiary care specialists and, worst case inappropriate and potentially toxic therapy for the patient. Among ANA, isolated anti-DFS70 antibodies represent a potentially important biomarker that can be clinically used to discriminate AARD from non-AARD patients in ANA IIF positive individuals. Therefore, their presence may avoid unnecessary follow-up testing and referrals. In our study, we investigated if the implementation of a new ANA workup algorithm allowing for the identification of anti-DFS70 antibodies is cost-effective through the reduction of both unnecessary follow-up testing and outpatient clinic visits generated by the clinical suspicion of a potential AARD. None of the 181 patients included with a positive monospecific anti-DFS70 antibody result developed SARD during the follow-up period of 10 years. The reduction in number of tests after ANA and anti-DFS70 positive results was significant for anti-ENA (230 vs. 114 tests; p < 0.001) and anti-dsDNA antibodies (448 vs. 114 tests; p < 0.001). In addition, the outpatient clinic visits decreased by 70 % (p < 0.001). In total, the adoption of the new algorithm including anti-DFS70 antibody testing resulted in a cost saving of 60869.53 € for this pilot study. In conclusion, the use of anti-DFS70 antibodies was clearly cost-efficient in our setting. PMID:27473142

  4. A Tandem Repeat in Decay Accelerating Factor 1 Is Associated with Severity of Murine Mercury-Induced Autoimmunity

    Directory of Open Access Journals (Sweden)

    David M. Cauvi

    2014-01-01

    Full Text Available Decay accelerating factor (DAF, a complement-regulatory protein, protects cells from bystander complement-mediated lysis and negatively regulates T cells. Reduced expression of DAF occurs in several systemic autoimmune diseases including systemic lupus erythematosus, and DAF deficiency exacerbates disease in several autoimmune models, including murine mercury-induced autoimmunity (mHgIA. Daf1, located within Hmr1, a chromosome 1 locus associated in DBA/2 mice with resistance to mHgIA, could be a candidate. Here we show that reduced Daf1 transcription in lupus-prone mice was not associated with a reduction in the Daf1 transcription factor SP1. Studies of NZB mice congenic for the mHgIA-resistant DBA/2 Hmr1 locus suggested that Daf1 expression was controlled by the host genome and not the Hmr1 locus. A unique pentanucleotide repeat variant in the second intron of Daf1 in DBA/2 mice was identified and shown in F2 intercrosses to be associated with less severe disease; however, analysis of Hmr1 congenics indicated that this most likely reflected the presence of autoimmunity-predisposing genetic variants within the Hmr1 locus or that Daf1 expression is mediated by the tandem repeat in epistasis with other genetic variants present in autoimmune-prone mice. These studies argue that the effect of DAF on autoimmunity is complex and may require multiple genetic elements.

  5. Long-Term Follow-Up of a Child with Autoimmune Thyroiditis and Recurrent Hyperthyroidism in the Absence of TSH Receptor Antibodies

    Directory of Open Access Journals (Sweden)

    Christopher Dunne

    2014-01-01

    Full Text Available Hashitoxicosis is an initial, transient, hyperthyroid phase that rarely affects patients with Hashimoto thyroiditis. We present here an unusual case of a child with Hashimoto thyroiditis and recurrent hyperthyroidism. A 4 yr 6/12 old male was diagnosed by us with autoimmune subclinical hypothyroidism (normal free T4, slightly elevated TSH, and elevated TG antibody titer. Two years and 6/12 later he experienced increased appetite and poor weight gain; a laboratory evaluation revealed suppressed TSH, elevated free T4, and normal TSI titer. In addition, an I123 thyroid uptake was borderline-low. A month later, the free T4 had normalized. After remaining asymptomatic for 3 years, the patient presented again with increased appetite, and he was found with low TSH and high free T4. Within the following 3 months, his free T4 and TSH normalized. At his most recent evaluation, his TSH was normal and the free T4 was borderline-high; the TG antibody titer was still elevated and the TSI titer was negative. To our knowledge, this is the first patient reported with Hashimoto thyroiditis and recurrent hyperthyroidism. This case exemplifies the variability of the manifestations and natural history of Hashimoto thyroiditis and supports the need for a long-term evaluation of patients with autoimmune thyroid disease.

  6. [Antibody therapy for Alzheimer's disease].

    Science.gov (United States)

    Tabira, Takeshi; Matsumoto, Shin-Ei; Jin, Haifeng

    2011-11-01

    In order to avoid Abeta-induced autoimmune encephalitis, several monoclonal and polyclonal antibodies are in clinical trials. These are bapineuzumab, solanezumab, ponezumab, gantenerumab, BAN2401, gammaguard and octagam. Since each antibody has a different antigen epitope of Abeta, anti-amyloid activities are different. It is unknown which antibody is effective for Alzheimer disease, and we must wait for the result of clinical trials. Some patients who developed tissue amyloid plaque immuno-reactive (TAPIR) antibody showed slower decline after AN-1792 vaccination. We developed TAPIR-like monoclonal antibody, which was found to react with Abeta oligomers preferentially. PMID:22277519

  7. Autoimmune hepatitis type 2 associated with an unexpected and transient presence of primary biliary cirrhosis-specific antimitochondrial antibodies: a case study and review of the literature

    Directory of Open Access Journals (Sweden)

    Invernizzi Pietro

    2012-07-01

    Full Text Available Abstract Background Unlike other autoimmune liver diseases, primary biliary cirrhosis (PBC has never been reported in early childhood, while type 2 autoimmune hepatitis (AIH is eminently a paediatric disease. Case presentation We describe a case of type 2 AIH with serological positivity for PBC-specific anti-mitochondrial antibodies (AMA in a 3-year old girl. We found this observation intriguing as AMA and indeed an overlap with PBC are virtually absent in Type 2 AIH, a pediatric form of AIH which is distinct precisely because it is characterized by pathognomonic anti-liver kidney microsomal type 1 (LKM-1 showing a remarkable antigen-specificity directed against cytochrome P4502D6. We also review the literature in relation to AMA positivity in paediatric age and adolescence. In our case, the presence of AIH-2-specific anti-LKM-1 and PBC-specific AMA was confirmed by indirect immunofluorescence (IIF, and immunoblotting and ELISA based on recombinant mitochondrial antigens. The clinical, laboratory and histological features of the child are given in detail. Interestingly the mother was AMA positive without other features of PBC. The child was successfully treated with immunosuppression and five years after the original diagnosis is on a low dose of prednisolone and azathioprine, with no signs of relapse. Anti-LKM-1 antibodies are still present in low titres. AMA were detectable for the first 4 years after the diagnosis and disappeared later. Conclusion This is the first case report in the literature of AIH type 2 with an unexpected PBC-specific AMA positivity in a young child. Response to immunosuppressive treatment was satisfactory and similar to that described in AIH. A review of published reports on AMA positivity in paediatric age shows that the antibody may arise in the context of immunodeficiency and is variably associated with liver damage.

  8. A rare presentation of hypopituitarism in hepatic overlap syndrome of autoimmune hepatitis and autoimmune cholangitis

    OpenAIRE

    Gupta V; Singh H.; Talapatra P; Ray S

    2016-01-01

    Autoimmune cholangitis is the antimitochondrial antibody-negative autoimmune hepatopathy with clinical and histological features similar to that of primary biliary cirrhosis. Autoimmune cholangitis has a predominant cholestatic phase. However, transaminasemia might be dominant in certain patients, indicating associated autoimmune hepatitis. Such an autoimmune hepatopathy has been termed as hepatic overlap syndrome. Due to the autoimmune nature of the disease, associated diseases of other orga...

  9. ROCK2 signaling is required to induce a subset of T follicular helper cells through opposing effects on STATs in autoimmune settings.

    Science.gov (United States)

    Weiss, Jonathan M; Chen, Wei; Nyuydzefe, Melanie S; Trzeciak, Alissa; Flynn, Ryan; Tonra, James R; Marusic, Suzana; Blazar, Bruce R; Waksal, Samuel D; Zanin-Zhorov, Alexandra

    2016-01-01

    Rho-associated kinase 2 (ROCK2) determines the balance between human T helper 17 (TH17) cells and regulatory T (Treg) cells. We investigated its role in the generation of T follicular helper (TFH) cells, which help to generate antibody-producing B cells under normal and autoimmune conditions. Inhibiting ROCK2 in normal human T cells or peripheral blood mononuclear cells from patients with active systemic lupus erythematosus (SLE) decreased the number and function of TFH cells induced by activation ex vivo. Moreover, inhibition of ROCK2 activity decreased the abundance of the transcriptional regulator Bcl6 (B cell lymphoma 6) and increased that of Blimp1 by reducing the binding of signal transducer and activator of transcription 3 (STAT3) and increasing that of STAT5 to the promoters of the genes Bcl6 and PRDM1, respectively. In the MRL/lpr murine model of SLE, oral administration of the selective ROCK2 inhibitor KD025 resulted in a twofold reduction in the numbers of TFH cells and antibody-producing plasma cells in the spleen, as well as a decrease in the size of splenic germinal centers, which are the sites of interaction between TFH cells and B cells. KD025-treated mice showed a substantial improvement in both histological and clinical scores compared to those of untreated mice and had reduced amounts of Bcl6 and phosphorylated STAT3, as well as increased STAT5 phosphorylation. Together, these data suggest that ROCK2 signaling plays a critical role in controlling the development of TFH cells induced by autoimmune conditions through reciprocal regulation of STAT3 and STAT5 activation. PMID:27436361

  10. Low incidence of positive smooth muscle antibody and high incidence of isolated IgM elevation in Chinese patients with autoimmune hepatitis and primary biliary cirrhosis overlap syndrome: a retrospective study

    Directory of Open Access Journals (Sweden)

    Zhao Pan

    2012-01-01

    Full Text Available Background Up to now, few data are available regarding the clinical characteristics of autoimmune hepatitis and primary biliary cirrhosis overlap syndrome. The study was to investigate and analyze the prevalent and clinical features of Chinese patients with this disease. Methods Clinical data on patients diagnosed as autoimmune hepatitis and primary biliary cirrhosis overlap syndrome in our hospital from January 2001 to December 2006 were collected and analyzed. Results Overlap syndrome of autoimmune hepatitis and primary biliary cirrhosis accounted for 10.33% of patients with autoimmune liver diseases during the past six years. For these patients with overlap syndrome, xanthochromia, lethargy and anorexia were the predominant complaints; a low incidence (14/146 of smooth muscle antibody positivity and a high incidence (37/89 of isolated IgM elevation were the main serological characteristics. Conclusions Overlap syndrome of autoimmune hepatitis and primary biliary cirrhosis was not rare in Chinese patients with clinical manifests of autoimmune liver diseases. Overlap of the diseases should not be disregarded when isolated IgM elevation was exhibited, and smooth muscle antibody might have little diagnostic significance in the overlap syndrome. If it was difficult to make a definite diagnosis, liver biopsy was necessary.

  11. Synthetic. cap alpha. subunit peptide 125-147 of human nicotinic acetylcholine receptor induces antibodies to native receptor

    Energy Technology Data Exchange (ETDEWEB)

    McCormick, D.J.; Griesmann, G.E.; Huang, Z.; Lennon, V.A.

    1986-03-05

    A synthetic peptide corresponding to residues 125-147 of the Torpedo acetylcholine receptor (AChR) ..cap alpha.. subunit proved to be a major antigenic region of the AChR. Rats inoculated with 50 ..mu..g of peptide (T ..cap alpha.. 125-147) developed T cell immunity and antibodies to native AChR and signs of experimental autoimmune myasthenia gravis. They report the synthesis and preliminary testing of a disulfide-looped peptide comprising residues 125-147 of the human AChR ..cap alpha.. subunit. Peptide H ..cap alpha.. 125-147 differs from T ..cap alpha.. 125-147 at residues 139 (Glu for Gln) and 143 (Ser for Thr). In immunoprecipitation assays, antibodies to Torpedo AChR bound /sup 125/I-labelled H..cap alpha.. 125-147 antibody bound H..cap alpha.. 125-147, but monoclonal antibodies to an immunodominant region of native AChR bound neither H..cap alpha.. 125-147 nor T ..cap alpha.. 125-147. Rats immunized with H ..cap alpha.. 125-147 produced anti-mammalian muscle AChR antibodies that induced modulation of AChRs from cultured human myotubes. Thus, region 125-147 of the human AChR ..cap alpha.. subunit is extracellular in muscle, and is both antigenic and immunogenic. It remains to be determined whether or not autoantibodies to this region may in part cause the weakness or myasthenia gravis in man.

  12. Preparation of monoclonal antibodies against radiation-induced protein

    International Nuclear Information System (INIS)

    We obtained the 6 monoclonal antibodies against gamma-induced proteins of Deinococcus radiodurans, and these antibodies were designated as Mab-3F, 4B, 4D, 4F, 4G and 12G. Using these antibodies, we investigated the relations between gamma-induced proteins and other stress protein in strain R1, and the induction of proteins were compared among strain R1, resistant mutant (rec1) and radiosensitive mutant (rec30). We found new 6 proteins recognized by these monoclonal antibodies which were induced after gamma-irradiation especially in strain R1 and rec 1, but not induced in strain rec30. We suppose that these proteins participate in repair of DNA damages including double strand breaks caused by gamma-irradiation. One of them was around 46kDa protein band recognized by Mab-12G, and this protein was so induced in a large quantity after irradiation that the protein could detect by gold staining. In addition to this observation, we found some proteins which were induced in R1 and rec 1 by gamma-irradiation and other stress, but not in strain rec30, such as 31kDa protein band recognized by Mab-3F, 4B and 4G, and other 11 proteins which were especially induced in irradiated strain R1. The latter proteins might be reinforcement factor to radioresistance such as GroE and DnaK, or participant in repair of damage by gamma-irradiation in strain R1. (author)

  13. Anticuerpos anti 21 hidroxilasa séricos en pacientes con anticuerpos antifracción microsomal: Síndrome poliendocrino autoinmune Seric 21- hydroxilase antibodies in patients with anti-microsomal fraction antibodies: Autoimmune polyendocrine syndrome

    Directory of Open Access Journals (Sweden)

    Silvia Botta

    2007-04-01

    these are induced by autoantibodies. Alopecia, vitiligo, myasthenia and other manifestations can be minor components. We sought to establish the prevalence of seric a21-OH in patients with positive anti-microsomal fraction autoantibodies, autoimmune thyroid disease and/or non-endocrine autoimmune diseases. We also aimed to diagnose incomplete forms of APS and to follow up patients at risk of progression to complete forms of APS. A population of 72 patients and another of 60 controls with negative anti-microsomal fraction autoantibodies were studied. Elevated seric a21-OH were found in two patients. Patient A with 47 U/ml had autoimmune hypothyroidism and myasthenia; and patient B with 8.75 U/ml had autoimmune hypothyrodism and vitiligo; they both lacked adrenal insufficiency. Seric a21-OH had a prevalence of 2.8%. Regarding the adrenal component, patients A and B had an incomplete and latent APS type 2. Considering a21-OH as markers of latent endocrine autoimmune diseases and taking into account the eventual risk of developing clinical manifestations, periodic biochemical and clinical follow-ups are recommended.

  14. Mouse Models of Multiple Sclerosis: Experimental Autoimmune Encephalomyelitis and Theiler’s Virus-Induced Demyelinating Disease

    OpenAIRE

    McCarthy, Derrick P.; Richards, Maureen H.; Miller, Stephen D.

    2012-01-01

    Experimental autoimmune encephalomyelitis (EAE) and Theiler’s Murine Encephalitis Virus-Induced Demyelinating Disease (TMEV-IDD) are two clinically relevant murine models of multiple sclerosis (MS). Like MS, both are characterized by mononuclear cell infiltration into the CNS and demyelination. EAE is induced by either the administration of myelin protein or peptide in adjuvant or by the adoptive transfer of encephalitogenic T cell blasts into naïve recipients. The relative merits of each of ...

  15. Treatment with anti-interferon-gamma monoclonal antibodies modifies experimental autoimmune encephalomyelitis in interferon-gamma receptor knockout mice

    DEFF Research Database (Denmark)

    Espejo, C; Penkowa, M; Sáez-Torres, I;

    2001-01-01

    The role of interferon-gamma (IFN-gamma) in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) is still controversial. We have studied the function of IFN-gamma and its receptor in the EAE model using two different IFN-gamma receptor knockout (IFN-gamma R......(-/-)) mouse types: C57Bl/6x129Sv, with a disruption of the IFN-gamma receptor cytoplasmic domain, and 129Sv, homozygous for a disrupted IFN-gamma receptor gene. Mice were immunized with peptide 40-55 from rat myelin oligodendrocyte glycoprotein. A subgroup of mice was treated with anti-IFN-gamma monoclonal...

  16. Role of antiviral antibodies in resistance against coxsackievirus B3 infection: interaction between preexisting antibodies and an interferon inducer.

    OpenAIRE

    Cho, C T; Feng, K. K.; McCarthy, V P; Lenahan, M F

    1982-01-01

    An experimental model of coxsackievirus B3 infection in newborn mice was utilized to examine the protective role of antiviral antibodies and an interferon inducer, polyinosinic acid-polycytidylic acid [poly(I:C)]. Subcutaneous administration to the infected mice of specific antiviral antibodies resulted in significant protection against coxsackievirus B3 infection. Antibody-treated animals had shortened viremia, early clearance of virus from tissues, and a reduced mortality rate. Dose respons...

  17. DIABETOGENIC T CELLS INDUCE AUTOIMMUNE DIABETES IN BALB/c MICE

    Institute of Scientific and Technical Information of China (English)

    Xiao-lei Zou; Zeng-yu Zhao; Yun-yang Wang; Zhi-qiang Su; Ming Xiang

    2008-01-01

    Objective To investigate the role of T cell and its subsets in the induction of insulitis and type 1 diabetes meilitus(T1DM) in BALB/c mice.Methods Autoimmune diabetes mellitus was developed by intraperitoneal injection of 40 mg/kg streptozotocin(STZ) daily for 5 consecutive days in BALB/c mice as sources of donor cells. Spleen cells from diabetic mice were then cultured for 7 days in the stimulation of interleukin-2 ( IL-2 ) to harvest diabetogenic T cells, which were subsequently transferred into normal BALB/c mice recipients. MTr, ELISA, and HE staining were used to analyze the lymphocyte proliferation, cytokine (IL-2, interferon-γ, IL-4, and IL-10) levels, and pathological changes in pancreatic islets.Results As few as 3 × 106 diabetogenic T cells successfully induced diabetes meilitus in recipients pretreated with STZ twice, whereas transfer of equal amount of normal splenocytes, T cell-depleted diabetogenie splenocytes, or diabetogenic CD4+ T cells alone in recipients receiving STZ twice pretreatment was proved not to induce diabetes mellitus either. A markedly increased lymphocyte proliferation, high levels of interferon-γ and IL-2 in the supematants of diabetogenie T cells were observed. In addition, a markedly enhanced lymphocyte proliferation, a high level of interferon-γ secretion in serum, and numerous lymphocytes infiltration in pancreatic islets were detected in the diabetic mice induced by diabetogenic T cells transfer.Conclusions A novel T1DM murine model is established in STZ-pretreated BALB/c mice by adoptive transfer of diabetogenic T cells. CD4M+ T cells with interferon-γ may promote the onset of diabetes mellitus.

  18. Enhanced expression of constitutive and inducible forms of nitric oxide synthase in autoimmune encephalomyelitis.

    Science.gov (United States)

    Kim, S; Moon, C; Wie, M B; Kim, H; Tanuma, N; Matsumoto, Y; Shin, T

    2000-06-01

    To elucidate the role of nitric oxide synthase (NOS) in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), we analyzed the expression of constitutive neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS) in the spinal cords of rats with EAE. We further examined the structural interaction between apoptotic cells and spinal cord cells including neurons and astrocytes, which are potent cell types of nitric oxide (NO) production in the brain. Western blot analysis showed that three forms of NOS significantly increased in the spinal cords of rats at the peak stage of EAE, while small amounts of these enzymes were identified in the spinal cords of rats without EAE. Immunohistochemical study showed that the expression of either nNOS or eNOS increased in the brain cells including neurons and astrocytes during the peak and recovery stages of EAE, while the expression of iNOS was found mainly in the inflammatory macrophages in the perivascular EAE lesions. Double labeling showed that apoptotic cells had intimate contacts with either neurons or astrocytes, which are major cell types to express nNOS and eNOS constitutively. Our results suggest that the three NOS may play an important role in the recovery of EAE. PMID:14612615

  19. Suppression of inflammatory responses during MOG-induced experimental autoimmune encephalomyelitis is regulated by AKT3 signaling

    OpenAIRE

    Tsiperson, Vladislav; Gruber, Ross C; Goldberg, Michael; Jordan, Ayana; Weinger, Jason G.; Macian, Fernando; Shafit-Zagardo, Bridget

    2013-01-01

    AKT3, a member of the serine/threonine kinase AKT family, is involved in a variety of biological processes. AKT3 is expressed in immune cells, and is the major AKT isoform in the CNS representing 30% of the total AKT expressed in spinal cord, and 50% in the brain. Myelin-oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) is a mouse model in which lymphocytes and monocytes enter the CNS, resulting in inflammation, demyelination, and axonal injury. We hyp...

  20. Gene Expression in the Spinal Cord in Female Lewis Rats with Experimental Autoimmune Encephalomyelitis Induced with Myelin Basic Protein

    OpenAIRE

    Inglis, Hayley R.; Judith M. Greer; Pamela A. McCombe

    2012-01-01

    Background Experimental autoimmune encephalomyelitis (EAE), the best available model of multiple sclerosis, can be induced in different animal strains using immunization with central nervous system antigens. EAE is associated with inflammation and demyelination of the nervous system. Micro-array can be used to investigate gene expression and biological pathways that are altered during disease. There are few studies of the changes in gene expression in EAE, and these have mostly been done in a...

  1. The innate immune response affects the development of the autoimmune response in Theiler’s virus- induced demyelinating disease

    OpenAIRE

    Olson, Julie K.; Miller, Stephen D.

    2009-01-01

    Multiple sclerosis (MS) is a human CNS autoimmune demyelinating disease. Epidemiological evidence has suggested a role for virus infection in the initiation and/or exacerbation of MS. Theiler’s murine encephalomyelitis virus (TMEV)- induced demyelinating disease serves as a relevant mouse model for MS. TMEV- infected mice develop a demyelinating disease with clinical symptoms beginning around 35 days post infection which is associated with development of myelin- specific, PLP139–151, CD4+ T c...

  2. Antibody

    Science.gov (United States)

    An antibody is a protein produced by the body's immune system when it detects harmful substances, called antigens. Examples ... microorganisms (bacteria, fungi, parasites, and viruses) and chemicals. Antibodies may be produced when the immune system mistakenly ...

  3. Psychotic and nonpsychotic mood disorders in autoimmune encephalitis: diagnostic issues and research implications

    OpenAIRE

    Giuseppe Quaranta; Nunzio Bucci; Cristina Toni; Giulio Perugi

    2015-01-01

    Recent research on autoimmune disorders suggests additional links between systemic and central nervous system (CNS) pathophysiology, among which the identification of antibody-induced limbic encephalitis provided the strongest evidence for the potential involvement of autoimmunity in the pathogenesis of severe mood and psychotic symptoms. In these illnesses, psychiatric symptoms predominate in the initial phase of the disorder in up to 70% of the cases, and they often lead patients to early p...

  4. Suppression of proteoglycan-induced autoimmune arthritis by myeloid-derived suppressor cells generated in vitro from murine bone marrow.

    Directory of Open Access Journals (Sweden)

    Júlia Kurkó

    Full Text Available Myeloid-derived suppressor cells (MDSCs are innate immune cells capable of suppressing T-cell responses. We previously reported the presence of MDSCs with a granulocytic phenotype in the synovial fluid (SF of mice with proteoglycan (PG-induced arthritis (PGIA, a T cell-dependent autoimmune model of rheumatoid arthritis (RA. However, the limited amount of SF-MDSCs precluded investigations into their therapeutic potential. The goals of this study were to develop an in vitro method for generating MDSCs similar to those found in SF and to reveal the therapeutic effect of such cells in PGIA.Murine bone marrow (BM cells were cultured for 3 days in the presence of granulocyte macrophage colony-stimulating factor (GM-CSF, interleukin-6 (IL-6, and granulocyte colony-stimulating factor (G-CSF. The phenotype of cultured cells was analyzed using flow cytometry, microscopy, and biochemical methods. The suppressor activity of BM-MDSCs was tested upon co-culture with activated T cells. To investigate the therapeutic potential of BM-MDSCs, the cells were injected into SCID mice at the early stage of adoptively transferred PGIA, and their effects on the clinical course of arthritis and PG-specific immune responses were determined.BM cells cultured in the presence of GM-CSF, IL-6, and G-CSF became enriched in MDSC-like cells that showed greater phenotypic heterogeneity than MDSCs present in SF. BM-MDSCs profoundly inhibited both antigen-specific and polyclonal T-cell proliferation primarily via production of nitric oxide. Injection of BM-MDSCs into mice with PGIA ameliorated arthritis and reduced PG-specific T-cell responses and serum antibody levels.Our in vitro enrichment strategy provides a SF-like, but controlled microenvironment for converting BM myeloid precursors into MDSCs that potently suppress both T-cell responses and the progression of arthritis in a mouse model of RA. Our results also suggest that enrichment of BM in MDSCs could improve the

  5. Measuring and evaluating interferon beta-induced antibodies in patients with multiple sclerosis

    DEFF Research Database (Denmark)

    Ross, C; Clemmesen, K M; Sørensen, P S;

    2006-01-01

    Administration of interferons (IFNs) may induce antibodies that interfere with therapeutic efficacy. We have optimized and validated methods for large-scale economic screening. Sera from patients with relapsing-remitting multiple sclerosis (MS) were investigated for binding antibody (BAb) by prot......Administration of interferons (IFNs) may induce antibodies that interfere with therapeutic efficacy. We have optimized and validated methods for large-scale economic screening. Sera from patients with relapsing-remitting multiple sclerosis (MS) were investigated for binding antibody (BAb...

  6. Development of Autoimmune Overt Hypothyroidism Is Highly Associated With Live Births and Induced Abortions but Only in Premenopausal Women

    DEFF Research Database (Denmark)

    Carle, Allan; Pedersen, Inge Buelow; Knudsen, Nils;

    2014-01-01

    . Design, Setting, and Subjects: In a population study, we included Danish women with new autoimmune overt hypothyroidism not diagnosed within the first year after a pregnancy (n = 117; median age 53.0 y) and age-andregion-matched euthyroid controls from the same population (n = 468). Main Outcome Measures......: In conditional multivariate logistic regression models, we analyzed the associations between the development of autoimmune hypothyroidism and age at menarche/menopause, years of menstruations, pregnancies, spontaneous and induced abortions, live births, and years on oral contraceptives and...... postmenopausal hormone replacement therapy, also taking various possible confounders into account. Results: In multivariate regression models with no event as reference, the odds ratios (ORs) for hypothyroidism [95% confidence interval (CI)] after one/two/three or more live births were 1.72 (0.56-5.32)/3.12 (1...

  7. Invariant Natural Killer T (iNKT Cells Prevent Autoimmunity, but Induce Pulmonary Inflammation in Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    Nanna Siegmann

    2014-06-01

    Full Text Available Background/Aims: Inflammation is a major and critical component of the lung pathology in the hereditary disease cystic fibrosis. The molecular mechanisms of chronic inflammation in cystic fibrosis require definition. Methods: We used several genetic mouse models to test a role of iNKT cells and ceramide in pulmonary inflammation of cystic fibrosis mice. Inflammation was determined by the pulmonary cytokine profil and the abundance of inflammatory cells in the lung. Results: Here we provide a new concept how inflammation in the lung of individuals with cystic fibrosis is initiated. We show that in cystic fibrosis mice the mutation in the Cftr gene provokes a significant up-regulation of iNKT cells in the lung. Accumulation of iNKT cells serves to control autoimmune disease, which is triggered by a ceramide-mediated induction of cell death in CF organs. Autoimmunity becomes in particular overt in cystic fibrosis mice lacking iNKT cells and although suppression of the autoimmune response by iNKT cells is beneficial, IL-17+ iNKT cells attract macrophages and neutrophils to CF lungs resulting in chronic inflammation. Genetic deletion of iNKT cells in cystic fibrosis mice prevents inflammation in CF lungs. Conclusion: Our data demonstrate an important function of iNKT cells in the chronic inflammation affecting cystic fibrosis lungs. iNKT cells suppress the auto-immune response induced by ceramide-mediated death of epithelial cells in CF lungs, but also induce a chronic pulmonary inflammation.

  8. Generation and characterization of integration-free induced pluripotent stem cells from patients with autoimmune disease

    Science.gov (United States)

    Son, Mi-Young; Lee, Mi-Ok; Jeon, Hyejin; Seol, Binna; Kim, Jung Hwa; Chang, Jae-Suk; Cho, Yee Sook

    2016-01-01

    Autoimmune diseases (AIDs), a heterogeneous group of immune-mediated disorders, are a major and growing health problem. Although AIDs are currently treated primarily with anti-inflammatory and immunosuppressive drugs, the use of stem cell transplantation in patients with AIDs is becoming increasingly common. However, stem cell transplantation therapy has limitations, including a shortage of available stem cells and immune rejection of cells from nonautologous sources. Induced pluripotent stem cell (iPSC) technology, which allows the generation of patient-specific pluripotent stem cells, could offer an alternative source for clinical applications of stem cell therapies in AID patients. We used nonintegrating oriP/EBNA-1-based episomal vectors to reprogram dermal fibroblasts from patients with AIDs such as ankylosing spondylitis (AS), Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE). The pluripotency and multilineage differentiation capacity of each patient-specific iPSC line was validated. The safety of these iPSCs for use in stem cell transplantation is indicated by the fact that all AID-specific iPSCs are integrated transgene free. Finally, all AID-specific iPSCs derived in this study could be differentiated into cells of hematopoietic and mesenchymal lineages in vitro as shown by flow cytometric analysis and induction of terminal differentiation potential. Our results demonstrate the successful generation of integration-free iPSCs from patients with AS, SS and SLE. These findings support the possibility of using iPSC technology in autologous and allogeneic cell replacement therapy for various AIDs, including AS, SS and SLE. PMID:27174201

  9. Presumed Isotretinoin-Induced, Concomitant Autoimmune Thyroid Disease and Ocular Myasthenia Gravis: A Case Report

    Directory of Open Access Journals (Sweden)

    Huseyin Gursoy

    2012-11-01

    Full Text Available Introduction: There are many adverse effects that have been described for isotretinoin. To the best of our knowledge, this is the first report of a possible association of oral isotretinoin intake with autoimmune thyroiditis and ocular myasthenia gravis (OMG. Case Presentation: A 19-year-old Caucasian male, who had used oral isotretinoin for severe acne disease for the previous six months, was referred to our clinic. He had a three-week history of diplopia and variable bilateral ptosis. Physical examination showed moderate periorbital edema and limitations of up- and down-gaze in the left eye. Laboratory findings and thyroid ultrasound were consistent with autoimmune thyroiditis. Antithyroid therapy did not relieve the clinical symptoms. Concomitant OMG was suspected. Variable ptosis and a positive response to oral prednisolone of 40 mg/day and pyridostigmine of 360 mg/day supported the diagnosis of concomitant autoimmune thyroiditis and OMG. Conclusion: Autoimmune disorders may be triggered by oral isotretinoin treatment. Clinicians prescribing isotretinoin should be aware of the possible association between isotretinoin intake and concomitant autoimmune thyroiditis and OMG.

  10. Autoimmune Hepatitis

    Science.gov (United States)

    ... diagnosed? A health care provider will make a diagnosis of autoimmune hepatitis based on symptoms, a physical exam, blood tests, ... 2. A health care provider will make a diagnosis of autoimmune hepatitis based on symptoms, a physical exam, blood tests, ...

  11. Resistance to Streptozotocin-Induced Autoimmune Diabetes in Absence of Complement C3: Myeloid-Derived Suppressor Cells Play a Role

    OpenAIRE

    Gao, Xiaogang; Liu, Huanhai; He, Bin; Fu, Zhiren

    2013-01-01

    The contribution of complement to the development of autoimmune diabetes has been proposed recently. The underlying mechanisms, however, remain poorly understood. We hypothesize that myeloid-derived suppressor cells (MDSC), which act as regulators in autoimmunity, play a role in resistance to diabetes in absence of complement C3. Indeed, MDSC number was increased significantly in STZ-treated C3−/− mice. These cells highly expressed arginase I and inducible nitric oxide synthase (iNOS). Import...

  12. [Current protease-antibody-based serodiagnostic tools and their use in the diagnosis of autoimmune thyroid diseases].

    Science.gov (United States)

    Isaeva, M A; Bogatyreva, Z I; Andreeva, A; Suchkova, E N; Korotkova, A A; Baĭsugurov, M A; Ivanova, E V; Notkins, A; Vinnitskiĭ, L I; Pal'tsev, M A; Suchkov, S V

    2010-04-01

    The purpose of the investigation was to comparatively study the possible clinicodiagnostic and clinicoprognostic value of thyroglobulin (TG) autoantibodies (anti-TG autoAB) and thyroid peroxidase (TPO) (anti-TPO autoAB) with proteolytic activity (protease-AB) and to develop additional clinicoimmunological criteria for working out a protease-AB-based laboratory serodiagnosis protocol. Sera from 240 patients with autoimmune thyroiditis (AIT), 124 with diffuse toxic goiter (DTG), and 172 with other thyroid diseases were studied. Serum from 40 clinically healthy donors served as a control. Sera were screened for anti-TG and anti-TPO autoAB by enzyme immunoassay and/or radioimmunoassay. Nonspecific proteolytic activity was determined, by incubating a highly purified AB IgG-isotype solution with nonspecific substrate (such as BSA-FITS or thyoredoxine/Trx), followed by the measurement of relative fluorescence shifts at a wavelength of 470 nm. The blood samples taken from patients with AIT or DTG and the highly purified anti-TG or anti-TRO autoAB of IgG isotype were incubated with appropriate human substrates to determine AG-specific proteolytic activity. Proteolysis products were detected by PAAG electrophoresis. An association was found between the rise in the frequency of protease AB, their catalytic activity, a tendency toward autoAB between themselves, and the degree of thyroid tissue degradation in AIT and DTG; some specific features of a serological pattern were noted in diferent dorms of AIT and DTG. For example, the prevailing autoABs have been shown to be TG-specific in AIT and TPO-specific proteases in DTG; also, the detectable catalytic activity of both autoAB in AIT is an order of magnitude higher than that in DTG. No protease ABs have been recorded in other forms of thyroid diseases in which antithyroid autoABs are also frequently detected. The screening procedure for protease AB may be considered as a highly sensitive and specific indicator test in the

  13. Autoimmune pancreatitis

    Directory of Open Access Journals (Sweden)

    Bo-Guang Fan

    2009-01-01

    Full Text Available Since the autoimmune pancreatitis was introduced in 1995, it has been recognized as a form of chronic pancreatitis, which is always associated with autoimmune manifestations. As the improvement of technical and instrumental made in ultrasonography, computed tomography and magnetic resonance imaging, the diagnoses of autoimmune pancreatitis is no longer such difficult. Even though the treatment of autoimmune pancreatitis is available with a conservative therapy, there are many points that are still unclearly. These have stimulated widespread interest in this disease from gastroenterologists, endoscopists, pathologists, and prevalent research. The present article provides with our better understanding of the diagnosis and treatment of autoimmune pancreatitis.

  14. Autoimmune pancreatitis

    Directory of Open Access Journals (Sweden)

    Bo-Guang Fan

    2009-09-01

    Full Text Available Since the autoimmune pancreatitis was introduced in 1995, it has been recognized as a form of chronic pancreatitis, which is always associated with autoimmune manifestations. As the improvement of technical and instrumental made in ultrasonography, computed tomography and magnetic resonance imaging, the diagnoses of autoimmune pancreatitis is no longer such difficult. Even though the treatment of autoimmune pancreatitis is available with a conservative therapy, there are many points that are still unclearly. These have stimulated widespread interest in this disease from gastroenterologists, endoscopists, pathologists, and prevalent research. The present article provides with our better understanding of the diagnosis and treatment of autoimmune pancreatitis.

  15. Autoimmunity in Addison's disease.

    Science.gov (United States)

    Martín Martorell, P; Roep, B O; Smit, J W A; Martorell, P M

    2002-08-01

    Addison's disease has a low incidence and is most frequently the result of an autoimmune disease in developed countries. Addison's disease can present as an isolated entity or in combination with other autoimmune diseases: Addison's disease can be part of the distinct polyglandular autoimmune syndromes APS I and II. Autoantibodies in patients with isolated Addison's disease are directed against the enzymes involved in steroid synthesis, P45oc21, P45oscc and P45oc17. Addison's disease, both isolated and in the context of APS II, has been associated with the haplotype HLA-A1, -B8 and DR3. The value of the increased expression of these molecules on adrenocortical cells could point towards an infectious pathogenesis. Given the prevalence, up to 80 %, of autoantibodies in Addison's disease as well as the high predictive value for developing the disease when antibodies are present (41% in three years), we advise screening high-risk populations, such as patients with other autoimmune endocrinopathies or their relatives for the presence of these antibodies. The adrenocortical function of patients positive for antibodies should be followed yearly. PMID:12430572

  16. Intrapatient Dose Escalation of Anti–CTLA-4 Antibody in Patients With Metastatic Melanoma

    OpenAIRE

    Maker, Ajay V; Yang, James C.; Sherry, Richard M.; Topalian, Suzanne L.; Kammula, Udai S; Royal, Richard E.; Hughes, Marybeth; Yellin, Michael J.; Haworth, Leah R.; Levy, Catherine; Allen, Tamika; Mavroukakis, Sharon A.; Attia, Peter; Rosenberg, Steven A.

    2006-01-01

    We previously reported our experience in treating 56 patients with metastatic melanoma using a human anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibody. Durable tumor regressions were seen that correlated with the induction of autoimmune toxicities. In this study, we treated 46 additional patients using an intrapatient dose escalation schema to test whether higher doses of anti–CTLA-4 antibody would induce increased autoimmunity and concomitant tumor regression. Twenty-three patients sta...

  17. Autoimmunity in visual loss.

    Science.gov (United States)

    Petzold, Axel; Wong, Sui; Plant, Gordon T

    2016-01-01

    There are a number of autoimmune disorders which can affect visual function. There are a very large number of mechanisms in the visual pathway which could potentially be the targets of autoimmune attack. In practice it is the retina and the anterior visual pathway (optic nerve and chiasm) that are recognised as being affected in autoimmune disorders. Multiple Sclerosis is one of the commonest causes of visual loss in young adults because of the frequency of attacks of optic neuritis in that condition, however the basis of the inflammation in Multiple Sclerosis and the confirmation of autoimmunity is lacking. The immune process is known to be highly unusual in that it is not systemic and confined to the CNS compartment. Previously an enigmatic partner to Multiple Sclerosis, Neuromyelitis Optica is now established to be autoimmune and two antibodies - to Aquaporin4 and to Myelin Oligodendrocyte Glycoprotein - have been implicated in the pathogenesis. The term Chronic Relapsing Inflammatory Optic Neuropathy is applied to those cases of optic neuritis which require long term immunosuppression and hence are presumed to be autoimmune but where no autoimmune pathogenesis has been confirmed. Optic neuritis occurring post-infection and post vaccination and conditions such as Systemic Lupus Erythematosus and various vasculitides may cause direct autoimmune attack to visual structures or indirect damage through occlusive vasculopathy. Chronic granulomatous disorders such as Sarcoidosis affect vision commonly by a variety of mechanisms, whether and how these are placed in the autoimmune panoply is unknown. As far as the retina is concerned Cancer Associated Retinopathy and Melanoma Associated Retinopathy are well characterised clinically but a candidate autoantibody (recoverin) is only described in the former disorder. Other, usually monophasic, focal retinal inflammatory disorders (Idiopathic Big Blind Spot Syndrome, Acute Zonal Occult Outer Retinopathy and Acute Macular

  18. Persistence of Antibodies Induced by Measles-Mumps-Rubella Vaccine in Children in India

    OpenAIRE

    S. K. Raut; Mr. P.S. Kulkarni; Phadke, M. A.; S. S Jadhav; Kapre, S. V.; Dhere, R. M.; Dhorje, S. P.; Godse, S. R.

    2008-01-01

    Antibody levels in 41 Indian girls were measured 6 years after measles-mumps-rubella (MMR) vaccination. Rates of seropositivity were 88% (measles antibodies), 95% (mumps antibodies), and 100% (rubella antibodies). The MMR vaccine induces long-term immunity in a majority of vaccinees; however, due to the observation of some seronegative vaccinees, the policy of administering a second dose of the MMR vaccine seems appropriate.

  19. Murine autoimmune oophoritis, epididymoorchitis, and gastritis induced by day 3 thymectomy. Autoantibodies.

    Science.gov (United States)

    Tung, K. S.; Smith, S.; Matzner, P.; Kasai, K.; Oliver, J.; Feuchter, F.; Anderson, R. E.

    1987-01-01

    In adult mice thymectomized at age 3 days (D3TX), increased incidences and/or levels of organ-specific antibodies to oocytes and/or zona pellucida, to testicular cell-sperm-differentiation antigens (TSDA), and to gastric parietal cells were detected, and these correlated significantly with oophoritis, orchitis (not epididymovasitis), and gastritis, respectively. The autoantibodies occurred in mice with the corresponding endogenous antigens. Thus, anti-oocyte/zona antibodies were detected in female, anti-TSDA antibodies in male, and anti-parietal cell antibodies in both sexes. Anti-oocyte/zona antibodies were first detected at age 5-6 weeks and were absent by 25 weeks. Serum antizona antibodies, but not anti-oocyte antibodies, inhibited mouse fertilization in vitro. In contrast, antibodies to sperm acrosome and antibodies to sperm surface did not correlate with testicular or epididymal disease. Moreover, both male and female mice had increased levels of anti-sperm surface antibodies, indicating that the sperm antigens detected may not be organ-specific. In addition, sera from 5-10% of D3TX mice reacted with a wide spectrum of epididymal and testicular antigens with defined cellular locations but of yet unknown specificity. Although the incidence of antibodies to cytoskeletal antigens was not significantly elevated after D3TX, anti-nuclear antibodies were more frequently detected in (SWR/J X A/J) F1 (SWRAF1) and (C57 BL/6J X A/J) F1 (B6AF1) mice after D3TX. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:3826296

  20. The role of autoimmunity in premature ovarian failure

    Directory of Open Access Journals (Sweden)

    Mahbod Ebrahimi

    2015-08-01

    Full Text Available Premature ovarian failure (POF is a heterogeneous syndrome with several causative factors. Autoimmune mechanisms are involved in pathogenesis of 4-30 % of POF cases. The present review focuses on the role of autoimmunity in the pathophysiology of POF. The evidences for an autoimmune etiology are: demonstration of ovarian autoantibodies, the presence of lymphocytic oophoritis, and association with other autoimmune disorders. Several ovarian antigenic targets have been identified in POF patients. The oocyte seems to be the most often targeted cell. Lymphocytic oophoritis is widely present in POF associated adrenal insufficiency. Addisonۥs disease is one of the most common autoimmune disorders associated with POF. Early detection of this potentially life threatening disease was recommended in several studies. The gold standard for detecting autoimmune POF is ovarian biopsy. This procedure is not recommended due to unknown clinical value, expense, and risks. Several immunoassays have been proposed as substitute diagnostic tools. Nevertheless, there is no clinically proven sensitive and specific serum test to confirm the diagnosis of autoimmune POF or to anticipate the patient’s chance of developing POF or associated diseases. Some authors suggested the possible effects of immuno-modulating therapy on the resumption of ovarian function and fertility in a selected group of autoimmune POF patients. However, in most instances, this treatment fails to reverse the course of the disease. Numerous studies illustrated that standard treatment outcome for infertility is less effective in the presence of ovarian autoimmunity. The antibody-induced damage could be a pathogenic factor. Nevertheless, the precise cause remains obscure.

  1. [Autoimmune hepatitis and overlap syndrome: therapy].

    Science.gov (United States)

    Löhr, H F

    2002-08-21

    Autoimmune Hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) represent acute and chronic inflammatory liver diseases in which immune reactions against host antigens are found to be the major pathological mechanism. Only for AIH there is evidence of an autoimmune etiology and humoral and cellular immune reactions are found directed against various liver cell antigens. By diverse autoantibodies several subgroups of autoimmune hepatitis can be distinguished. A very important disease promoting factor seems to be the genetically determined background for autoimmunity characterized by the HLA haplotype A1, B8 and DR3, respectively DR4. Although the histopathology of AIH shows no pathognomonic features distinguishing this type of hepatitis from virus induced chronic hepatitis there are some distinct characteristic morphological lesions. If untreated the prognosis of AIH is unfavourable but the benefit from immunosuppressive therapy with prednisolone and azathioprin is well established. In the last years there was increasing evidence for an overlap syndrome between AIH and PBC and rarely AIH and PSC. These patients are characterized by PBC characteristic bileduct lesions and oftenly antimitochondrial antibodies (AMA). They also show AIH typical inflammatory hepatic lesions in the periportal areas and portal tracts and oftenly the typical genetical background, the HLA haplotype A1, B8, DR3 or DR4. Most of these patients respond probably to a combination therapy containing prednisolon, azathioprine and ursodesoxycholic acid that leads to the reduction of the inflammatory activity. PMID:12233265

  2. N-Acetylcysteine protects against trichloroethene-mediated autoimmunity by attenuating oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Gangduo; Wang, Jianling; Ma, Huaxian; Ansari, G.A.S.; Khan, M. Firoze, E-mail: mfkhan@utmb.edu

    2013-11-15

    Exposure to trichloroethene (TCE), a ubiquitous environmental contaminant, is known to induce autoimmunity both in humans and animal models. However, mechanisms underlying TCE-mediated autoimmunity remain largely unknown. Previous studies from our laboratory in MRL +/+ mice suggest that oxidative stress may contribute to TCE-induced autoimmune response. The current study was undertaken to further assess the role of oxidative stress in TCE-induced autoimmunity by supplementing with an antioxidant N-acetylcysteine (NAC). Groups of female MRL +/+ mice were given TCE, NAC or TCE + NAC for 6 weeks (TCE, 10 mmol/kg, i.p., every 4th day; NAC, 250 mg/kg/day through drinking water). TCE exposure led to significant increases in serum levels of anti-nuclear, anti-dsDNA and anti-Sm antibodies. TCE exposure also led to significant induction of anti-malondiadelhyde (MDA)- and anti-hydroxynonenal (HNE)-protein adduct antibodies which were associated with increased ANA in the sera along with increased MDA-/HNE-protein adducts in the livers and kidneys, and increases in protein oxidation (carbonylation) in the sera, livers and kidneys, suggesting an overall increase in oxidative stress. Moreover, TCE exposure also resulted in increased release of IL-17 from splenocytes and increases in IL-17 mRNA expression. Remarkably, NAC supplementation attenuated not only the TCE-induced oxidative stress, IL-17 release and mRNA expression, but also the markers of autoimmunity, as evident from decreased levels of ANA, anti-dsDNA and anti-Sm antibodies in the sera. These results provide further support to a role of oxidative stress in TCE-induced autoimmune response. Attenuation of TCE-induced autoimmunity in mice by NAC provides an approach for preventive and/or therapeutic strategies. - Highlights: • TCE led to increased autoantibodies, supporting its potential to induce autoimmunity. • TCE exposure led to increases in lipid perioxidation and protein carbonyls. • TCE exposure resulted in

  3. Silica, Silicosis, and Autoimmunity.

    Science.gov (United States)

    Pollard, Kenneth Michael

    2016-01-01

    Inhalation of dust containing crystalline silica is associated with a number of acute and chronic diseases including systemic autoimmune diseases. Evidence for the link with autoimmune disease comes from epidemiological studies linking occupational exposure to crystalline silica dust with the systemic autoimmune diseases systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Although little is known regarding the mechanism by which silica exposure leads to systemic autoimmune disease, there is a voluminous literature on silica exposure and silicosis that may help identify immune processes that precede development of autoimmunity. The pathophysiology of silicosis consists of deposition of silica particles in the alveoli of the lung. Ingestion of these particles by macrophages initiates an inflammatory response, which stimulates fibroblasts to proliferate and produce collagen. Silica particles are encased by collagen leading to fibrosis and the nodular lesions characteristic of the disease. The steps in the development of silicosis, including acute and chronic inflammation and fibrosis, have different molecular and cellular requirements, suggesting that silica-induced inflammation and fibrosis may be mechanistically separate. Significantly, it is unclear whether silica-induced inflammation and fibrosis contribute similarly to the development of autoimmunity. Nonetheless, the findings from human and animal model studies are consistent with an autoimmune pathogenesis that begins with activation of the innate immune system leading to proinflammatory cytokine production, pulmonary inflammation leading to activation of adaptive immunity, breaking of tolerance, and autoantibodies and tissue damage. The variable frequency of these immunological features following silica exposure suggests substantial genetic involvement and gene/environment interaction in silica-induced autoimmunity. However, numerous questions remain unanswered. PMID:27014276

  4. Silica, Silicosis and Autoimmunity.

    Directory of Open Access Journals (Sweden)

    Kenneth Michael Pollard

    2016-03-01

    Full Text Available Inhalation of dust containing crystalline silica is associated with a number of acute and chronic diseases including systemic autoimmune diseases. Evidence for the link with autoimmune disease comes from epidemiological studies linking occupational exposure to crystalline silica dust with the systemic autoimmune diseases SLE, SSc and RA. Although little is known regarding the mechanism by which silica exposure leads to systemic autoimmune disease, there is a voluminous literature on silica exposure and silicosis that may help identify immune processes that precede development of autoimmunity. The pathophysiology of silicosis consists of deposition of silica particles in the alveoli of the lung. Ingestion of these particles by macrophages initiates an inflammatory response which stimulates fibroblasts to proliferate and produce collagen. Silica particles are encased by collagen leading to fibrosis and the nodular lesions characteristic of the disease. The steps in the development of silicosis, including acute and chronic inflammation and fibrosis, have different molecular and cellular requirements suggesting that silica-induced inflammation and fibrosis may be mechanistically separate. Significantly, it is unclear whether silica-induced inflammation and fibrosis contribute similarly to the development of autoimmunity. Nonetheless, the findings from human and animal model studies are consistent with an autoimmune pathogenesis that begins with activation of the innate immune system leading to proinflammatory cytokine production, pulmonary inflammation leading to activation of adaptive immunity, breaking of tolerance, autoantibodies and tissue damage. The variable frequency of these immunological features following silica exposure suggests substantial genetic involvement and gene/environment interaction in silica-induced autoimmunity. However numerous questions remain unanswered.

  5. Antigen-specific tolerance induced by IL-10 gene modified immature dendritic cells in experimental autoimmune myocarditis in rats

    Institute of Scientific and Technical Information of China (English)

    LI Wei-min; LI Yue; LIU Wei; GAO Cheng; ZHOU Bao-guo; YANG Shu-sen; WANG Zheng; ZHANG Rui-hong; GAN Run-tao; KONG Yi-hui

    2006-01-01

    Background Experimental autoimmune myocarditis (EAM) in rats is a T-cell-mediated disorder. The initiation and maintenance of autoimmune responses in EAM depend on the maturation state of dendritic cells. IL-10 is a pleiotrophic immunomodulatory cytokine that functions at different levels of the immune response, so it has emerged as a promising therapeutic factor for the treatment of autoimmune/inflammatory diseases. This study was designed to test the hypothesis that IL-10 gene modified bone marrow-derived immature dendritic cells (iDCs) ameliorate EAM and to explore the underlying mechanisms.Methods EAM was induced using the methods of cardiac myosin immunization on day 0 and day 7. Immature and mature bone marrow-derived dendritic cells (BMDCs) were generated without or with the stimulation by lipopolysaccharide (LPS) and the phenotype was analyzed by flow cytometry. Some of the iDCs were transfected by pcDNA3-IL-10 plasmid. 2 × 106/per rat mature DC (mDC), immature DC (iDC), pcDNA3 transfected iDC,pcDNA3-IL-10 transfected iDC or phosphate buffered saline (PBS) were injected intravenously for treatment 5 days after the first immunization. On day 21, HE staining was performed to detect the myocardial inflammation and T lymphocyte proliferation assay was used to determine the effects of IL-10 gene transfected iDC on autoreactive T cell proliferation. Expression of IκB, the inhibitor of NF-κB pathway, was determined by Western blot. Results BMDCs generated in a medium supplemented with granulocyte-macrophage-colony-stimulating factor (GM-CSF) were relatively immature, as determined by flow cytometry. However, stimulation with LPS induced these cells to become mature (m)DCs with higher levels of surface major histocompatibility complex (MHC)-Ⅱ and costimulatory molecules. Intravenous administration of iDCs, especially pcDNA3-IL-10 transfected iDC,ameliorated the histopathological severity of the myosin induced-EAM, and the effect was lost after the DCs

  6. Specific antibodies induce apoptosis in Trypanosoma cruzi epimastigotes.

    Science.gov (United States)

    Fernández-Presas, Ana María; Tato, Patricia; Becker, Ingeborg; Solano, Sandra; Copitin, Natalia; Kopitin, Natalia; Berzunza, Miriam; Willms, Kaethe; Hernández, Joselin; Molinari, José Luis

    2010-05-01

    The susceptibility of Trypanosoma cruzi epimastigotes to lysis by normal or immune sera in a complement-dependent reaction has been reported. Mouse immune sera depleted complement-induced damage in epimastigotes characterized by morphological changes and death. The purpose of this work was to study the mechanism of death in epimastigotes exposed to decomplemented mouse immune serum. Epimastigotes were maintained in RPMI medium. Immune sera were prepared in mice by immunization with whole crude epimastigote extracts. Viable epimastigotes were incubated with decomplemented normal or immune sera at 37 degrees C. By electron microscopy, agglutinated parasites showed characteristic patterns of membrane fusion between two or more parasites; this fusion also produced interdigitation of the subpellicular microtubules. Apoptosis was determined by flow cytometry using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and annexin V assays. Nuclear features were examined by 4'-,6-diamidino-2'-phenylindole diHCI cytochemistry that demonstrated apoptotic nuclear condensation. Caspase activity was also measured. TUNEL results showed that parasites incubated with decomplemented immune sera took up 26% of specific fluorescence as compared to 1.3% in parasites incubated with decomplemented normal sera. The Annexin-V-Fluos staining kit revealed that epimastigotes incubated with decomplemented immune sera exposed phosphatidylserine on the external leaflet of the plasma membrane. The incubation of parasites with immune sera showed caspase 3 activity. We conclude that specific antibodies are able to induce agglutination and apoptosis in epimastigotes, although the pathway is not elucidated. PMID:20237802

  7. Autoimmunity and Asbestos Exposure

    Directory of Open Access Journals (Sweden)

    Jean C. Pfau

    2014-01-01

    Full Text Available Despite a body of evidence supporting an association between asbestos exposure and autoantibodies indicative of systemic autoimmunity, such as antinuclear antibodies (ANA, a strong epidemiological link has never been made to specific autoimmune diseases. This is in contrast with another silicate dust, crystalline silica, for which there is considerable evidence linking exposure to diseases such as systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Instead, the asbestos literature is heavily focused on cancer, including mesothelioma and pulmonary carcinoma. Possible contributing factors to the absence of a stronger epidemiological association between asbestos and autoimmune disease include (a a lack of statistical power due to relatively small or diffuse exposure cohorts, (b exposure misclassification, (c latency of clinical disease, (d mild or subclinical entities that remain undetected or masked by other pathologies, or (e effects that are specific to certain fiber types, so that analyses on mixed exposures do not reach statistical significance. This review summarizes epidemiological, animal model, and in vitro data related to asbestos exposures and autoimmunity. These combined data help build toward a better understanding of the fiber-associated factors contributing to immune dysfunction that may raise the risk of autoimmunity and the possible contribution to asbestos-related pulmonary disease.

  8. Nitrosative stress and nitrated proteins in trichloroethene-mediated autoimmunity.

    Directory of Open Access Journals (Sweden)

    Gangduo Wang

    Full Text Available Exposure to trichloroethene (TCE, a ubiquitous environmental contaminant, has been linked to a variety of autoimmune diseases (ADs including SLE, scleroderma and hepatitis. Mechanisms involved in the pathogenesis of ADs are largely unknown. Earlier studies from our laboratory in MRL+/+ mice suggested the contribution of oxidative/nitrosative stress in TCE-induced autoimmunity, and N-acetylcysteine (NAC supplementation provided protection by attenuating oxidative stress. This study was undertaken to further evaluate the contribution of nitrosative stress in TCE-mediated autoimmunity and to identify proteins susceptible to nitrosative stress. Groups of female MRL +/+ mice were given TCE, NAC or TCE + NAC for 6 weeks (TCE, 10 mmol/kg, i.p., every 4th day; NAC, ∼ 250 mg/kg/day via drinking water. TCE exposure led to significant increases in serum anti-nuclear and anti-histone antibodies together with significant induction of iNOS and increased formation of nitrotyrosine (NT in sera and livers. Proteomic analysis identified 14 additional nitrated proteins in the livers of TCE-treated mice. Furthermore, TCE exposure led to decreased GSH levels and increased activation of NF-κB. Remarkably, NAC supplementation not only ameliorated TCE-induced nitrosative stress as evident from decreased iNOS, NT, nitrated proteins, NF-κB p65 activation and increased GSH levels, but also the markers of autoimmunity, as evident from decreased levels of autoantibodies in the sera. These findings provide support to the role of nitrosative stress in TCE-mediated autoimmune response and identify specific nitrated proteins which could have autoimmune potential. Attenuation of TCE-induced autoimmunity in mice by NAC provides an approach for designing therapeutic strategies.

  9. Hsp65-producing Lactococcus lactis prevents experimental autoimmune encephalomyelitis in mice by inducing CD4+LAP+ regulatory T cells.

    Science.gov (United States)

    Rezende, Rafael M; Oliveira, Rafael P; Medeiros, Samara R; Gomes-Santos, Ana C; Alves, Andrea C; Loli, Flávia G; Guimarães, Mauro A F; Amaral, Sylvia S; da Cunha, André P; Weiner, Howard L; Azevedo, Vasco; Miyoshi, Anderson; Faria, Ana M C

    2013-02-01

    Heat shock proteins (Hsps) participate in the cellular response to stress and they are hiperexpressed in inflammatory conditions. They are also known to play a major role in immune modulation, controlling, for instance, autoimmune responses. In this study, we showed that oral administration of a recombinant Lactococcus lactis strain that produces and releases LPS-free Hsp65 prevented the development of experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. This was confirmed by the reduced inflammatory cell infiltrate and absence of injury signs in the spinal cord. The effect was associated with reduced IL-17 and increased IL-10 production in mesenteric lymph node and spleen cell cultures. Hsp65-producing-L. lactis-fed mice had a remarkable increase in the number of natural and inducible CD4+Foxp3+ regulatory T (Treg) cells and CD4+LAP+ (Latency-associated peptide) Tregs - which express the membrane-bound TGF-β - in spleen, inguinal and mesenteric lymph nodes as well as in spinal cord. Moreover, many Tregs co-expressed Foxp3 and LAP. In vivo depletion of LAP+ cells abrogated the effect of Hsp65-producing L. lactis in EAE prevention and worsened disease in medium-fed mice. Thus, Hsp65-L.lactis seems to boost this critical regulatory circuit involved in controlling EAE development in mice. PMID:22939403

  10. Type 1 diabetes associated autoimmunity.

    Science.gov (United States)

    Kahaly, George J; Hansen, Martin P

    2016-07-01

    Diabetes mellitus is increasing in prevalence worldwide. The economic costs are considerable given the cardiovascular complications and co-morbidities that it may entail. Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the loss of insulin-producing pancreatic β-cells. The pathogenesis of T1D is complex and multifactorial and involves a genetic susceptibility that predisposes to abnormal immune responses in the presence of ill-defined environmental insults to the pancreatic islets. Genetic background may affect the risk for autoimmune disease and patients with T1D exhibit an increased risk of other autoimmune disorders such as autoimmune thyroid disease, Addison's disease, autoimmune gastritis, coeliac disease and vitiligo. Approximately 20%-25% of patients with T1D have thyroid antibodies, and up to 50% of such patients progress to clinical autoimmune thyroid disease. Approximately 0.5% of diabetic patients have concomitant Addison's disease and 4% have coeliac disease. The prevalence of autoimmune gastritis and pernicious anemia is 5% to 10% and 2.6% to 4%, respectively. Early detection of antibodies and latent organ-specific dysfunction is advocated to alert physicians to take appropriate action in order to prevent full-blown disease. Patients and family members should be educated to be able to recognize signs and symptoms of underlying disease. PMID:26903475

  11. Autoimmune paediatric liver disease

    Directory of Open Access Journals (Sweden)

    Giorgina Mieli-Vergani, Diego Vergani

    2008-06-01

    Full Text Available Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH, autoimmune sclerosing cholangitis (ASC, and de novo AIH after liver transplantation. AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1 or liver kidney microsomal antibody (LKM1, type 2. There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age, and commonly have partial IgA deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological, and histological presentation of ASC is often indistinguishable from that of AIH type 1. In both, there are high IgG, non-organ specific autoantibodies, and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalization of biochemical parameters, and decreased inflammatory activity on follow up liver biopsies. However, the cholangiopathy can progress. There may be evolution from AIH to ASC over the years, despite treatment. De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH, including elevated titres of serum antibodies, hypergammaglobulinaemia, and histological findings of interface hepatitis, bridging fibrosis, and collapse. Like classical AIH, it responds to treatment with prednisolone and azathioprine. De novo AIH post liver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection. Whether

  12. Autoimmune paediatric liver disease

    Institute of Scientific and Technical Information of China (English)

    Giorgina Mieli-Vergani; Diego Vergani

    2008-01-01

    Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC),and de novo AIH after liver transplantation.AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA,type 1) or liver kidney microsomal antibody (LKM1,type 2).There is a female predominance in both.LKM1 positive patients tend to present more acutely,at a younger age,and commonly have partial IgA deficiency,while duration of symptoms before diagnosis,clinical signs,family history of autoimmunity, presence of associated autoimmune disorders,response to treatment,and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC.The clinical,biochemical, immunological,and histological presentation of ASC is often indistinguishable from that of AIH type 1.In both,there are high IgG,non-organ specific autoantibodies,and interface hepatitis.Diagnosis is made by cholangiography.Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates,times to normalization of biochemical parameters, and decreased inflammatory activity on follow up liver biopsies. However,the cholangiopathy can progress.There may be evolution from AIH to ASC over the years,despite treatment.De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH,including elevated titres of serum antibodies, hypergammaglobulinaemia,and histological findings of interface hepatitis,bridging fibrosis,and collapse.Like classical AIH,it responds to treatment with prednisolone and azathioprine.De novo AIH post liver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection.Whether this condition is a distinct entity or a form of

  13. Autoimmunity in Rheumatic Diseases Is Induced by Microbial Infections via Crossreactivity or Molecular Mimicry

    Directory of Open Access Journals (Sweden)

    Taha Rashid

    2012-01-01

    Full Text Available A general consensus supports fundamental roles for both genetic and environmental, mainly microbial, factors in the development of autoimmune diseases. One form of autoimmune rheumatic diseases is confined to a group of nonpyogenic conditions which are usually preceded by or associated with either explicit or occult infections. A previous history of clinical pharyngitis, gastroenteritis/urethritis, or tick-borne skin manifestation can be obtained from patients with rheumatic fever, reactive arthritis, or Lyme disease, respectively, whilst, other rheumatic diseases like rheumatoid arthritis (RA, ankylosing spondylitis (AS, and Crohn’s disease (CD are usually lacking such an association with a noticeable microbial infection. A great amount of data supports the notion that RA is most likely caused by Proteus asymptomatic urinary tract infections, whilst AS and CD are caused by subclinical bowel infections with Klebsiella microbes. Molecular mimicry is the main pathogenetic mechanism that can explain these forms of microbe-disease associations, where the causative microbes can initiate the disease with consequent productions of antibacterial and crossreactive autoantibodies which have a great impact in the propagation and the development of these diseases.

  14. Spectrum of anti-neutrophil cytoplasmic antibodies in patients with pulmonary tuberculosis overlaps with that of Wegener′s granulomatosis

    OpenAIRE

    Pradhan Vandana; Badakere Suresh; Ghosh Kanjaksha; Pawar Aruna

    2004-01-01

    BACKGROUND AND OBJECTIVES: Mycobacterial infections are known to induce the development of autoantibodies and a few of these antibodies are also known to be diagnostic markers for some other diseases and it is uncertain whether these autoantibodies play a role in the pathogenesis of autoimmune disorders. This study was undertaken to determine the prevalence of autoantibodies like anti-neutrophil cytoplasmic antibodies (ANCA), anti-nuclear antibodies (ANA), anti-double stranded antibodies (ant...

  15. Enterocolitis induced by autoimmune targeting of enteric glial cells: A possible mechanism in Crohn's disease?

    Science.gov (United States)

    Cornet, Anne; Savidge, Tor C.; Cabarrocas, Julie; Deng, Wen-Lin; Colombel, Jean-Frederic; Lassmann, Hans; Desreumaux, Pierre; Liblau, Roland S.

    2001-11-01

    Early pathological manifestations of Crohn's disease (CD) include vascular disruption, T cell infiltration of nerve plexi, neuronal degeneration, and induction of T helper 1 cytokine responses. This study demonstrates that disruption of the enteric glial cell network in CD patients represents another early pathological feature that may be modeled after CD8+ T cell-mediated autoimmune targeting of enteric glia in double transgenic mice. Mice expressing a viral neoself antigen in astrocytes and enteric glia were crossed with specific T cell receptor transgenic mice, resulting in apoptotic depletion of enteric glia to levels comparable in CD patients. Intestinal and mesenteric T cell infiltration, vasculitis, T helper 1 cytokine production, and fulminant bowel inflammation were characteristic hallmarks of disease progression. Immune-mediated damage to enteric glia therefore may participate in the initiation and/or the progression of human inflammatory bowel disease.

  16. In vivo expression of a single viral DNA-binding protein generates systemic lupus erythematosus-related autoimmunity to double-stranded DNA and histones.

    OpenAIRE

    Moens, U; Seternes, O M; Hey, A W; Silsand, Y; Traavik, T.; Johansen, B.; Rekvig, O P

    1995-01-01

    Although the origin of autoimmune antibodies to double-stranded DNA is not known, the variable-region structures of such antibodies indicate that they are produced in response to antigen-selective stimulation. In accordance with this, results from experiments using artificial complexes of DNA and DNA-binding polypeptides for immunizations have indicated that DNA may induce these antibodies. Hence, the immunogenicity of DNA in vivo may depend upon other structures or processes that may render ...

  17. Autoimmune Diseases

    Science.gov (United States)

    ... Some examples of CAM are herbal products, chiropractic , acupuncture , and hypnosis . If you have an autoimmune disease, ... Toll-Free: 877-226-4267 National Institute of Diabetes and Digestive and Kidney Diseases, NIH, HHS Phone: ...

  18. Mercury and autoimmunity: implications for occupational and environmental health

    International Nuclear Information System (INIS)

    Mercury (Hg) has long been recognized as a neurotoxicant; however, recent work in animal models has implicated Hg as an immunotoxicant. In particular, Hg has been shown to induce autoimmune disease in susceptible animals with effects including overproduction of specific autoantibodies and pathophysiologic signs of lupus-like disease. However, these effects are only observed at high doses of Hg that are above the levels to which humans would be exposed through contaminated fish consumption. While there is presently no evidence to suggest that Hg induces frank autoimmune disease in humans, a recent epidemiological study has demonstrated a link between occupational Hg exposure and lupus. In our studies, we have tested the hypothesis that Hg does not cause autoimmune disease directly, but rather that it may interact with triggering events, such as genetic predisposition, exposure to antigens, or infection, to exacerbate disease. Treatment of mice that are not susceptible to Hg-induced autoimmune disease with very low doses and short term exposures of inorganic Hg (20-200 μg/kg) exacerbates disease and accelerates mortality in the graft versus host disease model of chronic lupus in C57Bl/6 x DBA/2 mice. Furthermore, low dose Hg exposure increases the severity and prevalence of experimental autoimmune myocarditis (induced by immunization with cardiac myosin peptide in adjuvant) in A/J mice. To test our hypothesis further, we examined sera from Amazonian populations exposed to Hg through small-scale gold mining, with and without current or past malaria infection. We found significantly increased prevalence of antinuclear and antinucleolar antibodies and a positive interaction between Hg and malaria. These results suggest a new model for Hg immunotoxicity, as a co-factor in autoimmune disease, increasing the risks and severity of clinical disease in the presence of other triggering events, either genetic or acquired

  19. Ctla-4 modulates the differentiation of inducible Foxp3+ Treg cells but IL-10 mediates their function in experimental autoimmune encephalomyelitis.

    Directory of Open Access Journals (Sweden)

    Johan Verhagen

    Full Text Available In vitro induced Foxp3+ T regulatory (iTreg cells form a novel and promising target for therapeutic tolerance induction. However, the potential of these cells as a target for the treatment of various immune diseases, as well as the factors involved in their development and function, remain debated. Here, we demonstrate in a myelin basic protein (MBP-specific murine model of CNS autoimmune disease that adoptive transfer of antigen-specific iTreg cells ameliorates disease progression. Moreover, we show that the co-stimulatory molecule CTLA-4 mediates in vitro differentiation of iTreg cells. Finally, we demonstrate that the secreted, immunosuppressive cytokine IL-10 controls the ability of antigen-specific iTreg cells to suppress autoimmune disease. Overall, we conclude that antigen-specific iTreg cells, which depend on various immune regulatory molecules for their differentiation and function, represent a major target for effective immunotherapy of autoimmune disease.

  20. Intracerebroventricular administration of TNF-like weak inducer of apoptosis induces depression-like behavior and cognitive dysfunction in non-autoimmune mice.

    Science.gov (United States)

    Wen, Jing; Chen, Christopher Holden; Stock, Ariel; Doerner, Jessica; Gulinello, Maria; Putterman, Chaim

    2016-05-01

    Fn14, the sole known signaling receptor for the TNF family member TWEAK, is inducibly expressed in the central nervous system (CNS) in endothelial cells, astrocytes, microglia, and neurons. There is increasing recognition of the importance of the TWEAK/Fn14 pathway in autoimmune neurologic conditions, including experimental autoimmune encephalomyelitis and neuropsychiatric lupus. Previously, we had found that Fn14 knockout lupus-prone MRL/lpr mice display significantly attenuated neuropsychiatric manifestations. To investigate whether this improvement in disease is secondary to inhibition of TWEAK/Fn14 signaling within the CNS or the periphery, and determine whether TWEAK-mediated neuropsychiatric effects are strain dependent, we performed intracerebroventricular (ICV) injection of Fc-TWEAK or an isotype matched control protein to C57Bl6/J non-autoimmune mice. We found that Fc-TWEAK injected C57Bl6/J mice developed significant depression-like behavior and cognitive dysfunction. Inflammatory mediators associated with lupus brain disease, including CCL2, C3, and iNOS, were significantly elevated in the brains of Fc-TWEAK treated mice. Furthermore, Fc-TWEAK directly increased blood brain barrier (BBB) permeability, as demonstrated by increased IgG deposition in the brain and reduced aquaporin-4 expression. Finally, Fc-TWEAK increased apoptotic cell death in the cortex and hippocampus. In conclusion, TWEAK can contribute to lupus-associated neurobehavioral deficits including depression and cognitive dysfunction by acting within the CNS to enhance production of inflammatory mediators, promote disruption of the BBB, and induce apoptosis in resident brain cells. Our study provides further support that the TWEAK/Fn14 signaling pathway may be a potential therapeutic target for inflammatory diseases involving the CNS. PMID:26721417

  1. Mercury-induced renal autoimmunity: changes in RT6+ T-lymphocytes of susceptible and resistant rats.

    OpenAIRE

    Kosuda, L L; Greiner, D. L.; Bigazzi, P E

    1993-01-01

    The repeated administration of mercury to rats of the Brown Norway (BN) inbred strain results in a self-limiting production of autoantibodies to renal antigens (e.g., laminin) and autoimmune glomerulonephritis. In contrast, rats of the Lewis (LEW) strain do not develop renal autoimmunity after mercury treatment. Suppressor T-cells and/or the idiotype-anti-idiotype network have been implicated in the control of autoimmunity in susceptible (BN) rats as well as the "resistant" state of nonsuscep...

  2. Adult autoimmune enteropathy

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Recent reports have suggested that autoimmune enteropathy involving the small bowel may occur in adults as well as in children. Apparently, the endoscopic and histological changes are similar to celiac disease before treatment, but these are not altered by any form of dietary restriction, including a gluten-free diet. As in celiac disease, histologic changes in gastric and colonic biopsies have also been recorded. Anti enterocyte antibodies detected with immunofluorescent methods have been reported by a few laboratories, but these antibodies appear not to be specific and may simply represent epiphenomena. A widely available, reproducible and quantitative anti-enterocyte antibody assay is needed that could be applied in small bowel disorders that have the histological appearance of celiac disease, but fail to respond to a gluten-free diet.

  3. Differential inhibition of lipopolysaccharide-induced phenomena by anti-tumor necrosis factor alpha antibody.

    OpenAIRE

    Vogel, S N; Havell, E A

    1990-01-01

    Tumor necrosis factor alpha (TNF alpha) has been implicated as a major mediator of lipopolysaccharide (LPS)-induced phenomena. Administration to mice of a polyclonal, monospecific antibody prepared against recombinant murine TNF alpha abolished detection of LPS-induced TNF alpha activity and significantly reduced levels of LPS-induced colony-stimulating factor but failed to reduce the production of LPS-induced interferon, corticosterone, or LPS-induced hypoglycemia.

  4. Rituximab for autoimmune blistering diseases: recent studies, new insights

    OpenAIRE

    Lunardon, Luisa; Payne, Aimee S.

    2012-01-01

    Rituximab, an anti-CD20 monoclonal antibody, has been successfully used off-label for treatment of autoimmune blistering diseases. We discuss rituximab mechanisms of action, host factors that may affect response to rituximab, and the efficacy and safety of rituximab in autoimmune blistering diseases, incorporating recent data on the use of rituximab in other autoimmune disease patients.

  5. Autoimmune sleep disorders.

    Science.gov (United States)

    Silber, Michael H

    2016-01-01

    A number of autoantibodies, some paraneoplastic, are associated with sleep disorders. Morvan syndrome and limbic encephalitis, associated with voltage-gated potassium channel-complex antibodies, principally against CASPR2 and LGI1, can result in profound insomnia and rapid eye movement sleep behavior disorder (RBD). Patients with aquaporin-4 antibodies and neuromyelitis optica may develop narcolepsy in association with other evidence of hypothalamic dysfunction, sometimes as the initial presentation. Central sleep apnea and central neurogenic hypoventilation are found in patients with anti-N-methyl-d-aspartate receptor antibody encephalitis, and obstructive sleep apnea, stridor, and hypoventilation are prominent features of a novel tauopathy associated with IgLON5 antibodies. In addition, paraneoplastic diseases may involve the hypothalamus and cause sleep disorders, particularly narcolepsy and RBD in those with Ma1 and Ma2 antibodies. Patients with antineuronal nuclear autoantibodies type 2 may develop stridor. Several lines of evidence suggest that narcolepsy is an autoimmune disorder. There is a strong relationship with the human leukocyte antigen (HLA) DQB1*06:02 haplotype and polymorphisms in the T-cell receptor alpha locus and purinergic receptor P2Y11 genes. Patients with recent-onset narcolepsy may have high titers of antistreptococcal or other antibodies, although none has yet been shown to be disease-specific but, supporting an immune basis, recent evidence indicates that narcolepsy in children can be precipitated by one type of vaccination against the 2009-2010 H1N1 influenza pandemic. PMID:27112685

  6. Amelioration of experimental autoimmune encephalomyelitis in C57BL/6 mice by photobiomodulation induced by 670 nm light.

    Directory of Open Access Journals (Sweden)

    Kamaldeen A Muili

    Full Text Available BACKGROUND: The approved immunomodulatory agents for the treatment of multiple sclerosis (MS are only partially effective. It is thought that the combination of immunomodulatory and neuroprotective strategies is necessary to prevent or reverse disease progression. Irradiation with far red/near infrared light, termed photobiomodulation, is a therapeutic approach for inflammatory and neurodegenerative diseases. Data suggests that near-infrared light functions through neuroprotective and anti-inflammatory mechanisms. We sought to investigate the clinical effect of photobiomodulation in the Experimental Autoimmune Encephalomyelitis (EAE model of multiple sclerosis. METHODOLOGY/PRINCIPAL FINDINGS: The clinical effect of photobiomodulation induced by 670 nm light was investigated in the C57BL/6 mouse model of EAE. Disease was induced with myelin oligodendrocyte glycoprotein (MOG according to standard laboratory protocol. Mice received 670 nm light or no light treatment (sham administered as suppression and treatment protocols. 670 nm light reduced disease severity with both protocols compared to sham treated mice. Disease amelioration was associated with down-regulation of proinflammatory cytokines (interferon-γ, tumor necrosis factor-α and up-regulation of anti-inflammatory cytokines (IL-4, IL-10 in vitro and in vivo. CONCLUSION/SIGNIFICANCE: These studies document the therapeutic potential of photobiomodulation with 670 nm light in the EAE model, in part through modulation of the immune response.

  7. [Diagnostics of autoimmune diseases].

    Science.gov (United States)

    Beleznay, Zsuzsanna; Regenass, Stephan

    2008-09-01

    Autoantibodies play a key role in diagnostic laboratories as markers of autoimmune diseases. In addition to their role as markers they mediate diverse effects in vivo. Autoantibodies with protective effect have been described. Natural protective IgM autoantibodies against tumour-antigens of malignant cells or their precursors may contribute to increased survival rates of carcinoma patients. In a mouse model of systemic lupus erythematosus it has been shown that anti-dsDNA IgM autoantibodies protect from glomerular damage. In contrast, a direct pathogenic role of autoantibodies has been well established e.g. in myasthenia gravis or in Goodpasture syndrome. Similarly autoantibodies against SSA Ro52 are detrimental in neonatal lupus erythematosus with congenital heart block. Moreover, putatively protective autoantibodies may become pathogenic during the course of the disease such as the onconeuronal autoantibodies whose pathogenicity depends on their compartmentalisation. In patients with paraneoplastic syndromes tumour cells express proteins that are also naturally present in the brain. Anti-tumour autoantibodies which temporarily suppress tumour growth can provoke an autoimmune attack on neurons once having crossed the blood-brain barrier and cause specific neurological symptoms. Only a restricted number of autoantibodies are useful follow-up markers for the effectiveness of treatment in autoimmune diseases. Certain autoantibodies hold prognostic value and appear years or even decades before the diagnosis of disease such as the antimitochondrial antibodies in primary biliary cirrhosis or anti-citrullinated protein (CCP)-antibodies in rheumatoid arthritis. It is crucial to know whether the autoantibodies in question recognise linear or conformational epitopes in order to choose the appropriate detection methods. Indirect immunofluorescence microscopy remains a very useful tool for confirmation of results of commercially available immunoassays and for detection of

  8. Anticardiolipin Antibodies in Patients with Chronic Hepatitis C Virus Infection: Characterization in Relation to Antiphospholipid Syndrome

    OpenAIRE

    Ordi-Ros, Josep; Villarreal, Julieta; Monegal, Francesc; Sauleda, Silvia; Esteban, Ignacio; Vilardell, Miquel

    2000-01-01

    The antiphospholipid syndrome (APS) is usually defined by the association of clinical manifestations that comprise venous and/or arterial thrombosis, recurrent fetal losses, and thrombocytopenia, along with the presence of anticardiolipin (aCL) antibodies and/or lupus anticoagulant. Various infectious diseases can induce aCL; however, these antibodies are not usually associated with thrombotic events, as happens with autoimmune diseases, in which these antibodies need the presence of β2-glyco...

  9. Maternal Antibody Protected Chicks from Growth Retardation and Immunosuppression Induced by Early Reticuloendotheliosis Virus Infection

    Institute of Scientific and Technical Information of China (English)

    SUN Shu-hong; GUI Zhi-zhong; QU Li-xin

    2007-01-01

    To determine if the maternal antibody from breeders vaccinated with cell culture-adapted reticuloendotheliosis virus (REV) could protect chicks from early REV infection, one-day-old chicks with or without anti-REV maternal antibodies were inoculated with REV, and then their growth rates and antibody tilers to Newcastle disease virus (NDV) and avian influenza virus (AIV), after vaccination with inactivated vaccines, were compared. This study indicated that REV infection could cause growth retardation and severely inhibit immune reactions to inactivated vaccines against NDV and Avian influenza virus (AIV, H9 and H5) in one-day-old broilers without maternal antibodies specific to REV. Maternal antibody from breeders vaccinated with an attenuated REV vaccine effectively protected REV-challenged birds from growth retardation and immunosuppression on antibody reactions to NDV and AIV vaccines. Four weeks after vaccination, the HI liters to NDV, AIV-H9, and AIV-H5 in maternal antibody positive and negative groups were 3.36±2.04 versus 1.58±1.69 (P<0.01), 6.27±3.87 versus 0.71±1.60(P<0.01), and 6.72 versus 0.54±1.44(p<0.01). Maternal antibodies from breeders vaccinated with REV vaccine could successfully protect chicks from REV infection and effectively prevent REV-induced growth retardation and immunosuppression in antibody responses to NDV and AIV.

  10. Characterization of Thyrotropin Receptor Antibody-Induced Signaling Cascades

    OpenAIRE

    Morshed, Syed A.; Latif, Rauf; Davies, Terry F.

    2008-01-01

    The TSH receptor (TSHR) is constitutively active and is further enhanced by TSH ligand binding or by stimulating TSHR antibodies (TSHR-Abs) as seen in Graves’ disease. TSH is known to activate the thyroid epithelial cell via both Gαs-cAMP/protein kinase A/ERK and Gαq-Akt/protein kinase C coupled signaling networks. The recent development of monoclonal antibodies to the TSHR has enabled us to investigate the hypothesis that different TSHR-Abs may have unique signaling imprints that differ from...

  11. Autoimmune synaptopathies.

    Science.gov (United States)

    Crisp, Sarah J; Kullmann, Dimitri M; Vincent, Angela

    2016-02-01

    Autoantibodies targeting proteins at the neuromuscular junction are known to cause several distinct myasthenic syndromes. Recently, autoantibodies targeting neurotransmitter receptors and associated proteins have also emerged as a cause of severe, but potentially treatable, diseases of the CNS. Here, we review the clinical evidence as well as in vitro and in vivo experimental evidence that autoantibodies account for myasthenic syndromes and autoimmune disorders of the CNS by disrupting the functional or structural integrity of synapses. Studying neurological and psychiatric diseases of autoimmune origin may provide new insights into the cellular and circuit mechanisms underlying a broad range of CNS disorders. PMID:26806629

  12. Autoimmun hypophysitis

    DEFF Research Database (Denmark)

    Krarup, Therese; Hagen, Claus

    2010-01-01

    Autoimmune hypophysitis (AH) - often referred to as lymphocytic hypophysitis - is a rare disease that affects the pituitary gland and causes inflammation. The disease enlarges the pituitary gland and the clinical presentations are lack of pituitary function and headaches. AH is mostly seen in women...... during pregnancy or postpartum, but also occurs in males and children. AH is often associated with other autoimmune diseases, most frequently with Hashimoto's thyroiditis. The symptoms are caused by enlargement of the pituitary gland and disturbances of the hormone function. Treatment is either...

  13. Hepatitis A vaccine associated with autoimmune hepatitis

    Institute of Scientific and Technical Information of China (English)

    PA Berry; G Smith-Laing

    2007-01-01

    To describe a case of probable relapsing autoimmune hepatitis associated with vaccination against hepatitis A virus (HAV). A case report and review of literature were written concerning autoimmune hepatitis in association with hepatitis A and other hepatotropic viruses. Soon after the administration of formalin-inactivated hepatitis A vaccine, a man who had recently recovered from an uncharacterized but self-limiting hepatitic illness,experienced a severe deterioration (AST 1687 U/L, INR 1.4). Anti-nuclear antibodies were detectable, and liver biopsy was compatible with autoimmune hepatitis. The observation supports the role of HAV as a trigger of autoimmune hepatitis. Studies in helper T-cell activity and antibody expression against hepatic proteins in the context of hepatitis A infection are summarized, and the concept of molecular mimicry with regard to other forms of viral hepatitis and autoimmunity is briefly explored.

  14. The Role of Pathogenic Autoantibodies in Autoimmunity

    Directory of Open Access Journals (Sweden)

    Merrill J. Rowley

    2015-11-01

    Full Text Available The serological presence of autoantibodies is diagnostic of autoimmunity, and these autoantibodies may be present for many years before the presentation of autoimmune disease (AID. Although a pathogenic role has been demonstrated for various autoantibodies reactive with cell surface and extracellular autoantigens, studies using monoclonal antibodies (mAb show not all antibodies in the polyclonal response are pathogenic. Differences depend on Fab-mediated diversity in epitope specificity, Fc-mediated effects based on immunoglobulin (Ig class and subclass, activation of complement, and the milieu in which the reaction occurs. These autoantibodies often occur in organ-specific AID and this review illustrates their pathogenic and highly specific effects. The role of autoantibodies associated with intracellular antigens is less clear. In vitro they may inhibit or adversely affect well-defined intracellular biochemical pathways, yet, in vivo they are separated from their autoantigens by multiple cellular barriers. Recent evidence that Ig can traverse cell membranes, interact with intracellular proteins, and induce apoptosis has provided new evidence for a pathogenic role for such autoantibodies. An understanding of how autoantibodies behave in the polyclonal response and their role in pathogenesis of AID may help identify populations of culprit B-cells and selection of treatments that suppress or eliminate them.

  15. Idiopathic Granulomatous Mastitis: An Autoimmune Disease?

    Directory of Open Access Journals (Sweden)

    Fatih Altintoprak

    2013-01-01

    Full Text Available Purpose. This study aimed to investigate the autoimmune basis of idiopathic granulomatous mastitis (IGM by determining the anti-nuclear antibody (ANA and extractable nuclear antigen (ENA levels of patients diagnosed with IGM. Material and Methods. Twenty-six IGM patients were evaluated. Serum samples were analyzed for autoantibodies by indirect immunofluorescence (IIF using a substrate kit that induced fluorescein-conjugated goat antibodies to human immunoglobulin G (IgG. IIF patterns were read at serum dilutions of 1 : 40 and 1 : 100 for ANA positivity. Using the immunoblot technique, the sera of patients were assayed at dilutions of 1 : 40 and 1 : 100 for human autoantibodies of the IgG class to 15 lines of highly purified ENAs. Results. In the IIF studies for ANA, positivity was identified for four different patterns in the 1 : 40 diluted preparations, for three different patients in the 1 : 100 diluted preparations and only one pattern was identified at the 1 : 320 dilution. In the ENA studies, positivity was identified for four different pattern in the 1 : 40 dilution, and only one pattern was identified at the 1 : 100 dilution. Conclusion. This study was not able to support the eventual existence of an autoimmune basis for IGM.

  16. Endocrine autoimmunity in Turner syndrome

    Science.gov (United States)

    2013-01-01

    Background Turner syndrome is caused by numeric and structural abnormalities of the X chromosome. An increased frequency of autoimmunity as well as an elevated incidence of autoantibodies was observed in Turner patients. The aim of this study was to conduct a retrospective analysis of the incidence of autoimmunity in 66 Italian patients affected by Turner syndrome. Methods Sixty-six unselected and consecutive Italian Turner patients were recruited. The association between age, karyotype and the presence of clinical/pre-clinical autoimmune disorders and of autoantibodies was examined. Results Out of the 66 Turner patients, 26 had thyroid autoimmune disorders (39.4%), 14 patients had Hashimoto’s thyroiditis with clinical or subclinical hypothyroidism (21.2%) and 12 patients had circulating anti-thyroid antibodies, echographic pattern of diffuse hypoechogenicity and normal thyroid hormone levels (18.2%). None were affected by Graves’ disease. We analyzed the overall incidence of thyroid autoimmunity within the 3 different age groups 0–9.9, 10–19.9 and 20–29.9 years. No statistically significant difference was observed in the incidence of thyroid autoimmunity within the age-groups (χ2-test p > 0.05). Out of the 66 patients, 31 patients had the 45,X karyotype; within this first group 14 out of 31 patients were affected by autoimmune thyroid disease. A second group of 29 patients included 19 patients with mosaicism, 5 patients with deletions and 5 patients with ring chromosome; out of these 29 patients 7 were affected by autoimmune thyroid disease. A third group included 6 patients with X isochromosome; 5 out of 6 were affected by autoimmune thyroid disease. A statistically significant difference in the frequency of thyroid autoimmunity within the different karyotype groups was observed (χ2-test p = 0.0173). When comparing the X isochromosome group with the pooled group of other karyotypes, of note, the frequency of thyroid autoimmunity was

  17. Role of soluble Fas ligand in autoimmune diseases

    Institute of Scientific and Technical Information of China (English)

    Ning-Li Li; Tong Zhou; Dong-Qing Zhang; Hong Nie; Qi-Wen Yu; Ji-Ying Zhang; An-Lun Ma; Bai-Hua Shen; Li Wang; Jun Bai; Xue-Hua Chen

    2004-01-01

    AIM: To investigate the role of soluble Fas ligand in autoimmune diseases.METHODS: RT-PCR was performed to amplify sFasL cDNA from the total RNA extracted from activated human peripheral blood lymphocytes. DNA fragments were cloned into PCR vector. After sequenced, sFasL gene fragments were inserted into pQE-31 vector and expressed in E. Coli M15respectively. Proteins were purified through affinity chromatography column with ligand of 6xHis tag and identified by SDS-PAGE and Western blot. Mice were immunized with sFasL protein and specific anti-serum was harvested 6 wk after immunization. Monoclonal anti-human FasL antibody was made from the immunized mice. Serum level of sFasL in different patients was detected using antiFasL antibodies from the immunized mice.RESULTS: The protein expressed was 24 ku by SDS-PAGE electrophrosis. The protein was specially bound to antihuman FasL antibody by Western blot analysis. The sFasL protein could induce Jurket cell apoptosis in vitro. The concentration of serum sFasL in patients with autoimmune diseases was higher than that in normal individuals. sFasL could reduce arthritis in collagen induced arthritis (CIA)mice model by subcutaneous injection.CONCLUSION: sFasL may be involved in either induction of apoptosis or autoimmune diseases. Furthermore, sFasL may have potential application in treatment of autoimmune diseases.

  18. Gangliosides and autoimmune diabetes.

    Science.gov (United States)

    Misasi, R; Dionisi, S; Farilla, L; Carabba, B; Lenti, L; Di Mario, U; Dotta, F

    1997-09-01

    Gangliosides are sialic acid-containing glycolipids which are formed by a hydrophobic portion, the ceramide, and a hydrophilic part, i.e. the oligosaccharide chain. First described in neural tissue, several studies have shown that gangliosides are almost ubiquitous molecules expressed in all vertebrate tissues. Within cells, gangliosides are usually associated with plasma membranes, where they can act as receptors for a variety of molecules and have been shown to take part in cell-to-cell interaction and in signal transduction. In addition, gangliosides are expressed in cytosol membranes like those of secretory granules of some endocrine cells (adrenal medulla, pancreatic islets). As far as the role of gangliosides in diseases is concerned, there are some cases in which an aberrant ganglioside expression plays a crucial role in the disease pathogenetic process. These diseases include two major forms of ganglioside storage, namely GM2-gangliosidosis (Tay-Sachs and its beta-hexosaminidase deficiency) and GM1-gangliosidosis (beta-galactosidase deficiency), where the most prominent pathological characteristic is the lysosomal ganglioside accumulation in neurons. Other inflammatory or degenerative diseases both within and outside the nervous system have been shown to be associated with an altered pattern of ganglioside expression in the target organ. Since monoclonal antibodies have been discovered and used in immunology, a large variety of ganglioside antigens has been described both as blood group antigens and as tumour-related antigens. Several studies have also indicated that gangliosides can act not only as antigens, but also as autoantigens. As a matter of fact, auto-antibodies to gangliosides, detected by immunostaining methods performed directly on TLC plates or by ELISA, have been described in several autoimmune disorders such as Guillain-Barré syndrome, multiple sclerosis, lupus erythematosus, Hashimoto's thyroiditis and, last but not least, insulin

  19. Gene expression in the spinal cord in female lewis rats with experimental autoimmune encephalomyelitis induced with myelin basic protein.

    Directory of Open Access Journals (Sweden)

    Hayley R Inglis

    Full Text Available BACKGROUND: Experimental autoimmune encephalomyelitis (EAE, the best available model of multiple sclerosis, can be induced in different animal strains using immunization with central nervous system antigens. EAE is associated with inflammation and demyelination of the nervous system. Micro-array can be used to investigate gene expression and biological pathways that are altered during disease. There are few studies of the changes in gene expression in EAE, and these have mostly been done in a chronic mouse EAE model. EAE induced in the Lewis with myelin basic protein (MBP-EAE is well characterised, making it an ideal candidate for the analysis of gene expression in this disease model. METHODOLOGY/PRINCIPAL FINDINGS: MBP-EAE was induced in female Lewis rats by inoculation with MBP and adjuvants. Total RNA was extracted from the spinal cords and used for micro-array analysis using AffimetrixGeneChip Rat Exon 1.0 ST Arrays. Gene expression in the spinal cords was compared between healthy female rats and female rats with MBP-EAE. Gene expression in the spinal cord of rats with MBP-EAE differed from that in the spinal cord of normal rats, and there was regulation of pathways involved with immune function and nervous system function. For selected genes the change in expression was confirmed with real-time PCR. CONCLUSIONS/SIGNIFICANCE: EAE leads to modulation of gene expression in the spinal cord. We have identified the genes that are most significantly regulated in MBP-EAE in the Lewis rat and produced a profile of gene expression in the spinal cord at the peak of disease.

  20. Immunoadsorption therapy in autoimmune encephalitides

    Science.gov (United States)

    Golombeck, Kristin S.; Bien, Corinna; Abu-Tair, Mariam; Brand, Marcus; Bulla-Hellwig, Michael; Lohmann, Hubertus; Münstermann, Dieter; Pavenstädt, Hermann; Thölking, Gerold; Valentin, Rainer; Wiendl, Heinz; Melzer, Nico; Bien, Christian G.

    2016-01-01

    Objective: It was hypothesized that in encephalitides with autoantibodies directed to CNS surface antigens an antibody-removing intervention might speed up recovery. Methods: The outcome of autoimmune encephalitis in 19 patients with antibodies against surface antigens (leucine-rich, glioma inactivated 1 [LGI1], n = 3; contactin-associated protein-2 [CASPR2], n = 4; NMDA receptor [NMDAR], n = 7) and intracellular antigens (glutamic acid decarboxylase [GAD], n = 5) after immunoadsorption in addition to corticosteroid therapy was evaluated retrospectively. Modified Rankin scale (mRS) scores and data on seizures, memory, and antibody titers directly after immunoadsorption (early follow-up) and after a median of 4 months (late follow-up) were compiled. Results: Immediately after immunoadsorption, 9 of 14 patients with antibodies against LGI1, CASPR2, or NMDAR (64%), but none with GAD antibodies, had improved by at least one mRS point. Five of the 7 patients with LGI1 or CASRP2 antibodies had become seizure-free, and 2 patients with NMDAR antibodies had a memory improvement of more than 1 SD of a normal control population. At late follow-up, 12 of 14 patients with surface antibodies had improved (86%), and none of the patients with GAD antibodies. Conclusions: It is suggested that addition of immunoadsorption to immunosuppression therapy in patients with surface antibodies may accelerate recovery. This supports the pathogenic role of surface antibodies. Classification of evidence: This study provides Class IV evidence that immunoadsorption combined with immunosuppression therapy is effective in patients with autoimmune encephalitis with surface antibodies. PMID:26977423

  1. Autoimmun pankreatitis

    DEFF Research Database (Denmark)

    Fjordside, Eva; Novovic, Srdan; Schmidt, Palle Nordblad;

    2015-01-01

    Autoimmune pancreatitis (AIP) is a rare inflammatory disease. AIP has characteristic histology, serology and imaging findings. Two types of AIP exist, type 1, which is a part of the systemic immunoglobulin G4-related disease, and type 2, which is only localized to the pancreas. Patients with type 1...

  2. Immunomodulatory strategies prevent the development of autoimmune emphysema

    Directory of Open Access Journals (Sweden)

    Kraskauskiene Vita

    2010-12-01

    Full Text Available Abstract Background The presence of anti-endothelial cell antibodies and pathogenic T cells may reflect an autoimmune component in the pathogenesis of emphysema. Whether immune modulatory strategies can protect against the development of emphysema is not known. Methods Sprague Dawley rats were immunized with human umbilical vein endothelial cells (HUVEC to induce autoimmune emphysema and treated with intrathymic HUVEC-injection and pristane. Measurements of alveolar airspace enlargement, cytokine levels, immuno histochemical, western blot analysis, and T cell repertoire of the lung tissue were performed. Results The immunomodulatory strategies protected lungs against cell death as demonstrated by reduced numbers of TUNEL and active caspase-3 positive cells and reduced levels of active caspase-3, when compared with lungs from HUVEC-immunized rats. Immunomodulatory strategies also suppressed anti-endothelial antibody production and preserved CNTF, IL-1alpha and VEGF levels. The immune deviation effects of the intrathymic HUVEC-injection were associated with an expansion of CD4+CD25+Foxp3+ regulatory T cells. Pristane treatment decreased the proportion of T cells expressing receptor beta-chain, Vβ16.1 in the lung tissue. Conclusions Our data demonstrate that interventions classically employed to induce central T cell tolerance (thymic inoculation of antigen or to activate innate immune responses (pristane treatment can prevent the development of autoimmune emphysema.

  3. Antibody to eosinophil cationic protein suppresses dextran sulfate sodium-induced colitis in rats

    Institute of Scientific and Technical Information of China (English)

    Kazuko Shichijo; Kazuya Makiyama; Chun-Yang Wen; Mutsumi Matsuu; Toshiyuki Nakayama; Masahiro Nakashima; Makoto Ihara; Ichiro Sekine

    2005-01-01

    AIM: To produce an antibody against rat eosinophil cationic protein (ECP) and to examine the effects of the antibody in rats with dextran sulfate sodium (DSS)-induced colitis.METHODS: An antibody was raised against rat ECP. Rats were treated with 3% DSS in drinking water for 7 d and received the antibody or normal serum. The colons were exarmined histologically and correlated with clinical symptoms.Immunohistochemistry and Western blot analysis were estimated as a grade of inflammation.RESULTS: The ECP antibody stained the activated eosinophils around the injured crypts in the colonic mucosa.Antibody treatment reduced the severity of colonic ulceration and acute clinical symptoms (diarrhea and/or blood-stained stool). Body weight gain was significantly greater and the colon length was significantly longer in anti-ECP-treated rats than in normal serum-treated rats. Expression of ECP in activated eosinophils was associated with the presence of erosions and inflammation. The number of Ki-67-positive cells in the regenerated surface epithelium increased in anti-ECP-treated rats compared with normal serum-treated rats. Western blot analysis revealed reduced expression of macrophage migration inhibitory factor (MIF) in anti-ECP-treated rats.CONCLUSION: Our results indicate that treatment with ECP antibody, improved DSS-induced colitis in rats, possibly by increasing the regenerative activity of the colonic epithelium and downregulation of the immune response,and suggest that anti-ECP may promote intestinal wound healing in patients with ulcerative colitis (UC).

  4. Multiple mechanisms in serum factor-induced resistance of Haemophilus influenzae type b to antibody.

    OpenAIRE

    Kuratana, M; Hansen, E J; Anderson, P

    1990-01-01

    Incubation of Haemophilus influenzae type b at less than or equal to 10(7) CFU/ml with serum ultrafiltrate induces a phenotypic conversion in which complement-mediated bactericidal activity by somatic antibodies decreases while killing by capsular antibody is unchanged. Conversion had been shown to occur in a capsule-deficient (b-) mutant of strain Eag (thus appearing independent of capsulation), to include an increase in lipopolysaccharide content, and to be inhibited by chloramphenicol or p...

  5. Endogenous IRBP can be dispensable for generation of natural CD4+CD25+ regulatory T cells that protect from IRBP-induced retinal autoimmunity

    OpenAIRE

    Grajewski, Rafael S.; Silver, Phyllis B.; Agarwal, Rajeev K.; Shao-bo SU; Chan, Chi-Chao; Liou, Gregory I.; Caspi, Rachel R.

    2006-01-01

    Susceptibility to experimental autoimmune uveitis (EAU), a model for human uveitis induced in mice with the retinal antigen interphotoreceptor retinoid-binding protein (IRBP), is controlled by “natural” CD4+CD25+ regulatory T (T reg) cells. To examine whether endogenous expression of IRBP is necessary to generate these T reg cells, we studied responses of IRBP knockout (KO) versus wild-type (WT) mice. Unexpectedly, not only WT but also IRBP KO mice immunized with a uveitogenic regimen of IRBP...

  6. Antigens of the basement membranes of the seminiferous tubules induce autoimmunity in Wistar rats.

    Science.gov (United States)

    Lustig, L; Satz, M L; Sztein, M B; Denduchis, B

    1982-05-01

    A preparation enriched in basement membranes from seminiferous tubules was isolated from rat testes (STBM) and injected with complete Freund's adjuvant into Wistar rats. In 60% of animals a mild multifocal orchitis was observed. In damaged areas, perivascular and peritubular mononuclear cell infiltrates and different degrees of cell sloughing of some seminiferous tubules were observed. Electron microscopy revealed focal thickenings and delamination of the basement membrane of the seminiferous tubules as well as vacuolization of Sertoli cell cytoplasm. Using immunofluorescence discontinuous linear deposits of IgG were detected along the seminiferous tubular wall. Moreover, the same pattern of immunofluorescence was observed when the IgG eluted from the testes of the immunized rats was layered on sections of normal rat testis. Circulating antibodies to STBM were detected using passive haemagglutination in approximately 45% of the immunized rats, with titers ranging from 1:20 to 1:80. Leukocyte migration was inhibited when the spleen cells of the immunized rats were incubated with antigens from the basement membrane of seminiferous tubules, whilst a negative reaction was obtained when the soluble fraction of testis homogenate was used. PMID:7050376

  7. Fusion proteins of HIV-1 envelope glycoprotein gp120 with CD4-induced antibodies showed enhanced binding to CD4 and CD4 binding site antibodies

    International Nuclear Information System (INIS)

    Highlights: ► Some recombinant HIV-1 gp120s do not preserve their conformations on gp140s. ► We hypothesize that CD4i antibodies could induce conformational changes in gp120. ► CD4i antibodies enhance binding of CD4 and CD4bs antibodies to gp120. ► CD4i antibody-gp120 fusion proteins could have potential as vaccine immunogens. -- Abstract: Development of successful AIDS vaccine immunogens continues to be a major challenge. One of the mechanisms by which HIV-1 evades antibody-mediated neutralizing responses is the remarkable conformational flexibility of its envelope glycoprotein (Env) gp120. Some recombinant gp120s do not preserve their conformations on gp140s and functional viral spikes, and exhibit decreased recognition by CD4 and neutralizing antibodies. CD4 binding induces conformational changes in gp120 leading to exposure of the coreceptor-binding site (CoRbs). In this study, we test our hypothesis that CD4-induced (CD4i) antibodies, which target the CoRbs, could also induce conformational changes in gp120 leading to better exposed conserved neutralizing antibody epitopes including the CD4-binding site (CD4bs). We found that a mixture of CD4i antibodies with gp120 only weakly enhanced CD4 binding. However, such interactions in single-chain fusion proteins resulted in gp120 conformations which bound to CD4 and CD4bs antibodies better than the original or mutagenically stabilized gp120s. Moreover, the two molecules in the fusion proteins synergized with each other in neutralizing HIV-1. Therefore, fusion proteins of gp120 with CD4i antibodies could have potential as components of HIV-1 vaccines and inhibitors of HIV-1 entry, and could be used as reagents to explore the conformational flexibility of gp120 and mechanisms of entry and immune evasion.

  8. Protein X of Streptococcus agalactiae induces opsonic antibodies in cows.

    OpenAIRE

    Rainard, P; Lautrou, Y; Sarradin, P.; Poutrel, B

    1991-01-01

    Protein X of Streptococcus agalactiae is a surface protein frequently associated with strains isolated from cases of mastitis of dairy cows. By immunizing cows with purified protein X, we obtained an antibody response which was restricted to X-bearing strains of S. agalactiae in a whole-cell enzyme-linked immunosorbent assay. This response resulted in an increase in the opsonic activity of serum for strains bearing protein X, as assessed through the augmentation of the chemiluminescence respo...

  9. Intranasal vaccination with proinsulin DNA induces regulatory CD4+ T cells that prevent experimental autoimmune diabetes.

    Science.gov (United States)

    Every, Alison L; Kramer, David R; Mannering, Stuart I; Lew, Andrew M; Harrison, Leonard C

    2006-04-15

    Insulin, an autoantigen in type 1 diabetes, when administered mucosally to diabetes-prone NOD mice induces regulatory T cells (T(reg)) that protect against diabetes. Compared with protein, Ag encoded as DNA has potential advantages as a therapeutic agent. We found that intranasal vaccination of NOD mice with plasmid DNA encoding mouse proinsulin II-induced CD4+ T(reg) that suppressed diabetes development, both after adoptive cotransfer with "diabetogenic" spleen cells and after transfer into NOD mice given cyclophosphamide to accelerate diabetes onset. In contrast to prototypic CD4+ CD25+ T(reg), CD4+ T(reg) induced by proinsulin DNA were both CD25+ and CD25- and not defined by markers such as glucocorticoid-induced TNFR-related protein (GITR), CD103, or Foxp3. Intriguingly, despite induction of T(reg) and reduced islet inflammation, diabetes incidence in proinsulin DNA-treated mice was unchanged. However, diabetes was prevented when DNA vaccination was performed under the cover of CD40 ligand blockade, known to prevent priming of CTL by mucosal Ag. Thus, intranasal vaccination with proinsulin DNA has therapeutic potential to prevent diabetes, as demonstrated by induction of protective T(reg), but further modifications are required to improve its efficacy, which could be compromised by concomitant induction of pathogenic immunity. PMID:16585551

  10. Preventative effects of the flowers of Inula britannica on autoimmune diabetes in C57BL/KsJ mice induced by multiple low doses of streptozotocin.

    Science.gov (United States)

    Kobayashi, Takao; Song, Qing-Hua; Hong, Tie; Kitamura, Hajime; Cyong, Jong-Chol

    2002-06-01

    We have reported that an aqueous extract from the flowers of Inula britannica L. subsp. japonica Kitam. (IB) prevented immunologically induced experimental hepatitis in mice and suggested that the antihepatitic effect of IB is due to inhibition of IFN-gamma production. We then investigated the effects of IB on diabetes in mice induced by multiple low doses of streptozotocin (MLDSTZ), which is a mouse model for IFN-gamma-dependent autoimmune diabetes. C57BL/KsJ mice (male, 7 weeks) were provided with IB extract (500 mg/ kg/ day) in drinking water ad libitum, starting 7 days before the first STZ injection. Autoimmune diabetes was induced by MLDSTZ (40 mg/kg/day for 5 daily doses, i.p.). The IB treatment significantly suppressed the increase of blood glucose levels. Histological analysis of the pancreas showed that the degree of insulitis and destruction of beta-cells were reduced by IB treatment. The IFN-gamma production from stimulated splenic T lymphocytes was inhibited by the IB treatment. Moreover, the proportion of IFN-gamma-producing cells in the CD4(+) population, which was increased by MLDSTZ, was significantly decreased by the IB treatment. These results suggest that IB has a preventative effect on autoimmune diabetes by regulating cytokine production. PMID:12112297

  11. Anti-Interleukin-6 Receptor Antibody Therapy-Induced Retinopathy in a Patient with Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Asumi Tada

    2012-01-01

    Full Text Available Tocilizumab, a humanized anti-human interleukin-6 (IL-6 receptor monoclonal antibody, is beneficial for treating autoimmune conditions such as rheumatoid arthritis (RA. The most common adverse event is upper respiratory tract infection; ocular side effects are rare. We describe a case of skin ulceration and bilateral retinopathy with multifocal cotton-wool spots and retinal hemorrhages in a patient with RA treated with tocilizumab. Tocilizumab administration increased the serum level of IL-6 without affecting the IL-8 levels. We could not exclude the possibility of blood coagulation or retinal vascular changes caused by tocilizumab. The current case highlights the need to consider that ocular adverse effects can develop in patients treated with tocilizumab.

  12. Comparisons of the effect of naturally acquired maternal pertussis antibodies and antenatal vaccination induced maternal tetanus antibodies on infant's antibody secreting lymphocyte responses and circulating plasma antibody levels.

    Science.gov (United States)

    Ahmad, Shaikh Meshbahuddin; Alam, Jahangir; Afsar, Nure Alam; Huda, Nazmul; Kabir, Yearul; Qadri, Firdausi; Raqib, Rubhana; Stephensen, Charles B

    2016-04-01

    The goal of this study was to explore the effects of trans-placental tetanus toxoid (TT) and pertussis (PT) antibodies on an infant's response to vaccination in the context of antenatal immunization with tetanus but not with pertussis. 38 mothers received a single dose of TT vaccine during pregnancy. Infants received tetanus and pertussis vaccines at 6, 10 and 14 wk of age. TT and PT anti-IgG secretion by infant lymphocytes was measured at 15 wk. Plasma antibodies were measured at 6 wk (pre-vaccination), 15 wk and 1 y of age. Prior to vaccination, TT and PT antibody were detected in 94.6% and 15.2% of infants. At 15 wk anti-TT-IgG and anti-PT-IgG in plasma was increased by 7-9 fold over pre-vaccination levels, while at 1 y plasma anti-TT-IgG was decreased by approximately 5-fold from the peak and had returned to near the pre-vaccination level. At 1 y plasma anti-PT-IgG was decreased by 2-fold 1 yfrom the 15 wk level. However, 89.5% and 82.3% of infants at 1 y had protective levels of anti-TT and anti-PT IgG, respectively. Pre-vaccination plasma IgG levels were associated with lower vaccine-specific IgG secretion by infant lymphocytes at 15 wk (p < 0.10). This apparent inhibition was seen for anti-TT-IgG at both 15 wk (p < 0.05) and t 1 y (p < 0.10) of age. In summary, we report an apparent inhibitory effect of passively derived maternal antibody on an infants' own antibody response to the same vaccine. However, since the cut-off values for protective titers are low, infants had protective antibody levels throughout infancy. PMID:27176823

  13. Dimethyl sulfoxide inhibits spontaneous diabetes and autoimmune recurrence in non-obese diabetic mice by inducing differentiation of regulatory T cells

    International Nuclear Information System (INIS)

    Type 1 diabetes mellitus (T1D) is caused by the destruction of insulin-producing β cells in pancreatic islets by autoimmune T cells. Islet transplantation has been established as an effective therapeutic strategy for T1D. However, the survival of islet grafts can be disrupted by recurrent autoimmunity. Dimethyl sulfoxide (DMSO) is a solvent for organic and inorganic substances and an organ-conserving agent used in solid organ transplantations. DMSO also exerts anti-inflammatory, reactive oxygen species scavenger and immunomodulatory effects and therefore exhibits therapeutic potential for the treatment of several human inflammatory diseases. In this study, we investigated the therapeutic potential of DMSO in the inhibition of autoimmunity. We treated an animal model of islet transplantation (NOD mice) with DMSO. The survival of the syngeneic islet grafts was significantly prolonged. The population numbers of CD8, DC and Th1 cells were decreased, and regulatory T (Treg) cell numbers were increased in recipients. The expression levels of IFN-γ and proliferation of T cells were also reduced following DMSO treatment. Furthermore, the differentiation of Treg cells from naive CD4 T cells was significantly increased in the in vitro study. Our results demonstrate for the first time that in vivo DMSO treatment suppresses spontaneous diabetes and autoimmune recurrence in NOD mice by inhibiting the Th1 immune response and inducing the differentiation of Treg cells. - Highlights: • We report a therapeutic potential of DMSO in autoimmune diabetes. • DMSO exhibits an immune modulatory effect. • DMSO treatment increases regulatory T cell differentiation. • The increase in STAT5 signaling pathway explains the effect of DMSO in Tregs

  14. Dimethyl sulfoxide inhibits spontaneous diabetes and autoimmune recurrence in non-obese diabetic mice by inducing differentiation of regulatory T cells

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Gu-Jiun [Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan, ROC (China); Sytwu, Huey-Kang [Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan, ROC (China); Yu, Jyh-Cherng [Department of General Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC (China); Chen, Yuan-Wu [School of Dentistry, National Defense Medical Center, Taipei, Taiwan, ROC (China); Department of Oral and Maxillofacial Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC (China); Kuo, Yu-Liang [Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan, ROC (China); School of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, Taiwan, ROC (China); Yu, Chiao-Chi [Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan, ROC (China); Department of General Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC (China); Chang, Hao-Ming; Chan, De-Chuan [Department of General Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC (China); Huang, Shing-Hwa, E-mail: h610129@gmail.com [Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan, ROC (China); Department of General Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC (China)

    2015-01-15

    Type 1 diabetes mellitus (T1D) is caused by the destruction of insulin-producing β cells in pancreatic islets by autoimmune T cells. Islet transplantation has been established as an effective therapeutic strategy for T1D. However, the survival of islet grafts can be disrupted by recurrent autoimmunity. Dimethyl sulfoxide (DMSO) is a solvent for organic and inorganic substances and an organ-conserving agent used in solid organ transplantations. DMSO also exerts anti-inflammatory, reactive oxygen species scavenger and immunomodulatory effects and therefore exhibits therapeutic potential for the treatment of several human inflammatory diseases. In this study, we investigated the therapeutic potential of DMSO in the inhibition of autoimmunity. We treated an animal model of islet transplantation (NOD mice) with DMSO. The survival of the syngeneic islet grafts was significantly prolonged. The population numbers of CD8, DC and Th1 cells were decreased, and regulatory T (Treg) cell numbers were increased in recipients. The expression levels of IFN-γ and proliferation of T cells were also reduced following DMSO treatment. Furthermore, the differentiation of Treg cells from naive CD4 T cells was significantly increased in the in vitro study. Our results demonstrate for the first time that in vivo DMSO treatment suppresses spontaneous diabetes and autoimmune recurrence in NOD mice by inhibiting the Th1 immune response and inducing the differentiation of Treg cells. - Highlights: • We report a therapeutic potential of DMSO in autoimmune diabetes. • DMSO exhibits an immune modulatory effect. • DMSO treatment increases regulatory T cell differentiation. • The increase in STAT5 signaling pathway explains the effect of DMSO in Tregs.

  15. Redefining strategies to introduce tolerance inducing cellular therapy in humans to combat autoimmunity and transplantation reactions

    Directory of Open Access Journals (Sweden)

    Anja eTen Brinke

    2014-08-01

    Full Text Available Clinical translation of tolerance-inducing cell therapies requires a novel approach focused on innovative networks, patient involvement and, foremost, a fundamental paradigm shift in thinking from both Academia, Industry and Regulatory Agencies. Tolerance-inducing cell products differ essentially from conventional drugs. They are personalized and target interactive immunological networks to shift the balance towards tolerance. The human cell products are often absent or fundamentally different in animals. This creates important limitations of pre-clinical animal testing for safety and efficacy of these products and calls for novel translational approaches, which require the combined efforts of the different parties involved. Dedicated international and multidisciplinary consortia that focus on clinical translation are of utmost importance. They can help inform and educate regulatory policy makers on the unique requirements for these cell products, ranging from preclinical studies in animals to in vitro human studies. In addition, they can promote reliable immunomonitoring tools. The development of tolerance-inducing cell products requires not only bench-to-bedside but also reverse translation, from bedside back to the bench.

  16. Induction of Graves' disease in patients with non-autoimmune hyperthyroidism or nontoxic goiter after radioiodine treatment

    International Nuclear Information System (INIS)

    Thyrotropin receptors antibodies may occur and induce Graves' disease (GD) several months after radioiodine therapy in a small number of patients with non-autoimmune hyperthyroidism or nontoxic goiter. The prevalence of radiation-induced GD is between 0.05% and 5%. The hypothesis of this disease includes induction by autoimmune reaction and others. Detection of the thyroid autoantibodise or of 99mTc pertechnetate scan can forecast the appearance of GD. Antithyroid drugs, again radioiodine therapy and surgery are the treatments. (authors)

  17. The role of parvovirus B19 in the pathogenesis of autoimmunity and autoimmune disease.

    Science.gov (United States)

    Kerr, Jonathan R

    2016-04-01

    Human parvovirus B19 is a single-stranded DNA virus which preferentially targets the erythroblasts in the bone marrow. B19 infection commonly causes erythema infectiosum, arthralgia, fetal death, transient aplastic crisis in patients with shortened red cell survival, and persistent infection in people who are immunocompromised. Less common clinical manifestations include atypical skin rashes, neurological syndromes, cardiac syndromes, and various cytopenias. B19 infection has also been associated with development of a variety of different autoimmune diseases, including rheumatological, neurological, neuromuscular, cardiovascular, haematological, nephrological and metabolic. Production of a variety of autoantibodies has been demonstrated to occur during B19 infection and these have been shown to be key to the pathogenesis of the particular disease process in a significant number of cases, for example, production of rheumatoid factor in cases of B19-associated rheumatoid arthritis and production of anti-glutamic acid decarboxylase (GAD) in patients with B19-associated type 1 diabetes mellitus. B19 infection has also been associated with the development of multiple autoimmune diseases in 12 individuals. Documented mechanisms in B19-associated autoimmunity include molecular mimicry (IgG antibody to B19 proteins has been shown to cross react with a variety of recognised human autoantigens, including collagen II, keratin, angiotensin II type 1 receptor, myelin basic protein, cardiolipin, and platelet membrane glycoprotein IIb/IIIa), B19-induced apoptosis with presentation of self-antigens to T lymphocytes, and the phospholipase activity of the B19 unique VP1 protein. PMID:26644521

  18. Autoimmun pankreatitis

    DEFF Research Database (Denmark)

    Fjordside, Eva; Novovic, Srdan; Schmidt, Palle Nordblad;

    2015-01-01

    Autoimmune pancreatitis (AIP) is a rare inflammatory disease. AIP has characteristic histology, serology and imaging findings. Two types of AIP exist, type 1, which is a part of the systemic immunoglobulin G4-related disease, and type 2, which is only localized to the pancreas. Patients with type 1...... are predominantly older men, have involvement of other organs and more often experience relapse than patients with type 2. Both types respond well to steroid treatment. The most important differential diagnose is pancreatic cancer....

  19. Vaccinia virus strain NYVAC induces substantially lower and qualitatively different human antibody responses compared with strains Lister and Dryvax

    OpenAIRE

    Midgley, Claire M.; Putz, Mike M.; Weber, Jonathan N.; Smith, Geoffrey L.

    2008-01-01

    The antibody responses elicited by immunization of humans with vaccinia virus (VACV) strains Lister, Dryvax and NYVAC have been determined and compared. Neutralizing antibodies against intracellular mature virus (IMV) and extracellular enveloped virus (EEV), and binding antibody titres (ELISA) against the EEV protein B5, the IMV proteins A27 and H3, and VACV-infected cell lysate were measured. Lister and Dryvax induced broadly similar antibody titres, consistent with the fact that these vacci...

  20. Fab-mediated binding of drug-dependent antibodies to platelets in quinidine- and quinine-induced thrombocytopenia.

    OpenAIRE

    Christie, D J; Mullen, P C; Aster, R H

    1985-01-01

    Platelets coated with quinine- or quinidine-induced antibodies form rosettes around protein A-Sepharose beads and normal platelets form rosettes about protein A-Sepharose beads coated with these antibodies. These reactions occurred only in the presence of sensitizing drug. Platelets also formed rosettes about protein A-Sepharose beads coated with an anti-PIA1 antibody, but drug was not required. Formation of rosettes between antibody-coated platelets and protein A-Sepharose was inhibited by F...

  1. Molecular definition of heterogeneous nuclear ribonucleoprotein R (hnRNP R) using autoimmune antibody: immunological relationship with hnRNP P.

    OpenAIRE

    Hassfeld, W; Chan, E K; Mathison, D A; Portman, D; Dreyfuss, G; Steiner, G; Tan, E M

    1998-01-01

    Serum from a patient showing symptoms related to autoimmunity was found to contain autoantibodies to the nuclear mitotic apparatus (NuMA) protein and to several novel nuclear antigens with estimated molecular weights of 40, 43, 72, 74 and 82 kDa. Using this serum for screening a human cDNA expression library a 2.5 kb cDNA clone was isolated which encoded the complete sequence of a protein of 633 amino acids. Sequence analysis revealed a modular structure of the protein: an acidic N-terminal r...

  2. Resistance to Streptozotocin-Induced Autoimmune Diabetes in Absence of Complement C3: Myeloid-Derived Suppressor Cells Play a Role.

    Directory of Open Access Journals (Sweden)

    Xiaogang Gao

    Full Text Available The contribution of complement to the development of autoimmune diabetes has been proposed recently. The underlying mechanisms, however, remain poorly understood. We hypothesize that myeloid-derived suppressor cells (MDSC, which act as regulators in autoimmunity, play a role in resistance to diabetes in absence of complement C3. Indeed, MDSC number was increased significantly in STZ-treated C3-/- mice. These cells highly expressed arginase I and inducible nitric oxide synthase (iNOS. Importantly, depletion of MDSC led to the occurrence of overt diabetes in C3-/- mice after STZ. Furthermore, C3-/- MDSC actively suppressed diabetogenic T cell proliferation and prevented/delayed the development of diabetes in arginase and/or iNOS-dependent manner. Both Tregs and transforming growth factor-β (TGF-β are crucial for MDSC induction in STZ-treated C3-/- mice as depletion of Tregs or blocking TGF-β bioactivity dramatically decreased MDSC number. These findings indicate that MDSC are implicated in resistance to STZ-induced diabetes in the absence of complement C3, which may be helpful for understanding of mechanisms underlying preventive effects of complement deficiency on autoimmune diseases.

  3. Axonal damage in myelin oligodendrocyte glycoprotein peptide-induced experimental autoimmune encephalomyelitis in a C57BL/6 mouse model may be not secondary to inflammatory demyelination

    Institute of Scientific and Technical Information of China (English)

    Boting Gao; Juan Chen; Qiong Wang; Wei Wang; Zhouping Tang

    2011-01-01

    The present study established a chronic experimental autoimmune encephalomyelitis model in C57BL/6 mice induced by myelin oligodendrocyte glycoprotein peptides and complete Freund's adjuvant. Onset latency was 12 days, with an incidence rate of 100%. Neuropathological characteristics included perivascular inflammatory cell infiltration, demyelination, neuronal degeneration, and axonal damage within cerebral and myelic white matter. Electron microscopy revealed swollen mitochondria, complete organ disappearance, and fused or broken myelin sheath structure, which were accompanied by myelin sheath reconstruction. Moreover, axonal damage was not consistent with demyelination distribution, and severity of axonal damage did not correlate with demyelination. Results suggested that axonal damage in an experimental autoimmune encephalomyelitis model is not secondary to inflammatory demyelination.

  4. Murine concanavalin A-induced hepatitis is prevented by interleukin 12 (IL-12) antibody and exacerbated by exogenous IL-12 through an interferon-gamma-dependent mechanism

    DEFF Research Database (Denmark)

    Nicoletti, F; Di Marco, R; Zaccone, P;

    2000-01-01

    Concanavalin A (ConA)-induced hepatitis is a cell-mediated immunoinflammatory condition similar to human autoimmune hepatitis. We investigated the role of interleukin 12 (IL-12) in hepatitis induced in NMRI and C57/BL6 mice by a single injection of ConA. Recombinant murine IL-12 administered 24...... hours and 1 hour prior to ConA exacerbated both transaminase activities in plasma and histologic signs of hepatitis. These markers of liver injury were significantly reduced by prophylactic, but not therapeutic treatment with anti-IL-12 monoclonal antibody (mAb). The disease-modulatory effects of IL-12...... augmented in IL-12/ConA-treated mice and diminished in anti-IL-12 mAb/ConA-treated mice. Anti-IFN-gamma mAb also impeded the appearance of IL-12/ConA-induced hepatitis. Thus, IL-12-induced production of IFN-gamma might play a role in mediating the hepatitis-inducing effect of ConA. However, IL-12p40...

  5. Polyanhydride Nanovaccines Induce Germinal Center B Cell Formation and Sustained Serum Antibody Responses.

    Science.gov (United States)

    Vela Ramirez, Julia E; Tygrett, Lorraine T; Hao, Jihua; Habte, Habtom H; Cho, Michael W; Greenspan, Neil S; Waldschmidt, Thomas J; Narasimhan, Balaji

    2016-06-01

    Biodegradable polymeric nanoparticle-based subunit vaccines have shown promising characteristics by enhancing antigen presentation and inducing protective immune responses when compared with soluble protein. Specifically, polyanhydride nanoparticle-based vaccines (i.e., nanovaccines) have been shown to successfully encapsulate and release antigens, activate B and T cells, and induce both antibody- and cell-mediated immunity towards a variety of immunogens. One of the characteristics of strong thymus-dependent antibody responses is the formation of germinal centers (GC) and the generation of GC B cells, which is part of the T helper cell driven cellular response. In order to further understand the role of nanovaccines in the induction of antigen-specific immune responses, their ability to induce germinal center B cell formation and isotype switching and the effects thereof on serum antibody responses were investigated in these studies. Polyanhydride nanovaccines based on 1,6-bis(p-carboxyphenoxy)hexane and 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane were used to subcutaneously administer a viral antigen. GC B cell formation and serum antibody responses induced by the nanovaccines were compared to that induced by alum-based vaccine formulations. It was demonstrated that a single dose of polyanhydride nanovaccines resulted in the formation of robust GCs and serum antibody in comparison to that induced by the alum-based formulation. This was attributed to the sustained release of antigen provided by the nanovaccines. When administered in a multiple dose regimen, the highest post-immunization titer and GC B cell number was enhanced, and the immune response induced by the nanovaccines was further sustained. These studies provide foundational information on the mechanism of action of polyanhydride nanovaccines. PMID:27319223

  6. Antigenic Complementarity in the Origins of Autoimmunity: A General Theory Illustrated With a Case Study of Idiopathic Thrombocytopenia Purpura

    Directory of Open Access Journals (Sweden)

    Jacob Couturier

    2006-01-01

    Full Text Available We describe a novel, testable theory of autoimmunity, outline novel predictions made by the theory, and illustrate its application to unravelling the possible causes of idiopathic thrombocytopenia purpura (ITP. Pairs of stereochemically complementary antigens induce complementary immune responses (antibody or T-cell that create loss of regulation and civil war within the immune system itself. Antibodies attack antibodies creating circulating immune complexes; T-cells attack T-cells creating perivascular cuffing. This immunological civil war abrogates the self-nonself distinction. If at least one of the complementary antigens mimics a self antigen, then this unregulated immune response will target host tissues as well. Data demonstrating that complementary antigens are found in some animal models of autoimmunity and may be present in various human diseases, especially ITP, are reviewed. Specific mechanisms for preventing autoimmunity or suppressing existing autoimmunity are derived from the theory, and critical tests proposed. Finally, we argue that Koch's postulates are inadequate for establishing disease causation for multiple-antigen diseases and discuss the possibility that current research has failed to elucidate the causes of human autoimmune diseases because we are using the wrong criteria.

  7. CEACAM1 induces B-cell survival and is essential for protective antiviral antibody production

    Science.gov (United States)

    Khairnar, Vishal; Duhan, Vikas; Maney, Sathish Kumar; Honke, Nadine; Shaabani, Namir; Pandyra, Aleksandra A.; Seifert, Marc; Pozdeev, Vitaly; Xu, Haifeng C.; Sharma, Piyush; Baldin, Fabian; Marquardsen, Florian; Merches, Katja; Lang, Elisabeth; Kirschning, Carsten; Westendorf, Astrid M.; Häussinger, Dieter; Lang, Florian; Dittmer, Ulf; Küppers, Ralf; Recher, Mike; Hardt, Cornelia; Scheffrahn, Inka; Beauchemin, Nicole; Göthert, Joachim R.; Singer, Bernhard B.; Lang, Philipp A.; Lang, Karl S.

    2015-01-01

    B cells are essential for antiviral immune defence because they produce neutralizing antibodies, present antigen and maintain the lymphoid architecture. Here we show that intrinsic signalling of CEACAM1 is essential for generating efficient B-cell responses. Although CEACAM1 exerts limited influence on the proliferation of B cells, expression of CEACAM1 induces survival of proliferating B cells via the BTK/Syk/NF-κB-axis. The absence of this signalling cascade in naive Ceacam1−/− mice limits the survival of B cells. During systemic infection with cytopathic vesicular stomatitis virus, Ceacam1−/− mice can barely induce neutralizing antibody responses and die early after infection. We find, therefore, that CEACAM1 is a crucial regulator of B-cell survival, influencing B-cell numbers and protective antiviral antibody responses. PMID:25692415

  8. CEACAM1 induces B-cell survival and is essential for protective antiviral antibody production.

    Science.gov (United States)

    Khairnar, Vishal; Duhan, Vikas; Maney, Sathish Kumar; Honke, Nadine; Shaabani, Namir; Pandyra, Aleksandra A; Seifert, Marc; Pozdeev, Vitaly; Xu, Haifeng C; Sharma, Piyush; Baldin, Fabian; Marquardsen, Florian; Merches, Katja; Lang, Elisabeth; Kirschning, Carsten; Westendorf, Astrid M; Häussinger, Dieter; Lang, Florian; Dittmer, Ulf; Küppers, Ralf; Recher, Mike; Hardt, Cornelia; Scheffrahn, Inka; Beauchemin, Nicole; Göthert, Joachim R; Singer, Bernhard B; Lang, Philipp A; Lang, Karl S

    2015-01-01

    B cells are essential for antiviral immune defence because they produce neutralizing antibodies, present antigen and maintain the lymphoid architecture. Here we show that intrinsic signalling of CEACAM1 is essential for generating efficient B-cell responses. Although CEACAM1 exerts limited influence on the proliferation of B cells, expression of CEACAM1 induces survival of proliferating B cells via the BTK/Syk/NF-κB-axis. The absence of this signalling cascade in naive Ceacam1(-/-) mice limits the survival of B cells. During systemic infection with cytopathic vesicular stomatitis virus, Ceacam1(-/-) mice can barely induce neutralizing antibody responses and die early after infection. We find, therefore, that CEACAM1 is a crucial regulator of B-cell survival, influencing B-cell numbers and protective antiviral antibody responses. PMID:25692415

  9. Rapid detection of antibodies against cytomegalovirus induced immediate early and early antigens by an enzyme linked immunosorbent assay.

    OpenAIRE

    M. Musiani; Carpi, C; Zerbini, M

    1984-01-01

    An enzyme linked immunosorbent assay (ELISA) for detecting antibodies against cytomegalovirus induced immediate early antigens and early antigens was developed using purified nuclear antigens and was compared with the indirect immunofluorescence test. The tests were comparable in their ability to detect positive and negative sera, and antibody titres determined by both assays were similar. The use of ELISA for the detection of antibodies against cytomegalovirus induced immediate early and ear...

  10. Optimizing IgG Therapy in Chronic Autoimmune Neuropathies: A Hypothesis Driven Approach

    OpenAIRE

    Berger, Melvin; Allen, Jeffrey A

    2015-01-01

    Prolonged intravenous immunoglobulin (IVIG) therapy is used for the chronic autoimmune neuropathies chronic idiopathic demyelinating polyneuropathy and multifocal motor neuropathy, but the doses and treatment intervals are usually chosen empirically due to a paucity of data from dose–response studies. Recent studies of the electrophysiology and immunology of these diseases suggest that antibody-induced reversible dysfunction of nodes of Ranvier may play a role in conduction block and disabili...

  11. Silicone oil- and agitation-induced aggregation of a monoclonal antibody in aqueous solution.

    Science.gov (United States)

    Thirumangalathu, Renuka; Krishnan, Sampathkumar; Ricci, Margaret Speed; Brems, David N; Randolph, Theodore W; Carpenter, John F

    2009-09-01

    Silicone oil, which is used as a lubricant or coating in devices such as syringes, needles and pharmaceutical containers, has been implicated in aggregation and particulation of proteins and antibodies. Aggregation of therapeutic protein products induced by silicone oil can pose a challenge to their development and commercialization. To systematically characterize the role of silicone oil on protein aggregation, the effects of agitation, temperature, pH, and ionic strength on silicone oil-induced loss of monomeric anti-streptavidin IgG 1 antibody were examined. Additionally, the influences of excipients polysorbate 20 and sucrose on protein aggregation were investigated. In the absence of agitation, protein absorbed to silicone oil with approximately monolayer coverage, however silicone oil did not stimulate aggregation during isothermal incubation unless samples were also agitated. A synergistic stimulation of aggregation by a combination of agitation and silicone oil was observed. Solution conditions which reduced colloidal stability of the antibody, as assessed by determination of osmotic second virial coefficients, accelerated aggregation during agitation with silicone oil. Polysorbate 20 completely inhibited silicone oil-induced monomer loss during agitation. A formulation strategy involving optimization of colloidal stability of the antibody as well as incorporation of surfactants such as polysorbate 20 is proposed to reduce silicone oil-induced aggregation of therapeutic protein products. PMID:19360857

  12. Copaiba Oil Suppresses Inflammatory Cytokines in Splenocytes of C57Bl/6 Mice Induced with Experimental Autoimmune Encephalomyelitis (EAE)

    OpenAIRE

    Débora S. Dias; Lívia B. A. Fontes; Antônio E.M. Crotti; Beatriz J. V. Aarestrup; Aarestrup, Fernando M; Ademar A. da Silva Filho; José O. A. Corrêa

    2014-01-01

    Experimental autoimmune encephalomyelitis (EAE) is a murine autoimmune disease used to study multiple sclerosis. We have investigated the immunomodulatory effects of copaiba oil (100, 50 and 25 µg/mL) on NO, H2O2, TNF-α, IFN-γ and IL-17 production in cultured cells from EAE-mice. Copaiba oil (100 µg/mL) inhibited H2O2, NO, IFN-γ TNF-α and IL-17 production spontaneously or after ConA and MOG35–55 stimulation. It is suggested that copaiba oil acts on the mechanism of development of EAE by IFN-γ...

  13. Incidence of radiation-induced Graves' disease in patients treated with radioiodine for thyroid autonomy before and after introduction of a high-sensitivity TSH receptor antibody assay

    International Nuclear Information System (INIS)

    Autoimmune hyperthyroidism may occur several months after radioiodine therapy (RIT) for functional thyroid autonomy. Exacerbation of pre-existing subclinical Graves' disease (GD) has been held responsible for this phenomenon. Determination of TSH receptor antibody using solubilised porcine epithelial cell membranes is insensitive and may have failed to diagnose GD in these patients before RIT. Following the introduction of a more sensitive assay, using the human TSH receptor as an antigen, it has been expected that the incidence of radiation-induced GD after RIT for functional thyroid autonomy will be reduced. In a first group of 1,428 patients treated between November 1993 and March 1997 (group I) we used the porcine TRAb assay to exclude GD, while in a second group comprising 1,408 patients treated between January 2000 and December 2001 (group II), GD was excluded using the human TRAb assay. A matched control group of 231 patients was derived from group II. In group I a total of 15 (1.05%) patients developed obvious or suspected radiation-induced GD, while in group II 17 (1.2%) did so; the interval until development of GD was 8.4 and 8.8 months, respectively, after RIT. Serum anti-thyroid peroxidase levels before RIT were elevated in 36.4% of group I patients and 47.1% of group II patients, but in only 5.6% of the control group. Other non-specific signs of mild immunopathy of the thyroid were seen retrospectively in 73.3%, 64.7% and 16.0% of the patients in these three groups, respectively. In conclusion, the introduction of a high-sensitivity TRAb assay did not reduce the incidence of autoimmune hyperthyroidism occurring late after RIT for functional thyroid autonomy, but mild immunopathy of the thyroid is seen more frequently in these patients and seems to be a predisposing factor in the development of radiation-induced GD. (orig.)

  14. Collision Induced Unfolding of Intact Antibodies: Rapid Characterization of Disulfide Bonding Patterns, Glycosylation, and Structures.

    Science.gov (United States)

    Tian, Yuwei; Han, Linjie; Buckner, Adam C; Ruotolo, Brandon T

    2015-11-17

    Monoclonal antibodies (mAbs) are among the fastest growing class of therapeutics due to their high specificity and low incidence of side effects. Unlike most drugs, mAbs are complex macromolecules (∼150 kDa), leading to a host of quality control and characterization challenges inherent in their development. Recently, we introduced a new approach for the analysis of the intact proteins based on ion mobility-mass spectrometry (IM-MS). Our protocol involves the collision induced unfolding (CIU) of intact antibodies, where collisional heating in the gas-phase is used to generate unfolded antibody forms, which are subsequently separated by IM and then analyzed by MS. Collisional energy is added to the antibody ions in a stepwise fashion, and "fingerprint plots" are created that track the amount of unfolding undergone as a function of the energy imparted to the ions prior to IM separation. In this report, we have used these fingerprints to rapidly distinguish between antibody isoforms, possessing different numbers and/or patterns of disulfide bonding and general levels of glycosylation. In addition, we validate our CIU protocols through control experiments and systematic statistical evaluations of CIU reproducibility. We conclude by projecting the impact of our approach for antibody-related drug discovery and development applications. PMID:26471104

  15. Identification of Novel Genetic Loci Associated with Thyroid Peroxidase Antibodies and Clinical Thyroid Disease

    DEFF Research Database (Denmark)

    Medici, Marco; Porcu, Eleonora; Pistis, Giorgio;

    2014-01-01

    Autoimmune thyroid diseases (AITD) are common, affecting 2-5% of the general population. Individuals with positive thyroid peroxidase antibodies (TPOAbs) have an increased risk of autoimmune hypothyroidism (Hashimoto's thyroiditis), as well as autoimmune hyperthyroidism (Graves' disease). As the ...

  16. Autoimmune liver disease panel

    Science.gov (United States)

    Liver disease test panel - autoimmune ... Autoimmune disorders are a possible cause of liver disease. The most common of these diseases are autoimmune hepatitis and primary biliary cirrhosis. This group of tests helps your health care provider ...

  17. Preparation of an antibody that recognizes and neutralizes Dictyostelium differentiation-inducing factor-1.

    Science.gov (United States)

    Kubohara, Yuzuru; Kikuchi, Haruhisa; Nakamura, Koji; Matsuo, Yusuke; Oshima, Yoshiteru

    2010-05-28

    In the development of the cellular slime mold Dictyostelium discoideum, the differentiation-inducing factor-1 (DIF-1; 1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl)hexan-1-one) plays an important role in the regulation of cell differentiation and chemotaxis; however, the cellular signaling systems involving DIF-1 remain to be elucidated. To obtain a probe for DIF-1, we synthesized a DIF derivative (DIF-1-NH(2); 6-amino-1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl)hexan-1-one), and prepared an anti-DIF-1 antibody using a DIF-1-NH(2)-conjugated macromolecule as the immunogen. A 100-fold dilution of the antibody bound to DIF-1-NH(2)-conjugated resin, and this binding was inhibited by co-addition of 20 microM DIF-1 or DIF-1-NH(2). In a monolayer culture of HM44 cells, a DIF-deficient D. discoideum strain, 0.5 nM exogenous DIF-1 induced stalk cell formation in approximately 60% of the cells; this induction was dose-dependently inhibited by the antibody (diluted 12.5- or 25-fold). Furthermore, this inhibition by the antibody was recovered by co-addition of 2.5 or10 nM DIF-1. The results indicate that the anti-DIF-1 antibody recognizes DIF-1 and neutralizes its function. PMID:20416278

  18. Delivering HIV Gagp24 to DCIR Induces Strong Antibody Responses In Vivo.

    Directory of Open Access Journals (Sweden)

    Anne-Laure Flamar

    Full Text Available Targeting dendritic cell-specific endocytic receptors using monoclonal antibodies fused to desired antigens is an approach widely used in vaccine development to enhance the poor immunogenicity of protein-based vaccines and to induce immune responses. Here, we engineered an anti-human DCIR recombinant antibody, which cross-reacts with the homologous cynomolgous macaque receptor and was fused via the heavy chain C-terminus to HIV Gagp24 protein (αDCIR.Gagp24. In vitro, αDCIR.Gagp24 expanded multifunctional antigen-specific memory CD4+ T cells recognizing multiple Gagp24 peptides from HIV-infected patient peripheral blood mononuclear cells. In non human primates, priming with αDCIR.Gagp24 without adjuvant elicited a strong anti-Gagp24 antibody response after the second immunization, while in the non-targeted HIV Gagp24 protein control groups the titers were weak. The presence of the double-stranded RNA poly(I:C adjuvant significantly enhanced the anti-Gagp24 antibody response in all the groups and reduced the discrimination between the different vaccine groups. The avidity of the anti-Gagp24 antibody responses was similar with either αDCIR.Gagp24 or Gagp24 immunization, but increased from medium to high avidity in both groups when poly(I:C was co-administered. This data provides a comparative analysis of DC-targeted and non-targeted proteins for their capacity to induce antigen-specific antibody responses in vivo. This study supports the further development of DCIR-based DC-targeting vaccines for protective durable antibody induction, especially in the absence of adjuvant.

  19. IL-17 Contributes to Autoimmune Hepatitis

    Institute of Scientific and Technical Information of China (English)

    余海静; 黄加权; 刘阳; 艾国; 严伟明; 王晓晶; 宁琴

    2010-01-01

    The role of interleukin-17 (IL-17) in autoimmune hepatitis (AIH) was investigated. A mouse model of experimental autoimmune hepatitis was established, and the syngeneic S-100 antigen emulsified in complete Freud's adjuvant was injected intraperitoneally into adult male C57BL/6 mice. The IL-17 expression in serum and the livers of the mice models was detected by using ELISA and immunohistochemistry, respectively. IL-17 neutralizing antibody was used to study the biological effect of IL-17 in the experimental...

  20. In vivo evidence for CD4+ and CD8+ suppressor T cells in vaccination-induced suppression of murine experimental autoimmune thyroiditis

    International Nuclear Information System (INIS)

    In several experimental autoimmune diseases, including experimental autoimmune thyroiditis (EAT), vaccination with attenuated autoantigen-specific T cells has provided protection against subsequent induction of disease. However, the mechanism(s) of vaccination-induced suppression remains to be clarified. Since the authors have previously shown that suppression generated by pretreatment with mouse thyroglobulin (MTg) or thyroid-stimulating hormone in EAT is mediated by CD4+, not CD8+, suppressor T cells, they examined the role of T cell subsets in vaccination-induced suppression of EAT. Mice were vaccinated with irradiated, MTg-primed, and MTg-activated spleen cells and then challenged. Pretreatment with these cells suppressed EAT induced by immunization with MTg and adjuvant, but not by adoptive transfer of thyroiditogenic cells, suggesting a mechanism of afferent suppression. The activation of suppressor mechanisms did not require CD8+ cells, since mice depleted of CD8+ cells before vaccination showed reduced EAT comparable to control vaccinated mice. Furthermore, depletion of either the CD4+ or the CD8+ subset after vaccination did not significantly abrogate suppression. However, suppression was eliminated by the depletion of both CD4+ and CD8+ cells in vaccinated mice. These results provide evidence for the cooperative effects of CD4+ and CD8+ T cells in vaccination-induced suppression of EAT

  1. Animal Models of Autoimmune Neuropathy

    OpenAIRE

    Soliven, Betty

    2014-01-01

    The peripheral nervous system (PNS) comprises the cranial nerves, the spinal nerves with their roots and rami, dorsal root ganglia neurons, the peripheral nerves, and peripheral components of the autonomic nervous system. Cell-mediated or antibody-mediated immune attack on the PNS results in distinct clinical syndromes, which are classified based on the tempo of illness, PNS component(s) involved, and the culprit antigen(s) identified. Insights into the pathogenesis of autoimmune neuropathy h...

  2. Update in Endocrine Autoimmunity

    OpenAIRE

    Anderson, Mark S.

    2008-01-01

    Context: The endocrine system is a common target in pathogenic autoimmune responses, and there has been recent progress in our understanding, diagnosis, and treatment of autoimmune endocrine diseases.

  3. In-vivo treatment with 5-azacytidine causes degeneration of central lymphatic organs and induces autoimmune disease in the chicken.

    Science.gov (United States)

    Schauenstein, K.; Csordas, A.; Krömer, G.; Dietrich, H.; Wick, G.

    1991-01-01

    In-vitro evidence suggests that DNA methylation may be involved in the development of forbidden immune responses that can result in autoimmune disease. In the present study we examined in-vivo effects of 5-azacytidine (5-azaC), a substance that inhibits DNA methylation, on the immune system and the occurrence of a spontaneous autoimmune disease in the chicken model. We found that (1) treatment of young normal chickens with 1.0 mg/kg 5-azaC on 7 consecutive days caused a rapid degeneration of the central lymphoid organs thymus and bursa; (2) this regimen with 5-azaC apparently inhibited B cell maturation, as the frequency of cytoplasmic Ig+ plasma cells in the bone marrow was found to be significantly reduced, whereas the total number of bone marrow cells was unchanged; and (3) a chronic low-dose (0.5 and 1.0 mg/kg) application of 5-azaC through 6 weeks was found to significantly enhance the spontaneous autoimmune thyroiditis in newly hatched chickens of the Cornell C strain, as determined by anti-thyroglobulin autoantibody titres and histological analysis of thyroid gland infiltration. The possible implications of these data for the generation of pathogenic autoimmune responses are discussed. Images Fig. 1 PMID:1726865

  4. Two cases of food additive-induced severe liver damage associated with positive results on lymphocyte stimulation test and for antinuclear antibodies.

    Science.gov (United States)

    Kaneko, Rena; Ohishi, Chitose; Kim, Miniru; Shiina, Masaaki; Kusayanagi, Satoshi; Ogawa, Masazumi; Munakata, Kazuo; Mizuno, Kyoichi; Sato, Yuzuru

    2012-08-01

    Two cases of severe liver injury and positive result for antinuclear antibodies induced by food additives are reported. The first patient reported long-term intake of Mabo Ramen(®) noodle soup, nutritional supplements, and over-the-counter drugs. Total bilirubin, aspartate aminotransferase, and alanine aminotransferase were 9.6 mg/dL, 1,048, and 1,574 IU/L, respectively. Antinuclear antibody was 80×. The drug-induced lymphocyte stimulation test (DLST) was positive for Mabo Ramen(®) and its additives such as Xanthan gum, guar gum, and Doubanjiang. Histologic examination of a liver biopsy specimen showed lymphocyte infiltration and necrosis. The autoimmune hepatitis score was 3. The second patient reported intake of dietary supplements, including Bimore C(®) and Chokora BB(®). Laboratory tests revealed that total bilirubin was 9.8 mg/dL, aspartate aminotransferase was 1,130 IU/L, and alanine aminotransferase was 1,094 IU/L. Antinuclear antibody was 320×. Co-existing pancreatic damage was confirmed by the findings on abdominal CT and elevation of serum lipase, span-1, and DUPAN-2. DLSTs were positive for both supplements. These two supplements contained additives such as titanium oxide, magnesium stearate, and hydroxypropylcellulose. DLSTs for all three additives were positive. Histologic examination revealed periportal necrosis and lymphocyte infiltration of lobular and portal areas. These two cases demonstrate that repeating DLSTs is useful for identifying causative constituents in foods and supplements. PMID:26182392

  5. GSN antibody pretreatment aggravates radiation-induced lung injury in mice

    International Nuclear Information System (INIS)

    Radiation-induced lung injury is one of the main dose limiting factors for thoracic radiation therapy. Gelsolin (GSN) is a widespread, multifunctional regulator of cellular structure and metabolism. In this work, the roles of GSN in radiation-induced lung injury in Balb/c mice were studied. The GSN levels in plasma reduced progressively in 72 hours after irradiation, and then increased gradually. GSN contents in the bronchoalveolar lavage (BAL) fluid increased after thoracic irradiation, whereas mRNA levels of GSN in the lung tissue decreased significantly within 24 hours after irradiation and then increased again. Mice were intravenously injected with 50 μg GSN antibody 0.5 hour before 20 Gy of thoracic irradiation. GSN antibody pretreatment increased lung inflammation, protein concentration in the BAL fluid and leukocytes infiltration in the irradiated mice. The activities of superoxidase dismutase (SOD) in the plasma and the BAL fluid in irradiated mice injected with GSN antibody were less than that of control groups, whereas the levels of malondialdehyde (MDA) increased. These results suggest that pretreatment of GSN antibody may aggravate radiation-induced pneumonitis. (authors)

  6. Modification of the FoxP3 transcription factor principally affects inducible T regulatory cells in a model of experimental autoimmune encephalomyelitis.

    Directory of Open Access Journals (Sweden)

    Johan Verhagen

    Full Text Available T regulatory (Treg cells expressing the transcription factor FoxP3 play a key role in protection against autoimmune disease. GFP-FoxP3 reporter mice have been used widely to study the induction, function and stability of both thymically- and peripherally-induced Treg cells. The N-terminal modification of FoxP3, however, affects its interaction with transcriptional co-factors; this can alter Treg cell development and function in certain self-antigen specific animal models. Interestingly, Treg cell function can be negatively or positively affected, depending on the nature of the model. In this study, we focused on the effect of the GFP-FoxP3 reporter on Treg cell development and function in the Tg4 mouse model. In this model, T cells express a transgenic T cell receptor (TCR specific for the Myelin Basic Protein (MBP peptide Ac1-9, making the animals susceptible to experimental autoimmune encephalomyelitis (EAE, a disease akin to multiple sclerosis in humans. Unlike diabetes-susceptible mice, Tg4 FoxP3(gfp mice did not develop spontaneous autoimmune disease and did not demonstrate augmented susceptibility to induced disease. Concurrently, thymic generation of natural Treg cells was not negatively affected. The induction of FoxP3 expression in naive peripheral T cells was, however, significantly impaired as a result of the transgene. This study shows that the requirements for the interaction of FoxP3 with co-factors, which governs its regulatory ability, differ not only between natural and inducible Treg cells but also between animal models of diseases such as diabetes and EAE.

  7. Antibody-Mediated Rejection of the Heart in the Setting of Autoimmune Demyelinating Polyneuropathy: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Kathryn J. Lindley

    2012-01-01

    Full Text Available Background. Antibody-mediated rejection (AMR is caused by the production of donor-specific antibodies (DSA which lead to allograft injury in part via complement activation. The inflammatory demyelinating polyneuropathies (IDP are inflammatory disorders of the nervous system, involving both cellular and humoral immune mechanisms directed against myelin. Case Report. A 58-year-old man five years after heart transplant presented with progressive dyspnea, imbalance, dysphagia, and weakness. Nerve conduction studies and electromyogram were consistent with IDP. Plasmapheresis and high-dose steroids resulted in improvement in neurologic symptoms. Within two weeks, he was readmitted with anasarca and acute renal failure, requiring intravenous furosemide and inotropic support. Echocardiogram and right heart catheterization revealed reduced cardiac function and elevated filling pressures. DSA was positive against HLA DR53, and endomyocardial biopsy revealed grade 1R chronic inflammation, with strong capillary endothelial immunostaining for C4d. Plasmapheresis and intravenous immunoglobulin (IVIG were initiated. His anasarca and renal failure subsequently resolved, echocardiogram showed improved function off inotropes, and anti-DR53 MFI was reduced by 57%. Conclusions. This is an example of a single immune-mediated process causing concurrent IDP and AMR. The improvement in cardiac function and neurologic symptoms with plasmapheresis, IVIG, and high-dose steroids argues for a unifying antibody-mediated mechanism.

  8. When uncommon and common coalesce: adult onset Still's disease associated with breast augmentation as part of autoimmune syndrome induced by adjuvants (ASIA).

    Science.gov (United States)

    Dagan, A; Kogan, M; Shoenfeld, Y; Segal, G

    2016-06-01

    Adult onset Still's disease (AOSD) is an uncommon, multisystemic, auto-inflammatory disorder, while breast augmentation is a very common cosmetic procedure. We describe a case in which these two coalesce, AOSD, manifested with pleuritis and pericarditis, developed after breast mammoplasty. The pathogenetic, missing link, behind the development of AOSD following mammoplasty, is thought to be the autoimmune (auto-inflammatory) syndrome induced by adjuvants (ASIA). We reviewed other cases of AOSD associated with breast mammoplasty published to date and the literature regarding AOSD and ASIA syndrome. The review is followed by a short debate of whether silicone implants should be explanted in similar, future cases. PMID:25604318

  9. 多重抗神经元抗体阳性的自身免疫性脑炎临床分析%Clinical analysis of autoimmune encephalitis with co-existence of multiple anti-neuronal antibodies

    Institute of Scientific and Technical Information of China (English)

    任海涛; 杨洵哲; 关鸿志; 高鑫雅; 彭斌; 朱以诚; 崔丽英

    2016-01-01

    antibodies to neuronal cell-surface or synaptic receptors (including N-methyl-D-aspartate receptor (NMDAR),contactin-associated protein-like 2 (CASPR2),α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR),leucine-rich glioma inactivated protein 1 (LGI1),and gamma-aminobutyric acid beta receptor (GABABR)).In those patients with positive antibodies,antibodies against intracellular neuronal antigens associated with paraneoplastic neurological symptoms were tested.Anti-aquaporin protein-4 (AQP4) antibody was tested depending on patients' clinical manifestations.Results Ten patients were detected combined with additional autoantibodies in 531 patients with positive antibodies related to autoimmune encephalitis.AntiHu antibody was positive in 5 patients with anti-GABABR encephalitis,in 1 of whom anti-NMDAR antibody was also identified;anti-AQP4 antibody was positive in 1 patient with relapsing anti-NMDAR encephalitis;anti-CASPR2 and anti-Yo antibodies were respectively positive in 2 patients with anti-LGI1 encephalitis;anti-CV2 and anti-Hu antibodies were respectively positive in 2 patients with anti-AMPAR encephalitis.Clinical presentation of all cases was consistent with typical encephalitis or limbic encephalitis.Brain stem was involved in 3 patients.Peripheral sensory neuropathy was present in 1 patient,while myalgia and fasciculation were present in 1 patient.Seven patients responded well to the immunotherapy.Tumors were pathologically or radiologically confirmed in 7 cases,including lung cancer in 5 cases,suspected thymoma in 1 case and highly suspected mediastinal tumor without pathological identification in 1 case.Conclusions Due to the pathological mechanism,co-existence of multiple autoantibodies affects clinical manifestations of patients and results in variation and overlap of them.The additional positivity of onconeuronal antibodies directs the search for occult tumor.

  10. A Bivalent, Chimeric Rabies Virus Expressing Simian Immunodeficiency Virus Envelope Induces Multifunctional Antibody Responses.

    Science.gov (United States)

    Dunkel, Amber; Shen, Shixue; LaBranche, Celia C; Montefiori, David; McGettigan, James P

    2015-11-01

    We previously showed that a matrix (M) gene-deleted rabies virus (RABV)-based vaccine (RABV-ΔM) is highly immunogenic and induces potent B cell responses in the context of RABV infection. We speculated that RABV-ΔM expressing HIV proteins would also induce potent B cell responses against HIV antigens. As a prerequisite to future studies in nonhuman primates, we completed immunogenicity studies in mice to confirm the ability of RABV-ΔM to induce polyfunctional B cell responses in the context of HIV. To that end, the envelope protein from the mac239 strain of SIV (SIVmac239Env) was cloned into RABV-ΔM, resulting in RABV-ΔM-Env. Infectious virus was recovered following standard methods and propagated on baby hamster kidney cells stably expressing RABV M [>10(7) focus forming units (ffu)/ml]. Western blot analysis of cell lysates or of purified virions confirmed Env expression on the surface of infected cells and within virus particles, respectively. Positive neutralization activity against a neutralization-sensitive SIV strain and to a lesser extent against a neutralization-resistant SIV strain was detected in mice after a single intramuscular inoculation with RABV-ΔM-Env. The quality, but not quantity, of the antibody response was enhanced via boosting with recombinant gp130 or RABV-ΔM-Env as measured by an increase in antibody avidity and a skewing toward a Th1-type antibody response. We also show that an intradermal inoculation induces higher antibodies than an intramuscular or intranasal inoculation. An intradermal inoculation of RABV-ΔM-Env followed by a boost inoculation with recombinant gp130 produced anti-SIV antibodies with neutralizing and nonneutralizing antibody (nNAb) effector functions. Together, RABV-ΔM-Env induces B cells to secrete antibodies against SIV with the potential to clear both "free" and cell-associated virus. Strategies capable of eliciting both NAbs as well as nNAbs might help to improve the efficacy of HIV-1 vaccines. PMID

  11. Autoimmune neurologic disorders in children.

    Science.gov (United States)

    Lim, Ming; Gorman, Mark

    2016-01-01

    Autoimmune neurologic diseases are of major clinical importance in children. Antibody-mediated diseases of the central nervous system are now increasingly recognized in childhood, where the antibodies bind to cell surface epitopes on neuronal or glial proteins, and the patients demonstrate either focal or more generalized clinical signs depending on the extent of brain regions targeted by the antibodies. The antibodies are directed towards ion channels, receptors, and membrane proteins; and the diseases include limbic encephalitis and N-methyl-d-aspartate receptor-antibody encephalitis, among many others. Additionally there are conditions where the wider immune system is implicated. Neurologic features like seizures, movement disorders, autonomic dysfunction, and sleep disorders, with neuroimaging and electrophysiologic features, may indicate a specific antibody-mediated or immune disorder. Often, phenotypic overlap is observed between these conditions, and phenotypic variation seen in children with the same condition. Nevertheless, many patients benefit from immunotherapy with substantial improvement, although huge efforts are still required to optimize the outcome for many patients. In many patients no antibodies have yet been identified, even though they respond to immunotherapies. Here we describe the known antibodies and associated diseases, discuss conditions that are thought to be immune-mediated but have no known immunologic biomarker, and provide guidelines for the investigation and classification of these disorders. PMID:27112693

  12. ACE inhibitors can induce circulating antibodies directed to antigens of the superficial epidermal cells.

    Science.gov (United States)

    Cozzani, Emanuele; Rosa, Gian Marco; Drosera, Massimo; Intra, Chiara; Barsotti, Antonio; Parodi, Aurora

    2011-07-01

    Drug-induced pemphigus has been reported in patients receiving angiotensin-converting enzyme inhibitors. The aim of this work was to study a group of hypertensive patients without skin diseases treated with angiotensin-converting enzyme (ACE) Inhibitors (I), to verify the presence of serum circulating anti-antibodies. The indirect immunofluorescence showed that 33 sera (52.38%) presented autoantibodies directed to an antigen of the cytoplasm of the superficial epidermal keratinocytes. Two of the 33 positive sera had antibodies to Dsg1 and/or 3 in ELISA. Immunoblot analyses were negative. All the 48 control sera were found to have no circulating antibodies using the three assays. Our results would confirm that ACEI drugs may trigger the production of circulating autoantibodies also in patients without clinical manifestations of pemphigus. PMID:20563876

  13. Encephalopathy Associated with Autoimmune Thyroid Disease: A Potentially Reversible Condition

    Directory of Open Access Journals (Sweden)

    Inês Correia

    2016-01-01

    Full Text Available Autoimmune thyroid disease may occasionally associate with unspecific neurological symptoms, which are more commonly insidious, include cognitive or behavioural symptoms, and may associate with tremor, myoclonus, or ataxia. We report a 61-year-old female patient who presented with chronic headache, insidious mood, and cognitive disturbance which evolved in a few months to dementia associated with exuberant limb myoclonus. Diagnostic workup revealed high anti-thyroid peroxidase antibody titers and an inflammatory CSF profile, and it was negative for other possible etiologies. Treatment with steroids induced significant improvement. The diagnosis of encephalopathy associated with autoimmune thyroid disease is still controversial given the fact that the clinical presentation and diagnostic workup are unspecific, the pathophysiology is still undetermined, and the diagnosis is mostly of exclusion. No direct correlation is found between anti-thyroid antibody titers and clinical presentation, and it is currently speculated that other still unrecognized antibodies may be responsible for this clinical entity. It is extremely important to recognize this entity because it is potentially treatable with immunotherapies. It is also increasingly recognized that clinical improvement with first-line treatment with steroids may be absent or incomplete, and other immunotherapies as immunosuppressants, intravenous immunoglobulin, or plasma exchange must be attempted in the clinical suspicion of EEAT.

  14. Encephalopathy Associated with Autoimmune Thyroid Disease: A Potentially Reversible Condition

    Science.gov (United States)

    Correia, Inês; Marques, Inês B.; Ferreira, Rogério; Sousa, Lívia

    2016-01-01

    Autoimmune thyroid disease may occasionally associate with unspecific neurological symptoms, which are more commonly insidious, include cognitive or behavioural symptoms, and may associate with tremor, myoclonus, or ataxia. We report a 61-year-old female patient who presented with chronic headache, insidious mood, and cognitive disturbance which evolved in a few months to dementia associated with exuberant limb myoclonus. Diagnostic workup revealed high anti-thyroid peroxidase antibody titers and an inflammatory CSF profile, and it was negative for other possible etiologies. Treatment with steroids induced significant improvement. The diagnosis of encephalopathy associated with autoimmune thyroid disease is still controversial given the fact that the clinical presentation and diagnostic workup are unspecific, the pathophysiology is still undetermined, and the diagnosis is mostly of exclusion. No direct correlation is found between anti-thyroid antibody titers and clinical presentation, and it is currently speculated that other still unrecognized antibodies may be responsible for this clinical entity. It is extremely important to recognize this entity because it is potentially treatable with immunotherapies. It is also increasingly recognized that clinical improvement with first-line treatment with steroids may be absent or incomplete, and other immunotherapies as immunosuppressants, intravenous immunoglobulin, or plasma exchange must be attempted in the clinical suspicion of EEAT.

  15. Autoimmune pancreatitis

    DEFF Research Database (Denmark)

    Detlefsen, Sönke; Drewes, Asbjørn M

    2009-01-01

    bile duct. Obstructive jaundice is a common symptom at presentation, and pancreatic cancer represents an important clinical differential diagnosis. In late stages of the disease, the normal pancreatic parenchyma is often replaced by large amounts of fibrosis. Histologically, there seem to be two...... AIP responds to steroid treatment, also a trial with steroids, can help to differentiate AIP from pancreatic cancer. OUTLOOK AND DISCUSSION: This review presents the pathological, radiologic and laboratory findings of AIP. Moreover, the treatment and pathogenesis are discussed.......BACKGROUND: Autoimmune pancreatitis (AIP) is a relatively newly recognized type of pancreatitis that is characterized by diffuse or focal swelling of the pancreas due to lymphoplasmacytic infiltration and fibrosis of the pancreatic parenchyma. MATERIAL AND METHODS: A PubMed literature search was...

  16. Collagenase-3 (MMP-13) deficiency protects C57BL/6 mice from antibody-induced arthritis

    OpenAIRE

    Singh, Anjana; Rajasekaran, Narendiran; Hartenstein, Bettina; Szabowski, Sibylle; Gajda, Mieczyslaw; Angel, Peter; Bräuer, Rolf; Illges, Harald

    2013-01-01

    Introduction Matrix metalloproteinases (MMPs) are important in tissue remodelling. Here we investigate the role of collagenase-3 (MMP-13) in antibody-induced arthritis. Methods For this study we employed the K/BxN serum-induced arthritis model. Arthritis was induced in C57BL/6 wild type (WT) and MMP-13-deficient (MMP-13 –/– ) mice by intraperitoneal injection of 200 μl of K/BxN serum. Arthritis was assessed by measuring the ankle swelling. During the course of the experiments, mice were sacri...

  17. Antinuclear antibodies are not increased in the early phase of Borrelia infection.

    NARCIS (Netherlands)

    Spiewak, R.W.; Stojek, NM; Chmielewska-Badora, J

    2004-01-01

    In the literature, there are case reports suggesting that Borrelia burgdorferi infection may induce autoimmune diseases dependent on antinuclear antibodies (ANA). The present study was undertaken in order to verify this possibility in a prospective manner. The study group comprised 78 consecutive pa

  18. Dicarbonyl Induced Structural Perturbations Make Histone H1 Highly Immunogenic and Generate an Auto-Immune Response in Cancer.

    Directory of Open Access Journals (Sweden)

    Abdul Rouf Mir

    Full Text Available Increased oxidative stress under hyperglycemic conditions, through the interaction of AGEs with RAGE receptors and via activation of interleukin mediated transcription signalling, has been reported in cancer. Proteins modifications are being explored for their roles in the development and progression of cancer and autoantibody response against them is gaining interest as a probe for early detection of the disease. This study has analysed the changes in histone H1 upon modification by methylglyoxal (MG and its implications in auto-immunopathogenesis of cancer. Modified histone showed modifications in the aromatic residues, changed tyrosine microenvironment, intermolecular cross linking and generation of AGEs. It showed masking of hydrophobic patches and a hypsochromic shift in the in ANS specific fluorescence. MG aggressively oxidized histone H1 leading to the accumulation of reactive carbonyls. Far UV CD measurements showed di-carbonyl induced enhancement of the alpha structure and the induction of beta sheet conformation; and thermal denaturation (Tm studies confirmed the thermal stability of the modified histone. FTIR analysis showed amide I band shift, generation of a carboxyethyl group and N-Cα vibrations in the modified histone. LCMS analysis confirmed the formation of Nε-(carboxyethyllysine and electron microscopic studies revealed the amorphous aggregate formation. The modified histone showed altered cooperative binding with DNA. Modified H1 induced high titre antibodies in rabbits and the IgG isolated form sera of rabbits immunized with modified H1 exhibited specific binding with its immunogen in Western Blot analysis. IgG isolated from the sera of patients with lung cancer, prostate cancer, breast cancer and cancer of head and neck region showed better recognition for neo-epitopes on the modified histone, reflecting the presence of circulating autoantibodies in cancer. Since reports suggest a link between AGE-RAGE axis and

  19. Autoimmune Progesterone Anaphylaxis

    Directory of Open Access Journals (Sweden)

    Mohammad Hassan Bemanian

    2007-06-01

    Full Text Available Progesterone induced dermatitis is a rare disorder. It typically occurs in females due to anautoimmune phenomenon to endogenous progesterone production, but can also be caused byexogenous intake of a synthetic progestin. Here in, we present a case of autoimmune progesterone anaphylaxis (AIPA observed in an adolescent female.The patient is an 18-year-old Caucasian female with no significant past medical history and noprior exogenous hormone use, who presented to her primary care physician complaining of cyclic skin eruptions with dyspnea, cough and respiratory distress. She noted that her symptoms occurred monthly, just prior to her menses. An intradermal skin test using 0.1 cml of progesterone was performed. The patient developed a 15mm wheal after 15 minutes, confirming the diagnosis of AIPA.The patient was started on a continuous regimen of an oral conjugated estrogen (0.625mg. The skin eruptions and respiratory symptoms have not returned since the initiation of this therapy.Autoimmune progesterone dermatitis manifests via the occurrence of cyclic skin eruptions.Women with the disorder commonly present with dermatologic lesions in the luteal phase of themenstrual cycle, if there are any other organ involvement in addition to skin (e.g. lung, GI thereaction should be called as autoimmune progesterone anaphylaxis. Diagnosis of AIPA is confirmed by performing a skin allergen test using progesterone.

  20. RBC Antibody Screen

    Science.gov (United States)

    ... the baby is Rh-positive and the mother's antibody status is negative for anti-D, the mother is given additional RhIG. This test also may be used to help diagnose autoimmune-related hemolytic anemia ... when a person produces antibodies against his or her own RBC antigens. This ...

  1. Rehabilitation or the death penalty: autoimmune B cells in the dock.

    Science.gov (United States)

    Dahal, Lekh N; Cragg, Mark S

    2015-03-01

    CD20-based monoclonal antibodies have become established as treatments for lymphoma, rheumatoid arthritis, systemic lupus erythematosus, vasculitis and dermatomyositis, with the principle therapeutic mechanism relating to B-cell depletion through effector cell engagement. An article by Brühl et al. in this issue of the European Journal of Immunology [Eur. J. Immunol. 2015. 45: 705-715] reveals a fundamentally distinct mechanism of silencing autoimmune B-cell responses. Rather than B-cell depletion, the authors use anti-CD79b antibodies to induce B-cell tolerance and suppress humoral immune responses against collagen to prevent the development of arthritis in mice. Here we highlight the differences in the mechanisms used by anti-CD20 and anti-CD79b Ab therapy and discuss why depletion of B cells may not be required to treat autoimmune arthritis and other B-cell-associated pathologies. PMID:25639261

  2. Antibodies with higher bactericidal activity induced by a Neisseria gonorrhoeae Rmp deletion mutant strain.

    Directory of Open Access Journals (Sweden)

    Guocai Li

    Full Text Available Neisseria gonorrhoeae (N. gonorrhoeae outer membrane protein reduction modifiable protein (Rmp has strong immunogenicity. However, anti-Rmp antibodies block rather than preserve the antibacterial effects of protective antibodies, which hampers the development of vaccines for gonococcal infections. We herein constructed an Rmp deletion mutant strain of N. gonorrhoeae by gene homologous recombination. The 261-460 nucleotide residues of Rmp gene amplified from N. gonorrhoeae WHO-A strain were replaced with a kanamycin-resistant Kan gene amplified from pET-28a. The resultant hybridized DNA was transformed into N. gonorrhoeae WHO-A strain. PCR was used to screen the colonies in which wild-type Rmp gene was replaced with a mutant gene fragment. Western blotting revealed that the Rmp deletion mutant strain did not express Rmp protein. Rmp deletion did not alter the morphological and Gram staining properties of the mutant strain that grew slightly more slowly than the wild-type one. Rmp gene mutated stably throughout 25 generations of passage. Antibody-mediated complement-dependent cytotoxicity assay indicated that the antibodies induced by the mutant strain had evidently higher bactericidal activities than those induced by the wild-type strain. Further modification of the Rmp deletion mutant strain is still required in the development of novel live attenuated vaccines for gonorrhea by Opa genes deletion or screening of phenotypic variant strains that do not express Opa proteins.

  3. Evaluation of the 2. generation radio-receptional assay for anti-TSH receptor antibodies (TRAb) in autoimmune thyroid diseases. Comparison with 1. generation and anti-thyroperoxidae antibodies (AbTPO)

    International Nuclear Information System (INIS)

    The detection of autoantibodies to the TSH-receptor (TRAb) by radio-receptor assays (RRA) is widely requested in clinical practice for the diagnostic work-up of Graves' disease and its differentiation from diffuse thyroid autonomy. Additionally, TRAb measurement can be useful during antithyroid drug treatment of Graves' disease to evaluate the risk of relapse after therapy discontinuation. Nevertheless, some patients affected by Graves' disease are TRAb-negative when 1. generation assay is used. In this study the diagnostic performance of a newly developed 2. generation TRAb assay (TRAK human DYNOtest(R), BRAHMS Diagnostica GmbH, Berlin, Germany) was evaluated in 74 untreated patients affected by Graves' disease, in 53 untreated patients affected by Hashimoto's thyroiditis and in 88 patients affected by euthyroid nodular goiter. It was also compared the new TRAb assay with the 1. generation test (TRAK(R) Assay, BRAHMS Diagnostica GmbH, Berlin, Germany) and anti-thyroperoxidase assay (AbTPO DYNOtest(R), BRAHMS GmbH, Berlin). The 2. generation TRAb assay showed the better diagnostic sensitivity in Graves' disease (97%) with respect to the 1. generation assay (85%) and AbTPO assay (64%). The AbTPO assay was positive in 50 of 53 (94%) patients affected by autoimmune thyroiditis. The 1. and 2. generation TRAb assays were positive in 4 (7%) and 7 (13%) of 53 patients affected by autoimmune thyroiditis, respectively. No patients affected by nodular goiter showed positive 1. and 2. generation TRAb assay while AbTPO levels were positive in 8 of 88 patients (specificity 91%). In conclusion, the 2. generation TRAb assay is clearly more sensitive than the 1. generation test and should be used in clinical practice to minimize the incidence of TRAb-negative Graves' disease. Long term prospective studies are needed to evaluate the prognostic role of 2. generation TRAb assay in Graves' disease. The assay of AbTPO is the best marker for autoimmune thyroiditis but is clearly less

  4. Pathogenesis of Autoimmune Diseases: A Short Review

    Directory of Open Access Journals (Sweden)

    Jithin Jose

    2014-01-01

    Full Text Available Autoimmunity is characterized by the reaction of cells (auto reactive T-lymphocytes or products (autoantibodies of the immune system against the organism’s own antigens (autoantigen. It may be part of the physiological immune response (natural autoimmunity or pathologically induced, which may eventually lead to development of clinical abnormalities (autoimmune disease. Different mechanisms are involved in the induction and progression of autoimmunity. These include genetic or acquired defects in immune tolerance or immune regulatory pathways, molecular mimicry to viral or bacterial protein, an impaired clearance of apoptotic cell material. A A number of diseases have been identified in which there is autoimmunity, due to copious production of autoantibodies and autoreactive cells. The aim of the present article is to review on the pathogenesis of autoimmune diseases.

  5. The autoimmune tautology

    OpenAIRE

    Anaya, Juan-Manuel

    2010-01-01

    Although autoimmune diseases exhibit contrasting epidemiological features, pathology, and clinical manifestations, three lines of evidence demonstrate that these diseases share similar immunogenetic mechanisms (that is, autoimmune tautology). First, clinical evidence highlights the co-occurrence of distinct autoimmune diseases within an individual (that is, polyautoimmunity) and within members of a nuclear family (that is, familial autoimmunity). Second, physiopathologic evidence indicates th...

  6. Copaiba oil suppresses inflammatory cytokines in splenocytes of C57Bl/6 mice induced with experimental autoimmune encephalomyelitis (EAE).

    Science.gov (United States)

    Dias, Débora S; Fontes, Lívia B A; Crotti, Antônio E M; Aarestrup, Beatriz J V; Aarestrup, Fernando M; da Silva Filho, Ademar A; Corrêa, José O A

    2014-01-01

    Experimental autoimmune encephalomyelitis (EAE) is a murine autoimmune disease used to study multiple sclerosis. We have investigated the immunomodulatory effects of copaiba oil (100, 50 and 25 µg/mL) on NO, H2O2, TNF-α, IFN-γ and IL-17 production in cultured cells from EAE-mice. Copaiba oil (100 µg/mL) inhibited H2O2, NO, IFN-γ TNF-α and IL-17 production spontaneously or after ConA and MOG35-55 stimulation. It is suggested that copaiba oil acts on the mechanism of development of EAE by IFN-γ, IL-17 and TNF-α inhibition, modulating the immune response on both Th1 and Th17 cells. PMID:25153880

  7. Copaiba Oil Suppresses Inflammatory Cytokines in Splenocytes of C57Bl/6 Mice Induced with Experimental Autoimmune Encephalomyelitis (EAE

    Directory of Open Access Journals (Sweden)

    Débora S. Dias

    2014-08-01

    Full Text Available Experimental autoimmune encephalomyelitis (EAE is a murine autoimmune disease used to study multiple sclerosis. We have investigated the immunomodulatory effects of copaiba oil (100, 50 and 25 µg/mL on NO, H2O2, TNF-α, IFN-γ and IL-17 production in cultured cells from EAE-mice. Copaiba oil (100 µg/mL inhibited H2O2, NO, IFN-γ TNF-α and IL-17 production spontaneously or after ConA and MOG35–55 stimulation. It is suggested that copaiba oil acts on the mechanism of development of EAE by IFN-γ, IL-17 and TNF-α inhibition, modulating the immune response on both Th1 and Th17 cells.

  8. Historical reflections on autoimmune hepatitis

    Institute of Scientific and Technical Information of China (English)

    Ian R Mackay

    2008-01-01

    Autoimmune hepatitis (AIH),initially known as chronic active or active chronic hepatitis (and by various other names),first came under clinical notice in the late 1940s.However,quite likely,chronic active hepatitis (CAH) had been observed prior to this and was attributed to a persistently destructive virus infection of the liver.An earlier (and controversial) designation in 1956 as lupoid hepatitis was derived from associated L.E.cell test positivity and emphasized accompanying multisystem features and immunological aberrations.Young women featured prominently in early descriptions of CAH.AIH was first applied in 1965 as a descriptive term.Disease-characteristic autoantibodies were defined from the early 1960s,notably antinuclear antibody (ANA),smooth muscle antibody (SMA) and liver-kidney microsomal (LKM) antibody.These are still widely used diagnostically but their relationship to pathogenesis is still not evident.A liver and disease specific autoantigen has long been searched for but unsuccessfully.Prolonged immunosuppressive therapy with predisolone and azathioprine in the 1960s proved beneficial and remains standard therapy today.AIH like many other autoimmune diseases is associated with particular HLA alleles especially with the "ancestral" B8,DR3 haplotype,and also with DR4.Looking forwards,AIH is one of the several enigmatic autoimmune diseases that,despite being (relatively) organ specific,are marked by autoimmune reactivities with non-organ-specific autoantigens.New paradigms are needed to explain the occurrence,expressions and pathogenesis of such diseases.

  9. Sex Differences in Autoimmune Disease from a Pathological Perspective

    OpenAIRE

    Fairweather, DeLisa; Frisancho-Kiss, Sylvia; Rose, Noel R.

    2008-01-01

    Autoimmune diseases affect ∼8% of the population, 78% of whom are women. The reason for the high prevalence in women is unclear. Women are known to respond to infection, vaccination, and trauma with increased antibody production and a more T helper (Th)2-predominant immune response, whereas a Th1 response and inflammation are usually more severe in men. This review discusses the distribution of autoimmune diseases based on sex and age, showing that autoimmune diseases progress from an acute p...

  10. Autoimmune myasthenia gravis, immunotherapy and thymectomy in children.

    Science.gov (United States)

    Ware, Tyson L; Ryan, Monique M; Kornberg, Andrew J

    2012-02-01

    Autoimmune myasthenia gravis is a rare condition in children. Identifying antibodies directed against the acetylcholine receptor is helpful in making the diagnosis. However, seronegative cases do exist and need to be distinguished from congenital forms of myasthenia. There is little published experience to inform the judicious management of autoimmune myasthenia gravis in children. In this article, we report our experience in the management of 12 cases of autoimmune myasthenia gravis in children in the modern era of medical immunotherapy and thymectomy. PMID:21911294

  11. Autoimmune disease-associated variants of extracellular endoplasmic reticulum aminopeptidase 1 induce altered innate immune responses by human immune cells

    OpenAIRE

    Aldhamen, Yasser A; Pepelyayeva, Yuliya; Rastall, David P. W.; Seregin, Sergey S.; Zervoudi, Efthalia; Koumantou, Despoina; Charles F Aylsworth; Quiroga, Dionisia; Godbehere, Sarah; Georgiadis, Dimitris; Stratikos, Efstratios; Amalfitano, Andrea

    2015-01-01

    ERAP1 gene polymorphisms have been linked to several autoimmune diseases; however, the molecular mechanisms underlying these associations are not well understood. Recently, we have demonstrated that ERAP1 regulates key aspects of the innate immune response. Moreover, previous studies show ERAP1 to be ER-localized and secreted during inflammation. Herein, we investigate the possible roles that ERAP1 polymorphic variants may have in modulating innate immune responses of human PBMCs using two ex...

  12. Autoimmune disease-associated variants of extracellular endoplasmic reticulum aminopeptidase 1 induce altered innate immune responses by human immune cells.

    Science.gov (United States)

    Aldhamen, Yasser A; Pepelyayeva, Yuliya; Rastall, David P W; Seregin, Sergey S; Zervoudi, Efthalia; Koumantou, Despoina; Aylsworth, Charles F; Quiroga, Dionisia; Godbehere, Sarah; Georgiadis, Dimitris; Stratikos, Efstratios; Amalfitano, Andrea

    2015-01-01

    Endoplasmic reticulum aminopeptidase 1 (ERAP1) gene polymorphisms have been linked to several autoimmune diseases; however, the molecular mechanisms underlying these associations are not well understood. Recently, we demonstrated that ERAP1 regulates key aspects of the innate immune response. Previous studies show ERAP1 to be endoplasmic reticulum-localized and secreted during inflammation. Herein, we investigate the possible roles that ERAP1 polymorphic variants may have in modulating the innate immune responses of human peripheral blood mononuclear cells (hPBMCs) using two experimental methods: extracellular exposure of hPBMCs to ERAP1 variants and adenovirus (Ad)-based ERAP1 expression. We found that exposure of hPBMCs to ERAP1 variant proteins as well as ERAP1 overexpression by Ad5 vectors increased inflammatory cytokine and chemokine production, and enhanced immune cell activation. Investigating the molecular mechanisms behind these responses revealed that ERAP1 is able to activate innate immunity via multiple pathways, including the NLRP3 (NOD-like receptor, pyrin domain-containing 3) inflammasome. Importantly, these responses varied if autoimmune disease-associated variants of ERAP1 were examined in the assay systems. Unexpectedly, blocking ERAP1 cellular internalization augmented IL-1β production. To our knowledge, this is the first report identifying ERAP1 as being involved in modulating innate responses of human immune cells, a finding that may explain why ERAP1 has been genetically associated with several autoimmune diseases. PMID:25591727

  13. Nivolumab, an Anti-Programmed Cell Death-1 Antibody, Induces Fulminant Type 1 Diabetes.

    Science.gov (United States)

    Miyoshi, Yuka; Ogawa, Osamu; Oyama, Yu

    2016-01-01

    Programmed cell death-1 (PD-1), an immunoreceptor, is located on T cells and pro-B cells and interacts with its ligands to inhibit T cell activation and proliferation, thereby promoting immunological self-tolerance. Nivolumab, an anti-PD1 antibody, blocks PD-1 and can restore anticancer immune responses by abrogating PD-1 pathway-mediated T-cell inhibition. Autoimmune adverse events are expected with PD-1 therapy. Fulminant type 1 diabetes is the subtype of type 1 diabetes. The clinical feature is the extremely rapid progression of hyperglycemia and ketoacidosis. Here we describe a 66-year-old woman with advanced melanoma who was treated with nivolumab. After 4 months and six doses of the medicine, the patient was admitted to the hospital with complaints of nausea and vomiting. The laboratory data showed ketonuria, hyperglycemia (531 mg/dl), high anion gap metabolic acidosis, HbA1c (7.3%), and absence of insulin-secreting capacity. These data are compatible with the criteria of fulminant type 1 diabetes. The patient was diagnosed with diabetic ketoacidosis because of fulminant type 1 diabetes. The findings of this case indicated that nivolumab can cause fulminant type 1 diabetes. Diabetic ketoacidosis due to fulminant type 1 diabetes is potentially fatal condition. Thus, diabetic ketoacidosis due to fulminant type 1 diabetes should be considered in the differential diagnosis when patients treated with nivolumab complain of gastrointestinal symptoms. PMID:27297738

  14. Origin and pathogenesis of antiphospholipid antibodies

    Directory of Open Access Journals (Sweden)

    C.M. Celli

    1998-06-01

    Full Text Available Antiphospholipid antibodies (aPL are a heterogeneous group of antibodies that are detected in the serum of patients with a variety of conditions, including autoimmune (systemic lupus erythematosus, infectious (syphilis, AIDS and lymphoproliferative disorders (paraproteinemia, myeloma, lymphocytic leukemias. Thrombosis, thrombocytopenia, recurrent fetal loss and other clinical complications are currently associated with a subgroup of aPL designating the antiphospholipid syndrome. In contrast, aPL from patients with infectious disorders are not associated with any clinical manifestation. These findings led to increased interest in the origin and pathogenesis of aPL. Here we present the clinical features of the antiphospholipid syndrome and review the origin of aPL, the characteristics of experimentally induced aPL and their historical background. Within this context, we discuss the most probable pathogenic mechanisms induced by these antibodies.

  15. Neonatal molecular pathologies induced by maternal anti-Ro and anti-La antibodies

    OpenAIRE

    Herrera-Esparza R.; Avalos-Díaz E

    2015-01-01

    Maternal antinuclear antibodies with anti-Ro or anti-La specificity might be pathogenic to the fetus and could induce molecular neonatal pathologies, such as neonatal lupus (NL) with or without congenital heart block (CHB). The cutaneous manifestations of neonatal lupus appear at birth or a few weeks later, and skin lesions may persist for weeks. While CHB is characterized by intrauterine bradycardia or low heart rates at birth and may persist for months, depending on the degree of blockage....

  16. Nebulized Anti-IL-13 Monoclonal Antibody Fab' Fragment Reduces Allergen-Induced Asthma

    OpenAIRE

    Hacha, Jonathan; Tomlinson, K; Maertens, Ludovic; Paulissen, Geneviève; Rocks, Natacha; Foidart, Jean-Michel; Noël, Agnès; Palframan, R; Guéders, Maud; Cataldo, Didier

    2012-01-01

    Rationale: Interleukin-13 (IL-13) is a prototypic Th2 cytokine and a central mediator of the complex cascade of events leading to asthmatic phenotype. Indeed, IL-13 plays key roles in IgE synthesis, bronchial hyperresponsiveness, mucus hypersecretion, subepithelial fibrosis and eosinophil infiltration. Objectives: We assessed the potential efficacy of inhaled anti-IL-13 monoclonal antibody Fab' fragment on allergen-induced airway inflammation, hyperresponsiveness and remodeling in an experime...

  17. Antibody contributes to heterosubtypic protection against influenza A-induced tachypnea in cotton rats

    OpenAIRE

    Ottolini Martin G; Straight Timothy M; Prince Gregory A; Eichelberger Maryna C

    2008-01-01

    Abstract Background Influenza virus infection or vaccination evokes an antibody response to viral hemagglutinin (HA) and neuraminidase (NA) surface glycoproteins, which results in immunity against influenza A viruses of the same HA and NA subtype. A heterosubtypic immune response that offers some protection against different influenza A subtypes has been suggested from epidemiologic studies in human influenza outbreaks, and has been induced in experimental animal models. Original studies of s...

  18. Warm Autoimmune Haemolytic Anaemia and autoimmune hepatitis in an asymptomatic carrier of hepatitis B virus

    International Nuclear Information System (INIS)

    Warm antibody autoimmune haemolytic anaemia, a rare disease (0.2-1 per 100,000 populations), is due to the presence of warm agglutinins that react with protein antigens on the surface of red blood cells causing their premature destruction. Here, we present a case report of a 10 year old girl who came with features of haemolytic anaemia and history of blood transfusion since 3 years. On admission, laboratory test revealed that she had autoimmune hepatitis type 1 and was also an asymptomatic carrier of hepatitis B virus with positive HBs Ag. Steroid therapy resulted in clinical and laboratory remission. Direct antiglobulin test was negative after anaemia resolution, hepatitis B virus antigenemia persisted. To our knowledge, warm antibody autoimmune hemolytic anaemia has not previously been described in association with autoimmune hepatitis and asymptomatic carrier state of hepatitis B virus. (author)

  19. Delayed adaptive immunity is related to higher MMR vaccine-induced antibody titers in children.

    Science.gov (United States)

    Strömbeck, Anna; Lundell, Anna-Carin; Nordström, Inger; Andersson, Kerstin; Adlerberth, Ingegerd; Wold, Agnes E; Rudin, Anna

    2016-04-01

    There are notable inter-individual variations in vaccine-specific antibody responses in vaccinated children. The aim of our study was to investigate whether early-life environmental factors and adaptive immune maturation prior and close to measles-mumps-rubella (MMR) immunization relate to magnitudes of vaccine-specific antibody titers. In the FARMFLORA birth cohort, including both farming and non-farming families, children were immunized with the MMR vaccine at 18 months of age. MMR vaccine-induced antibody titers were measured in plasma samples obtained at 36 months of age. Infants' blood samples obtained at birth, 3-5 days and at 4 and 18 months of age were analyzed for T- and B-cell numbers, proportions of naive and memory T and B cells, and fractions of putative regulatory T cells. Multivariate factor analyses show that higher anti-MMR antibody titers were associated with a lower degree of adaptive immune maturation, that is, lower proportions of memory T cells and a lower capacity of mononuclear cells to produce cytokines, but with higher proportions of putative regulatory T cells. Further, children born by cesarean section (CS) had significantly higher anti-measles titers than vaginally-born children; and CS was found to be associated with delayed adaptive immunity. Also, girls presented with significantly higher anti-mumps and anti-rubella antibody levels than boys at 36 months of age. These results indicate that delayed adaptive immune maturation before and in close proximity to immunization seems to be advantageous for the ability of children to respond with higher anti-MMR antibody levels after vaccination. PMID:27195118

  20. An elderly ‘kawara’ craftsman with acute kidney injury and haemoptysis: a case of silica-induced autoimmunity

    OpenAIRE

    Matsui, Satoshi; Tsuji, Hiroko; Ono, Shinji

    2010-01-01

    A 62-year-old Japanese ‘kawara’ (ceramic roof tile) craftsman presented with acute kidney injury and haemoptysis. This case met the systemic lupus erythematosus and microscopic polyangiitis criteria, with high titres of myeloperoxidase–antineutrophil cytoplasmic antibody (570 EU). Results showed the presence of antinuclear antibody at a high titre (1:2560), but detection of rheumatoid factor, anti-dsDNA, anti-SSA and anti-SSB antibodies was not apparent. This serology was similar to drug-indu...

  1. Anti-neutrophil cytoplasm autoantibodies (ANCA) in autoimmune liver diseases

    NARCIS (Netherlands)

    Roozendaal, C.; Kallenberg, Cees

    1999-01-01

    Anti-neutrophil cytoplasm antibodies (ANCA) are autoantibodies directed against cytoplasmic constituents of neutrophil granulocytes and monocytes. ANCA have been detected in serum from patients with inflammatory bowel diseases (mainly ulcerative colitis) and autoimmune mediated liver diseases (mainl

  2. Antibody-induced down-regulation of a mutated insulin receptor lacking an intact cytoplasmic domain

    International Nuclear Information System (INIS)

    Insulin receptor down-regulation was studied in various Chinese hamster ovary (CHO) cell lines expressing transfected human insulin receptor cDNAs. In addition to a cell line expressing the normal receptor (CHO.T line), three lines expressing mutated receptors were studied: the CHO.T-t line, which expresses a receptor with a degraded cytoplasmic domain due to the removal of the C-terminal 112 amino acids, and the CHO.YF1 and CHO.YF3 lines, in which important autophosphorylation sites of the receptor kinase (tyrosines-1162 and -1163) have been replaced by phenylalanine. A monoclonal anti-receptor antibody, but not insulin itself, was found to down-regulate cell surface receptor levels in all four cell lines by 60-80% after 18-h treatment at 370C. Down-regulation of the CHO.T and CHO.T-t receptors occurred at similar antibody concentrations and with a similar time course, although the maximum level of CHO.T-t down-regulation (60%) was generally lower than the level of CHO.T down-regulation (80%). Pulse-chase labeling of these two cell types with [35S]methionine revealed that antibody treatment of both CHO.T and CHO.T-t cells resulted in a similar increase in the rate of degradation of mature receptor subunits. These results indicate that antibody-induced down-regulation of the insulin receptor in these cells can occur in the absence of various autophosphorylation sites of the receptor and that the mechanism of antibody-induced down-regulation is different from that for insulin

  3. Mimotopes selected with a neutralizing antibody against urease B from Helicobacter pylori induce enzyme inhibitory antibodies in mice upon vaccination

    Directory of Open Access Journals (Sweden)

    Long Min

    2010-11-01

    Full Text Available Abstract Background Urease B is an important virulence factor that is required for Helicobacter pylori to colonise the gastric mucosa. Mouse monoclonal antibodies (mAbs that inhibit urease B enzymatic activity will be useful as vaccines for the prevention and treatment of H. pylori infection. Here, we produced murine mAbs against urease B that neutralize the enzyme's activity. We mapped their epitopes by phage display libraries and investigated the immunogenicity of the selected mimotopes in vivo. Results The urease B gene was obtained (GenBank accession No. DQ141576 and the recombinant pGEX-4T-1/UreaseB protein was expressed in Escherichia coli as a 92-kDa recombinant fusion protein with glutathione-S-transferase (GST. Five mAbs U001-U005 were produced by a hybridoma-based technique with urease B-GST as an immunogen. Only U001 could inhibit urease B enzymatic activity. Immunoscreening via phage display libraries revealed two different mimotopes of urease B protein; EXXXHDM from ph.D.12-library and EXXXHSM from ph.D.C7C that matched the urease B proteins at 347-353 aa. The antiserum induced by selected phage clones clearly recognised the urease B protein and inhibited its enzymatic activity, which indicated that the phagotope-induced immune responses were antigen specific. Conclusions The present work demonstrated that phage-displayed mimotopes were accessible to the mouse immune system and triggered a humoral response. The urease B mimotope could provide a novel and promising approach for the development of a vaccine for the diagnosis and treatment of H. pylori infection.

  4. Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of coxsackievirus b3-induced viral myocarditis reduces myocardium inflammation

    OpenAIRE

    Fan Yang; Weifeng Wu; Yuluan Yan; Qing Kong; Yu Pang; Yanlan Huang

    2011-01-01

    Abstract Background Recently, some studies indicate that interleukin (IL)-17, known as a T cell (Th17)-derived proinflammatory cytokine, is the major mediator of tissue inflammation in inflammatory and autoimmune diseases. Viral myocarditis (VMC) is a T cell-mediated autoimmune disease, but the role for IL-17 in VMC is not well defined. Results Using IL-17 monoclonal antibody (IL-17mAb)-treated VMC mice, we tested the pathogenic role of IL-17 in the development of VMC. VMC mice were treated w...

  5. Porphyria cutanea tarda associated with autoimmune hypothyroidism, vitiligo and alopecia universalis.

    Science.gov (United States)

    Sabán, J; Rodríguez-García, J L; Gil, J; País, J R; Medina, S

    1991-12-01

    The aetiology of porphyria cutanea tarda (PCT) has not been elucidated, but the possibility of an autoimmune mechanism has been proposed. We report a case of an unknown clinical combination of PCT with autoimmune hypothyroidism, alopecia universalis and vitiligo with thyroid and parietal cell circulating antibodies. This is highly suggestive of underlying autoimmune damage in this patient. PMID:1803247

  6. Arg deficiency does not influence the course of Myelin Oligodendrocyte Glycoprotein (MOG35-55)-induced experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Jacobsen, Freja Aksel; Hulst, Camilla; Bäckström, Thomas;

    2016-01-01

    Background: Inhibition of Abl kinases has an ameliorating effect on the rodent model for multiple sclerosis, experimental autoimmune encephalomyelitis, and arrests lymphocyte activation. The family of Abl kinases consists of the Abl1/Abl and Abl2/Arg tyrosine kinases. While the Abl kinase has bee...... encephalomyelitis is not dependent on Arg, but Arg plays a role for the number of B cells in immunized mice. This might suggest a novel role for the Arg kinase in B-cell trafficking or regulation. Furthermore, the results suggest that Arg is important for normal embryonic development....

  7. Autoimmune Cytopenias in Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Giovanni D'Arena

    2013-01-01

    Full Text Available The clinical course of chronic lymphocytic leukemia (CLL may be complicated at any time by autoimmune phenomena.The most common ones are hematologic disorders, such as autoimmune hemolytic anemia (AIHA and immune thrombocytopenia (ITP. Pure red cell aplasia (PRCA and autoimmune agranulocytosis (AG are, indeed, more rarely seen. However, they are probably underestimated due to the possible misleading presence of cytopenias secondary to leukemic bone marrow involvement or to chemotherapy cytotoxicity. The source of autoantibodies is still uncertain, despite the most convincing data are in favor of the involvement of resting normal B-cells. In general, excluding the specific treatment of underlying CLL, the managementof these complications is not different from that of idiopathic autoimmune cytopenias or of those associated to other causes. Among different therapeutic approaches, monoclonal antibody rituximab, given alone or in combination, has shown to be very effective.

  8. Association between chronic urticaria and thyroid autoimmunity.

    Science.gov (United States)

    Cebeci, Filiz; Tanrikut, Ayşenur; Topcu, Elif; Onsun, Nahide; Kurtulmus, Neslihan; Uras, Ahmet R

    2006-01-01

    The association between chronic idiopathic urticaria (CIU) and thyroid autoimmunity has most often been suggested in studies investigating thyroid microsomal antibodies, which are less sensitive and specific than anti-thyroperoxidase antibodies, moreover these studies were not case-control studies in large series. By comparing a large patient series presenting with CIU with a large numbered control group we aimed to learn the extent of autoimmune thyroid disease. We compared the frequency of thyroid autoantibodies in 140 patients with CIU with 181 age-and sex-matched volunteers. Thyroid function tests and thyroid autoantibodies were measured by chemiluminescent immunometric assay in study groups. The frequency of thyroid autoantibodies was significantly higher in patients with CIU than that in healthy controls (29.28 %/5.52%; p CIU and thyroid autoimmunity. PMID:16935798

  9. MicroRNA-674-5p/5-LO axis involved in autoimmune reaction of Concanavalin A-induced acute mouse liver injury.

    Science.gov (United States)

    Su, Kunkai; Wang, Qi; Qi, Luoyang; Hua, Dasong; Tao, Jingjing; Mangan, Connor J; Lou, Yijia; Li, Lanjuan

    2016-09-01

    Autoimmune hepatitis is characterized, in part, by the pathways involving cysteinyl-leukotriene metabolites of arachidonic acid, the dynamics of which remain unclear. Here, we explored post-transcriptional regulation in the 5-lipoxygenase (5-LO) pathway of arachidonic acid in a Concanavalin A (Con A) induced mouse model. We found that Con A administration lead to 5-LO overexpression and cysteinyl-leukotriene release in early hepatic injury, which was attenuated by cyclosporin A pretreatment. Subsequent microarray and qRT-PCR analysis further showed that microRNA-674-5p (miR-674-5p) displayed a significant decrease in expression in Con A-damaged liver. Noting that miR-674-5p harbors a potential binding region for 5-LO, we further transfected hepatic cell lines with overexpressing miR-674-5p mimic and discovered a negative regulating effect of miR-674-5p on 5-LO expression in the presence of IL-6 or TNF-α. These findings suggest that miR-674-5p might be a negative regulator in 5-LO mediated autoimmune liver injury, representing a compelling avenue towards future therapeutic interventions. PMID:27313091

  10. Monoclonal antibodies against ROR1 induce apoptosis of chronic lymphocytic leukemia (CLL) cells.

    Science.gov (United States)

    Daneshmanesh, A H; Hojjat-Farsangi, M; Khan, A S; Jeddi-Tehrani, M; Akhondi, M M; Bayat, A A; Ghods, R; Mahmoudi, A-R; Hadavi, R; Österborg, A; Shokri, F; Rabbani, H; Mellstedt, H

    2012-06-01

    ROR1 is a receptor tyrosine kinase (RTK) recently identified to be overexpressed at the gene and protein levels in chronic lymphocytic leukemia (CLL). Monoclonal antibodies (MAbs) against RTKs have been successfully applied for therapy of solid tumors. We generated five MAbs against the Ig (n = 1), cysteine-rich (CRD) (n = 2) and kringle (KNG) (n = 2) domains, respectively, of the extracellular part of ROR1. All CLL patients (n = 20) expressed ROR1 on the surface of the leukemic cells. A significantly higher frequency of ROR1 expression was found in patients with progressive versus non-progressive disease, and in those with unmutated versus mutated IgVH genes. All five MAbs alone induced apoptosis in the absence of complement or added effector cells (Annexin-V and MTT, as well as cleavage of poly-(ADP ribose)-polymerase, caspase-8 and caspase-9) of CLL cells but not of normal B cells. Most effective were MAbs against CRD and KNG, significantly superior to rituximab (P < 0.005). Cross-linking of anti-ROR1 MAbs using the F(ab')(2) fragments of anti-Fc antibodies significantly augmented apoptosis. Two of the MAbs induced complement-dependent cytotoxicity (CDC) similar to that of rituximab and one anti-ROR1 MAb (KNG) (IgG1) showed killing activity by antibody-dependent cellular cytotoxicity. The identified ROR1 epitopes may provide a basis for generating human ROR1 MAbs for therapy. PMID:22289919

  11. Questions and Answers on Autoimmunity and Autoimmune Diseases

    Science.gov (United States)

    ... dermatomyositis . What are some of the treatments for autoimmune diseases? Of first importance in treating any autoimmune disease ... being researched. What is the family connection in autoimmune diseases? The ability to develop an autoimmune disease is ...

  12. Antibody against the insulin receptor causes disappearance of insulin receptors in 3T3-L1 cells: a possible explanation of antibody-induced insulin resistance.

    OpenAIRE

    Grunfeld, C.

    1984-01-01

    The effect of a rabbit antibody induced against the rat insulin receptor (RAR) was tested using cultured 3T3-L1 fat cells. As previously seen with antibodies against the insulin receptor from patients with the type B syndrome of insulin resistance and acanthosis nigricans, RAR acutely mimicked the action of insulin by stimulating deoxyglucose uptake. After prolonged exposure of 3T3-L1 cells to RAR, insulinomimetic activity was lost and the cells became resistant to the action of insulin. This...

  13. Preventing and curing citrulline-induced autoimmune arthritis in a humanized mouse model using a Th2-polarizing iNKT cell agonist.

    Science.gov (United States)

    Walker, Kyle M; Rytelewski, Mateusz; Mazzuca, Delfina M; Meilleur, Shannon A; Mannik, Lisa A; Yue, David; Brintnell, William C; Welch, Ian; Cairns, Ewa; Haeryfar, S M Mansour

    2012-07-01

    Invariant natural killer T (iNKT) cells are innate lymphocytes with unique reactivity to glycolipid antigens bound to non-polymorphic CD1d molecules. They are capable of rapidly releasing pro- and/or anti-inflammatory cytokines and constitute attractive targets for immunotherapy of a wide range of diseases including autoimmune disorders. In this study, we have explored the beneficial effects of OCH, a Th2-polarizing glycolipid agonist of iNKT cells, in a humanized mouse model of rheumatoid arthritis (RA) in which citrullinated human proteins are targeted by autoaggressive immune responses in mice expressing an RA susceptibility human leukocyte antigen (HLA) DR4 molecule. We found for the first time that treatment with OCH both prevents and cures citrulline-induced autoimmune arthritis as evidenced by resolved ankle swelling and reversed histopathological changes associated with arthritis. Also importantly, OCH treatment blocked the arthritogenic capacity of citrullinated antigen-experienced splenocytes without compromising their global responsiveness or altering the proportion of splenic naturally occurring CD4(+)CD25(+)FoxP3(+) regulatory T cells. Interestingly, administering the Th1-promoting iNKT cell glycolipid ligand α-C-galactosylceramide into HLA-DR4 transgenic mice increased the incidence of arthritis in these animals and exacerbated their clinical symptoms, strongly suggesting a role for Th1 responses in the pathogenesis of citrulline-induced arthritis. Therefore, our findings indicate a role for Th1-mediated immunopathology in citrulline-induced arthritis and provide the first evidence that iNKT cell manipulation by Th2-skewing glycolipids may be of therapeutic value in this clinically relevant model, a finding that is potentially translatable to human RA. PMID:21912419

  14. Immune enhancement by novel vaccine adjuvants in autoimmune-prone NZB/W F1 mice: relative efficacy and safety

    Directory of Open Access Journals (Sweden)

    Ghosh Swapan K

    2011-10-01

    Full Text Available Abstract Background Vaccines have profoundly impacted global health although concerns persist about their potential role in autoimmune or other adverse reactions. To address these concerns, vaccine components like immunogens and adjuvants require critical evaluation not only in healthy subjects but also in those genetically averse to vaccine constituents. Evaluation in autoimmune-prone animal models of adjuvants is therefore important in vaccine development. The objective here was to assess the effectiveness of experimental adjuvants: two phytol-derived immunostimulants PHIS-01 (phytanol and PHIS-03 (phytanyl mannose, and a new commercial adjuvant from porcine small intestinal submucosa (SIS-H, relative to a standard adjuvant alum. Phytol derivatives are hydrophobic, oil-in water diterpenoids, while alum is hydrophilic, and SIS is essentially a biodegradable and collagenous protein cocktail derived from extracellular matrices. Results We studied phthalate -specific and cross-reactive anti-DNA antibody responses, and parameters associated with the onset of autoimmune disorders. We determined antibody isotype and cytokine/chemokine milieu induced by the above experimental adjuvants relative to alum. Our results indicated that the phytol-derived adjuvant PHIS-01 exceeded alum in enhancing anti-phthalate antibody without much cross reactivity with ds-DNA. Relatively, SIS and PHIS-03 proved less robust, but they were also less inflammatory. Interestingly, these adjuvants facilitated isotype switching of anti-hapten, but not of anti-DNA response. The current study reaffirms our earlier reports on adjuvanticity of phytol compounds and SIS-H in non autoimmune-prone BALB/c and C57BL/6 mice. These adjuvants are as effective as alum also in autoimmune-prone NZB/WF1 mice, and they have little deleterious effects. Conclusion Although all adjuvants tested impacted cytokine/chemokine milieu in favor of Th1/Th2 balance, the phytol compounds fared better in

  15. 卵巢早衰抗卵巢抗体和抗透明带抗体及其分类%Study on anti-ovarian antibodies and anti-zona pellucida antibodies and their classfication in auto-immune premature ovarian failure

    Institute of Scientific and Technical Information of China (English)

    杨宁; 欧汝强; 陈巧儿; 王一峰

    2001-01-01

    Objective To study the level and classfication of anti-ovarian antibodies (AoAb) and anti-zona pellucida antibodies (AZpAb) in the sera of premature ovarian failure (POF) patients and to study the pathogenesis of POF. Methods The level and classfication of AoAb and AZpAb in the sera from patient with POF, female infertility with the positive AsAb and the female patient with unexplained infertility were detected by using an enzyme-linked immunosorbent assay (ELISA). Results The level of AoAb and AZpAb in the sera from patient with POF, female infertility with the positive AsAb and female unexplaned infertile patients were significantly higher than those in normal control (P<0.01). Classfication of antibodies demonstrated that they were major IgG in the sera of POF, positive AsAb infertile and unexplaned infertile group. IgA and IgM were less. Conclusion There are significant relation between POF and auto-immunity, important for further study and prevention of auto-immune POF.%目的 探讨卵巢早衰(POF)患者血清中抗卵巢抗体(AoAb)、抗透明带抗体(AZpAb)水平及其分类情况,研究免疫性卵巢早衰的发病机理。方法 用酶联免疫法测定卵巢早衰、抗精子抗体(ASAb)阳性不孕妇女和不明原因不孕症妇女血清中AoAb,AZpAb并对其进行分类。结果 POF患者、ASAb阳性不孕妇女组及不育患者组血清中AoAb\\,AZpAb均比正常妇女组高(P<0.01)。在抗体的分类证明,各组抗体以IgG为主,IgA,IgM也有一定的比例。结论 POF与自身免疫异常密切相关,该结果对于深入研究和预防自身免疫性卵巢早衰有重要意义。

  16. Results analysis of antinuclear antibodies spectrum tests in four kinds of autoimmune diseases%自身免疫性疾病的抗核抗体谱检测

    Institute of Scientific and Technical Information of China (English)

    张园园; 潘宝龙; 马骏; 李俊娥

    2016-01-01

    目的:探讨抗核抗体谱(ANAs)检测在系统性红斑狼疮(SLE)、干燥综合征(SS)、混合性结缔组织病(MCTD)、类风湿性关节炎(RA)患者中的诊断价值。方法回顾性分析1359例自身免疫性疾病患者血清抗核抗体谱16项检测,对单个抗体在4种疾病患者中的阳性率每种疾病中ANAs的构成比进行分析。结果 ANA在前3种疾病中阳性率均高于RA;抗ds-DNA、抗nRNP主要见于SLE和MCTD;抗Sm主要见于SLE;抗SSA、抗Ro-52、抗SSB阳性率表现为SS>MCTD>SLE>RA;抗SCL-70、抗PM-SCL、抗Jo-1均为较低阳性率;其余自身抗体阳性率表现为SLE>MCTD>SS≈RA。在数据基础上形成了4种自身免疫性疾病诊断的ANAs阳性率参考模型。结论可根据ANA谱中单个抗体在4种疾病中的阳性率特点,建立4种自身免疫性疾病诊断和鉴别诊断的ANAs阳性率参考模型。%ObjectiveTo explore the value of antinuclear antibodies(ANAs) spectrum tests in SLE、SS、MCTD and RA.Methods Retrospectively analyzed ANAs test results of 1359 cases patients with autoimmune diseases in our hospital since January 2011, made statistical analysis on positive rate of each autoantibody in four kinds of disease and ANAs constituent ratio in each disease.Results The positive rate of each autoantibody had certain characteristics :(1)The ANA positive rate in the previous three diseases reached more than 92.8%, while somewhat less in RA (48.5%);(2)Anti-dsDNA and anti-nRNP were mainly in SLE and MCTD;(3)Anti-Sm was mainly in SLE(26.5%);(4)The positive rates of anti-SSA,anti-Ro-52 and anti-SSB showed: SS>MCTD>SLE>RA; (5)The positive rates of anti-SCL70, anti-PM-SCL and anti-Jo1 were lower, no significant difference;(6)The other remaining autoantibodies were: SLE>MCTD>SS≈RA. The diagnostic reference model of ANAs constituent ratio of the four kinds of autoimmune disease: (1)SLE: ANA (93.1%), Ro-52 (50.4%), SSA (47.3%), Ans (42.5%), anti-dsDNA (41

  17. Thyroid autoimmunity in pregnant Nigerians

    Directory of Open Access Journals (Sweden)

    Oluwatosin O Kayode

    2015-01-01

    Full Text Available Context: Thyroid autoimmunity is a recognized disorder in pregnancy and is associated with a number of adverse pregnancy outcomes. Aim: This study set out to determine the relationship between pregnancy and thyroid autoimmunity in Nigerian women. Settings and Design: This was an analytical cross-sectional study carried out in a tertiary hospital in South Western Nigeria with a total study population of 108 pregnant and 52 nonpregnant women. Subjects and Methods: Serum thyroid stimulating hormone, free thyroxine and thyroid peroxidase antibodies (TPO-Ab were quantitatively determined using enzyme linked immuno-assays. Pregnant women were grouped into three categories ( 28 weeks. The relationship between pregnancy and thyroid autoimmunity was determined using Spearman correlation. Analysis of variance was used in comparison of means, Chi-square test used in analyzing proportions while P ≤ 0.05 was considered as significant. Results: The mean age of the pregnant women was 30.4 ± 6.0 years while the mean gestational age of all pregnant women was 20.6 ± 9.6 weeks. The mean TPO-Ab of 11.58 IU/ml in the pregnant was significantly higher than that of the controls of 7.23 IU/ml (P < 0.001. Out of 108 pregnant women, 27 (25% had elevated TPO-Ab as against about 2% of the nonpregnant women levels P < 0.001. The number of pregnant women with elevated TPO-Ab levels decreased from 33.3% in the first group to 25.6% and 15.2% in the second and third groups. Conclusion: Thyroid autoimmunity expressed by the presence of TPO-Ab is high among pregnant Nigerian women and the frequency of autoimmunity appears to decline with advancing gestational age.

  18. Short- and long-term effects of T-cell modulating agents in experimental autoimmunity

    International Nuclear Information System (INIS)

    Due to the easy and reliable induction of a disease condition with many of the features present in human autoimmunity, mercury-induced autoimmunity (mHgAI) in rodents is a favourable autoimmune model. Genetically susceptible (H-2s) mice develop in response to mercury (Hg) a systemic autoimmune condition with antinucleolar antibodies (ANoA) targeting the protein fibrillarin, transient polyclonal B-cell activation, hyperimmunoglobulinemia, and systemic immune-complex (IC) deposits. In order to study the short- and long-term effects of treatment with immunomodulating agents on the disease parameters in HgAI, groups of B10.S (H-2s) mice were given 6 mg HgCl2/l drinking water for 22 weeks. Three weeks initial treatment with cyclosporin A (CyA), a high dose of tacrolimus (HD tacrolimus), or anti-CD4 monoclonal antibody (a-CD4) inhibited induction of ANoA and IC deposit by Hg. This effect persisted for the subsequent 19 weeks when the mice were only treated with Hg. Initial treatment with anti-IL-4 monoclonal antibody (a-IL-4) for 3 weeks inhibited induction of IgE and IC deposits by Hg, but not ANoA. However, subsequent treatment with Hg without a-IL-4 for 19 weeks induced IC deposits. The T-cell modulating agents aggravated some of the HgAI disease parameters: a-CD4 stimulated the polyclonal B-cell activation, a-IL-4 increased the IgG antichromatin antibody response, and a low dose of tacrolimus (LD tacrolimus) enhanced the ANoA, the polyclonal B-cell activation, and the IC deposits. We conclude that a short initial treatment with a-CD4 or CyA efficiently protects against induction of systemic autoimmunity for an extended period of time. However, some of the T-cell modulating agents, especially a low dose of tacrolimus, aggravate autoimmune manifestations not only during ongoing treatment, but also after treatment with these agents has ceased

  19. Detection of newly antibody-defined epitopes on HLA class I alleles reacting with antibodies induced during pregnancy.

    Science.gov (United States)

    Duquesnoy, R J; Hönger, G; Hösli, I; Marrari, M; Schaub, S

    2016-08-01

    The determination of HLA mismatch acceptability at the epitope level can be best performed with epitopes that have been verified experimentally with informative antibodies. The website-based International Registry of HLA Epitopes (http://www.epregistry.com.br) has a list of 81 antibody-verified HLA-ABC epitopes but more epitopes need to be added. Pregnancy offers an attractive model to study antibody responses to mismatched HLA epitopes which can be readily determined from the HLA types of child and mother. This report describes a HLAMatchmaker-based analysis of 16 postpregnancy sera tested in single HLA-ABC allele binding assays. Most sera reacted with alleles carrying epitopes that have been antibody-verified, and this study focused on the reactivity of additional alleles that share other epitopes corresponding to eplets and other amino acid residue configurations. This analysis led in the identification of 16 newly antibody-defined epitopes, seven are equivalent to eplets and nine correspond to combinations of eplets in combination with other nearby residue configurations. These epitopes will be added to the repertoire of antibody-verified epitopes in the HLA Epitope Registry. PMID:27312793

  20. Screening tests for autoimmune-related immunotoxicity.

    OpenAIRE

    Pieters, R; Albers, R

    1999-01-01

    A large number of chemicals induce or exacerbate autoimmune-like diseases in man. Because of the complexity of processes involved, these adverse effects are often if not always missed in standard toxicity testing. To date no validated and generally applicable predictive animal model exists and only a few chemicals have actually been shown to induce adverse autoimmune effects in certain animals. The popliteal lymph node assay (PLNA) is a very promising animal test to (pre)screen for systemic i...

  1. Clinical implications of a new TSH-receptor-antibody-assay (DYNOtest {sup trademark} TRAKhuman) in autoimmune thyroid diseases; Klinische Implikationen eines neuen TSH-Rezeptor-Antikoerper-Assays (DYNOtest {sup trademark} TRAKhuman) bei autoimmunen Schilddruesenerkrankungen

    Energy Technology Data Exchange (ETDEWEB)

    Meller, J.; Schreivogel, I.; Becker, W. [Goettingen Univ. (Germany). Abt. fuer Nuklearmedizin; Bergmann, A.; Morgenthaler, N. [B.R.A.H.M.S Diagnostica, Berlin (Germany); Huefner, M. [Goettingen Univ. (Germany). Abt. Innere Medizin

    2000-07-01

    Aim: Conventional radioreceptor-antibody-assays (RAAs) fail in the detection of TSH-receptor antibodies (TRAKs) in 10-30% of patients with Graves' disease (GD). The aim of this study was the evaluation of the diagnostic and clinical impact of a new RRA (DYNOtest {sup trademark} TRAKhuman) which uses the human recombinant TSH-Receptor in the diagnosis of autoimmune thyroid disease. Methods: Sera from 142 consecutive patients (GD: n=50, autoimmune thyroiditis/AIT: n=92) and from 55 controls (31 patients without any thyroid disease and 14 with euthyroid goiter) were evaluated both with the DYNOtest {sup trademark} TRAKhuman-assay and a conventional RRA (TRAK-Assay {sup trademark}). Thyroid in vitro parameters and thyroid sonography were performed in all patients. Results: The DYNOtest {sup trademark} TRAK-assay was significantly superior to the conventional RRA in the diagnosis of GD (p<0,00012), especially in those who were treated by thionamides (p<0,003) and in the diagnosis of TRAK-positive patients with AIT (p<0,003). The majority of TRAK-positive AIT-patients suffered from hypothyroidism. One false positive result in patients with euthyroid goiter was found in the TRAK-Assay {sup trademark} as well as in the DYNOtest {sup trademark} TRAKhuman-Assay. Therefore the specifity of the DYNOtest {sup trademark} TRAKhuman was not inferior compared with the conventional assay. Conclusion: The DYNOtest {sup trademark} TRAK-assay is superior in the diagnostic work up of Graves' disease compared with a conventional TRAK-assay and offers an equal specifity. (orig.) [German] Ziel: Bei konventionellen Radiorezeptor-Antikoerper-Assays (RRAs) misslingt der Nachweis von TSH-Rezeptor Antikoerpern (TRAKS) bei 10-30% der immunogenen Hyperthyreosen (IH). Ziel der Studie war es, den diagnostischen und klinischen Stellenwertes eines neuen RRA (DYNOtest {sup trademark} TRAKhuman) bei autoimmunen Schilddruesenerkrankungen zu evaluieren. Methoden: Serumproben von 142

  2. Flagellin induces antibody responses through a TLR5- and inflammasome-independent pathway1

    Science.gov (United States)

    López-Yglesias, Américo Harry; Zhao, Xiaodan; Quarles, Ellen K.; Lai, Marvin A.; VandenBos, Tim; Strong, Roland K.; Smith, Kelly D.

    2014-01-01

    Flagellin is a potent immunogen that activates the innate immune system via TLR5 and Naip5/6, and generates strong T and B cell responses. The adaptor protein MyD88 is critical for signaling by TLR5, as well as IL-1 and IL-18 receptors, major downstream mediators of the Naip5/6 Nlrc4-inflammasome. Herein we define roles of known flagellin receptors and MyD88 in antibody responses generated towards flagellin. We used mice genetically deficient in flagellin recognition pathways to characterize innate immune components that regulate isotype specific antibody responses. Using purified flagellin from Salmonella, we dissected the contribution of innate flagellin recognition pathways to promote antibody responses towards flagellin and co-administered ovalbumin in C57BL/6 mice. We demonstrate IgG2c responses towards flagellin were TLR5- and inflammasome-dependent; IgG1 was the dominant isotype and partially TLR5- and inflammasome-dependent. Our data indicates a substantial flagellin-specific IgG1 response was induced through a TLR5-, inflammasome-, and MyD88-independent pathway. IgA anti-FliC responses were TLR5- & MyD88-dependent and caspase-1-independent. Unlike C57BL/6 mice, flagellin immunized A/J mice induced co-dominant IgG1 and IgG2a responses. Furthermore, MyD88-independent flagellin-induced antibody responses were even more pronounced in A/J MyD88−/− mice, and IgA anti-FliC responses were suppressed by MyD88. Flagellin also worked as an adjuvant toward co-administered ovalbumin, but it only promoted IgG1 anti-OVA responses. Our results demonstrate that a novel pathway for flagellin recognition contributes to antibody production. Characterization of this pathway will be useful for understanding immunity to flagellin and the rationale design of flagellin-based vaccines. PMID:24442437

  3. Autoimmune Inner Ear Disease

    Science.gov (United States)

    ... Find an ENT Doctor Near You Autoimmune Inner Ear Disease Autoimmune Inner Ear Disease Patient Health Information ... with a hearing loss. How Does the Healthy Ear Work? The ear has three main parts: the ...

  4. Autoimmune Autonomic Ganglionopathy

    Science.gov (United States)

    ... Accessed 9/2/2015. Autoimmune Autonomic Ganglionopathy Summary. Dysautonomia International . http://www.dysautonomiainternational.org/page.php?ID= ... page Basic Information In Depth Information Basic Information Dysautonomia International offers an information page on Autoimmune autonomic ...

  5. Protective role of antibodies induced by Brucella melitensis B115 against B. melitensis and Brucella abortus infections in mice.

    Science.gov (United States)

    Adone, Rosanna; Francia, Massimiliano; Pistoia, Claudia; Petrucci, Paola; Pesciaroli, Michele; Pasquali, Paolo

    2012-06-01

    It has been demonstrated that antibodies specific for O-PS antigen of Brucella smooth strains are involved in the protective immunity of brucellosis. Since the rough strain Brucella melitensis B115 was able to protect mice against wild Brucella strains brucellosis despite the lack of anti-OPS antibodies, in this study we evaluated the biological significance of antibodies induced by this strain, directed to antigens other than O-PS, passively tranferred to untreated mice prior to infection with Brucella abortus 2308 and B. melitensis 16M virulent strains. The protective ability of specific antisera collected from mice vaccinated with B. melitensis B115, B. abortus RB51 and B. abortus S19 strains was compared. The results indicated that antibodies induced by B115 were able to confer a satisfactory protection, especially against B. abortus 2308, similar to that conferred by the antiserum S19, while the RB51 antiserum was ineffective. These findings suggest that antibodies induced by B115 could act as opsonins as well as antibodies anti-O-PS, thus triggering more efficient internalization and degradation of bacteria within phagocytes. This is the first study assessing the efficacy of antibodies directed to antigens other than O-PS in the course of brucellosis infection. PMID:22521283

  6. Autoimmune vitiligo in rheumatic disease in the mestizo Mexican population

    Science.gov (United States)

    Avalos-Díaz, Esperanza; Pérez-Pérez, Elena; Rodríguez-Rodríguez, Mayra; Pacheco-Tovar, María-Guadalupe; Herrera-Esparza, Rafael

    2016-01-01

    Vitiligo is a chronic disease characterized by the dysfunction or destruction of melanocytes with secondary depigmentation. The aim of the present study was to determine the prevalence of vitiligo associated with autoimmune rheumatic diseases. The clinical records from a 10-year database of patients with rheumatic diseases and associated vitiligo was analysed, with one group of patients having autoimmune rheumatic disease and another non-autoimmune rheumatic disease. Available serum samples were used to assess the anti-melanocyte antibodies. A total of 5,251 individual clinical files were archived in the last 10 years, and these patients underwent multiple rheumatology consultations, with 0.3% of the group presenting with vitiligo. The prevalence of vitiligo in the autoimmune rheumatic disease group was 0.672%, which was mainly associated with lupus and arthritis. However, patients with more than one autoimmune disease had an increased relative risk to develop vitiligo, and anti-melanocyte antibodies were positive in 92% of these patients. By contrast, the prevalence was 0.082% in the group that lacked autoimmune rheumatic disease and had negative autoantibodies. In conclusion, the association between vitiligo and autoimmune rheumatic diseases was relatively low. However, the relative risk increased when there were other autoimmune comorbidities, such as thyroiditis or celiac disease. Therefore, the presence of multiple autoimmune syndromes should be suspected. PMID:27446537

  7. How one TSH receptor antibody induces thyrocyte proliferation while another induces apoptosis

    OpenAIRE

    Morshed, Syed A.; Ma, Risheng; Latif, Rauf; Davies, Terry F.

    2013-01-01

    Thyroid stimulating hormone (TSH) activates two major G-protein arms, Gsα and Gq leading to initiation of down-stream signaling cascades for survival, proliferation and production of thyroid hormones. Antibodies to the TSH receptor (TSHR-Abs), found in patients with Graves’ disease, may have stimulating, blocking, or neutral actions on the thyroid cell. We have shown previously that such TSHR-Abs are distinct signaling imprints after binding to the TSHR and that such events can have variable ...

  8. Quantitative evaluation of colloidal stability of antibody solutions using PEG-induced liquid-liquid phase separation.

    Science.gov (United States)

    Wang, Ying; Latypov, Ramil F; Lomakin, Aleksey; Meyer, Julie A; Kerwin, Bruce A; Vunnum, Suresh; Benedek, George B

    2014-05-01

    Colloidal stability of antibody solutions, i.e., the propensity of the folded protein to precipitate, is an important consideration in formulation development of therapeutic monoclonal antibodies. In a protein solution, different pathways including crystallization, colloidal aggregation, and liquid-liquid phase separation (LLPS) can lead to the formation of precipitates. The kinetics of crystallization and aggregation are often slow and vary from protein to protein. Due to the diverse mechanisms of these protein condensation processes, it is a challenge to develop a standardized test for an early evaluation of the colloidal stability of antibody solutions. LLPS would normally occur in antibody solutions at sufficiently low temperature, provided that it is not preempted by freezing of the solution. Poly(ethylene glycol) (PEG) can be used to induce LLPS at temperatures above the freezing point. Here, we propose a colloidal stability test based on inducing LLPS in antibody solutions and measuring the antibody concentration of the dilute phase. We demonstrate experimentally that such a PEG-induced LLPS test can be used to compare colloidal stability of different antibodies in different solution conditions and can be readily applied to high-throughput screening. We have derived an equation for the effects of PEG concentration and molecular weight on the results of the LLPS test. Finally, this equation defines a binding energy in the condensed phase, which can be determined in the PEG-induced LLPS test. This binding energy is a measure of attractive interactions between antibody molecules and can be used for quantitative characterization of the colloidal stability of antibody solutions. PMID:24679215

  9. CEACAM1 induces B-cell survival and is essential for protective antiviral antibody production

    OpenAIRE

    Khairnar, Vishal; Duhan, Vikas; Maney, Sathish Kumar; Honke, Nadine; Shaabani, Namir; Pandyra, Aleksandra A; Seifert, Marc; Pozdeev, Vitaly; Xu, Haifeng C.; Sharma, Piyush; Baldin, Fabian; Marquardsen, Florian; Merches, Katja; Lang, Elisabeth; Kirschning, Carsten

    2015-01-01

    B cells are essential for antiviral immune defence because they produce neutralizing antibodies, present antigen and maintain the lymphoid architecture. Here we show that intrinsic signalling of CEACAM1 is essential for generating efficient B-cell responses. Although CEACAM1 exerts limited influence on the proliferation of B cells, expression of CEACAM1 induces survival of proliferating B cells via the BTK/Syk/NF-κB-axis. The absence of this signalling cascade in naive Ceacam1 −/− mice limits...

  10. A single dose biodegradable vaccine depot that induces persistently high levels of antibody over a year.

    Science.gov (United States)

    Chua, Brendon Y; Sekiya, Toshiki; Al Kobaisi, Mohammad; Short, Kirsty R; Mainwaring, David E; Jackson, David C

    2015-06-01

    In this study, we describe a biodegradable vaccine depot which persists in vivo for at least 4-months, provides synergistic adjuvant effects and also allows dose sparing of both antigen and adjuvant. A single administration results in immediate release of a priming dose of vaccine, by a process of syneresis, which is then followed by release of remaining vaccine which maintains robust antibody levels that last for more than a year. The platform technology comprises two aqueous components; one contains chitosan and hydroxyapatite, in which the vaccine is incorporated, and the other consists of a crosslinking agent, tripolyphosphate (TPP) and chondroitin sulphate. When co-injected into tissue, they spontaneously crosslink forming a firm yet compliant vaccine-containing depot. Whole body imaging of animals inoculated with the material show that the depot persists in situ for up to 19 weeks. Vaccination of mice with depot formulations containing ovalbumin (OVA) emulsified in Montanide ISA 61 adjuvant results in the induction of robust antibody responses using doses of adjuvant 40-fold less than those recommended by the manufacturer. Dose sparing effects were also apparent with antigen when delivered in the depot. Similar dose sparing effects were observed with Montanide ISA 50, complete and incomplete Freund's adjuvants but not with aluminium hydroxide nor Quil A. Antibody titres, induced by a single dose of antigen/adjuvant formulation incorporated in the depot, persisted at high levels for at least 55 weeks following a single dose of vaccine. PMID:25890706

  11. 349 Detection of Anti-nucclear Antibodies (ana) Used for Diagnostic Approach of Systemic Autoimmune Diseases. Correlation with Double Stranded DNA (DSDNA) and Extractable Nuclear Antigen (ENA) Antibodies

    Science.gov (United States)

    Anastasiou, Ekarerini; Vakaloudi, Anastasia; Papadopoulos, Georgios; Mavridou, Styliani; Koteli, Asimoula

    2012-01-01

    Background To determine the correlation between the titer of ANA and anti-dsDNA and anti-ENA antibodies and the contribution of ANA detection to the diagnosis of connective tissue diseases (CTD). Methods Our samples consisted of 516 specimens, from Rheumatology Department, collected during January 2010 – July 2010. The detection of ANA was performed using indirect immunofluorescence (IFA) and the detection of anti-dsDNA and anti-ENA using ELISA. Results Of the 364 (70.54%) samples with negative ANA 4 (1%) had positive anti-ENA and 2 (0.5%) had positive anti-dsDNA while positive anti-ENA and anti-dsDNA were detected in the 44.73% (n = 68) and 21% (n = 32) of the specimens with positive ANA respectively. The probability of detecting positive anti-ENA and anti-dsDNA rises proportionately to the titer of ANA. Specifically, the correlation between the probability of detecting positive anti-ENA and the titer of ANA is 0.577 (P < 0.001) while the correlation between the probability of detecting positive anti-dsDNA and the titer of ANA is 0.18 (P = 0.003). Probability calculations on the basis of the ANA titer showed that samples with low titer ANAs (1:160 or less) had low probabilities for positive anti-ENA. The receiver operating (ROC) curves of the ANA titer for anti-ENA had a larger under the curve area compared to the ROC curve for anti-dsDNA, indicating that ANA titer is better for predicting anti-ENA than anti-dsDNA. The sensitivity of positive ANA in the prediction of the anti-ENA and anti-dsDNA was 94.40% and 94.10%, the specificity was 81% and 75.10%, the positive prognostic value was 44.70% and 21.10% and negative prognostic value was 98.90 and 99.50%. Conclusions The detection of ANA using indirect IFA has high sensitivity in predicting the presence of specialized antibodies and may be used as a screening method for the diagnosis of CTD. It is cost and time effective too. Our study also shows that the ANA titer is useful in predicting anti-ENA. Samples with

  12. PREVELANCE OF ANTI-TPO ANTIBODY IN TYPE-1 DIABETES AND THYROID DYSFUNCTION IN TPO ANTIBODY POSITIVE DIABET ICS

    OpenAIRE

    Ganesan; Josephine Latha

    2012-01-01

    ABSTRACT: BACKGROUND: The appearance of TPO-Abs precedes thyroid dysfunction and increases in autoimmune diseases like type1diabetes. Thyroid peroxidase (TPO) antibodies are one of the major secondary antibodies associated wi th autoimmune thyroid disease and can be used as diagnostic marker. The prevalence of thyroid auto antibodies is increased when patients have non-thyroid autoimmune diseases such as type 1 diabetes and pernicious anemia. Thyroid dysfuncti...

  13. HAHA--nothing to laugh about. Measuring the immunogenicity (human anti-human antibody response) induced by humanized monoclonal antibodies applying ELISA and SPR technology.

    Science.gov (United States)

    Nechansky, Andreas

    2010-01-01

    Immunogenicity induced by passively applied proteins is a serious issue because it is directly related to the patient's safety. The out-come of an immune reaction to a therapeutic protein can range from transient appearance of antibodies without any clinical significance to severe life threatening conditions. Within this article, enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) methodology to measure immunogenicity are compared and the pros and cons are discussed. PMID:19679421

  14. Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma

    OpenAIRE

    Phan, Giao Q.; Yang, James C.; Sherry, Richard M.; Hwu, Patrick; Topalian, Suzanne L.; Schwartzentruber, Douglas J.; Restifo, Nicholas P; Haworth, Leah R.; Seipp, Claudia A.; Freezer, Linda J.; Morton, Kathleen E.; Mavroukakis, Sharon A.; Duray, Paul H.; Steinberg, Seth M.; Allison, James P.

    2003-01-01

    Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a critical immunoregulatory molecule (expressed on activated T cells and a subset of regulatory T cells) capable of down-regulating T cell activation. Blockade of CTLA-4 has been shown in animal models to improve the effectiveness of cancer immunotherapy. We thus treated 14 patients with metastatic melanoma by using serial i.v. administration of a fully human anti-CTLA-4 antibody (MDX-010) in conjunction with s.c....

  15. SSB peptide and DNA co-immunization induces inhibition of anti-dsDNA antibody production in rabbits

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Background Patients with systemic lupus erythematosus often have various autoantibodies.The relationship between these antibodies is still poorly understood.The aim of the present study was to observe the anti-SSB antibody and anti-dsDNA antibody production profiles following immunization with synthetic SSB peptide alone,DNA alone or co-immunization with these two antigens.Methods SSB 214-225 aa peptide was synthesized by organic chemistry solid-phase peptide synthesis.Rabbits were immunized with the foliowing antigens:synthetic SSB peptide linked with keyhole limpet hemocyanin (KLH),DNA,SSB plus dsDNA,KLH and PBS.Antibodies were measured by ELISA.Histopathology and direct immufluorescence assays were also applied.Results Ainit-SSB and anti-dsDNA antibodies were produced following immunization with SSB peptide and DNA respectively.The level of SSB antibody in the co-immunization group was higher than that of the SSB peptide immunization group.The level of anti-dsDNA antibody in the co-immunization group was,however,lower than that in the DNA immunization group.Meanwhile,the level of anti-SSB antibody was higher than that of anti-DNA antibody in the co-immunization group.No morphological or immunological abnormalities were found in the heart,liver,kidney,spleen or skin tissues.Conclusion Inhibition of anti-dsDNA-antibody was induced by co-immunization with synthesized SSB peptide and DNA,which might explain,at least partly,the mild disease in some LE subsets associated with SSB antibody.

  16. Murine concanavalin A-induced hepatitis is prevented by interleukin 12 (IL-12) antibody and exacerbated by exogenous IL-12 through an interferon-gamma-dependent mechanism

    DEFF Research Database (Denmark)

    Nicoletti, F; Di Marco, R; Zaccone, P;

    2000-01-01

    Concanavalin A (ConA)-induced hepatitis is a cell-mediated immunoinflammatory condition similar to human autoimmune hepatitis. We investigated the role of interleukin 12 (IL-12) in hepatitis induced in NMRI and C57/BL6 mice by a single injection of ConA. Recombinant murine IL-12 administered 24...

  17. Osthole prevents anti-Fas antibody-induced hepatitis in mice by affecting the caspase-3-mediated apoptotic pathway.

    Science.gov (United States)

    Okamoto, Toshihiro; Kawasaki, Toru; Hino, Okio

    2003-02-15

    Fas (Apo-1/CD95) ligand, which is a type II membrane protein, is a major inducer of apoptosis. Osthole is a coumarin derivative present in medicinal plants. The effect of osthole on hepatitis induced by anti-Fas antibody in mice was studied. Pretreatment of mice with osthole (10, 50, and 100 mg/kg, i.p.) prevented the elevation of plasma alanine aminotransferase (ALT) caused by anti-Fas antibody (175 microg/kg, i.v.). Administration of osthole to mice even at a dose of 10 mg/kg significantly inhibited of anti-Fas antibody-induced elevation of plasma ALT. Capase-3 is a cysteine protease, and treatment of mice with anti-Fas antibody caused an elevation of caspase-3 activity at 3.5 and 6 hr. Pretreatment of mice with osthole (100 mg/kg, i.p.) inhibited the elevation of caspase-3 activity caused by anti-Fas antibody. However, the addition of osthole (up to 10(-4)M) to a liver cytosol fraction isolated from mice treated with anti-Fas antibody did not inhibit caspase-3 activity in vitro. Thus, treatment of mice with osthole inhibited caspase-3 activity by an effect upstream of caspase-3 activation. The livers of mice treated with anti-Fas antibody contained apoptotic and dead cells; osthole attenuated the development of this apoptosis and cell death. The present results show that osthole prevented anti-Fas antibody-induced hepatitis by inhibiting the Fas-mediated apoptotic pathway. PMID:12566097

  18. Diagnostic criteria of autoimmune hepatitis.

    Science.gov (United States)

    Liberal, Rodrigo; Grant, Charlotte R; Longhi, Maria Serena; Mieli-Vergani, Giorgina; Vergani, Diego

    2014-01-01

    Autoimmune hepatitis (AIH) is a chronic immune-mediated liver disorder characterised by female preponderance, elevated transaminase and immunoglobulin G levels, seropositivity for autoantibodies and interface hepatitis. Presentation is highly variable, therefore AIH should be considered during the diagnostic workup of any increase in liver enzyme levels. A set of inclusion and exclusion criteria for the diagnosis of AIH have been established by the International Autoimmune Hepatitis Group (IAIHG). There are two main types of AIH: type 1, positive for anti-nuclear (ANA) and/or anti-smooth muscle antibodies (SMAs) and type 2, defined by the presence of anti-liver kidney microsomal antibody type 1 (LKM-1) and/or anti-liver cytosol type 1 (LC-1) autoantibodies. The central role of autoantibodies in the diagnosis of AIH has led the IAIHG to produce a consensus statement detailing appropriate and effective methods for their detection. Autoantibodies should be tested by indirect immunofluorescence at an initial dilution of 1/40 in adults and 1/10 in children on a freshly prepared rodent substrate that includes kidney, liver and stomach sections to allow for the simultaneous detection of all reactivities relevant to AIH. Anti-LKM-1 is often confused with anti-mitochondrial antibody (AMA) if rodent kidney is used as the sole immunofluorescence substrate. The identification of the molecular targets of anti-LKM-1 and AMA has led to the establishment of immuno-assays based on the use of the recombinant or purified autoantigens. Perinuclear anti-nuclear neutrophil antibody (p-ANNA) is an additional marker of AIH-1; anti soluble liver antigen (SLA) antibodies are specific for autoimmune liver disease, can be present in AIH-1 and AIH-2 and are associated with a more severe clinical course. Anti-SLA are detectable by ELISA or radio-immuno-assays, but not by immunofluorescence. AIH is exquisitely responsive to immunosuppressive treatment, which should be instituted promptly to

  19. Neonatal molecular pathologies induced by maternal anti-Ro and anti-La antibodies

    Directory of Open Access Journals (Sweden)

    Herrera-Esparza R

    2015-08-01

    Full Text Available Maternal antinuclear antibodies with anti-Ro or anti-La specificity might be pathogenic to the fetus and could induce molecular neonatal pathologies, such as neonatal lupus (NL with or without congenital heart block (CHB. The cutaneous manifestations of neonatal lupus appear at birth or a few weeks later, and skin lesions may persist for weeks. While CHB is characterized by intrauterine bradycardia or low heart rates at birth and may persist for months, depending on the degree of blockage. Clinical and experimental data demonstrated that anti-Ro and anti-La autoantibodies functionally inhibit L-type calcium channels and induce abnormalities in electrical conduction of the cardiac myocytes. It has been 38 years since the first clinical description of CHB. Presently, the pathophysiology of CHB has been clarified through clinical and basic research studies.

  20. Laser-induced breakdown detection of temperature-ramp generated aggregates of therapeutic monoclonal antibody.

    Science.gov (United States)

    Menzen, Tim; Friess, Wolfgang; Niessner, Reinhard; Haisch, Christoph

    2015-08-01

    The detection and characterization of protein aggregation is essential during development and quality control of therapeutic proteins, as aggregates are typically inactive and may trigger anti-drug-antibody formation in patients. Especially large multi-domain molecules, such as the important class of therapeutic monoclonal antibodies (mAbs), can form various aggregates that differ in size and morphology. Although particle analysis advanced over the recent years, new techniques and orthogonal methods are highly valued. To our knowledge, the physical principle of laser-induced breakdown detection (LIBD) was not yet applied to sense aggregates in therapeutic protein formulations. We established a LIBD setup to monitor the temperature-induced aggregation of a mAb. The obtained temperature of aggregation was in good agreement with the results from previously published temperature-ramped turbidity and dynamic light scattering measurements. This study demonstrates the promising applicability of LIBD to investigate aggregates from therapeutic proteins. The technique is also adaptive to online detection and size determination, and offers interesting opportunities for morphologic characterization of protein particles and impurities, which will be part of future studies. PMID:26158409

  1. 不孕不育妇女五项免疫性抗体检测结果分析%Analysis of the Results of Five Autoimmune Antibodies in Female Infertility

    Institute of Scientific and Technical Information of China (English)

    周艳; 韦启雕

    2015-01-01

    Objective To investigate the relationship between five autoimmune antibodies and the female infertility. Methods The 49 blood serum samples of the female infertility were col ected from the section for outpatients in our hospital. The serum AsAb, EmAb , AoAb , ZpAb and ATAb of cases of female infertility were detected by Indirect immunofluorescence assay. Results The positive rate in 49 female infertility was 34.7%, 28.6%, 20.4%, 20.4%and 12.2%respectively. AsAb,EmAb and AoAb were detected from 37 blood serum samples of the healthy group,and the positive rates was 5.4%、2.7%、2.7%, and the dif erence significant between the two groups( <0.05).Among the testing of al immune antibodies,there were 26(53.1%) patients who were masculine in one items and 13(26.5%)patients who were masculine in two items. Conclusion AsAb,EmAb,AoAb,ZpAb and ATAb are the important immune factors in female infertility,and the patients should strengthen the test of immune antibodies in couples.%目的:探讨妇女不孕不育症与五项免疫性抗体的关系。方法收集我院就诊的49例不孕不育妇女的血清,37例健康体检者的血清作为对照组,采用间接免疫荧光法(IFA)检测抗精子抗体(AsAb)、抗子宫内膜抗体(EmAb)、抗卵巢抗体(AoAb)、抗透明带抗体(ZpAb)及抗滋养层抗体(ATAb)。结果49例不孕不育患者血清中检出AsAb阳性17例(34.7%),EmAb阳性14例(28.6%),AoAb阳性10例(20.4%),ZpAb阳性10例(20.4%),ATAb阳性6例(12.2%);对照组中检出AsAb、EmAb和AoAb的阳性例数和阳性率分别为2(5.4%)、1(2.7%)、1(2.7%),未检出ZpAb和ATAb;两组差异有统计学意义(<0.05)。其中2项或以上抗体同时阳性的,不孕不育组有13例(26.5%),健康组无同时阳性的。结论 AsAb、EmAb、AoAb、ZpAb和ATAb是引起女性不孕不育的重要免疫因素,不孕不育患者应进行免疫性抗体的检测。

  2. Distribution of autoimmune antibodies and clinical features in 54 cases with recurrent optic neuritis%复发性视神经炎54例临床特点及自身免疫抗体的分布

    Institute of Scientific and Technical Information of China (English)

    王颖云; 魏世辉; 范珂; 闫洪欣; 张译心; 戴艳丽

    2013-01-01

    目的 观察复发性视神经炎的临床特点以及自身免疫抗体(水通道蛋白4抗体和血清抗核抗体)的分布.方法 收集2010年10月至2012年4月间在解放军总医院神经眼科住院诊治的复发性视神经炎患者54例的临床资料,回顾分析其一般临床特点,统计其水通道蛋白4抗体(AQP4-Ab)(36例)和血清抗核抗体(ANAs)的阳性率,并与相关文献数据分析比较.结果 男女比例1∶2.6,发病年龄平均30.3岁;病程50d~20年,发病次数2~8次.病程中最差视力(矫正后)在0.1以下者44例,占81.5%.ANAs阳性率22.2% (12/54),AQP4-Ab阳性率27.8% (10/36);颅脑和/或脊髓核磁异常者占48.0% (24/50);脑脊液异常70.0% (16/23).结论 复发性视神经炎多发于青壮年,视力损害较重,自身免疫抗体(AQP4-Ab和ANAs)阳性率较视神经脊髓炎及复发性长节段横贯性脊髓炎略低,中枢神经系统影像检查对其诊治有重要价值.%ObJective To investigate the clinical features and seroprevalence of autoimmune antibodies (aquaporin-4 antibodies,AQP4-Ab and antinuclear antibodies,ANAs) in patients with recurrent optic neuritis (RON).Methods Fifty-four RON patients who were in-hospital in Ophthalmology Department of PLA from October 2010 to April 2012 were enrolled in the study.The general clinical features and statistic the positive rate of AQP4-Ab and ANAs were analyzed retrospectively,and the relative data in other studies were compared.Results The ratio of male to female was 1:2.6 and the average age of onset was 30.3 years old.The recurrent attacks of optic neuritis were 2 to 8 times during 50 days to 20 years.There were 44 patients (81.5%) who had ever appeared the lowest visual acuity (corrected) of <0.1 in the course of disease.The rate of seropositive ANAs was 22.2% (12/54) while 27.8% (10/36) for AQP4-Ab.The 48.0% (24/50) cases were abnormal in Brain and/or spinal cord MRI and 70.0% (16/23) in CSF.Conclusions RON is more appeared in

  3. Molecular mimicry as a mechanism for food immune reactivities and autoimmunity.

    Science.gov (United States)

    Vojdani, Aristo

    2015-01-01

    The mucosal immune system is constantly exposed to challenges from the antigenic substances found in food and released from the body's own microbial flora. The body's normal tolerance to friendly antigenic substances can be disrupted by a number of factors, such as disease, injury, shock, trauma, surgery, drugs, blood transfusion, environmental triggers, etc. When this disruption happens, the ingestion of foods containing antigenic substances that have compositions similar to those of the body's autoantigens can result in the production of antibodies that react not only against the food antigens but also the body's own tissues. This response is known as food autoimmune reactivity. Between 7% and 10% of the world's population suffers from some form of autoimmune disease. Each patient's antibodies, both immunoglobulin A (IgA) + immunoglobulin M (IgM) in the saliva and immunoglobulin G (IgG) and IgA in the blood must be examined to give a complete picture of food immune reactivity. A host of health problems and autoimmune disorders have increasingly become associated with some of the most commonly consumed foods in the world, such as wheat and milk. Many of these problems can be traced to molecular mimicry. The peptide sequences of foods such as milk and wheat are similar to those of human molecules, such as myelin oligodendrocyte glycoprotein, human islet cell tissue, and human aquaporin 4 (AQP4). This similarity can result in cross-reactivity that leads to food autoimmunity and even autoimmune disorders, such as multiple sclerosis (MS), celiac disease (CD), and neuromyelitis optica. Further research is needed to determine what other foods have dangerous sequence similarities to human tissues and what methods are available to test for the autoantibodies resulting from these molecular, mimicry-induced misfires of the immune system. The identification and removal of corresponding food triggers can then be used as the basis of therapy. PMID:25599184

  4. Infections and autoimmune diseases.

    Science.gov (United States)

    Bach, Jean-François

    2005-01-01

    The high percentage of disease-discordant pairs of monozygotic twins demonstrates the central role of environmental factors in the etiology of autoimmune diseases. Efforts were first focussed on the search for triggering factors. The study of animal models has clearly shown that infections may trigger autoimmune diseases, as in the case of Coxsackie B4 virus in type I diabetes and the encephalomyocarditis virus in autoimmune myositis, two models in which viruses are thought to act by increasing immunogenicity of autoantigens secondary to local inflammation. The induction of a Guillain-Barré syndrome in rabbits after immunization with a peptide derived from Campylobacter jejuni is explained by mimicry between C. jejuni antigens and peripheral nerve axonal antigens. Other models involve chemical modification of autoantigens, as in the case of iodine-induced autoimmune thyroiditis. These mechanisms have so far only limited clinical counterparts (rheumatic fever, Guillain-Barré syndrome and drug-induced lupus or myasthenia gravis) but one may assume that unknown viruses may be at the origin of a number of chronic autoimmune diseases, such as type I diabetes and multiple sclerosis) as illustrated by the convergent data incriminating IFN-alpha in the pathophysiology of type I diabetes and systemic lupus erythematosus. Perhaps the difficulties met in identifying the etiologic viruses are due to the long lag time between the initial causal infection and onset of clinical disease. More surprisingly, infections may also protect from autoimmune diseases. Western countries are being confronted with a disturbing increase in the incidence of most immune disorders, including autoimmune and allergic diseases, inflammatory bowel diseases, and some lymphocyte malignancies. Converging epidemiological evidence indicates that this increase is linked to improvement of the socio-economic level of these countries, posing the question of the causal relationship and more precisely the

  5. Identification of aneuploidy-inducing agents using cytokinesis-blocked human lymphocytes and an antikinetochore antibody

    Energy Technology Data Exchange (ETDEWEB)

    Eastmond, D.A.; Tucker, J.D.

    1989-01-01

    The identification of agents causing aneuploidy in humans, a condition associated with carcinogenesis and birth defects, is currently limited due to the highly skilled and time-consuming nature of cytogenetic analyses. We report the development of a new simple and rapid assay to identify aneuploidy-inducing agents (aneuploidogens). The assay involves the chemical- or radiation-induced formation of micronuclei in cytokinesis-blocked human lymphocytes and the use of an antikinetochore antibody to determine whether the micronuclei contain centromeres--a condition indicating a high potential for aneuploidy. All agents tested produced dose-related increases in the frequency of micronucleated cells. The micronucleated cells induced by the known aneuploidogens--colchicine, vincristine sulfate, and diethylstilbestrol--contained kinetochore-positive micronuclei 92, 87, and 76% of the time, respectively. In contrast, the micronucleated cells induced by the potent clastogens--ionizing radiation and sodium arsenite--contained kinetochore-positive micronuclei only 3 and 19% of the time, respectively. These results indicate that this relatively simple assay can discriminate between aneuploidogens and clastogens and may allow a more rapid identification of environmental and therapeutic agents with aneuploidy-inducing potential.

  6. TRAIL-R2 Superoligomerization Induced by Human Monoclonal Agonistic Antibody KMTR2.

    Science.gov (United States)

    Tamada, Taro; Shinmi, Daisuke; Ikeda, Masahiro; Yonezawa, Yasushi; Kataoka, Shiro; Kuroki, Ryota; Mori, Eiji; Motoki, Kazuhiro

    2015-01-01

    The fully human monoclonal antibody KMTR2 acts as a strong direct agonist for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor 2 (TRAIL-R2), which is capable of inducing apoptotic cell death without cross-linking. To investigate the mechanism of direct agonistic activity induced by KMTR2, the crystal structure of the extracellular region of TRAIL-R2 and a Fab fragment derived from KMTR2 (KMTR2-Fab) was determined to 2.1 Å resolution. Two KMTR2-Fabs assembled with the complementarity-determining region 2 of the light chain via two-fold crystallographic symmetry, suggesting that the KMTR2-Fab assembly tended to enhance TRAIL-R2 oligomerization. A single mutation at Asn53 to Arg located at the two-fold interface in the KMTR2 resulted in a loss of its apoptotic activity, although it retained its antigen-binding activity. These results indicate that the strong agonistic activity, such as apoptotic signaling and tumor regression, induced by KMTR2 is attributed to TRAIL-R2 superoligomerization induced by the interdimerization of KMTR2. PMID:26672965

  7. Pregnancy outcomes with thyroxine replacement for subclinical hypothyroidism: Role of thyroid autoimmunity

    Directory of Open Access Journals (Sweden)

    Muthukrishnan Jayaraman

    2013-01-01

    Full Text Available Objective: To study pregnancy outcomes in relation to thyroid peroxidase antibody (TPOAb status with optimum thyroxine replacement for subclinical hypothyroidism. Materials and Methods: Ninety-eight women with subclinical hypothyroidism were followed up until the end of their pregnancy. TPO antibody status was performed for 59 women (positive 20, negative 39. Levothyroxine was supplemented to maintain TSH between 0.3-3 mIU/l in all patients, irrespective of TPOAb status. Pregnancy outcomes were noted as pregnancy-induced hypertension (PIH, antepartum or postpartum hemorrhage, preterm delivery, and spontaneous abortion. Outcomes were compared between 3 groups as per TPO antibody status (positive, negative, and undetermined, which were matched for age and gestational period. Results: Thyroid autoimmunity was noted in 34% of women screened for TPO antibody. A total of 11 adverse pregnancy outcomes were recorded (4 spontaneous abortions, 4 preterm deliveries, 3 PIH with no significant difference between the groups. Conclusion: Adverse pregnancy outcomes were not different in the 3 groups with adequate thyroxine replacement for pregnant women with subclinical hypothyroidism targeting TSH in euthyroid range, irrespective of thyroid autoimmunity status.

  8. Heterosubtypic antiviral activity of hemagglutinin-specific antibodies induced by intranasal immunization with inactivated influenza viruses in mice.

    Directory of Open Access Journals (Sweden)

    Mieko Muramatsu

    Full Text Available Influenza A virus subtypes are classified on the basis of the antigenicity of their envelope glycoproteins, hemagglutinin (HA; H1-H17 and neuraminidase. Since HA-specific neutralizing antibodies are predominantly specific for a single HA subtype, the contribution of antibodies to the heterosubtypic immunity is not fully understood. In this study, mice were immunized intranasally or subcutaneously with viruses having the H1, H3, H5, H7, H9, or H13 HA subtype, and cross-reactivities of induced IgG and IgA antibodies to recombinant HAs of the H1-H16 subtypes were analyzed. We found that both subcutaneous and intranasal immunizations induced antibody responses to multiple HAs of different subtypes, whereas IgA was not detected remarkably in mice immunized subcutaneously. Using serum, nasal wash, and trachea-lung wash samples of H9 virus-immunized mice, neutralizing activities of cross-reactive antibodies were then evaluated by plaque-reduction assays. As expected, no heterosubtypic neutralizing activity was detected by a standard neutralization test in which viruses were mixed with antibodies prior to inoculation into cultured cells. Interestingly, however, a remarkable reduction of plaque formation and extracellular release of the H12 virus, which was bound by the H9-induced cross-reactive antibodies, was observed when infected cells were subsequently cultured with the samples containing HA-specific cross-reactive IgA. This heterosubtypic plaque reduction was interfered when the samples were pretreated with anti-mouse IgA polyclonal serum. These results suggest that the majority of HA-specific cross-reactive IgG and IgA antibodies produced by immunization do not block cellular entry of viruses, but cross-reactive IgA may have the potential to inhibit viral egress from infected cells and thus to play a role in heterosubtypic immunity against influenza A viruses.

  9. Sirolimus for Autoimmune Disease of Blood Cells

    Science.gov (United States)

    2016-04-22

    Autoimmune Pancytopenia; Autoimmune Lymphoproliferative Syndrome (ALPS); Evans Syndrome; Idiopathic Thrombocytopenic Purpura; Anemia, Hemolytic, Autoimmune; Autoimmune Neutropenia; Lupus Erythematosus, Systemic; Inflammatory Bowel Disease; Rheumatoid Arthritis

  10. CD32a antibodies induce thrombocytopenia and type II hypersensitivity reactions in FCGR2A mice.

    Science.gov (United States)

    Meyer, Todd; Robles-Carrillo, Liza; Davila, Monica; Brodie, Meghan; Desai, Hina; Rivera-Amaya, Mildred; Francis, John L; Amirkhosravi, Ali

    2015-11-01

    The CD32a immunoglobulin G (IgG) receptor (Fcγ receptor IIa) is a potential therapeutic target for diseases in which IgG immune complexes (ICs) mediate inflammation, such as heparin-induced thrombocytopenia, rheumatoid arthritis, and systemic lupus erythematosus. Monoclonal antibodies (mAbs) are a promising strategy for treating such diseases. However, IV.3, perhaps the best characterized CD32a-blocking mAb, was recently shown to induce anaphylaxis in immunocompromised "3KO" mice. This anaphylactic reaction required a human CD32a transgene because mice lack an equivalent of this gene. The finding that IV.3 induces anaphylaxis in CD32a-transgenic mice was surprising because IV.3 had long been thought to lack the intrinsic capacity to trigger cellular activation via CD32a. Such an anaphylactic reaction would also limit potential therapeutic applications of IV.3. In the present study, we examine the molecular mechanisms by which IV.3 induces anaphylaxis. We now report that IV.3 induces anaphylaxis in immunocompetent CD32a-transgenic "FCGR2A" mice, along with the novel finding that IV.3 and 2 other well-characterized CD32a-blocking mAbs, AT-10 and MDE-8, also induce severe thrombocytopenia in FCGR2A mice. Using recombinant variants of these same mAbs, we show that IgG "Fc" effector function is necessary for the induction of anaphylaxis and thrombocytopenia in FCGR2A mice. Variants of these mAbs lacking the capacity to activate mouse IgG receptors not only failed to induce anaphylaxis or thrombocytopenia, but also very potently protected FCGR2A mice from near lethal doses of IgG ICs. Our findings show that effector-deficient IV.3, AT-10, and MDE-8 are promising candidates for developing therapeutic mAbs to treat CD32a-mediated diseases. PMID:26396093

  11. Anti-ganglioside antibody-induced tumor cell death by loss of membrane integrity.

    Science.gov (United States)

    Roque-Navarro, Lourdes; Chakrabandhu, Krittalak; de León, Joel; Rodríguez, Sandra; Toledo, Carlos; Carr, Adriana; de Acosta, Cristina Mateo; Hueber, Anne-Odile; Pérez, Rolando

    2008-07-01

    Gangliosides have been involved in multiple cellular processes such as growth, differentiation and adhesion, and more recently as regulators of cell death signaling pathways. Some of these molecules can be considered as tumor-associated antigens, in particular, N-glycolyl sialic acid-containing gangliosides, which are promising candidates for cancer-targeted therapy because of their low expression in normal human tissues. In this study, we provided the molecular and cellular characterization of a novel cell death mechanism induced by the anti-NGcGM3 14F7 monoclonal antibody (mAb) in L1210 murine tumor cell line but not in mouse normal cells (B and CD4(+) T lymphocytes) that expressed the antigen. Impairment of ganglioside synthesis in tumor cells abrogated the 14F7 mAb cytotoxic effect; however, exogenous reincorporation of the ganglioside did not restore tumor cell sensitivity to 14F7 mAb-induced cytotoxicity. 14F7 F(ab')(2) but not Fab fragments retained the cytotoxic capacity of the whole mAb. By contrary, other mAb, which recognizes N-glycolylated gangliosides, did not show any cytotoxic effect. These mAbs showed quite different capacities to bind NGcGM3-positive cell lines measured by binding inhibition experiments. Interestingly, this complement-independent cell death mechanism did not resemble apoptosis, because no DNA fragmentation, caspase activation, or Fas mediation were observed. However, NGcGM3 ganglioside-mediated 14F7 mAb-induced cell death was accompanied by cellular swelling, membrane lesion formation, and cytoskeleton activation, suggesting an oncosis-like phenomenon. This novel mechanism of cell death lets us to support further therapeutic approaches using NGcGM3 as a molecular target for antibody-based cancer immunotherapy. PMID:18645013

  12. Assessment of pulmonary antibodies with induced sputum and bronchoalveolar lavage induced by nasal vaccination against Pseudomonas aeruginosa: a clinical phase I/II study

    Directory of Open Access Journals (Sweden)

    Freihorst Joachim

    2007-08-01

    Full Text Available Abstract Background Vaccination against Pseudomonas aeruginosa is a desirable albeit challenging strategy for prevention of airway infection in patients with cystic fibrosis. We assessed the immunogenicity of a nasal vaccine based on the outer membrane proteins F and I from Pseudomonas aeruginosa in the lower airways in a phase I/II clinical trial. Methods N = 12 healthy volunteers received 2 nasal vaccinations with an OprF-OprI gel as a primary and a systemic (n = 6 or a nasal booster vaccination (n = 6. Antibodies were assessed in induced sputum (IS, bronchoalveolar lavage (BAL, and in serum. Results OprF-OprI-specific IgG and IgA antibodies were found in both BAL and IS at comparable rates, but differed in the predominant isotype. IgA antibodies in IS did not correlate to the respective serum levels. Pulmonary antibodies were detectable in all vaccinees even 1 year after the vaccination. The systemic booster group had higher IgG levels in serum. However, the nasal booster group had the better long-term response with bronchial antibodies of both isotypes. Conclusion The nasal OprF-OprI-vaccine induces a lasting antibody response at both, systemic and airway mucosal site. IS is a feasible method to non-invasively assess bronchial antibodies. A further optimization of the vaccination schedule is warranted.

  13. Mapping of epitopes recognized by antibodies induced by immunization of mice with PspA and PspC.

    Science.gov (United States)

    Vadesilho, Cintia F M; Ferreira, Daniela M; Gordon, Stephen B; Briles, David E; Moreno, Adriana T; Oliveira, Maria Leonor S; Ho, Paulo L; Miyaji, Eliane N

    2014-07-01

    Pneumococcal surface protein A (PspA) and pneumococcal surface protein C (PspC) are important candidates for an alternative vaccine against pneumococcal infections. Since these antigens show variability, the use of variants that do not afford broad protection may lead to the selection of vaccine escape bacteria. Epitopes capable of inducing antibodies with broad cross-reactivities should thus be the preferred antigens. In this work, experiments using peptide arrays show that most linear epitopes recognized by antibodies induced in mice against different PspAs were located at the initial 44 amino acids of the mature protein and that antibodies against these linear epitopes did not confer protection against a lethal challenge. Conversely, linear epitopes recognized by antibodies to PspC included the consensus sequences involved in the interaction with human factor H and secretory immunoglobulin A (sIgA). Since linear epitopes of PspA were not protective, larger overlapping fragments containing 100 amino acids of PspA of strain Rx1 were constructed (fragments 1 to 7, numbered from the N terminus) to permit the mapping of antibodies with conformational epitopes not represented in the peptide arrays. Antibodies from mice immunized with fragments 1, 2, 4, and 5 were capable of binding onto the surface of pneumococci and mediating protection against a lethal challenge. The fact that immunization of mice with 100-amino-acid fragments located at the more conserved N-terminal region of PspA (fragments 1 and 2) induced protection against a pneumococcal challenge indicates that the induction of antibodies against conformational epitopes present at this region may be important in strategies for inducing broad protection against pneumococci. PMID:24807052

  14. Radiolabeled isatin binding to caspase-3 activation induced by anti-Fas antibody

    International Nuclear Information System (INIS)

    Introduction: Noninvasive imaging methods that can distinguish apoptosis from necrosis may be useful in furthering our understanding of diseases characterized by apoptotic dysregulation as well as aiding drug development targeting apoptotic pathways. We evaluated the ability of radiolabeled isatins to quantify caspase-3 activity induced by the activation of the extrinsic apoptotic pathway by the anti-Fas antibody in mice. Methods: The behavior of three different radiolabeled isatins ([18F]WC-II-89, [18F]WC-IV-3 and [11C]WC-98) was characterized in mice with and without anti-Fas antibody treatment by microPET imaging and biodistribution studies. The activity of [18F]WC-II-89 was also compared with [99mTc]mebrofenin. The effect of pan-caspase inhibition with quinolyl-valyl-O-methylaspartyl-[2,6-difluorophenoxy]-methyl ketone (Q-VD-OPh) on [18F]WC-II-89 uptake was studied. Caspase-3 activity was confirmed by a fluorometric enzyme assay. Results: All three tracers behaved similarly in microPET and biodistribution studies. Increased retention of all tracers was observed in the livers of treated animals and several other organs, all of which demonstrated increased caspase-3 enzyme activity; however, impaired hepatobiliary excretion made attribution of these findings to caspase-3 activity difficult. The isatin [18F]WC-II-89 was retained at statistically significantly higher levels in the organs after anti-Fas antibody treatment while [99mTc]mebrofenin activity cleared, suggesting specific binding to activated caspase-3, but the magnitude of increased binding was still relatively low. Caspase inhibition with Q-VD-OPh partially blocked [18F]WC-II-89 retention but completely blocked caspase-3 enzyme activity in the liver. Conclusions: The radiolabeled isatins appear to bind specifically to caspase-3 in vivo, but their sensitivity is limited. Further optimization is required for these tracers to be useful for clinical applications.

  15. A sequence in subdomain 2 of DBL1α of Plasmodium falciparum erythrocyte membrane protein 1 induces strain transcending antibodies.

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    Karin Blomqvist

    Full Text Available Immunity to severe malaria is the first level of immunity acquired to Plasmodium falciparum. Antibodies to the variant antigen PfEMP1 (P. falciparum erythrocyte membrane protein 1 present at the surface of the parasitized red blood cell (pRBC confer protection by blocking microvascular sequestration. Here we have generated antibodies to peptide sequences of subdomain 2 of PfEMP1-DBL1α previously identified to be associated with severe or mild malaria. A set of sera generated to the amino acid sequence KLQTLTLHQVREYWWALNRKEVWKA, containing the motif ALNRKE, stained the live pRBC. 50% of parasites tested (7/14 were positive both in flow cytometry and immunofluorescence assays with live pRBCs including both laboratory strains and in vitro adapted clinical isolates. Antibodies that reacted selectively with the sequence REYWWALNRKEVWKA in a 15-mer peptide array of DBL1α-domains were also found to react with the pRBC surface. By utilizing a peptide array to map the binding properties of the elicited anti-DBL1α antibodies, the amino acids WxxNRx were found essential for antibody binding. Complementary experiments using 135 degenerate RDSM peptide sequences obtained from 93 Ugandan patient-isolates showed that antibody binding occurred when the amino acids WxLNRKE/D were present in the peptide. The data suggests that the ALNRKE sequence motif, associated with severe malaria, induces strain-transcending antibodies that react with the pRBC surface.

  16. Mucosal Antibodies Induced by Intranasal but Not Intramuscular Immunization Block Norovirus GII.4 Virus-Like Particle Receptor Binding.

    Science.gov (United States)

    Tamminen, Kirsi; Malm, Maria; Vesikari, Timo; Blazevic, Vesna

    2016-06-01

    Noroviruses (NoVs) account for the majority of diagnosed cases of viral acute gastroenteritis worldwide. Virus-like particle (VLP)-based vaccines against NoV are currently under development. Serum antibodies that block the binding of NoV VLPs to histo-blood group antigens, the putative receptors for NoV, correlate with protection against NoV infection. The role of functional mucosal antibodies in protection is largely unknown, even though the intestinal mucosa is the entry port for NoV. Balb/c mice were immunized intramuscularly (IM) or intranasally (IN) with NoV GII.4 VLPs, and systemic and mucosal blocking antibody responses were studied. IN immunization elicited NoV-specific serum and mucosal IgG and IgA antibodies, whereas IM immunized animals completely lacked IgA. Both immunization routes induced similar blocking activity in serum but only IN route generated blocking antibodies in mucosa. The level of IgA in the mucosal (nasal) lavages strongly correlated (r = 0.841) with the blocking activity, suggesting that IgA, but not IgG, is the major NoV blocking antibody on mucosal surfaces. The results indicate that only mucosal immunization route induces the development of functional anti-NoV IgA on mucosal surface. PMID:27135874

  17. NK cell autoreactivity and autoimmune diseases

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    Alessandro ePoggi

    2014-02-01

    Full Text Available Increasing evidences have pointed out the relevance of Natural Killer (NK cells in organ specific and systemic autoimmune diseases. NK cells bear a plethora of activating and inhibiting receptors that can play a role in regulating reactivity with autologous cells. The activating receptors recognize natural ligands upregulated on virus-infected or stressed or neoplastic cells. Of note, several autoimmune diseases are thought to be linked to viral infections as one of the first event in inducing autoimmunity. Also, it is conceivable that autoimmunity can be triggered when a dysregulation of innate immunity occurs, activating T and B lymphocytes to react with self-components. This would imply that NK cells can play a regulatory role during adaptive immunity; indeed, innate lymphoid cells (ILC, comprising the classical CD56+ NK cells, have a role in maintaining or alterating tissue homeostasis secreting protective and/or proinflammatory cytokines. In addition, NK cells display activating receptors involved in natural cytotoxicity and the activating isoforms of receptors for HLA class I that can interact with healthy host cells and induce damage without any evidence of viral infection or neoplastic-induced alteration. In this context, the interrelationship among ILC, extracellular matrix components and mesenchymal stromal cells can be considered a key point for the control of homeostasis. Herein, we summarize evidences for a role of NK cells in autoimmune diseases and will give a point of view of the interplay between NK cells and self-cells in triggering autoimmunity.

  18. Environmental Basis of Autoimmunity.

    Science.gov (United States)

    Floreani, Annarosa; Leung, Patrick S C; Gershwin, M Eric

    2016-06-01

    The three common themes that underlie the induction and perpetuation of autoimmunity are genetic predisposition, environmental factors, and immune regulation. Environmental factors have gained much attention for their role in triggering autoimmunity, with increasing evidence of their influence as demonstrated by epidemiological studies, laboratory research, and animal studies. Environmental factors known to trigger and perpetuate autoimmunity include infections, gut microbiota, as well as physical and environmental agents. To address these issues, we will review major potential mechanisms that underlie autoimmunity including molecular mimicry, epitope spreading, bystander activation, polyclonal activation of B and T cells, infections, and autoinflammatory activation of innate immunity. The association of the gut microbiota on autoimmunity will be particularly highlighted by their interaction with pharmaceutical agents that may lead to organ-specific autoimmunity. Nonetheless, and we will emphasize this point, the precise mechanism of environmental influence on disease pathogenesis remains elusive. PMID:25998909

  19. Overexpression of membrane-bound fas ligand (CD95L) exacerbates autoimmune disease and renal pathology in pristane-induced lupus.

    Science.gov (United States)

    Bossaller, Lukas; Rathinam, Vijay A K; Bonegio, Ramon; Chiang, Ping-I; Busto, Patricia; Wespiser, Adam R; Caffrey, Daniel R; Li, Quan-Zhen; Mohan, Chandra; Fitzgerald, Katherine A; Latz, Eicke; Marshak-Rothstein, Ann

    2013-09-01

    Loss-of-function mutations in the Fas death receptor or its ligand result in a lymphoproliferative syndrome and exacerbate clinical disease in most lupus-prone strains of mice. One exception is mice injected with 2,6,10,14-tetramethylpentadecane (TMPD), a hydrocarbon oil commonly known as pristane, which induces systemic lupus erythematosus-like disease. Although Fas/Fas ligand (FasL) interactions have been strongly implicated in the activation-induced cell death of both lymphocytes and other APCs, FasL can also trigger the production of proinflammatory cytokines. FasL is a transmembrane protein with a matrix metalloproteinase cleavage site in the ectodomain. Matrix metalloproteinase cleavage inactivates membrane-bound FasL and releases a soluble form reported to have both antagonist and agonist activity. To better understand the impact of FasL cleavage on both the proapoptotic and proinflammatory activity of FasL, its cleavage site was deleted through targeted mutation to produce the deleted cleavage site (ΔCS) mouse line. ΔCS mice express higher levels of membrane-bound FasL than do wild-type mice and fail to release soluble FasL. To determine to what extent FasL promotes inflammation in lupus mice, TMPD-injected FasL-deficient and ΔCS BALB/c mice were compared with control TMPD-injected BALB/c mice. We found that FasL deficiency significantly reduced the early inflammatory exudate induced by TMPD injection. In contrast, ΔCS mice developed a markedly exacerbated disease profile associated with a higher frequency of splenic neutrophils and macrophages, a profound change in anti-nuclear Ab specificity, and markedly increased proteinuria and kidney pathology compared with controls. These results demonstrate that FasL promotes inflammation in TMPD-induced autoimmunity, and its cleavage limits FasL proinflammatory activity. PMID:23918976

  20. Cure of Chronic Viral Infection and Virus-Induced Type 1 Diabetes by Neutralizing Antibodies

    Directory of Open Access Journals (Sweden)

    Mette Ejrnaes

    2006-01-01

    Full Text Available The use of neutralizing antibodies is one of the most successful methods to interfere with receptor-ligand interactions in vivo. In particular blockade of soluble inflammatory mediators or their corresponding cellular receptors was proven an effective way to regulate inflammation and/or prevent its negative consequences. However, one problem that comes along with an effective neutralization of inflammatory mediators is the general systemic immunomodulatory effect. It is therefore important to design a treatment regimen in a way to strike at the right place and at the right time in order to achieve maximal effects with minimal duration of immunosuppression or hyperactivation. In this review we reflect on two examples of how short time administration of such neutralizing antibodies can block two distinct inflammatory consequences of viral infection. First, we review recent findings that blockade of IL-10/IL-10R interaction can resolve chronic viral infection and second, we reflect on how neutralization of the chemokine CXCL10 can abrogate virus-induced type 1 diabetes.

  1. Regulation of IL-2 induced proliferation and cytotoxicity in human natural killer cells by monoclonal antibodies

    International Nuclear Information System (INIS)

    Natural killer (NK) activity is mediated by a subpopulation of cells termed large granular lymphocytes (LGL), which exhibit cytotoxic activity against a variety of tumor targets. LGL express OKT8, OKT9, OKT10, OKT11, 3G8 (FcγR), OKM1, NKH1. The addition of recombinant IL-2 (rIL-2), increases cytotoxicity, induces IFN-γ production and leads to LGL proliferation. Since monoclonal antibodies (MoAb) represent highly specific probes to analyze possible surface molecules, they have studied the role of various MoAbs in the regulation of cytotoxicity, proliferation, and secretory function of purified LGL. LGL were isolated from nonadherent human peripheral blood leukocytes on discontinuous Percoll density gradients, followed by 290C E-rosette depletion of contaminating T cells. These preparations were ≥ 85% LGL and contained ≥ 5% OKT3+ cells. Using a limiting dilution assay, purified LGL were incubated with rIL-2 and the MoAbs (10 μg/ml) for 7 days. These cells were tested for cytotoxicity against K562 in a 51Cr- release assay, and for proliferation as determined by 3H-thymidine incorporation. Results indicate that the OKT9 antibody inhibited both the cytotoxicity and proliferation. MoAb against LGl markers (OKT11, OKT8, OKM1, 3G8, and NKH1) had no effect on cytotoxicity or proliferation. Unlike the T cell receptor complex (with OKT3), the surface molecules examined do not regulate LGL lysis or proliferation

  2. Evaluation of autoimmune phenomena in patients with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS).

    Science.gov (United States)

    Stagi, Stefano; Rigante, Donato; Lepri, Gemma; Bertini, Federico; Matucci-Cerinic, Marco; Falcini, Fernanda

    2014-12-01

    The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are basically characterized by obsessive-compulsive symptoms and/or tics triggered by group-A beta-hemolytic Streptococcus infections. Poor data are available about the clear definition of PANDAS's autoimmune origin. The aim of our study was to evaluate the prevalence of autoimmune phenomena, including thyroid function abnormalities, specific celiac disease antibodies, and positivity of organ- or nonorgan-specific autoantibodies in a large cohort of Caucasian children and adolescents with PANDAS. Seventy-seven consecutive patients (59 males, 18 females; mean age 6.3±2.5 years, range 2.0-14.5 years) strictly fulfilling the clinical criteria for PANDAS diagnosis were recruited. In all subjects we evaluated serum concentrations of free-T3, free-T4, thyrotropin, and the following auto-antibodies: anti-thyroperoxidase, anti-thyroglobulin, anti-thyrotropin receptor, anti-gliadin, anti-endomysium, anti-tissue transglutaminase, anti-nuclear, anti-smooth muscle, anti-extractable nuclear antigens, anti-phospholipid, plus lupus-like anticoagulant. The results were compared with those obtained from 197 age- and sex-matched healthy controls (130 males, 67 females; mean age 6.8±2.9 years, range 2.3-14.8 years). The frequencies of subclinical (3.8% vs 3.6%) and overt hypothyroidism (1.2% vs 0%), autoimmune thyroiditis (2.46% vs 1.14%), celiac disease (1.2% vs 0.05%), and positivity of organ- and nonorgan-specific autoantibodies (5.1% vs 4.8%) were not statistically significant between patients with PANDAS and controls. Evaluating the overall disease duration, we did not observe any significant difference between patients with (3.4±2.15 years) and without (3.4±2.89 years) autoimmune abnormalities. However, PANDAS patients with autoimmune diseases or positivity for any organ- and nonorgan-specific antibodies showed significantly higher anti-streptolysin O and anti-DNAse B

  3. Experimental drugs for treatment of autoimmune myocarditis

    Institute of Scientific and Technical Information of China (English)

    Han Lina; Guo Shuli; Wang Yutang; Yang Liming; Liu Siyu

    2014-01-01

    Objective To review the experimental drugs for the treatment of autoimmune myocarditis.Data sources The literatures published in English about different kinds of experimental drugs based on different therapeutic mechanisms for the treatment of autoimmune myocarditis were obtained from PubMed from 2002 to 2013.Study selection Original articles regarding the experimental drugs for treatment of autoimmune myocarditis were selected.Results This study summarized the effects of the experimental drugs for the treatment of autoimmune myocarditis,such as immunomodulators and immunosuppressants,antibiotics,Chinese medicinal herbs,cardiovascular diseases treatment drugs,etc.These drugs can significantly attenuate autoimmune myocarditis-induced inflammation and fibrosis,alleviate autoimmune myocarditis-triggered overt lymphocyte proliferation,and meanwhile reduce Th1 cytokines (IFN-γ and IL-2) and increase Th2 cytokines (IL-4 and IL-10).Conclusion This study summarized recent advances in autoimmune myocarditis treatment and further proposes that traditional Chinese medicine and immune regulators will play important roles in the future.

  4. Bistability in autoimmune diseases

    DEFF Research Database (Denmark)

    Rapin, Nicolas; Mosekilde, Erik; Lund, Ole

    2011-01-01

    Autoimmune diseases damage host tissue, which, in turn, may trigger a stronger immune response. Systems characterized by such positive feedback loops can display co-existing stable steady states. In a mathematical model of autoimmune disease, one steady state may correspond to the healthy state and...... another to an autoimmune steady state characterized by widespread tissue damage and immune activation. We show how a triggering event may move the system from the healthy to the autoimmune state and how transient immunosuppressive treatment can move the system back to the healthy state....

  5. Study of the immune response to thyroglobulin through a model of experimental autoimmune thyroiditis

    International Nuclear Information System (INIS)

    The cellular and humoral immune response to thyroglobulin of different species was studied in guinea pigs. The experiments described suggested that the immune system can be activated against self-determinants. Human and pork thyroglobulin were able to induce the experimental thyroiditis as well as some immune responses, such as in vitro proliferative response, delayed hypersensitivity and antibodies. Although guinea pig thyroglobulin was unable to induce specific T-lymphocyte proliferation in vitro, delayed hypersensitivity response and antibodies, it was very efficient in inducing the autoimmune thyroiditis. On the contrary, bovine thyroglobulin did not induce experimental autoimmune thyroiditis despite producing good responses as determined by similar in vitro proliferative response, delayed hypersensitivity and on the humoral level. These results suggest that the assays utilised were not able to evaluate the relevant immune response to genesis of the thyroiditis. The determinant selection mechanisms operating in these immune responses are probably selecting determinants not responsible for self-recognition in vivo. It was suggested that the macrophage could be the cell responsible for the presentation of these determinants to the lymphocyte in an immunogenic form. (Author)

  6. The role of antibodies in myasthenia gravis.

    Science.gov (United States)

    De Baets, M; Stassen, M H W

    2002-10-15

    Myasthenia gravis is an autoimmune disease associated with antibodies directed to the postsynaptic acetylcholine receptor. These antibodies reduce the number of receptors. Autoantibodies against AChR and other muscle antigens can be used for the diagnosis of myasthenia gravis and related disorders. The origin and the role of these antibodies in the disease are discussed. Experimental autoimmune myasthenia gravis, an experimental model closely mimicking the disease, has provided answers to many questions about the role of antibodies, complement macrophages and AChR anchor proteins. Genetically modified anti-AChR antibodies may also be used in the future to treat myasthenia. PMID:12220686

  7. Bromocriptine and low dose cyclosporine in the treatment of experimental autoimmune uveitis in the rat.

    OpenAIRE

    Palestine, A G; Muellenberg-Coulombre, C G; Kim, M K; Gelato, M C; Nussenblatt, R. B.

    1987-01-01

    The immunologic effects of bromocriptine and low dose cyclosporine on experimental autoimmune uveitis (EAU) induced in Lewis rats by S-antigen immunization were studied. Rats treated with a sub-optimal dose (low dose) of cyclosporine (2 mg/kg per d), bromocriptine (1.8 mg/kg per d), or both drugs were compared with untreated rats in regard to the development of EAU, lymphocyte proliferative responses, and anti-S-antigen serum antibodies. Bromocriptine alone decreased the incidence of EAU only...

  8. Autoimmune liver disease, autoimmunity and liver transplantation.

    Science.gov (United States)

    Carbone, Marco; Neuberger, James M

    2014-01-01

    Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) represent the three major autoimmune liver diseases (AILD). PBC, PSC, and AIH are all complex disorders in that they result from the effects of multiple genes in combination with as yet unidentified environmental factors. Recent genome-wide association studies have identified numerous risk loci for PBC and PSC that host genes involved in innate or acquired immune responses. These loci may provide a clue as to the immune-based pathogenesis of AILD. Moreover, many significant risk loci for PBC and PSC are also risk loci for other autoimmune disorders, such type I diabetes, multiple sclerosis and rheumatoid arthritis, suggesting a shared genetic basis and possibly similar molecular pathways for diverse autoimmune conditions. There is no curative treatment for all three disorders, and a significant number of patients eventually progress to end-stage liver disease requiring liver transplantation (LT). LT in this context has a favourable overall outcome with current patient and graft survival exceeding 80% at 5years. Indications are as for other chronic liver disease although recent data suggest that while lethargy improves after transplantation, the effect is modest and variable so lethargy alone is not an indication. In contrast, pruritus rapidly responds. Cholangiocarcinoma, except under rigorous selection criteria, excludes LT because of the high risk of recurrence. All three conditions may recur after transplantation and are associated with a greater risk of both acute cellular and chronic ductopenic rejection. It is possible that a crosstalk between alloimmune and autoimmune response perpetuate each other. An immunological response toward self- or allo-antigens is well recognised after LT in patients transplanted for non-autoimmune indications and sometimes termed "de novo autoimmune hepatitis". Whether this is part of the spectrum of rejection or an autoimmune

  9. Hypothalamic-Pituitary Autoimmunity and Traumatic Brain Injury

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    Federica Guaraldi

    2015-05-01

    Full Text Available Background: Traumatic brain injury (TBI is a leading cause of secondary hypopituitarism in children and adults, and is responsible for impaired quality of life, disabilities and compromised development. Alterations of pituitary function can occur at any time after the traumatic event, presenting in various ways and evolving during time, so they require appropriate screening for early detection and treatment. Although the exact pathophysiology is unknown, several mechanisms have been hypothesized, including hypothalamic-pituitary autoimmunity (HP-A. The aim of this study was to systematically review literature on the association between HP-A and TBI-induced hypopituitarism. Major pitfalls related to the HP-A investigation were also discussed. Methods: The PubMed database was searched with a string developed for this purpose, without temporal or language limits, for original articles assessing the association of HP-A and TBI-induced hypopituitarism. Results: Three articles from the same group met the inclusion criteria. Anti-pituitary and anti-hypothalamic antibodies were detected using indirect immunofluorescence in a significant number of patients with acute and chronic TBI. Elevated antibody titer was associated with an increased risk of persistent hypopituitarism, especially somatotroph and gonadotroph deficiency, while no correlations were found with clinical parameters. Conclusion: HPA seems to contribute to TBI-induced pituitary damage, although major methodological issues need to be overcome and larger studies are warranted to confirm these preliminary data.

  10. Structural Constraints of Vaccine-Induced Tier-2 Autologous HIV Neutralizing Antibodies Targeting the Receptor-Binding Site

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    Todd Bradley

    2016-01-01

    Full Text Available Antibodies that neutralize autologous transmitted/founder (TF HIV occur in most HIV-infected individuals and can evolve to neutralization breadth. Autologous neutralizing antibodies (nAbs against neutralization-resistant (Tier-2 viruses are rarely induced by vaccination. Whereas broadly neutralizing antibody (bnAb-HIV-Envelope structures have been defined, the structures of autologous nAbs have not. Here, we show that immunization with TF mutant Envs gp140 oligomers induced high-titer, V5-dependent plasma neutralization for a Tier-2 autologous TF evolved mutant virus. Structural analysis of autologous nAb DH427 revealed binding to V5, demonstrating the source of narrow nAb specificity and explaining the failure to acquire breadth. Thus, oligomeric TF Envs can elicit autologous nAbs to Tier-2 HIVs, but induction of bnAbs will require targeting of precursors of B cell lineages that can mature to heterologous neutralization.

  11. American Autoimmune Related Diseases Association

    Science.gov (United States)

    ... Its 25th Anniversary With #25FOR25 Campaign During National Autoimmune Disease Awareness Month AARDA officially kicks of National Autoimmune ... will benefit AARDA. Click here to read more. Autoimmune Disease Awareness Month AARDA and the NCAPG held two ...

  12. A Case of Autoimmune Pancreatitis Associated with Retroperitoneal Fibrosis

    Directory of Open Access Journals (Sweden)

    Koushiro Ohtsubo

    2007-05-01

    Full Text Available Context Autoimmune pancreatitis is characterized by diffuse enlargement of the pancreas, diffuse irregular narrowing of the main pancreatic duct, severe lymphoplasmacytic infiltration and fibrosis of the pancreas. Retroperitoneal fibrosis may occasionally be associated with autoimmune pancreatitis. Case report We report a 77-year-old man with autoimmune pancreatitis associated with retroperitoneal fibrosis. Abdominal ultrasonography and computed tomography demonstrated diffuse enlargement of the pancreas and a capsule-like rim. Furthermore, a retroperitoneal mass was recognized anterior to the abdominal aorta. Antinuclear antibody, IgG and IgG4 values were elevated. Therefore, this patient was diagnosed as having autoimmune pancreatitis associated with retroperitoneal fibrosis. We performed steroid therapy using prednisolone. After 4 weeks, both IgG and IgG4 values decreased and both the swelling of the pancreas and also the retroperitoneal mass were obviously diminished. Conclusion This is a rare case of autoimmune pancreatitis associated with retroperitoneal fibrosis.

  13. Autoimmunity in differentiated thyroid cancer: significance and related clinical problems

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, Ulla; Rasmussen, Ase Krogh

    2011-01-01

    autoimmune thyroid diseases should have a careful follow-up. Furthermore, the presence of thyroglobulin antibodies (TgAb) in patients with DTC may limit the use of serum thyroglobulin as a tumor marker due to methodological problems in the determination of serum thyroglobulin. However, in such cases serial......Coexistence of differentiated thyroid cancer (DTC) and thyroid autoimmune diseases could represent a mere coincidence due to the frequent occurrence of autoimmunity, but there may also be a pathological and causative link between the two conditions. The coincidence of DTC with Hashimoto's disease...... has been variably reported at between 0.5 and 22.5% and of DTC with Graves' disease between 0 and 9.8%. In this review available evidence for thyroid autoimmunity in DTC is summarized and it is concluded that thyroid cancer does coexist with thyroid autoimmunity, implying that patients treated for...

  14. Autoimmunity in differentiated thyroid cancer: significance and related clinical problems

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, Ulla; Rasmussen, Ase Krogh

    2010-01-01

    autoimmune thyroid diseases should have a careful follow-up. Furthermore, the presence of thyroglobulin antibodies (TgAb) in patients with DTC may limit the use of serum thyroglobulin as a tumor marker due to methodological problems in the determination of serum thyroglobulin. However, in such cases serial......Coexistence of differentiated thyroid cancer (DTC) and thyroid autoimmune diseases could represent a mere coincidence due to the frequent occurrence of autoimmunity, but there may also be a pathological and causative link between the two conditions. The coincidence of DTC with Hashimoto's disease...... has been variably reported at between 0.5 and 22.5% and of DTC with Graves' disease between 0 and 9.8%. In this review available evidence for thyroid autoimmunity in DTC is summarized and it is concluded that thyroid cancer does coexist with thyroid autoimmunity, implying that patients treated for...

  15. Autoimmune diseases in pregnancy: maternal and fetal outcomes

    OpenAIRE

    Pavithra M. Vengetesh; Shripad Hebbar; Lavanya Rai

    2015-01-01

    Background: The aim of this study was to assess the impact of autoimmune connective tissue disorders on the outcomes of pregnancy and the influence of treatment on pregnancy. Methods: Thirty-seven antenatal patients with autoimmune connective tissue diseases, comprising of Systemic Lupus Erythematosus (SLE), primary antiphospholipid antibody syndrome (APS), Mixed Connective Tissue Diseases (MCTD), ankylosing spondylitis and Takayasu arteritis were analysed. Results: Multigravidas con...

  16. Familial Autoimmune Myasthenia Gravis (Report Of 3 Cases)

    OpenAIRE

    Girija A. S; Madhukar M; John John K

    2003-01-01

    Familial Autoimmune myasthenia gravis is rare, occurring in only about 1.3% cases of myasthenia gravis (MG). Here in we report a family with three family members affected by MG. Proband presented with generalised myasthenia where as the other two affected family members had only ocular myasthenia. Anti-acetylcholinereceptor antibody was strongly positive in the proband and he responded to steroids. His brother in addition had vitiligo over his face substantiating the autoimmune natu...

  17. Ameliorative effects of human adipose tissue-derived mesenchymal stem cells on myelin basic protein-induced experimental autoimmune encephalomyelitis in Lewis rats

    Institute of Scientific and Technical Information of China (English)

    Myung-Soon Ko; Hyeong-geun Park; Young-Min Yun; Jeong Chan Ra; Taekyun Shin; Kyoung-Kap Lee

    2011-01-01

    Mesenchymal stem cells have been previously shown to exert an immunomodulatory function. The present study sought to investigate the effects of multipotential human adipose tissue-derived mesenchymal stem cells (hAdMSCs) on disease progression and cytokine expression in Lewis rats with experimental autoimmune encephalomyelitis (EAE) induced by myelin basic protein. The duration of EAE paralysis in the group treated on day 7 postimmunization with 5 × 106 hAdMSCs was significantly reduced compared with the vehicle-treated controls and the 1 × 106 hAdMSC- treated group. The duration of EAE paralysis in the groups treated with 5 × 106 hAdMSCs on both day 1 and day 7 postimmunization was significantly reduced compared with the vehicle-treated controls and the groups treated with 5 × 106 hAdMSCs on both day 7 and day 10 postimmunization. The mRNA expression of interleukin-10 and indoleamine 2, 3-dioxygenase was significantly decreased in the hAdMSC-treated group compared with the vehicle-treated group. These findings suggest that the ameliorative effects of hAdMSCs on EAE symptoms operate in a dose- and time-dependent manner and can be mediated in part by the ample production of anti-inflammatory cytokines.

  18. Evaluation of Vaccine-induced Antibody Responses: Impact of New Technologies

    OpenAIRE

    Zaccaro, Daniel J.; Wagener, Diane K.; Whisnant, Carol C; Staats, Herman F.

    2013-01-01

    Host response to vaccination has historically been evaluated based on a change in antibody titer that compares the post-vaccination titer to the pre-vaccination titer. A four-fold or greater increase in antigen-specific antibody has been interpreted to indicate an increase in antibody production in response to vaccination. New technologies, such as the bead-based assays, provide investigators and clinicians with precise antibody levels (reported as concentration per mL) in ranges below and ab...

  19. Autoimmune thyroiditis in girls of pubertal age

    International Nuclear Information System (INIS)

    Two hundred twenty five girls with autoimmune thyroiditis aged 11-16 living in Belarus permanently have been examined in 8-10 years after Chernobyl accident. The disease at girls of pubertal age living on the contaminated territories is characterized by more frequent asthenoneurotic symptoms, more marked immunologic changes and higher levels of both antibodies to thyroglobulin and thyrocytes microsome antigens as compared to those from 'clean' regions

  20. Incidence of radiation-induced Graves' disease in patients treated with radioiodine for thyroid autonomy before and after introduction of a high-sensitivity TSH receptor antibody assay

    Energy Technology Data Exchange (ETDEWEB)

    Dunkelmann, Simone; Wolf, Ricarda; Koch, Annedore; Kittner, Christian; Groth, Peter; Schuemichen, Carl [University of Rostock, Clinic of Nuclear Medicine, Rostock (Germany)

    2004-10-01

    Autoimmune hyperthyroidism may occur several months after radioiodine therapy (RIT) for functional thyroid autonomy. Exacerbation of pre-existing subclinical Graves' disease (GD) has been held responsible for this phenomenon. Determination of TSH receptor antibody using solubilised porcine epithelial cell membranes is insensitive and may have failed to diagnose GD in these patients before RIT. Following the introduction of a more sensitive assay, using the human TSH receptor as an antigen, it has been expected that the incidence of radiation-induced GD after RIT for functional thyroid autonomy will be reduced. In a first group of 1,428 patients treated between November 1993 and March 1997 (group I) we used the porcine TRAb assay to exclude GD, while in a second group comprising 1,408 patients treated between January 2000 and December 2001 (group II), GD was excluded using the human TRAb assay. A matched control group of 231 patients was derived from group II. In group I a total of 15 (1.05%) patients developed obvious or suspected radiation-induced GD, while in group II 17 (1.2%) did so; the interval until development of GD was 8.4 and 8.8 months, respectively, after RIT. Serum anti-thyroid peroxidase levels before RIT were elevated in 36.4% of group I patients and 47.1% of group II patients, but in only 5.6% of the control group. Other non-specific signs of mild immunopathy of the thyroid were seen retrospectively in 73.3%, 64.7% and 16.0% of the patients in these three groups, respectively. In conclusion, the introduction of a high-sensitivity TRAb assay did not reduce the incidence of autoimmune hyperthyroidism occurring late after RIT for functional thyroid autonomy, but mild immunopathy of the thyroid is seen more frequently in these patients and seems to be a predisposing factor in the development of radiation-induced GD. (orig.)

  1. THE AUTOIMMUNE ECOLOGY.

    Directory of Open Access Journals (Sweden)

    Juan-Manuel eAnaya

    2016-04-01

    Full Text Available Autoimmune diseases (ADs represent a heterogeneous group of disorders that affect specific target organs or multiple organ systems. These conditions share common immunopathogenic mechanisms (i.e., the autoimmune tautology, which explain the clinical similarities they have among them as well as their familial clustering (i.e., coaggregation. As part of the autoimmune tautology, the influence of environmental exposure on the risk of developing ADs is paramount (i.e., the autoimmune ecology. In fact, environment, more than genetics, shapes immune system. Autoimmune ecology is akin to exposome, that is all the exposures - internal and external - across the lifespan, interacting with hereditary factors (both genetics and epigenetics to favor or protect against autoimmunity and its outcomes. Herein we provide an overview of the autoimmune ecology, focusing on the immune response to environmental agents in general, and microbiota, cigarette smoking, alcohol and coffee consumption, socioeconomic status, gender and sex hormones, vitamin D, organic solvents and vaccines in particular. Inclusion of the autoimmune ecology in disease etiology and health will improve the way personalized medicine is currently conceived and applied.

  2. Autoimmune pancreatitis in an 11-year-old boy

    Energy Technology Data Exchange (ETDEWEB)

    Refaat, Rania [Johann-Wolfgang-Goethe University, Department of Diagnostic and Interventional Radiology, Frankfurt am Main (Germany); Ain Shams University, Department of Diagnostic and Interventional Radiology, Cairo (Egypt); Harth, Marc; Proschek, Petra; Lindemayr, Sebastian; Vogl, Thomas J. [Johann-Wolfgang-Goethe University, Department of Diagnostic and Interventional Radiology, Frankfurt am Main (Germany)

    2009-04-15

    We report a case of histopathologically proven autoimmune pancreatitis in an 11-year-old boy. Abdominal US and MRI showed a focal swelling of the pancreatic head, the latter also showing delayed contrast enhancement. There was diffuse irregular pancreatic duct narrowing, compression of the intrapancreatic common bile duct, and mild proximal biliary dilatation on MR cholangiopancreatography. Laboratory results revealed normal serum IgG and subclass 4 with negative autoimmune antibodies, and slightly elevated carbohydrate antigen 19-9. This highlights the differentiation of autoimmune pancreatitis from pancreatic head cancer and, to a lesser extent, other forms of pancreatitis in children. (orig.)

  3. Anti-GD(2) with an FC point mutation reduces complement fixation and decreases antibody-induced allodynia.

    Science.gov (United States)

    Sorkin, Linda S; Otto, Mario; Baldwin, William M; Vail, Emily; Gillies, Stephen D; Handgretinger, Rupert; Barfield, Raymond C; Ming Yu, Hui; Yu, Alice L

    2010-04-01

    Monoclonal antibodies against GD(2) ganglioside, such as ch14.18, the human-mouse chimeric antibody, have been shown to be effective for the treatment of neuroblastoma. However, treatment is associated with generalized, relatively opiate-resistant pain. We investigated if a point mutation in ch14.18 antibody (hu14.18K332A) to limit complement-dependent cytotoxicity (CDC) would ameliorate the pain behavior, while preserving antibody-dependent cellular cytotoxicity (ADCC). In vitro, CDC and ADCC were measured using europium-TDA assay. In vivo, allodynia was evaluated by measuring thresholds to von Frey filaments applied to the hindpaws after injection of either ch14.18 or hu14.18K332 into wild type rats or rats with deficient complement factor 6. Other rats were pretreated with complement factor C5a receptor antagonist and tested following ch14.18 injection. The mutation reduces the antibody's ability to activate complement, while maintaining its ADCC capabilities. Injection of hu14.18K322 (1 or 3mg/kg) produced faster resolving allodynia than that engendered by ch14.18 (1mg/kg). Injection of ch14.18 (1mg/kg) into rats with C6 complement deficiency further reduced antibody-induced allodynia, while pre-treatment with complement factor C5a receptor antagonist completely abolished ch14.18-induced allodynia. These findings showed that mutant hu14.18 K322 elicited less allodynia than ch14.18 and that ch14.18-elicited allodynia is due to activation of the complement cascade: in part, to formation of membrane attack complex, but more importantly to release of complement factor C5a. Development of immunotherapeutic agents with decreased complement-dependent lysis while maintaining cellular cytotoxicity may offer treatment options with reduced adverse side effects, thereby allowing dose escalation of therapeutic antibodies. PMID:20171010

  4. Long-term follow-up of seven patients with ophthalmopathy not associated with thyroid autoimmunity: heterogeneity of autoimmune ophthalmopathy

    OpenAIRE

    McCorquodale, Tom; Lahooti, Hooshang; Gopinath, Bamini; Wall, Jack R

    2012-01-01

    Background Ophthalmopathy is the most common extrathyroidal manifestation of Graves’ disease. However, in approximately 5% of cases this autoimmune eye disorder occurs in the apparent absence of Graves’ hyperthyroidism: the so-called euthyroid Graves’ disease (EGD). Methods Seven patients with EGD were followed for evidence of thyroid and orbital autoimmunity, for up to 10 years. Calsequestrin and collagen XIII antibodies were measured by enzyme linked immunosorbent assay (ELISA), and TSH-rec...

  5. Intratypic heterologous vaccination of calves can induce an antibody response in presence of maternal antibodies against foot-and-mouth disease virus

    OpenAIRE

    Dekker, A.; Eble, P.L.; Stockhofe-Zurwieden, N; Chenard, G.

    2014-01-01

    Background - Maternal antibodies can interfere with foot-and-mouth disease vaccination. In this study we determined whether intratypic heterologous vaccination could help to improve herd immunity. Results - In unvaccinated calves, a half-life of maternal antibodies of 21 days was determined. At two weeks of age, calves without maternal antibodies showed a good antibody response against both vaccines used in the trial, while in calves with maternal antibodies no antibody response to homologous...

  6. Autoimmune polyglandular syndrome, type 2 associated with myasthenia gravis

    Directory of Open Access Journals (Sweden)

    Pejin Radoslav

    2012-01-01

    Full Text Available Introduction. Autoimmune polyglandular syndrome type 2 is defined as adrenal insufficiency associated with autoimmune primary hypothyroidism and/or with autoimmune type 1 diabetes mellitus, but very rare with myasthenia gravis. Case report. We presented a case of an autoimmune polyglandular syndrome, type 2 associated with myasthenia gravis. A 49-year-old female with symptoms of muscle weakness and low serum levels of cortisol and aldosterone was already diagnosed with primary adrenal insufficiency. Primary hypothyroidism was identified with low values of free thyroxine 4 (FT4 and raised values of thyroidstumulating hormone (TSH. The immune system as a cause of hypothyroidism was confirmed by the presence of thyroid antibodies to peroxidase and TSH receptors. Myasthenia gravis was diagnosed on the basis of a typical clinical feature, positive diagnostic tests and an increased titre of antibodies against the acetylcholine receptors. It was not possible to confirm the immune nature of adrenal insufficiency by the presence of antibodies to 21- hydroxylase. The normal morphological finding of the adrenal glands was an indirect confirmation of the condition as well as the absence of other diseases that might have led to adrenal insufficiency and low levels of both serum cortisol and aldosterone. Hormone replacement therapy, anticholinergic therapy and corticosteroid therapy for myasthenia gravis improved the patient’s general state of health and muscle weakness. Conclusion. This case report indicates a need to examine each patient with an autoimmune disease carefully as this condition may be associated with another autoimmune diseases.

  7. Alpha1A-adrenergic receptor-directed autoimmunity induces left ventricular damage and diastolic dysfunction in rats.

    Directory of Open Access Journals (Sweden)

    Katrin Wenzel

    Full Text Available BACKGROUND: Agonistic autoantibodies to the alpha(1-adrenergic receptor occur in nearly half of patients with refractory hypertension; however, their relevance is uncertain. METHODS/PRINCIPAL FINDINGS: We immunized Lewis rats with the second extracellular-loop peptides of the human alpha(1A-adrenergic receptor and maintained them for one year. Alpha(1A-adrenergic antibodies (alpha(1A-AR-AB were monitored with a neonatal cardiomyocyte contraction assay by ELISA, and by ERK1/2 phosphorylation in human alpha(1A-adrenergic receptor transfected Chinese hamster ovary cells. The rats were followed with radiotelemetric blood pressure measurements and echocardiography. At 12 months, the left ventricles of immunized rats had greater wall thickness than control rats. The fractional shortening and dp/dt(max demonstrated preserved systolic function. A decreased E/A ratio in immunized rats indicated a diastolic dysfunction. Invasive hemodynamics revealed increased left ventricular end-diastolic pressures and decreased dp/dt(min. Mean diameter of cardiomyocytes showed hypertrophy in immunized rats. Long-term blood pressure values and heart rates were not different. Genes encoding sarcomeric proteins, collagens, extracellular matrix proteins, calcium regulating proteins, and proteins of energy metabolism in immunized rat hearts were upregulated, compared to controls. Furthermore, fibrosis was present in immunized hearts, but not in control hearts. A subset of immunized and control rats was infused with angiotensin (Ang II. The stressor raised blood pressure to a greater degree and led to more cardiac fibrosis in immunized, than in control rats. CONCLUSIONS/SIGNIFICANCE: We show that alpha(1A-AR-AB cause diastolic dysfunction independent of hypertension, and can increase the sensitivity to Ang II. We suggest that alpha(1A-AR-AB could contribute to cardiovascular endorgan damage.

  8. Olmesartan, an AT1 Antagonist, Attenuates Oxidative Stress, Endoplasmic Reticulum Stress and Cardiac Inflammatory Mediators in Rats with Heart Failure Induced by Experimental Autoimmune Myocarditis

    Directory of Open Access Journals (Sweden)

    Vijayakumar Sukumaran, Kenichi Watanabe, Punniyakoti T. Veeraveedu, Narasimman Gurusamy, Meilei Ma, Rajarajan A. Thandavarayan, Arun Prasath Lakshmanan, Ken'ichi Yamaguchi, Kenji Suzuki, Makoto Kodama

    2011-01-01

    Full Text Available Studies have demonstrated that angiotensin II has been involved in immune and inflammatory responses which might contribute to the pathogenesis of immune-mediated diseases. Recent evidence suggests that oxidative stress may play a role in myocarditis. Here, we investigated whether olmesartan, an AT1R antagonist protects against experimental autoimmune myocarditis (EAM by suppression of oxidative stress, endoplasmic reticulum (ER stress and inflammatory cytokines. EAM was induced in Lewis rats by immunization with porcine cardiac myosin, were divided into two groups and treated with either olmesartan (10 mg/kg/day or vehicle for a period of 21 days. Myocardial functional parameters measured by hemodynamic and echocardiographic analyses were significantly improved by the treatment with olmesartan compared with those of vehicle-treated rats. Treatment with olmesartan attenuated the myocardial mRNA expressions of proinflammatory cytokines, [Interleukin (IL-1β, monocyte chemoattractant protein-1, tumor necrosis factor-α and interferon-γ] and the protein expression of tumor necrosis factor-α compared with that of vehicle-treated rats. Myocardial protein expressions of AT1R, NADPH oxidase subunits (p47phox, p67phox, gp91phox and the expression of markers of oxidative stress (3-nitrotyrosine and 4-hydroxy-2-nonenal, and the cardiac apoptosis were also significantly decreased by the treatment with olmesartan compared with those of vehicle-treated rats. Furthermore, olmesartan treatment down-regulated the myocardial expressions of glucose regulated protein-78, growth arrest and DNA damage-inducible gene, caspase-12, phospho-p38 mitogen-activated protein kinase (MAPK and phospho-JNK. These findings suggest that olmesartan protects against EAM in rats, at least in part via suppression of oxidative stress, ER stress and inflammatory cytokines.

  9. DNA-dependent protein kinase inhibits AID-induced antibody gene conversion.

    Directory of Open Access Journals (Sweden)

    Adam J L Cook

    2007-04-01

    Full Text Available Affinity maturation and class switching of antibodies requires activation-induced cytidine deaminase (AID-dependent hypermutation of Ig V(DJ rearrangements and Ig S regions, respectively, in activated B cells. AID deaminates deoxycytidine bases in Ig genes, converting them into deoxyuridines. In V(DJ regions, subsequent excision of the deaminated bases by uracil-DNA glycosylase, or by mismatch repair, leads to further point mutation or gene conversion, depending on the species. In Ig S regions, nicking at the abasic sites produced by AID and uracil-DNA glycosylases results in staggered double-strand breaks, whose repair by nonhomologous end joining mediates Ig class switching. We have tested whether nonhomologous end joining also plays a role in V(DJ hypermutation using chicken DT40 cells deficient for Ku70 or the DNA-dependent protein kinase catalytic subunit (DNA-PKcs. Inactivation of the Ku70 or DNA-PKcs genes in DT40 cells elevated the rate of AID-induced gene conversion as much as 5-fold. Furthermore, DNA-PKcs-deficiency appeared to reduce point mutation. The data provide strong evidence that double-strand DNA ends capable of recruiting the DNA-dependent protein kinase complex are important intermediates in Ig V gene conversion.

  10. Effects of Cytokine IL-18 Gene on Antibody Production Induced by Ag85A DNA Vaccine

    Institute of Scientific and Technical Information of China (English)

    CHENHai-wen; WANGZi-ming; FANXiong-lin; GANWei-min; SHITao; XUZhi-kai; LIYuan

    2004-01-01

    Objective: To investigate the effects of plasmid containing human IL-18 gene on the humoral immune response of mice immunized by Ag85A DNA vaccines of Mycobacterium tuberculosis H37 Rv strain. Methods: Human IL-18 cDNA was amplified from RNA of peripheral blood mononuclear cells(PBMCs)by RT-PCR and cloned into the pGEM-TEasy vector.After sequencing IL-18 gene was subcloned into the the sites of BamH I and EooR I digestion of pcDNA3.1. BALB/c mice were injected intramuscularly with eukaryotic expression plasmid pclL18, together with MTB pcAg85A DNA vaccines. The same immunization was repeated three times at intervals of two weeks. Mouse serawere collected at two weeks after the each injection. The titers of anti-Ag85A antibody were detected by ELISA. Results:IL-18 cDNA was amplified successfully from RNA of human PBMCs by RT-PCR and the result of sequencing was correct. The IL-18 gene was correctly inserted into the vector pcDNA3.1, which was confirmed with BamH I and EooR I digestion analysis. The positive plasmid was called pcIL18.After being immtmized with DNA vaccines,the titers of antibody obtained from mice being immtmized by pcAg85A combining with pclL18 were superior to mice inmunized by pcAg85A independently. Conc/us/on: Combination of IL-18 gene with MTB pcAg85A DNA vaccine could observably enhance the humoral immune responses to pcAg85A. It remains further investigated whether IL-18 gene plus MTB pcAg85A DNA vaccine could markedly induce the cellular mediated immune response to Ag85A or not.

  11. The NTS-DBL2X region of VAR2CSA Induces cross-reactive antibodies that inhibit adhesion of several Plasmodium falciparum isolates to chondroitin sulfate A

    DEFF Research Database (Denmark)

    Bigey, Pascal; Gnidehou, Sédami; Doritchamou, Justin;

    2011-01-01

    -adapted parasite lines and field isolates expressing VAR2CSA. Competition enzyme-linked immunosorbent assay (ELISA) was employed to analyze functional resemblance between antibodies induced in animals and those naturally acquired by immune multigravidae. Results. Antibodies targeting the N-terminal sequence (NTS......) up to DBL2X (NTS-DBL2X) efficiently blocked parasite adhesion to chondroitin sulfate A in a manner similar to that of antibodies raised against the entire VAR2CSA extracellular domain. Interestingly, naturally acquired antibodies and those induced by vaccination against NTS-DBL2X target overlapping...

  12. Anti-thromboxane B2 antibodies protect against acetaminophen-induced liver injury in mice

    Directory of Open Access Journals (Sweden)

    Ivan Ćavar

    2011-12-01

    Full Text Available Prostanoids are lipid compounds that mediate a variety of physiological and pathological functions in almost all body tissues and organs. Thromboxane (TX A2 is a powerful inducer of platelet aggregation and vasoconstriction and it has ulcerogenic activity in the gastrointestinal tract. Overdose or chronic use of a high dose of acetaminophen (N-acetyl-paminophenol, APAP is a major cause of acute liver failure in the Western world. We investigated whether TXA2 plays a role in host response to toxic effect of APAP. CBA/H Zg mice of both sexes were intoxicated with a single lethal or high sublethal dose of APAP, which was administered to animals by oral gavage. The toxicity of APAP was determined by observing the survival of mice during 48 h, by measuring concentration of alanine-aminotransferase (ALT in plasma 20-22 h after APAP administration and by liver histology. The results have shown that anti-thromboxane (TX B2 antibodies (anti-TXB2 and a selective inhibitor of thromboxane (TX synthase, benzylimidazole (BZI, were significantly hepatoprotective, while a selective thromboxane receptor (TPR antagonist, daltroban, was slightly protective in this model of acute liver injury. A stabile metabolite of TXA2, TXB2, and a stabile agonist of TPR, U-46619, had no influence on APAP-induced liver damage. Our findings suggest that TXA2 has a pathogenic role in acute liver toxicity induced with APAP, which was highly abrogated by administration of anti-TXB2. According to our results, this protection is mediated, at least in part, through decreased production of TXB2 by liver fragments ex vivo.

  13. Analysis by Flow Cytometry of B-Cell Activation and Antibody Responses Induced by Toll-Like Receptors.

    Science.gov (United States)

    Pone, Egest J

    2016-01-01

    Toll-like receptors (TLRs) are expressed in B lymphocytes and contribute to B-cell activation, antibody responses, and their maturation. TLR stimulation of mouse B cells induces class switch DNA recombination (CSR) to isotypes specified by cytokines, and also induces formation of IgM(+) as well as class-switched plasma cells. B-cell receptor (BCR) signaling, while on its own inducing limited B-cell proliferation and no CSR, can enhance CSR driven by TLRs. Particular synergistic or antagonistic interactions among TLR pathways, BCR, and cytokine signaling can have important consequences for B-cell activation, CSR, and plasma cell formation. This chapter outlines protocols for the induction and analysis of B-cell activation and antibody production by TLRs with or without other stimuli. PMID:26803633

  14. Characterization of a Novel Anti-DR5 Monoclonal Antibody WD1 with the Potential to Induce Tumor Cell Apoptosis

    Institute of Scientific and Technical Information of China (English)

    Jing Wang; Beifen Shen; Yuanfang Ma; Yan Li; Zhou Lin; Chunxia Qiao; Ming Lv; Ming Yu; He Xiao; Qingyang Wang; Liyan Wang; Jiannan Feng

    2008-01-01

    TNF-related apoptosis. inducing ligand (TRAIL) is a TNF family member capable of inducing apoptosis. Death receptor 5(DR 51 is a key receptor of TRAIL and plays an important role in TRAIL-induced apoptosis. To prepare monoclonal antibodies (mAbs) against DR5, cDNA encoding soluble DR5(sDR5)was firstly amplified by revere transcriptase. polymerase chain reaction (RT-PCR) with specific primers, and then inserted into a prokaryotic expression vector pET-30a. The recombinant plasmid Was expressed in Escherichia coil strain BL21(DE3), and sDR5 was purified by nickel affinity chromatography. As an antigen. sDR5 Was used to immunize mice. Hybridomas secreting antibodies against sDR5 were identified. One positive clone Was selected to produce antibody, WD1. ELISA and immunofluorescence demonstrated that WD1 could bind recombinant sDR5 and membrane bound DR5 (mDR5)on Jurkat and Molt-4 cells. ATPLite assays showed that Jurkat and Molt-4 cells were sensitive to the antibody in a dose dependent manner. The Annexin V/PI assays and Giemsa's staining both showed that WD1 could induce Jurkat cell apoptosis efficiently. Transient transfection of 293T cells and indirect immunofluorescence assay demonstrated that mAb(WD1)couldn't cross. react with DR4.Our findings indicated that the novel antibody, WD1 could act as a direct agonist, bind DR5 characteristically, and initiate efficient apoptotic signaling and tumor regression. Thus, WD1 would be a leading candidate for potential cancer therapeutics. Cellular & Molecular Immunology. 2008;5(1):55-60.

  15. Antinuclear antibodies are not increased in the early phase of Borrelia infection.

    OpenAIRE

    Spiewak, R.W.; Stojek, NM; Chmielewska-Badora, J.

    2004-01-01

    In the literature, there are case reports suggesting that Borrelia burgdorferi infection may induce autoimmune diseases dependent on antinuclear antibodies (ANA). The present study was undertaken in order to verify this possibility in a prospective manner. The study group comprised 78 consecutive patients (51 women and 27 men, median age 41.5 years) referred to our Department for the serologic diagnosis of Borrelia infection. The patients' sera were tested for Borrelia-specific IgM and IgG (R...

  16. Cytolytic antibodies to melanocytes in vitiligo.

    Science.gov (United States)

    Cui, J; Arita, Y; Bystryn, J C

    1993-06-01

    Patients with vitiligo have been found to have circulating antibodies to pigment cells. To evaluate the functional activity of these antibodies, a highly sensitive europium release assay was used to compare complement-mediated cytolysis of human melanocytes by sera of 56 patients with vitiligo (20 with active disease, 25 with inactive disease, 11 with unidentified disease activity) and 47 control individuals. Significant melanocyte lysis was mediated by 32 (57%) of the patients with vitiligo but by only three (6%) of the control sera (p < 0.001), and by 17 (85%) of 20 patients with active vitiligo versus 11 (44%) of 25 patients with inactive disease (p < 0.025). Mean melanocyte lysis by vitiligo sera was 24% versus 6% by control sera (p < 0.0001). A subset of 12 vitiligo sera with high titers of cytolytic antibodies to melanocytes (34% mean cytolysis) reacted minimally (< 2% mean cytolysis) to a panel of control cells that included human and murine melanomas, human fibroblasts, lung carcinoma, and rhabdomyosarcoma. These findings indicate that antibodies present in patients with vitiligo have the functional ability to selectively kill melanocytes and are more common in active disease. These observations support, but do not prove, the hypothesis that vitiligo is an autoimmune disease and that anti-pigment cell antibodies have a role in inducing the disease. PMID:8496621

  17. Autoimmunity and the Gut

    Directory of Open Access Journals (Sweden)

    Andrew W. Campbell

    2014-01-01

    Full Text Available Autoimmune diseases have increased dramatically worldwide since World War II. This is coincidental with the increased production and use of chemicals both in industrial countries and agriculture, as well as the ease of travel from region to region and continent to continent, making the transfer of a pathogen or pathogens from one part of the world to another much easier than ever before. In this review, triggers of autoimmunity are examined, principally environmental. The number of possible environmental triggers is vast and includes chemicals, bacteria, viruses, and molds. Examples of these triggers are given and include the mechanism of action and method by which they bring about autoimmunity.

  18. Polyclonal anti-idiotypic antibodies mimicking the small cell lung carcinoma antigen cluster-5A interact with a panel of antibodies and induce specific immune response in animals.

    OpenAIRE

    Zwicky, C.; Stahel, R A; Jaksche, H.; Waibel, R.; Lehmann, H. P.; Loibner, H

    1991-01-01

    Polyclonal anti-idiotypic antibodies (ab2) were generated by immunising goats with the murine IgG2a monoclonal antibody SWA20 which recognises the SCLC antigen cluster-5A, a tumour-associated sialoglycoprotein. Ab2 was shown to bind specifically to antibody SWA20, but not to isotype matched control antibodies. Pre-incubation with ab2 completely inhibited target cell binding of antibody SWA20 and of four other antibodies to cluster-5A antigen, while no effect was seen with antibodies to cluste...

  19. Endothelial cells' activation and apoptosis induced by a subset of antibodies against human cytomegalovirus: relevance to the pathogenesis of atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Claudio Lunardi

    Full Text Available BACKGROUND: Human cytomegalovirus (hCMV is involved in the pathogenesis of atherosclerosis. We have previously shown in patients with atherosclerosis that antibodies directed against the hCMV-derived proteins US28 and UL122 are able to induce endothelial cell damage and apoptosis of non-stressed endothelial cells through cross-rection with normally expressed surface molecules. Our aim was to dissect the molecular basis of such interaction and to investigate mechanisms linking innate immunity to atherosclerosis. METHODOLOGY/PRINCIPAL FINDINGS: We analysed the gene expression profiles in endothelial cells stimulated with antibodies affinity-purified against either the UL122 or the US28 peptides using the microarray technology. Microarray results were validated by quantitative PCR and by detection of proteins in the medium. Supernatant of endothelial cells incubated with antibodies was analysed also for the presence of Heat Shock Protein (HSP60 and was used to assess stimulation of Toll-Like Receptor-4 (TLR4. Antibodies against UL122 and US28 induced the expression of genes encoding for adhesion molecules, chemokines, growth factors and molecules involved in the apoptotis process together with other genes known to be involved in the initiation and progression of the atherosclerotic process. HSP60 was released in the medium of cells incubated with anti-US28 antibodies and was able to engage TLR4. CONCLUSIONS/SIGNIFICANCE: Antibodies directed against hCMV modulate the expression of genes coding for molecules involved in activation and apoptosis of endothelial cells, processes known to play a pivotal role in the pathogenesis of atherosclerosis. Moreover, endothelial cells exposed to such antibodies express HSP60 on the cell surface and release HSP60 in the medium able to activate TLR4. These data confirm that antibodies directed against hCMV-derived proteins US28 and UL122 purified from patients with coronary artery disease induce endothelial cell

  20. Autoimmune Pancreatitis: A Succinct Overview

    OpenAIRE

    Juan Putra; Xiaoying Liu

    2015-01-01

    Autoimmune pancreatitis is a rare type of chronic pancreatitis with characteristic clinical, radiologic, and histopathologic findings. Diagnosis of autoimmune pancreatitis is often challenging due to its low incidence and nonspecific clinical and radiologic findings. Patients with autoimmune pancreatitis and pancreatic cancer share similar clinical presentations, including obstructive jaundice, abdominal pain and weight loss. Due to these overlapping features, autoimmune pancreatitis patients...

  1. [Platelet factor 4, target of anti-heparin antibodies: application to biological diagnosis of heparin-induced thrombopenia].

    Science.gov (United States)

    Amiral, J

    1997-01-01

    Heparin-platelet factor 4 (H-PF4) complexes are the target for heparin-dependent antibodies present in most of heparin-induced thrombocytopenias (HIT). The highest reactivity is obtained with 27 IU of heparin per mg of PF4. Low molecular weight heparin (LMWH) and pentosane polysulphate can also form these complexes. Antibodies to H-PF4, may be of the IgG, IgA or IgM isotypes. In some HIT, IgGs are absent and only IgMs and/or IgAs are observed. These antibodies may also develop in heparin (15%) or LMWH (8%) treated patients in the absence of thrombocytopenia. IgGs rarely develop in these cases. Presence of antibodies to H-PF4 is therefore a risk factor for developing HIT. Development of pathology requires additional factors such as: PF4 and heparin at an optimised ratio allowing formation of macromolecular complexes; presence of activated platelets exposing increased Fc gamma RII-A and heparin receptors; His. 131 phenotype of Fc gamma RII-A; pre-thrombotic and/or inflammatory clinical manifestations. Assay of antibodies to H-PF4 improves HIT diagnosis and could be predictive for monitoring heparin-therapies. PMID:9238439

  2. Rapid assessment of antibody-induced ricin neutralization by employing a novel functional cell-based assay.

    Science.gov (United States)

    Gal, Yoav; Alcalay, Ron; Sabo, Tamar; Noy-Porat, Tal; Epstein, Eyal; Kronman, Chanoch; Mazor, Ohad

    2015-09-01

    Ricin is one of the most potent and lethal toxins known against which there is no available antidote. Currently, the most promising countermeasures against the toxin are based on neutralizing antibodies elicited by active vaccination or administered passively. A cell-based assay is widely applied for the primary screening and evaluation of anti-ricin antibodies, yet such assays are usually time-consuming (18-72 h). Here, we report of a novel assay to monitor ricin activity, based on HeLa cells that stably express the rapidly-degraded ubiquitin-luciferase (Ub-FL, half-life of 2 min). Ricin-induced arrest of protein synthesis could be quantified within 3 to 6h post intoxication (IC90 of 300 and 100 ng/ml, respectively). Furthermore, by stabilizing the intracellular levels of Ub-FL in the last hour of the assay, a 3-fold increase in the assay sensitivity was attained. We applied this assay to monitor the efficacy of a ricin holotoxin-based vaccine by measuring the formation of neutralizing antibodies throughout the immunization course. The potency of anti-ricin monoclonal antibodies (directed to either subunit of the toxin) could also be easily and accurately measured in this assay format. Owing to its simplicity, this assay may be implemented for high-throughput screening of ricin-neutralizing antibodies and for identification of small-molecule inhibitors of the toxin, as well as other ribosome-inactivating toxins. PMID:26003675

  3. Generation and characterization of function-blocking anti-ectodysplasin A (EDA) monoclonal antibodies that induce ectodermal dysplasia.

    Science.gov (United States)

    Kowalczyk-Quintas, Christine; Willen, Laure; Dang, Anh Thu; Sarrasin, Heidi; Tardivel, Aubry; Hermes, Katharina; Schneider, Holm; Gaide, Olivier; Donzé, Olivier; Kirby, Neil; Headon, Denis J; Schneider, Pascal

    2014-02-14

    Development of ectodermal appendages, such as hair, teeth, sweat glands, sebaceous glands, and mammary glands, requires the action of the TNF family ligand ectodysplasin A (EDA). Mutations of the X-linked EDA gene cause reduction or absence of many ectodermal appendages and have been identified as a cause of ectodermal dysplasia in humans, mice, dogs, and cattle. We have generated blocking antibodies, raised in Eda-deficient mice, against the conserved, receptor-binding domain of EDA. These antibodies recognize epitopes overlapping the receptor-binding site and prevent EDA from binding and activating EDAR at close to stoichiometric ratios in in vitro binding and activity assays. The antibodies block EDA1 and EDA2 of both mammalian and avian origin and, in vivo, suppress the ability of recombinant Fc-EDA1 to rescue ectodermal dysplasia in Eda-deficient Tabby mice. Moreover, administration of EDA blocking antibodies to pregnant wild type mice induced in developing wild type fetuses a marked and permanent ectodermal dysplasia. These function-blocking anti-EDA antibodies with wide cross-species reactivity will enable study of the developmental and postdevelopmental roles of EDA in a variety of organisms and open the route to therapeutic intervention in conditions in which EDA may be implicated. PMID:24391090

  4. Generation and Characterization of Function-blocking Anti-ectodysplasin A (EDA) Monoclonal Antibodies That Induce Ectodermal Dysplasia*

    Science.gov (United States)

    Kowalczyk-Quintas, Christine; Willen, Laure; Dang, Anh Thu; Sarrasin, Heidi; Tardivel, Aubry; Hermes, Katharina; Schneider, Holm; Gaide, Olivier; Donzé, Olivier; Kirby, Neil; Headon, Denis J.; Schneider, Pascal

    2014-01-01

    Development of ectodermal appendages, such as hair, teeth, sweat glands, sebaceous glands, and mammary glands, requires the action of the TNF family ligand ectodysplasin A (EDA). Mutations of the X-linked EDA gene cause reduction or absence of many ectodermal appendages and have been identified as a cause of ectodermal dysplasia in humans, mice, dogs, and cattle. We have generated blocking antibodies, raised in Eda-deficient mice, against the conserved, receptor-binding domain of EDA. These antibodies recognize epitopes overlapping the receptor-binding site and prevent EDA from binding and activating EDAR at close to stoichiometric ratios in in vitro binding and activity assays. The antibodies block EDA1 and EDA2 of both mammalian and avian origin and, in vivo, suppress the ability of recombinant Fc-EDA1 to rescue ectodermal dysplasia in Eda-deficient Tabby mice. Moreover, administration of EDA blocking antibodies to pregnant wild type mice induced in developing wild type fetuses a marked and permanent ectodermal dysplasia. These function-blocking anti-EDA antibodies with wide cross-species reactivity will enable study of the developmental and postdevelopmental roles of EDA in a variety of organisms and open the route to therapeutic intervention in conditions in which EDA may be implicated. PMID:24391090

  5. 21 CFR 866.5100 - Antinuclear antibody immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Antinuclear antibody immunological test system....5100 Antinuclear antibody immunological test system. (a) Identification. An antinuclear antibody... the autoimmune antibodies in serum, other body fluids, and tissues that react with cellular...

  6. Intestinal barrier dysfunction develops at the onset of experimental autoimmune encephalomyelitis, and can be induced by adoptive transfer of auto-reactive T cells.

    Directory of Open Access Journals (Sweden)

    Mehrnaz Nouri

    Full Text Available Multiple sclerosis (MS is a chronic inflammatory demyelinating disease of the central nervous system with a pathogenesis involving a dysfunctional blood-brain barrier and myelin-specific, autoreactive T cells. Although the commensal microbiota seems to affect its pathogenesis, regulation of the interactions between luminal antigens and mucosal immune elements remains unclear. Herein, we investigated whether the intestinal mucosal barrier is also targeted in this disease. Experimental autoimmune encephalomyelitis (EAE, the prototypic animal model of MS, was induced either by active immunization or by adoptive transfer of autoreactive T cells isolated from these mice. We show increased intestinal permeability, overexpression of the tight junction protein zonulin and alterations in intestinal morphology (increased crypt depth and thickness of the submucosa and muscularis layers. These intestinal manifestations were seen at 7 days (i.e., preceding the onset of neurological symptoms and at 14 days (i.e., at the stage of paralysis after immunization. We also demonstrate an increased infiltration of proinflammatory Th1/Th17 cells and a reduced regulatory T cell number in the gut lamina propria, Peyer's patches and mesenteric lymph nodes. Adoptive transfer to healthy mice of encephalitogenic T cells, isolated from EAE-diseased animals, led to intestinal changes similar to those resulting from the immunization procedure. Our findings show that disruption of intestinal homeostasis is an early and immune-mediated event in EAE. We propose that this intestinal dysfunction may act to support disease progression, and thus represent a potential therapeutic target in MS. In particular, an increased understanding of the regulation of tight junctions at the blood-brain barrier and in the intestinal wall may be crucial for design of future innovative therapies.

  7. Glassy Dynamics in the Adaptive Immune Response Prevents Autoimmune Disease

    Science.gov (United States)

    Sun, Jun; Deem, Michael

    2006-03-01

    The immune system normally protects the human host against death by infection. However, when an immune response is mistakenly directed at self antigens, autoimmune disease can occur. We describe a model of protein evolution to simulate the dynamics of the adaptive immune response to antigens. Computer simulations of the dynamics of antibody evolution show that different evolutionary mechanisms, namely gene segment swapping and point mutation, lead to different evolved antibody binding affinities. Although a combination of gene segment swapping and point mutation can yield a greater affinity to a specific antigen than point mutation alone, the antibodies so evolved are highly cross-reactive and would cause autoimmune disease, and this is not the chosen dynamics of the immune system. We suggest that in the immune system a balance has evolved between binding affinity and specificity in the mechanism for searching the amino acid sequence space of antibodies. Our model predicts that chronic infection may lead to autoimmune disease as well due to cross-reactivity and suggests a broad distribution for the time of onset of autoimmune disease due to chronic exposure. The slow search of antibody sequence space by point mutation leads to the broad of distribution times.

  8. AAV Natural Infection Induces Broad Cross-Neutralizing Antibody Responses to Multiple AAV Serotypes in Chimpanzees.

    Science.gov (United States)

    Calcedo, Roberto; Wilson, James M

    2016-06-01

    Cross-sectional studies of primates have revealed that natural neutralizing antibody (NAb) responses to adeno-associated viruses (AAV) span multiple serotypes. This differs from the phenotype of the NAb response to an AAV vector delivered to seronegative nonhuman primates that is typically restricted to the administered AAV serotype. To better understand the mechanism by which natural AAV infections result in broad NAb responses, we conducted a longitudinal study spanning 10 years in which we evaluated serum-circulating AAV NAb levels in captive-housed chimpanzees. In a cohort of 25 chimpanzees we identified 3 distinct groups of animals: those that never seroconverted to AAV (naïve), those that were persistently seropositive (chronic), and those that seroconverted during the 10-year period (acute). For the chronic group we found a broad seroresponse characterized by NAbs reacting to multiple AAV serotypes. A similar cross-neutralization pattern of NAbs was observed in the acute group. These data support our hypothesis that a single natural infection with AAV induces a broadly cross-reactive NAb response to multiple AAV serotypes. PMID:27314914

  9. Ebola virus-like particles produced in insect cells exhibit dendritic cell stimulating activity and induce neutralizing antibodies

    International Nuclear Information System (INIS)

    Recombinant baculoviruses (rBV) expressing Ebola virus VP40 (rBV-VP40) or GP (rBV-GP) proteins were generated. Infection of Sf9 insect cells by rBV-VP40 led to assembly and budding of filamentous particles from the cell surface as shown by electron microscopy. Ebola virus-like particles (VLPs) were produced by coinfection of Sf9 cells with rBV-VP40 and rBV-GP, and incorporation of Ebola GP into VLPs was demonstrated by SDS-PAGE and Western blot analysis. Recombinant baculovirus infection of insect cells yielded high levels of VLPs, which were shown to stimulate cytokine secretion from human dendritic cells similar to VLPs produced in mammalian cells. The immunogenicity of Ebola VLPs produced in insect cells was evaluated by immunization of mice. Analysis of antibody responses showed that most of the GP-specific antibodies were of the IgG2a subtype, while no significant level of IgG1 subtype antibodies specific for GP was induced, indicating the induction of a Th1-biased immune response. Furthermore, sera from Ebola VLP immunized mice were able to block infection by Ebola GP pseudotyped HIV virus in a single round infection assay, indicating that a neutralizing antibody against the Ebola GP protein was induced. These results show that production of Ebola VLPs in insect cells using recombinant baculoviruses represents a promising approach for vaccine development against Ebola virus infection

  10. Antibody-targeted horseradish peroxidase associated with indole-3-acetic acid induces apoptosis in vitro in hematological malignancies.

    Science.gov (United States)

    Dalmazzo, Leandro F F; Santana-Lemos, Bárbara A; Jácomo, Rafael H; Garcia, Aglair B; Rego, Eduardo M; da Fonseca, Luiz M; Falcão, Roberto P

    2011-05-01

    Indole-3-acetic acid (IAA), when oxidized by horseradish peroxidase (HRP), is transformed into cytotoxic molecules capable of inducing cell injury. The aim of this study was to test if, by targeting hematopoietic tumors with HRP-conjugated antibodies in association with IAA treatment, there is induction of apoptosis. We used two lineages of hematologic tumors: NB4, derived from acute promyelocytic leukemia (APL) and Granta-519 from mantle cell lymphoma (MCL). We also tested cells from 12 patients with acute myeloid leukemia (AML) and from 10 patients with chronic lymphocytic leukemia (CLL). HRP targeting was performed with anti-CD33 or anti-CD19 antibodies (depending on the origin of the cell), followed by incubation with goat anti-mouse antibody conjugated with HRP. Eight experimental groups were analyzed: control, HRP targeted, HRP targeted and incubated with 1, 5 and 10mM IAA, and cells not HRP targeted but incubated with 1, 5 and 10mM IAA. Apoptosis was analyzed by flow cytometry using annexin V-FITC and propidium iodide labeling. Results showed that apoptosis was dependent on the dose of IAA utilized, the duration of exposure to the prodrug and the origin of the neoplasia. Targeting HRP with antibodies was efficient in activating IAA and inducing apoptosis. PMID:21168913

  11. Autoimmune liver diseases

    Institute of Scientific and Technical Information of China (English)

    Pietro Invernizzi; Ian R Mackay

    2008-01-01

    The liver was one of the earliest recognized sites among autoimmune diseases yet autoimmune hepatitis,primary biliary cirrhosis,primary sclerosing cholangitis,and their overlap forms,are still problematic in diagnosis and causation.The contributions herein comprise 'pairs of articles' on clinical characteristics,and concepts of etiopathogenesis,for each of the above diseases,together with childhood autoimmune liver disease,overlaps,interpretations of diagnostic serology,and liver transplantation.This issue is timely,since we are witnessing an ever increasing applicability of immunology to a wide variety of chronic diseases,hepatic and non-hepatic,in both developed and developing countries.The 11 invited expert review articles capture the changing features over recent years of the autoimmune liver diseases,the underlying immunomolecular mechanisms of development,the potent albeit still unexplained genetic influences,the expanding repertoire of immunoserological diagnostic markers,and the increasingly effective therapeutic possibilities.

  12. Etiopathogenesis of insulin autoimmunity.

    OpenAIRE

    Åke Lenmark; Moustakas, Antonis K; Papadopoulos, George K; Norio Kanatsuna

    2012-01-01

    Autoimmunity against pancreatic islet beta cells is strongly associated with proinsulin, insulin, or both. The insulin autoreactivity is particularly pronounced in children with young age at onset of type 1 diabetes. Possible mechanisms for (pro)insulin autoimmunity may involve beta-cell destruction resulting in proinsulin peptide presentation on HLA-DR-DQ Class II molecules in pancreatic draining lymphnodes. Recent data on proinsulin peptide binding to type 1 diabetes-associated HLA-DQ2 and ...

  13. Alterations in nuclear structure promote lupus autoimmunity in a mouse model

    Science.gov (United States)

    Singh, Namrata; Johnstone, Duncan B.; Martin, Kayla A.; Tempera, Italo; Kaplan, Mariana J.

    2016-01-01

    ABSTRACT Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by the development of autoantibodies that recognize components of the cell nucleus. The vast majority of lupus research has focused on either the contributions of immune cell dysfunction or the genetics of the disease. Because granulocytes isolated from human SLE patients had alterations in neutrophil nuclear morphology that resembled the Pelger–Huet anomaly, and had prominent mis-splicing of mRNA encoding the nuclear membrane protein lamin B receptor (LBR), consistent with their Pelger–Huet-like nuclear morphology, we used a novel mouse model system to test the hypothesis that a disruption in the structure of the nucleus itself also contributes to the development of lupus autoimmunity. The lupus-prone mouse strain New Zealand White (NZW) was crossed with c57Bl/6 mice harboring a heterozygous autosomal dominant mutation in Lbr (B6.Lbric/+), and the (NZW×B6.Lbric)F1 offspring were evaluated for induction of lupus autoimmunity. Only female (NZW×B6.Lbric)F1 mice developed lupus autoimmunity, which included splenomegaly, kidney damage and autoantibodies. Kidney damage was accompanied by immune complex deposition, and perivascular and tubule infiltration of mononuclear cells. The titers of anti-chromatin antibodies exceeded those of aged female MRL-Faslpr mice, and were predominantly of the IgG2 subclasses. The anti-nuclear antibody staining profile of female (NZW×B6.Lbric)F1 sera was complex, and consisted of an anti-nuclear membrane reactivity that colocalized with the A-type lamina, in combination with a homogeneous pattern that was related to the recognition of histones with covalent modifications that are associated with gene activation. An anti-neutrophil IgM recognizing calreticulin, but not myeloperoxidase (MPO) or proteinase 3 (PR3), was also identified. Thus, alterations in nuclear structure contribute to lupus autoimmunity when expressed in the context of a lupus

  14. Imaging combined autoimmune and infectious disease microarrays

    Science.gov (United States)

    Ewart, Tom; Raha, Sandeep; Kus, Dorothy; Tarnopolsky, Mark

    2006-09-01

    Bacterial and viral pathogens are implicated in many severe autoimmune diseases, acting through such mechanisms as molecular mimicry, and superantigen activation of T-cells. For example, Helicobacter pylori, well known cause of stomach ulcers and cancers, is also identified in ischaemic heart disease (mimicry of heat shock protein 65), autoimmune pancreatitis, systemic sclerosis, autoimmune thyroiditis (HLA DRB1*0301 allele susceptibility), and Crohn's disease. Successful antibiotic eradication of H.pylori often accompanies their remission. Yet current diagnostic devices, and test-limiting cost containment, impede recognition of the linkage, delaying both diagnosis and therapeutic intervention until the chronic debilitating stage. We designed a 15 minute low cost 39 antigen microarray assay, combining autoimmune, viral and bacterial antigens1. This enables point-of-care serodiagnosis and cost-effective narrowly targeted concurrent antibiotic and monoclonal anti-T-cell and anti-cytokine immunotherapy. Arrays of 26 pathogen and 13 autoimmune antigens with IgG and IgM dilution series were printed in triplicate on epoxysilane covalent binding slides with Teflon well masks. Sera diluted 1:20 were incubated 10 minutes, washed off, anti-IgG-Cy3 (green) and anti-IgM-Dy647 (red) were incubated for 5 minutes, washed off and the slide was read in an ArrayWoRx(e) scanning CCD imager (Applied Precision, Issaquah, WA). As a preliminary model for the combined infectious disease-autoimmune diagnostic microarray we surveyed 98 unidentified, outdated sera that were discarded after Hepatitis B antibody testing. In these, significant IgG or IgM autoantibody levels were found: dsDNA 5, ssDNA 11, Ro 2, RNP 7, SSB 4, gliadin 2, thyroglobulin 13 cases. Since control sera showed no autoantibodies, the high frequency of anti-DNA and anti-thyroglobulin antibodies found in infected sera lend increased support for linkage of infection to subsequent autoimmune disease. Expansion of the antigen

  15. Type 1 autoimmune pancreatitis

    Directory of Open Access Journals (Sweden)

    Zen Yoh

    2011-12-01

    Full Text Available Abstract Before the concept of autoimmune pancreatitis (AIP was established, this form of pancreatitis had been recognized as lymphoplasmacytic sclerosing pancreatitis or non-alcoholic duct destructive chronic pancreatitis based on unique histological features. With the discovery in 2001 that serum IgG4 concentrations are specifically elevated in AIP patients, this emerging entity has been more widely accepted. Classical cases of AIP are now called type 1 as another distinct subtype (type 2 AIP has been identified. Type 1 AIP, which accounts for 2% of chronic pancreatitis cases, predominantly affects adult males. Patients usually present with obstructive jaundice due to enlargement of the pancreatic head or thickening of the lower bile duct wall. Pancreatic cancer is the leading differential diagnosis for which serological, imaging, and histological examinations need to be considered. Serologically, an elevated level of IgG4 is the most sensitive and specific finding. Imaging features include irregular narrowing of the pancreatic duct, diffuse or focal enlargement of the pancreas, a peri-pancreatic capsule-like rim, and enhancement at the late phase of contrast-enhanced images. Biopsy or surgical specimens show diffuse lymphoplasmacytic infiltration containing many IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. A dramatic response to steroid therapy is another characteristic, and serological or radiological effects are normally identified within the first 2 or 3 weeks. Type 1 AIP is estimated as a pancreatic manifestation of systemic IgG4-related disease based on the fact that synchronous or metachronous lesions can develop in multiple organs (e.g. bile duct, salivary/lacrimal glands, retroperitoneum, artery, lung, and kidney and those lesions are histologically identical irrespective of the organ of origin. Several potential autoantigens have been identified so far. A Th2-dominant immune reaction and the activation of

  16. Follicular Helper T Cells in Autoimmunity.

    Science.gov (United States)

    Scherm, Martin G; Ott, Verena B; Daniel, Carolin

    2016-08-01

    The development of multiple disease-relevant autoantibodies is a hallmark of autoimmune diseases. In autoimmune type 1 diabetes (T1D), a variable time frame of autoimmunity precedes the clinically overt disease. The relevance of T follicular helper (TFH) cells for the immune system is increasingly recognized. Their pivotal contribution to antibody production by providing help to germinal center (GC) B cells facilitates the development of a long-lived humoral immunity. Their complex differentiation process, involving various stages and factors like B cell lymphoma 6 (Bcl6), is strictly controlled, as anomalous regulation of TFH cells is connected with immunopathologies. While the adverse effects of a TFH cell-related insufficient humoral immunity are obvious, the role of increased TFH frequencies in autoimmune diseases like T1D is currently highlighted. High levels of autoantigen trigger an excessive induction of TFH cells, consequently resulting in the production of autoantibodies. Therefore, TFH cells might provide promising approaches for novel therapeutic strategies. PMID:27324759

  17. 抗β2糖蛋白Ⅰ抗体对自身免疫性溶血性贫血临床结局的影响%Effect of Anti-beta2 Glycoprotein I Antibodies on Outcome of the Patients with Autoimmune Hemolytic Anemia

    Institute of Scientific and Technical Information of China (English)

    曾晓虹; 薛原; 林臖芳; 郑玲; 康日辉

    2015-01-01

    Objective To assess the relationship of anti-beta2 glycoprotein I antibodies (anti-β2GPI)and the outcome of patients with autoimmune hemolytic anemia (AIHA).Methods During December 2008 to April 2013,consecutive case series of patients with AIHA were studied in the First affiliated hospital of Fujian Medical university.Patients were classified as Primary autoimmune hemolytic anemia (Primary AIHA Group)and autoimmune hemolytic anemia secondary to SLE (SLE-AIHA Group).Levels of IgG subtype anti-β2GPI were assessed in all cases.Data were analyzed by SPSS 11.5.Results A total of 42 patients with AIHA were enrolled in the study,22 cases were primary AIHA,while 20 cases were SLE-AIHA.In the SLE-AIHA Group,patients with positive IgG subtype anti-β2GPI,revealed longer time in achieving partial remission than patients without the antibody [(18 ±7)d vs.(13 ±4)d,P 0.05].Conclusion IgG subtype anti-β2GPI antibody may be one of the factors related to the prognosis of patients with systemic lupus erythematosus complicated with autoimmune hemolytic anemia.%目的:评估抗β2糖蛋白 I 抗体(anti β2 glycoprotein Ⅰ,aβ2GPI)与自身免疫性溶血性贫血(autoimmune hemolytic anemia,AIHA)临床结局的相关性。方法连续收集2008年12月至2013年4月在福建医科大学附属第一医院血液风湿科门诊和病房诊治的 AIHA 患者,包括继发于 SLE 的 AIHA 患者(SLE-AIHA 组)和原发性 AIHA 患者(原发性 AIHA 组)。检测所有患者 IgG 类抗β2GPI。采用 SPSS11.5软件统计分析。结果共纳入 AIHA 患者42例,SLE-AIHA 组22例,原发性AIHA 组20例。SLE-AIHA 组 IgG 类抗β2GPI 阳性患者溶血达部分缓解所需时间显著长于该抗体阴性患者,差异有统计学意义[(18±7)d vs.(13±4)d,P <0.05]。原发性 AIHA 组 IgG 类抗β2GPI 阳性组和阴性组患者溶血达部分缓解所需时间无统计学差异[(15±5)d vs.(11±3)d,P >0.05]。结论IgG 类抗β2

  18. Immunotherapy Treatments of Warm Autoimmune Hemolytic Anemia

    Directory of Open Access Journals (Sweden)

    Bainan Liu

    2013-01-01

    Full Text Available Warm autoimmune hemolytic anemia (WAIHA is one of four clinical types of autoimmune hemolytic anemia (AIHA, with the characteristics of autoantibodies maximally active at body temperature. It produces a variable anemia—sometimes mild and sometimes severe. With respect to the absence or presence of an underlying condition, WAIHA is either idiopathic (primary or secondary, which determines the treatment strategies in practice. Conventional treatments include immune suppression with corticosteroids and, in some cases, splenectomy. In recent years, the number of clinical studies with monoclonal antibodies and immunosuppressants in the treatment of WAIHA increased as the knowledge of autoimmunity mechanisms extended. This thread of developing new tools of treating WAIHA is well exemplified with the success in using anti-CD20 monoclonal antibody, Rituximab. Following this success, other treatment methods based on the immune mechanisms of WAIHA have emerged. We reviewed these newly developed immunotherapy treatments here in order to provide the clinicians with more options in selecting the best therapy for patients with WAIHA, hoping to stimulate researchers to find more novel immunotherapy strategies.

  19. A genetically detoxified derivative of heat-labile Escherichia coli enterotoxin induces neutralizing antibodies against the A subunit

    OpenAIRE

    1994-01-01

    Escherichia coli enterotoxin (LT) and the homologous cholera toxin (CT) are A-B toxins that cause travelers' diarrhea and cholera, respectively. So far, experimental live and killed vaccines against these diseases have been developed using only the nontoxic B portion of these toxins. The enzymatically active A subunit has not been used because it is responsible for the toxicity and it is reported to induce a negligible titer of toxin neutralizing antibodies. We used site- directed mutagenesis...

  20. A case of transfusion-related acute lung injury induced by anti-human leukocyte antigen antibodies in acute leukemia

    OpenAIRE

    Jin, Sun Mi; Jang, Moon Ju; Huh, Ji Young; Park, Myoung Hee; Song, Eun Young; Oh, Doyeun

    2012-01-01

    Transfusion-related acute lung injury (TRALI) is a noncardiogenic pulmonary edema that occurs during or within 6 hours after transfusion. Risk factors for TRALI, which is relatively common in critically ill patients, include recent surgery, hematologic malignancy, and sepsis. Here, we report a case of TRALI induced by anti-human leukocyte antigen (anti-HLA) class II antibodies (HLA-DR) occurring after transfusion of platelet concentrates in a patient with acute leukemia. Although most patient...

  1. HPV16/18 L1 VLP Vaccine Induces Cross-Neutralizing Antibodies that May Mediate Cross-Protection

    OpenAIRE

    Kemp, Troy J; Hildesheim, Allan; Safaeian, Mahboobeh; Dauner, Joseph G.; Pan, Yuanji; Porras, Carolina; Schiller, John T.; Lowy, Douglas R.; Herrero, Rolando; Pinto, Ligia A.

    2011-01-01

    Human papillomavirus (HPV) L1 VLP-based vaccines are protective against HPV vaccine-related types; however, the correlates of protection have not been defined. We observed that vaccination with Cervarix™ induced cross-neutralizing antibodies for HPV types for which evidence of vaccine efficacy has been demonstrated (HPV31/45) but not for other types (HPV52/58). In addition, HPV31/45 cross-neutralizing titers showed a significant increase with number of doses (HPV31, p

  2. Self DNA from lymphocytes that have undergone activation-induced cell death enhances murine B cell proliferation and antibody production.

    Directory of Open Access Journals (Sweden)

    Qing Lu

    Full Text Available Systemic lupus erythematosus (SLE is characterized by prominent autoinflammatory tissue damage associated with impaired removal of dying cells and DNA. Self DNA-containing immune complexes are able to activate both innate and adaptive immune responses and play an important role in the maintenance and exacerbation of autoimmunity in SLE. In this study, we used DNA from lymphocytes that have undergone activation-induced cell death (ALD-DNA and analyzed its role on the activation and differentiation of B cells from normal BALB/c mice as well as lupus-prone MRL+/+ and MRL/lpr mice. We found that ALD-DNA directly increased the expression of costimulatory molecules and the survival of naïve B cells in vitro. Although ALD-DNA alone had little effect on the proliferation of naïve B cells, it enhanced LPS-activated B cell proliferation in vitro and in vivo. In addition, ALD-DNA increased plasma cell numbers and IgG production in LPS-stimulated cultures of naïve B cells, in part via enhancing IL-6 production. Importantly, B cells from lupus mice were hyperresponsive to ALD-DNA and/or LPS relative to normal control B cells in terminal plasma cell differentiation, as evidenced by increases in CD138+ cell numbers, IgM production, and mRNA levels of B lymphocyte-induced maturation protein-1 (Blimp-1 and the X-box binding protein 1 (XBP1. Furthermore, ALD-DNA enhanced CD40-activated naïve B cell proliferation. Collectively, these data indicate that self DNA can serve as a DAMP (damage-associated molecular pattern that cooperates with signals from both innate and adaptive immunity to promote polyclonal B cell activation, a common characteristic of autoimmune diseases.

  3. Oral Application of T4 Phage Induces Weak Antibody Production in the Gut and in the Blood

    Directory of Open Access Journals (Sweden)

    Joanna Majewska

    2015-08-01

    Full Text Available A specific humoral response to bacteriophages may follow phage application for medical purposes, and it may further determine the success or failure of the approach itself. We present a long-term study of antibody induction in mice by T4 phage applied per os: 100 days of phage treatment followed by 112 days without the phage, and subsequent second application of phage up to day 240. Serum and gut antibodies (IgM, IgG, secretory IgA were analyzed in relation to microbiological status of the animals. T4 phage applied orally induced anti-phage antibodies when the exposure was long enough (IgG day 36, IgA day 79; the effect was related to high dosage. Termination of phage treatment resulted in a decrease of IgA again to insignificant levels. Second administration of phage induces secretory IgA sooner than that induced by the first administrations. Increased IgA level antagonized gut transit of active phage. Phage resistant E. coli dominated gut flora very late, on day 92. Thus, the immunological response emerges as a major factor determining phage survival in the gut. Phage proteins Hoc and gp12 were identified as highly immunogenic. A low response to exemplary foreign antigens (from Ebola virus presented on Hoc was observed, which suggests that phage platforms can be used in oral vaccine design.

  4. Oral Application of T4 Phage Induces Weak Antibody Production in the Gut and in the Blood.

    Science.gov (United States)

    Majewska, Joanna; Beta, Weronika; Lecion, Dorota; Hodyra-Stefaniak, Katarzyna; Kłopot, Anna; Kaźmierczak, Zuzanna; Miernikiewicz, Paulina; Piotrowicz, Agnieszka; Ciekot, Jarosław; Owczarek, Barbara; Kopciuch, Agnieszka; Wojtyna, Karolina; Harhala, Marek; Mąkosa, Mateusz; Dąbrowska, Krystyna

    2015-08-01

    A specific humoral response to bacteriophages may follow phage application for medical purposes, and it may further determine the success or failure of the approach itself. We present a long-term study of antibody induction in mice by T4 phage applied per os: 100 days of phage treatment followed by 112 days without the phage, and subsequent second application of phage up to day 240. Serum and gut antibodies (IgM, IgG, secretory IgA) were analyzed in relation to microbiological status of the animals. T4 phage applied orally induced anti-phage antibodies when the exposure was long enough (IgG day 36, IgA day 79); the effect was related to high dosage. Termination of phage treatment resulted in a decrease of IgA again to insignificant levels. Second administration of phage induces secretory IgA sooner than that induced by the first administrations. Increased IgA level antagonized gut transit of active phage. Phage resistant E. coli dominated gut flora very late, on day 92. Thus, the immunological response emerges as a major factor determining phage survival in the gut. Phage proteins Hoc and gp12 were identified as highly immunogenic. A low response to exemplary foreign antigens (from Ebola virus) presented on Hoc was observed, which suggests that phage platforms can be used in oral vaccine design. PMID:26308042

  5. Kinetics of antibody-induced modulation of respiratory syncytial virus antigens in a human epithelial cell line

    Directory of Open Access Journals (Sweden)

    Gómez-Garcia Beatriz

    2007-07-01

    Full Text Available Abstract Background The binding of viral-specific antibodies to cell-surface antigens usually results in down modulation of the antigen through redistribution of antigens into patches that subsequently may be internalized by endocytosis or may form caps that can be expelled to the extracellular space. Here, by use of confocal-laser-scanning microscopy we investigated the kinetics of the modulation of respiratory syncytial virus (RSV antigen by RSV-specific IgG. RSV-infected human epithelial cells (HEp-2 were incubated with anti-RSV polyclonal IgG and, at various incubation times, the RSV-cell-surface-antigen-antibody complexes (RSV Ag-Abs and intracellular viral proteins were detected by indirect immunoflourescence. Results Interaction of anti-RSV polyclonal IgG with RSV HEp-2 infected cells induced relocalization and aggregation of viral glycoproteins in the plasma membrane formed patches that subsequently produced caps or were internalized through clathrin-mediated endocytosis participation. Moreover, the concentration of cell surface RSV Ag-Abs and intracellular viral proteins showed a time dependent cyclic variation and that anti-RSV IgG protected HEp-2 cells from viral-induced death. Conclusion The results from this study indicate that interaction between RSV cell surface proteins and specific viral antibodies alter the expression of viral antigens expressed on the cells surface and intracellular viral proteins; furthermore, interfere with viral induced destruction of the cell.

  6. CX3CL1 (fractalkine and CX3CR1 expression in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis: kinetics and cellular origin

    Directory of Open Access Journals (Sweden)

    Olsson Tomas

    2005-07-01

    Full Text Available Abstract Background Multiple sclerosis (MS is a chronic inflammatory disease of the central nervous system (CNS. It is associated with local activation of microglia and astroglia, infiltration of activated macrophages and T cells, active degradation of myelin and damage to axons and neurons. The proposed role for CX3CL1 (fractalkine in the control of microglia activation and leukocyte infiltration places this chemokine and its receptor CX3CR1 in a potentially strategic position to control key aspects in the pathological events that are associated with development of brain lesions in MS. In this study, we examine this hypothesis by analyzing the distribution, kinetics, regulation and cellular origin of CX3CL1 and CX3CR1 mRNA expression in the CNS of rats with an experimentally induced MS-like disease, myelin oligodendrocyte glycoprotein (MOG-induced autoimmune encephalomyelitis (EAE. Methods The expression of CX3CL1 and its receptor CX3CR1 was studied with in situ hybridization histochemical detection of their mRNA with radio labeled cRNA probes in combination with immunohistochemical staining of phenotypic cell markers. Both healthy rat brains and brains from rats with MOG EAE were analyzed. In defined lesional stages of MOG EAE, the number of CX3CR1 mRNA-expressing cells and the intensity of the in situ hybridization signal were determined by image analysis. Data were statistically evaluated by ANOVA, followed by Tukeyprimes multiple comparison test. Results Expression of CX3CL1 mRNA was present within neuronal-like cells located throughout the neuraxis of the healthy rat. Expression of CX3CL1 remained unaltered in the CNS of rats with MOG-induced EAE, with the exception of an induced expression in astrocytes within inflammatory lesions. Notably, the brain vasculature of healthy and encephalitic animals did not exhibit signs of CX3CL1 mRNA expression. The receptor, CX3CR1, was expressed by microglial cells in all regions of the healthy brain

  7. The protective antibodies induced by a novel epitope of human TNF-alpha could suppress the development of collagen-induced arthritis.

    Directory of Open Access Journals (Sweden)

    Jie Dong

    Full Text Available Tumor necrosis factor alpha (TNF-alpha is a major inflammatory mediator that exhibits actions leading to tissue destruction and hampering recovery from damage. At present, two antibodies against human TNF-alpha (hTNF-alpha are available, which are widely used for the clinic treatment of certain inflammatory diseases. This work was undertaken to identify a novel functional epitope of hTNF-alpha. We performed screening peptide library against anti-hTNF-alpha antibodies, ELISA and competitive ELISA to obtain the epitope of hTNF-alpha. The key residues of the epitope were identified by means of combinatorial alanine scanning and site-specific mutagenesis. The N terminus (80-91 aa of hTNF-alpha proved to be a novel epitope (YG1. The two amino acids of YG1, proline and valine, were identified as the key residues, which were important for hTNF-alpha biological function. Furthermore, the function of the epitope was addressed on an animal model of collagen-induced arthritis (CIA. CIA could be suppressed in an animal model by prevaccination with the derivative peptides of YG1. The antibodies of YG1 could also inhibit the cytotoxicity of hTNF-alpha. These results demonstrate that YG1 is a novel epitope associated with the biological function of hTNF-alpha and the antibodies against YG1 can inhibit the development of CIA in animal model, so it would be a potential target of new therapeutic antibodies.

  8. Autoimmunity in hereditary retinal degeneration. I. Basic studies.

    OpenAIRE

    Chant, S M; Heckenlively, J; Meyers-Elliott, R H

    1985-01-01

    One hundred and sixteen patients with retinitis pigmentosa (RP), 64 patients with other eye diseases, and 36 control subjects with no known eye disease were examined for antiretinal autoimmune activity. Sera were screened by indirect immunofluorescence on normal donor human eye sections to detect antibodies to human retinal antigens. Forty three of 116 RP patients (37%), 21 out of 64 non-RP patients with other eye diseases (33%), and 1 out of 42 controls (2%) had antibodies reacting with dono...

  9. Budesonide in previously untreated autoimmune hepatitis

    NARCIS (Netherlands)

    Wiegand, J; Schuler, A; Kanzler, S; Lohse, A; Beuers, U; Kreisel, W; Spengler, U; Koletzko, S; Jansen, PLM; Hochhaus, G; Mollmann, HW; Prols, M; Manns, MP

    2005-01-01

    Background: Autoimmune hepatitis (AIH) is a chronic liver disease that is effectively treated with immunosuppressive therapy. Predniso(lo)ne, often in combination with azathioprine, is the basic therapeutic option to induce remission. However, this regimen can cause numerous side effects. The aim of

  10. A case of polyglandular autoimmune syndrome type III complicated with autoimmune hepatitis.

    Science.gov (United States)

    Oki, Kenji; Yamane, Kiminori; Koide, Junko; Mandai, Koichi; Nakanishi, Shuhei; Fujikawa, Rumi; Kohno, Nobuoki

    2006-10-01

    A 58-year-old woman complaining of finger tremor was referred to our hospital. The diagnosis of Graves' disease was made based on increased free triiodothyronine (18.88 pg/ml) and free thyroxine (7.47 ng/dl), low TSH (TSH receptor binding antibody activity (70.9%). Serum level of AST (62 U/l) and ALT (93 U/l) were increased and liver biopsy revealed linkage of adjacent portal areas by lymphoplasmacytic infiltrates and fibrosis with piecemeal necrosis. Although antinuclear antibody was negative, these findings indicated that she had autoimmune hepatitis (AIH) according to the criteria of the International Autoimmune Hepatitis Scoring System. Slowly progressive type 1 diabetes mellitus (DM) was confirmed by a diabetic response pattern due to 75 g-oral glucose tolerance test, and seropositivity towards anti-glutamic acid decarboxylase (725 U/ml) and islet cell (80 JDF Units) antibodies. This case exhibited an extremely rare combination of three different autoimmune diseases, including Graves' disease, slowly progressive type 1 DM and AIH, and had no known sensitive human leukocyte antigen (HLA) typing or haplotype for these disorders. Although it is common for patients with Graves' disease to exhibit abnormal liver function, it is important to make an accurate diagnosis of AIH because of this life-threatening disorder. PMID:16946565

  11. Detection of antibodies to single-stranded DNA in naturally acquired and experimentally induced viral hepatitis

    International Nuclear Information System (INIS)

    A sensitive ''Farr'' assay, utilizing 125I-labelled DNA was developed for detecting antibody to single-stranded DNA (anti-ssDNA). The test was shown to be specific and as sensitive as assays using 14C-labelled DNA, for the detection of antibody in patients with connective tissue diseases. Groups of sera from patients with naturally acquired viral hepatitis and experimentally infected chimpanzees were tested for anti-ssDNA by the 125I assay and by counterimmunoelectrophoresis (CIEP). No consistent pattern was observed with either technique, indicating the elevated levels of this antibody are not as reliable markers of parenchymal liver damage as had been previously suggested

  12. Novel Adenoviral Vector Induces T Cell Responses Despite Anti-Adenoviral Neutralizing Antibodies in Colorectal Cancer Patients

    OpenAIRE

    Morse, Michael A; Chaudhry, Arvind; Gabitzsch, Elizabeth S; Hobeika, Amy C.; Osada, Takuya; Clay, Timothy M.; Amalfitano, Andrea; Burnett, Bruce K.; Devi, Gayathri R.; Hsu, David S; Xu, Younong; Balcaitis, Stephanie; Dua, Rajesh; Nguyen, Susan; Balint, Joseph P.

    2013-01-01

    First generation, E1-deleted Adenovirus subtype 5 (Ad5)-based vectors, although promising platforms for use as cancer vaccines, are impeded in activity by naturally occurring or induced Ad-specific neutralizing antibodies. Ad5-based vectors with deletions of the E1 and the E2b regions (Ad5 [E1-, E2b-]), the latter encoding the DNA polymerase and the pre-terminal protein, by virtue of diminished late phase viral protein expression, were hypothesized to avoid immunological clearance and induce ...

  13. Variability in detection and quantification of interferon β-1b–induced neutralizing antibodies

    Directory of Open Access Journals (Sweden)

    Hartung Hans-Peter

    2012-06-01

    Full Text Available Abstract Background Interferon-beta (IFNB therapy for multiple sclerosis can lead to the induction of neutralizing antibodies (NAbs against IFNB. Various methods are used for detection and quantification of NAbs. Methods Blood samples from 125 IFNB-1b–treated patients, which were tested NAb negative or NAb positive after conclusion of a clinical study, were retested three years after first being assessed in four different laboratories that offer routine NAb testing to practicing neurologists. The myxovirus protein A (MxA induction assay, the cytopathic effect (CPE assay (two laboratories, or the luciferase assay were used. Intra- and inter-laboratory agreement between assays with respect to NAb detection and NAb titer quantification were evaluated. Results High agreement for NAb detection (kappa coefficient, 0.86 and for titer levels was observed for the intra-laboratory comparison in the laboratory using the MxA induction assay performed three years ago and now. A similarly high agreement for NAb detection (kappa coefficient, 0.87 and for titer quantification was noted for the MxA assay of this laboratory with one of two laboratories using the CPE assay. All other inter-laboratory comparisons showed kappa values between 0.57 and 0.68 and remarkable differences in individual titer levels. Conclusions There are considerable differences in the detection and quantification of IFNB-induced NAbs among laboratories offering NAb testing for clinical practice using different assay methods. It is important that these differences are considered when interpreting NAb results for clinical decision-making and when developing general recommendations for potentially clinically meaningful NAb titer levels.

  14. Pharmacologic Therapies for Rheumatologic and Autoimmune Conditions.

    Science.gov (United States)

    Bays, Alison M; Gardner, Gregory

    2016-07-01

    Disease-modifying antirheumatic drugs (DMARDs) are commonly prescribed by rheumatologists to reduce disease activity and induce remission in autoimmune conditions such as systemic lupus erythematosus and rheumatoid arthritis. Steroids are sometimes used in combination with DMARD therapy and should be used at the lowest effective dose for the least amount of time. There are many biologic agents available for use for inflammatory arthritis and other autoimmune conditions. Care should be taken when prescribing and managing DMARDS, steroids and biologic agents medications with a careful eye towards screening for infectious disease, vaccination, bone heath and lab monitoring. PMID:27235612

  15. Estrogens and autoimmune diseases.

    Science.gov (United States)

    Cutolo, Maurizio; Capellino, Silvia; Sulli, Alberto; Serioli, Bruno; Secchi, Maria Elena; Villaggio, Barbara; Straub, Rainer H

    2006-11-01

    Sex hormones are implicated in the immune response, with estrogens as enhancers at least of the humoral immunity and androgens and progesterone (and glucocorticoids) as natural immune-suppressors . Several physiological, pathological, and therapeutic conditions may change the serum estrogen milieu and/or peripheral conversion rate, including the menstrual cycle, pregnancy, postpartum period, menopause, being elderly, chronic stress, altered circadian rhythms, inflammatory cytokines, and use of corticosteroids, oral contraceptives, and steroid hormonal replacements, inducing altered androgen/estrogen ratios and related effects. In particular, cortisol and melatonin circadian rhythms are altered, at least in rheumatoid arthritis (RA), and partially involve sex hormone circadian synthesis and levels as well. Abnormal regulation of aromatase activity (i.e., increased activity) by inflammatory cytokine production (i.e., TNF-alpha, IL-1, and IL-6) may partially explain the abnormalities of peripheral estrogen synthesis in RA (i.e., increased availability of 17-beta estradiol and possible metabolites in synovial fluids) and in systemic lupus erythematosus, as well as the altered serum sex-hormone levels and ratio (i.e., decreased androgens and DHEAS). In the synovial fluids of RA patients, the increased estrogen concentration is observed in both sexes and is more specifically characterized by the hydroxylated forms, in particular 16alpha-hydroxyestrone, which is a mitogenic and cell proliferative endogenous hormone. Local effects of sex hormones in autoimmune rheumatic diseases seems to consist mainly in modulation of cell proliferation and cytokine production (i.e., TNF-alpha, Il-1, IL-12). In this respect, it is interesting that male patients with RA seem to profit more from anti-TNFalpha strategies than do female patients. PMID:17261796

  16.  Molecular mimicry in the etiology of autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Jolanta Lis

    2012-07-01

    Full Text Available  There are currently more than 80 different autoimmune diseases, affecting approximately 100 million people worldwide. The etiology of most autoimmune diseases is unknown. The highest incidence of these diseases is in the developed countries and they are more common in women than in men. Among the most often listed factors responsible for the onset of autoimmunity are genetic predisposition and the phenomenon known as molecular mimicry. The latter stems from a similarity between microbial antigens and antigens present in the human body (self antigens. It is believed that such homology is responsible for the production of auto-antibodies and in consequence attack of the immune system against host tissues and organs. However, the main molecular factors responsible for these diseases in most cases remain unknown. While pathogenesis of many autoimmune diseases indicates the presence of molecular mimicry, at the same time the similarities between the own and foreign structures do not always result in autoimmunity. Therefore, prediction of such crucial homology responsible for the development of autoimmune disease is extremely difficult. In this paper we present examples of autoimmune diseases such as type 1 diabetes, multiple sclerosis, reactive arthritis and the potential contribution of micro-organisms to the mechanism of molecular mimicry.

  17. Coombs Antiglobulin Test Using Brucella abortus 99 as Antigen To Detect Incomplete Antibodies Induced by B. abortus RB51 Vaccine in Cattle

    OpenAIRE

    Ciuchini, Franco; Adone, Rosanna; Pasquali, Paolo

    2002-01-01

    This study showed that vaccination of cattle with Brucella abortus rough strain RB51 induces incomplete antibodies that can be detectable by a Coombs antiglobulin test using the B. abortus 99 smooth strain.

  18. Guillain-Barré syndrome- and Miller Fisher syndrome-associated Campylobacter jejuni lipopolysaccharides induce anti-GM1 and anti-GQ1b Antibodies in rabbits.

    NARCIS (Netherlands)

    M.A. de Klerk; H.P. Endtz (Hubert); B.C. Jacobs (Bart); J.D. Laman (Jon); F.G.A. van der Meché; P.A. van Doorn (Pieter); C.W. Ang (Wim)

    2001-01-01

    textabstractCampylobacter jejuni infections are thought to induce antiganglioside antibodies in patients with Guillain-Barre syndrome (GBS) and Miller Fisher syndrome (MFS) by molecular mimicry between C. jejuni lipopolysaccharides (LPS) and gangliosides. We used purifi

  19. Dengue E Protein Domain III-Based DNA Immunisation Induces Strong Antibody Responses to All Four Viral Serotypes.

    Directory of Open Access Journals (Sweden)

    Monica Poggianella

    Full Text Available Dengue virus (DENV infection is a major emerging disease widely distributed throughout the tropical and subtropical regions of the world affecting several millions of people. Despite constants efforts, no specific treatment or effective vaccine is yet available. Here we show a novel design of a DNA immunisation strategy that resulted in the induction of strong antibody responses with high neutralisation titres in mice against all four viral serotypes. The immunogenic molecule is an engineered version of the domain III (DIII of the virus E protein fused to the dimerising CH3 domain of the IgG immunoglobulin H chain. The DIII sequences were also codon-optimised for expression in mammalian cells. While DIII alone is very poorly secreted, the codon-optimised fusion protein is rightly expressed, folded and secreted at high levels, thus inducing strong antibody responses. Mice were immunised using gene-gun technology, an efficient way of intradermal delivery of the plasmid DNA, and the vaccine was able to induce neutralising titres against all serotypes. Additionally, all sera showed reactivity to a recombinant DIII version and the recombinant E protein produced and secreted from mammalian cells in a mono-biotinylated form when tested in a conformational ELISA. Sera were also highly reactive to infective viral particles in a virus-capture ELISA and specific for each serotype as revealed by the low cross-reactive and cross-neutralising activities. The serotype specific sera did not induce antibody dependent enhancement of infection (ADE in non-homologous virus serotypes. A tetravalent immunisation protocol in mice showed induction of neutralising antibodies against all four dengue serotypes as well.

  20. Autoimmune basal ganglia disorders.

    Science.gov (United States)

    Dale, Russell C; Brilot, Fabienne

    2012-11-01

    The basal ganglia are deep nuclei in the brain that include the caudate, putamen, globus pallidus, and substantia nigra. Pathological processes involving the basal ganglia often result in disorders of movement and behavior. A number of different autoimmune disorders predominantly involve the basal ganglia and can result in movement and psychiatric disorders. The classic basal ganglia autoimmune disorder is Sydenham chorea, a poststreptococcal neuropsychiatric disorder. Resurgence in the interest in Sydenham chorea is the result of the descriptions of other poststreptococcal neuropsychiatric disorders including tics and obsessive-compulsive disorder, broadly termed pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection. Encephalitic processes affecting the basal ganglia are also described including the syndromes basal ganglia encephalitis, encephalitis lethargica, and bilateral striatal necrosis. Last, systemic autoimmune disorders such as systemic lupus erythematosus and antiphospholipid syndrome can result in chorea or parkinsonism. Using paradigms learned from other autoantibody associated disorders, the authors discuss the autoantibody hypothesis and the role of systemic inflammation in autoimmune basal ganglia disorders. Identification of these entities is important as the clinician has an increasing therapeutic repertoire to modulate or suppress the aberrant immune system. PMID:22832771

  1. Evaluation of antineutrophil cytoplasmic antibody seroconversion induced by minocycline, sulfasalazine, or penicillamine

    NARCIS (Netherlands)

    Choi, HK; Slot, MC; Pan, GL; Weissbach, CA; Niles, JL; Merkel, PA

    2000-01-01

    Objective, Case reports have suggested that minocycline, sulfasalazine, and penicillamine are associated with antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis, This study evaluated ANCA seroconversion due to these agents in serum samples prospectively collected in randomized, double-bl

  2. Pain-induced skin autoimmunity

    OpenAIRE

    Odoardi, Francesca; Neuhuber, Winfried; Flügel, Alexander

    2014-01-01

    A recent paper published in Nature reports sensory nerve fibers in the skin that give local immune cells important instructions for the organization of an immune response; in this particular case the cooperation between the nervous and immune systems had disastrous consequences, namely an auto-destruction of the skin.

  3. Neutralization of Japanese Encephalitis Virus by heme-induced broadly reactive human monoclonal antibody

    OpenAIRE

    Nimesh Gupta; Mélissanne de Wispelaere; Maxime Lecerf; Manjula Kalia; Tobias Scheel; Sudhanshu Vrati; Claudia Berek; Kaveri, Srinivas V.; Philippe Desprès; Sébastien Lacroix-Desmazes; Dimitrov, Jordan D.

    2015-01-01

    International audience Geographical expansion and re-emerging new genotypes of the Japanese encephalitis virus (JEV) require the development of novel therapeutic approaches. Here, we studied a non-conventional approach for antibody therapy and show that, upon exposure to heme, a fraction of natural human immunoglobulins acquires high-affinity reactivity with the antigenic domain-III of JEV E glycoprotein. These JEV-reactive antibodies exhibited neutralizing activity against recently domina...

  4. Delayed adaptive immunity is related to higher MMR vaccine-induced antibody titers in children

    OpenAIRE

    Strömbeck, Anna; Lundell, Anna-Carin; Nordström, Inger; Andersson, Kerstin; Adlerberth, Ingegerd; Wold, Agnes E.; Rudin, Anna

    2016-01-01

    There are notable inter-individual variations in vaccine-specific antibody responses in vaccinated children. The aim of our study was to investigate whether early-life environmental factors and adaptive immune maturation prior and close to measles–mumps–rubella (MMR) immunization relate to magnitudes of vaccine-specific antibody titers. In the FARMFLORA birth cohort, including both farming and non-farming families, children were immunized with the MMR vaccine at 18 months of age. MMR vaccine-...

  5. Malaria-induced acquisition of antibodies to Plasmodium falciparum variant surface antigens

    DEFF Research Database (Denmark)

    Ofori, Michael F; Dodoo, Daniel; Staalsoe, Trine; Kurtzhals, Jørgen; Koram, Kwadwo; Theander, Thor G; Akanmori, Bartholomew D; Hviid, Lars

    2002-01-01

    In areas of intense Plasmodium falciparum transmission, protective immunity is acquired during childhood in parallel with acquisition of agglutinating antibodies to parasite-encoded variant surface antigens (VSA) expressed on parasitized red blood cells. In a semi-immune child in such an area, cl...... donors (the malaria patient). The data from this first detailed longitudinal study of acquisition of VSA antibodies support the hypothesis that naturally acquired protective immunity to P. falciparum malaria is mediated, at least in part, by VSA-specific antibodies.......In areas of intense Plasmodium falciparum transmission, protective immunity is acquired during childhood in parallel with acquisition of agglutinating antibodies to parasite-encoded variant surface antigens (VSA) expressed on parasitized red blood cells. In a semi-immune child in such an area...... antibody responses to other parasite isolates are relatively unaffected. However, the detailed kinetics of this VSA antibody acquisition are unknown and hence were the aim of this study. We show that P. falciparum malaria in Ghanaian children generally caused a rapid and sustained increase in variant...

  6. Sclerosing cholecystitis associated with autoimmune pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Terumi Kamisawa; Yuyang Tu; Hitoshi Nakajima; Naoto Egawa; Kouji Tsuruta; Atsutake Okamoto; Shinichirou Horiguchi

    2006-01-01

    AIM: To evaluate the histopathological and radiological findings of the gallbladder in patients with autoimmune pancreatitis (AIP).METHODS: The radiological findings of the gallbladder of 19 AIP patients were retrospectively reviewed.Resected gallbladders of 8 AIP patients were examined histologically and were immunostained with antiIgG4 antibody. Controls consisted of gallbladders resected for symptomatic gallstones (n=10) and those removed during pancreatoduodenectomy for pancreatic carcinoma (n=10), as well as extrahepatic bile ducts and pancreases removed by pancreatoduodenectomy for pancreatic carcinoma (n=10).RESULTS: Thickening of the gallbladder wall was detected by ultrasound and/or computed tomography in 10 patients with AIP (3 severe and 7 moderate);in these patients severe stenosis of the extrahepatic bile duct was also noted. Histologically, thickening of the gallbladder was detected in 6 of 8 (75%) patients with AIP; 4 cases had transmural lymphoplasmacytic infiltration with fibrosis, and 2 cases had mucosal-based lymphoplasmacytic infiltration. Considerable transmural thickening of the extrahepatic bile duct wall with dense fibrosis and diffuse ly rnphoplasmacytic infiltration was detected in 7 patients. Immunohistochemically, severe or moderate infiltration of IgG4-positive plasma cells was detected in the gallbladder, bile duct, and pancreas of all 8 patients, but was not detected in controls.CONCLUSION: Gallbladder wall thickening with fibrosis and abundant infiltration of IgG4-positive plasma cells is frequently detected in patients with AIR We propose the use of a new term, sclerosing cholecystitis, for these cases that are induced by the same mechanism as sclerosing pancreatitis or sclerosing cholangitis in AIP.

  7. Rett syndrome: An autoimmune disease?

    Science.gov (United States)

    De Felice, Claudio; Leoncini, Silvia; Signorini, Cinzia; Cortelazzo, Alessio; Rovero, Paolo; Durand, Thierry; Ciccoli, Lucia; Papini, Anna Maria; Hayek, Joussef

    2016-04-01

    Rett syndrome (RTT) is a devastating neurodevelopmental disease, previously included into the autistic spectrum disorders, affecting almost exclusively females (frequency 1:10,000). RTT leads to intellective deficit, purposeful hands use loss and late major motor impairment besides featuring breathing disorders, epilepsy and increased risk of sudden death. The condition is caused in up to 95% of the cases by mutations in the X-linked methyl-CpG binding protein 2 (MECP2) gene. Our group has shown a number of previously unrecognized features, such as systemic redox imbalance, chronic inflammatory status, respiratory bronchiolitis-associated interstitial lung disease-like lung disease, and erythrocyte morphology changes. While evidence on an intimate involvement of MeCP2 in the immune response is cumulating, we have recently shown a cytokine dysregulation in RTT. Increasing evidence on the relationship between MeCP2 and an immune dysfunction is reported, with, apparently, a link between MECP2 gene polymorphisms and autoimmune diseases, including primary Sjögren's syndrome, systemic lupus erythematosus, rheumatoid arthritis, and systemic sclerosis. Antineuronal (i.e., brain proteins) antibodies have been shown in RTT. Recently, high levels of anti-N-glucosylation (N-Glc) IgM serum autoantibodies [i.e., anti-CSF114(N-Glc) IgMs] have been detected by our group in a statistically significant number of RTT patients. In the current review, the Authors explore the current evidence, either in favor or against, the presence of an autoimmune component in RTT. PMID:26807990

  8. Autoimmunity in 2015.

    Science.gov (United States)

    Selmi, Carlo

    2016-08-01

    Compared to the clear trend observed in previous years, the number of peer-reviewed articles published during 2015 and retrieved using the "autoimmunity" key word declined by 4 %, while remaining 5 % of immunology articles. On the other hand, a more detailed analysis of the published articles in leading immunology and autoimmunity journals revealed exciting scenarios, with fascinating lines of evidence being supported by convincing data and likely followed by rapid translational or clinical developments. As examples, the study of the microbiome, the development of new serum or other tissue biomarkers, and a more solid understanding of disease pathogenesis and tolerance breakdown mechanisms have been central issues in the past year. Furthermore and similar to the oncology field, progress in the understanding of single autoimmune condition is becoming most specific with psoriatic and rheumatoid arthritis being ideal paradigms with treatment options diverging after decades of common therapies, as illustrated by IL17-targeting approaches. The ultimate result of these advances is towards personalized medicine with an ideal approach being tailored on a single patient, based on a finely tuned definition of the immunogenetics, epigenetics, microbiome, and biomarkers. Finally, experimental reports suggest that cancer-associated immune mechanisms or the role of T and B cell subpopulations should be better understood in autoimmune diseases. While we hailed the 2014 literature in the autoimmunity world as part of an annus mirabilis, we should not be mistaken in the strong stimulus of research in autoimmunity represented by the 2015 articles that will be summarized in this article. PMID:27422713

  9. Myelin protein zero and its antibody in serum as biomarkers of n-hexane-induced peripheral neuropathy and neurotoxicity effects

    Institute of Scientific and Technical Information of China (English)

    Jia Xiaowei; Liu Qingjun; Zhang Yanshu; Dai Yufei; Duan Huawei; Bin Ping; Niu Yong

    2014-01-01

    Background Chronic exposure to n-hexane can lead to peripheral neuropathy that no effective treatment regimen could be applied presently.This study investigated whether myelin protein zero (P0) protein and its antibody could be used to distinguish n-hexane intoxication and protect workers from peripheral neuropathy.Methods We compared P0 protein and its antibody among three levels of n-hexane-exposed groups,which included 18 patients with n-hexane-induced peripheral neuropathy as case group,120 n-hexane-exposed workers as n-hexaneexposed control group,and 147 non-hexane-exposed participants used as control group.ELISA method was applied to detect P0 protein and its antibody.Results P0 protein in serum was significantly higher in the case group and n-hexane-exposed control group in comparison with the control group (P<0.01).Compared with the n-hexane-exposed control group,the case group also had significant increase of P0 protein (P<0.01).After 6 months therapy,P0 protein was observed to decrease significantly in the case group (P<0.01).The P0 antibody in serum was significantly higher in the n-hexane-exposed control group than in the control group (P<0.01),but not significantly different between cases and controls.Conclusions P0 antibodies in serum may be a short-term effect biomarker for n-hexane exposure.P0 protein in serum may be an early effective biomarker for peripheral nerve neuropathy and its biological limit value needs investigation in the future study.

  10. Vaccination of dogs with Trypanosoma rangeli induces antibodies against Trypanosoma cruzi in a rural area of Córdoba, Argentina

    Science.gov (United States)

    Basso, Beatriz; Marini, Vanina; Gauna, Diego; Frias, Maria

    2016-01-01

    Dogs play a major role in the domestic cycle of Trypanosoma cruzi, acting as reservoirs. In a previous work we have developed a model of vaccination of dogs in captivity with nonpathogenic Trypanosoma rangeli epimastigotes, resulting in the production of protective antibodies against T. cruzi, with dramatic decrease of parasitaemia upon challenge with 100,000 virulent forms of this parasite. The aim of this work was to evaluate the immunogenicity of this vaccine in dogs living in a rural area. Domestic dogs, free from T. cruziinfection, received three immunisations with fixed T. rangeliepimastigotes. Dogs were not challenged with T. cruzi, but they were left in their environment. This immunisation induced antibodies againstT. cruzi for more than three years in dogs in their natural habitat, while control dogs remained serologically negative. PMID:27074257

  11. Intestinal commensal bacteria promote T cell hyporesponsiveness and down-regulate the serum antibody responses induced by dietary antigen.

    Science.gov (United States)

    Tsuda, Masato; Hosono, Akira; Yanagibashi, Tsutomu; Kihara-Fujioka, Miran; Hachimura, Satoshi; Itoh, Kikuji; Hirayama, Kazuhiro; Takahashi, Kyoko; Kaminogawa, Shuichi

    2010-08-16

    Colonization of the gut by commensal bacteria modulates the induction of oral tolerance and allergy. However, how these intestinal bacteria modulate antigen-specific T cell responses induced by oral antigens remains unclear. In order to investigate this, we used germ-free (GF) ovalbumin (OVA)-specific T cell receptor transgenic (OVA23-3) mice. Conventional (CV) or GF mice were administered an OVA-containing diet. Cytokine production by CD4(+) cells from spleen (SP), mesenteric lymph nodes (MLN) and Peyer's patches (PP) was evaluated by ELISA, as was the peripheral antibody titer. T cell phenotype was assessed by flow cytometry. CD4(+) cells from the SP and MLN of CV and GF mice fed an OVA diet for 3 weeks produced significantly less IL-2 than the corresponding cells from mice receiving a control diet, suggesting that oral tolerance could be induced at the T cell level in the systemic and intestinal immune systems of both bacterial condition of mice. However, we also observed that the T cell hyporesponsiveness induced by dietary antigen was delayed in the systemic immune tissues and was weaker in the intestinal immune tissues of the GF mice. Intestinal MLN and PP CD4(+) T cells from these animals also produced lower levels of IL-10, had less activated/memory type CD45RB(low) cells, and expressed lower levels of CTLA-4 but not Foxp3 compared to their CV counterparts. Furthermore, GF mice produced higher serum levels of OVA-specific antibodies than CV animals. CD40L expression by SP CD4(+) cells from GF mice fed OVA was higher than that of CV mice. These results suggest that intestinal commensal bacteria promote T cell hyporesponsiveness and down-regulate serum antibody responses induced by dietary antigens through modulation of the intestinal and systemic T cell phenotype. PMID:20621647

  12. Human agonistic TRAIL receptor antibodies Mapatumumab and Lexatumumab induce apoptosis in malignant mesothelioma and act synergistically with cisplatin

    Directory of Open Access Journals (Sweden)

    Felley-Bosco Emanuela

    2007-10-01

    Full Text Available Abstract Background The incidence of malignant pleural mesothelioma (MPM is associated with exposure to asbestos, and projections suggest that the yearly number of deaths in Western Europe due to MPM will increase until 2020. Despite progress in chemo- and in multimodality therapy, MPM remains a disease with a poor prognosis. Inducing apoptosis by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or agonistic monoclonal antibodies which target TRAIL-receptor 1 (TRAIL-R1 or TRAIL-R2 has been thought to be a promising cancer therapy. Results We have compared the sensitivity of 13 MPM cell lines or primary cultures to TRAIL and two fully human agonistic monoclonal antibodies directed to TRAIL-R1 (Mapatumumab and TRAIL-R2 (Lexatumumab and examined sensitization of the MPM cell lines to cisplatin-induced by the TRAIL-receptor antibodies. We found that sensitivity of MPM cells to TRAIL, Mapatumumab and Lexatumumab varies largely and is independent of TRAIL-receptor expression. TRAIL-R2 contributes more than TRAIL-R1 to death-receptor mediated apoptosis in MPM cells that express both receptors. The combination of cisplatin with Mapatumumab or Lexatumumab synergistically inhibited the cell growth and enhanced apoptotic death. Furthermore, pre-treatment with cisplatin followed by Mapatumumab or Lexatumumab resulted in significant higher cytotoxic effects as compared to the reverse sequence. Combination-induced cell growth inhibition was significantly abrogated by pre-treatment of the cells with the antioxidant N-acetylcysteine. Conclusion Our results suggest that the sequential administration of cisplatin followed by Mapatumumab or Lexatumumab deserves investigation in the treatment of patients with MPM.

  13. Expression and biological characterization of an anti-CD20 biosimilar candidate antibody: a case study.

    Science.gov (United States)

    Dorvignit, Denise; Palacios, Julio L; Merino, Maylin; Hernández, Tays; Sosa, Katya; Casaco, Angel; López-Requena, Alejandro; Mateo de Acosta, Cristina

    2012-01-01

    The CD20 molecule is a non-glycosylated protein expressed mainly on the surface of B lymphocytes. In some pathogenic B cells, it shows an increased expression, thus becoming an attractive target for diagnosis and therapy. Rituximab is a chimeric antibody that specifically recognizes the human CD20 molecule. This antibody is indicated for the treatment of non-Hodgkin lymphomas and autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. In this work, we describe the stable expression and biological evaluation of an anti-CD20 biosimilar antibody. While rituximab is produced in fed-batch culture of recombinant Chinese hamster ovary (CHO) cells, our biosimilar antibody expression process consists of continuous culture of recombinant murine NS0 myeloma cells. The ability of the purified biosimilar antibody to recognize the CD20 molecule on human tumor cell lines, as well as on peripheral blood mononuclear cells from humans and primates, was demonstrated by flow cytometry. The biosimilar antibody induced complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity and apoptosis on human cell lines with high expression of CD20. In addition, this antibody depleted CD20-positive B lymphocytes from peripheral blood in monkeys. These results indicate that the biological properties of the biosimilar antibody compare favorably with those of the innovator product, and that it should be evaluated in future clinical trials. PMID:22647435

  14. Expression and biological characterization of an anti-CD20 biosimilar candidate antibody

    Science.gov (United States)

    Dorvignit, Denise; Palacios, Julio L.; Merino, Maylin; Hernández, Tays; Sosa, Katya; Casacó, Angel; López-Requena, Alejandro; Mateo de Acosta, Cristina

    2012-01-01

    The CD20 molecule is a non-glycosylated protein expressed mainly on the surface of B lymphocytes. In some pathogenic B cells, it shows an increased expression, thus becoming an attractive target for diagnosis and therapy. Rituximab is a chimeric antibody that specifically recognizes the human CD20 molecule. This antibody is indicated for the treatment of non-Hodgkin lymphomas and autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. In this work, we describe the stable expression and biological evaluation of an anti-CD20 biosimilar antibody. While rituximab is produced in fed-batch culture of recombinant Chinese hamster ovary (CHO) cells, our biosimilar antibody expression process consists of continuous culture of recombinant murine NS0 myeloma cells. The ability of the purified biosimilar antibody to recognize the CD20 molecule on human tumor cell lines, as well as on peripheral blood mononuclear cells from humans and primates, was demonstrated by flow cytometry. The biosimilar antibody induced complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity and apoptosis on human cell lines with high expression of CD20. In addition, this antibody depleted CD20-positive B lymphocytes from peripheral blood in monkeys. These results indicate that the biological properties of the biosimilar antibody compare favorably with those of the innovator product, and that it should be evaluated in future clinical trials. PMID:22647435

  15. [Autoimmune hemolytic anemia in children].

    Science.gov (United States)

    Becheur, M; Bouslama, B; Slama, H; Toumi, N E H

    2015-01-01

    Autoimmune hemolytic anemia is a rare condition in children which differs from the adult form. It is defined by immune-mediated destruction of red blood cells caused by autoantibodies. Characteristics of the autoantibodies are responsible for the various clinical entities. Classifications of autoimmune hemolytic anemia include warm autoimmune hemolytic anemia, cold autoimmune hemolytic anemia, and paroxysmal cold hemoglobinuria. For each classification, this review discusses the epidemiology, etiology, clinical presentation, laboratory evaluation, and treatment options. PMID:26575109

  16. Thyrotropin receptor antibodies and its clinical application

    International Nuclear Information System (INIS)

    Thyrotropin receptor antibodies (TRAb) are not homogeneous, which are composed by four antibodies at least. TRAb plays very important roles in autoimmune thyroid diseases ad off-thyroid symptoms associated, and other thyroiditis in clinical diagnosis, assessment of curative effects, determination of the time to stop medicine, prognostication of recurrence and inspection of high risk population

  17. Markers of autoimmune liver diseases in postmenopausal women with osteoporosis

    Directory of Open Access Journals (Sweden)

    Umit Secil Demirdal

    2010-01-01

    Full Text Available INTRODUCTION: Osteoporosis is a common complication of chronic liver diseases. However, there is limited information about autoimmune liver diseases as a factor of secondary osteoporosis. Therefore, we aimed to investigate the autoantibodies of autoimmune liver diseases in patients with osteoporosis. METHODS: One hundred fifty female patients with postmenopausal osteoporosis were included. Bone mineral density was measured by dual energy X-ray absorptiometry. We analysized autoantibodies including antinuclear antibodies, liver membrane antibodies, anti-liver/kidney microsomal autoantibodies1, liver-specific protein, antismooth muscle antibodies, and anti-mitochondrial antibodies by indirect immunofluorescence. Serum was assayed for the levels of aminotransferases. RESULTS: The mean age of the patients was 63,13±8,6 years. The mean values of L1-L4 T-scores and femur total T-scores were -3,08±0,58 and -1,53±0,81, respectively. Among the 150 patients with osteoporosis, 14 (9.3% were antinuclear antibodies, four (2.7% were liver membrane antibodies, three (2.0% were anti-liver/kidney microsomal autoantibodies1, and two (1.3% were liver-specific protein positive. None of the patients had anti-mitochondrial antibodies or smooth muscle antibodies positivity. The mean values of levels of aminotransferases were within normal range. CONCLUSIONS: The presence of liver membrane antibodies, liver-specific protein, and anti-liver/kidney microsomal autoantibodies1 has permitted us to see that there may be some suspicious clues of autoimmune liver diseases in patients with osteoporosis as a secondary risk factor. On the other hand, there is a need for comprehensive studies with a larger sample size and studies designed to compare the results with a normal population to understand the clinical importance of our findings.

  18. T Cell Vaccination as an Immunotherapy for Autoimmune Diseases

    Institute of Scientific and Technical Information of China (English)

    JingwuZhang

    2004-01-01

    Immunization with inactivated autoreactive T cells (T cell vaccination) selected from individual's own T cellrepertoire provides a unique in vivo setting for testing immune regulation that is known to involve interactionsof a variety of related surface molecules (1). It induces regulatory immune responses that closely resemble thein vivo situation where the immune system is challenged by clonal activation and expansion of given T cellpopulations in various autoimmune diseases. T cell vaccination provides a powerful means of eliciting naturalreactions of the immune system in response to clonal expansion of T cells, which can used as a therapeuticapproach to suppress or eliminate specific pathogenic autoreactive T cells in autoimmune conditions. Clinicaltrials using T cell vaccination to deplete autoreactive T cells in human autoimmune conditions have begun toreveal the pathologic relevance of various autoimmune T cell populations in the disease processes, providing aunique opportunity to test the autoimmune theories in a clinical setting. Cellular & Molecular Immunology.2004; 1(5):321-327.

  19. The Epidemiologic Evidence Linking Autoimmune Diseases and Psychosis

    DEFF Research Database (Denmark)

    Benros, Michael E; Eaton, William W; Mortensen, Preben B

    2014-01-01

    This review summarizes the epidemiologic evidence linking autoimmune diseases and psychosis. The associations between autoimmune diseases and psychosis have been studied for more than a half century, but research has intensified within the last decades, since psychosis has been associated with...... genetic markers of the immune system and with excess autoreactivity and other immune alterations. A range of psychiatric disorders, including psychosis, have been observed to occur more frequently in some autoimmune diseases, such as systemic lupus erythematosus and multiple sclerosis. Many autoimmune...... diseases involve multiple organs and general dysfunction of the immune system, which could affect the brain and induce psychiatric symptoms. Most studies have been cross-sectional, observing an increased prevalence of a broad number of autoimmune diseases in people with psychotic disorders. Furthermore...

  20. Autoimmun hepatitis. Fremtroedelsesformer, diagnostik og behandling

    DEFF Research Database (Denmark)

    Poulsen, L O; Tage-Jensen, U; Vyberg, M

    1992-01-01

    A retrospective study concerning ten patients with autoimmune hepatitis (AiH), diagnosed during a 2 1/2-year period is presented. The age of the patients ranged from 25 to 82 years and nine of the patients were women. Their symptoms included jaundice, pruritus, fever, anorexia and fatigue during a...... detected in nine patients, while none had increased levels of anti-nuclear antibody titer. Histological features of moderate or severe chronic active hepatitis were demonstrated in nine patients. One patient presented with clinical and histological features of acute hepatitis. Prednisolone therapy was...

  1. Detection of antibodies to single-stranded DNA in naturally acquired and experimentally induced viral hepatitis

    Energy Technology Data Exchange (ETDEWEB)

    Gust, I.D.; Feinstone, S.M.; Purcell, R.H.; Alter, H.J.

    1980-01-01

    A sensitive ''Farr'' assay, utilizing /sup 125/I-labelled DNA was developed for detecting antibody to single-stranded DNA (anti-ssDNA). The test was shown to be specific and as sensitive as assays using /sup 14/C-labelled DNA, for the detection of antibody in patients with connective tissue diseases. Groups of sera from patients with naturally acquired viral hepatitis and experimentally infected chimpanzees were tested for anti-ssDNA by the /sup 125/I assay and by counterimmunoelectrophoresis (CIEP). No consistent pattern was observed with either technique, indicating the elevated levels of this antibody are not as reliable markers of parenchymal liver damage as had been previously suggested.

  2. Hepatitis C virus hypervariable region 1 variants presented on hepatitis B virus capsid-like particles induce cross-neutralizing antibodies.

    Directory of Open Access Journals (Sweden)

    Milena Lange

    Full Text Available Hepatitis C virus (HCV infection is still a serious global health burden. Despite improved therapeutic options, a preventative vaccine would be desirable especially in undeveloped countries. Traditionally, highly conserved epitopes are targets for antibody-based prophylactic vaccines. In HCV-infected patients, however, neutralizing antibodies are primarily directed against hypervariable region I (HVRI in the envelope protein E2. HVRI is the most variable region of HCV, and this heterogeneity contributes to viral persistence and has thus far prevented the development of an effective HVRI-based vaccine. The primary goal of an antibody-based HCV vaccine should therefore be the induction of cross-reactive HVRI antibodies. In this study we approached this problem by presenting selected cross-reactive HVRI variants in a highly symmetric repeated array on capsid-like particles (CLPs. SplitCore CLPs, a novel particulate antigen presentation system derived from the HBV core protein, were used to deliberately manipulate the orientation of HVRI and therefore enable the presentation of conserved parts of HVRI. These HVRI-CLPs induced high titers of cross-reactive antibodies, including neutralizing antibodies. The combination of only four HVRI CLPs was sufficient to induce antibodies cross-reactive with 81 of 326 (24.8% naturally occurring HVRI peptides. Most importantly, HVRI CLPs with AS03 as an adjuvant induced antibodies with a 10-fold increase in neutralizing capability. These antibodies were able to neutralize infectious HCVcc isolates and 4 of 19 (21% patient-derived HCVpp isolates. Taken together, these results demonstrate that the induction of at least partially cross-neutralizing antibodies is possible. This approach might be useful for the development of a prophylactic HCV vaccine and should also be adaptable to other highly variable viruses.

  3. Autoimmunity and Turner's syndrome.

    Science.gov (United States)

    Lleo, Ana; Moroni, Luca; Caliari, Lisa; Invernizzi, Pietro

    2012-05-01

    Turner Syndrome (TS) is a common genetic disorder, affecting female individuals, resulting from the partial or complete absence of one sex chromosome, and occurring in approximately 50 per 100,000 liveborn girls. TS is associated with reduced adult height and with gonadal dysgenesis, leading to insufficient circulating levels of female sex steroids and to infertility. Morbidity and mortality are increased in TS but average intellectual performance is within the normal range. TS is closely associated to the presence of autoantibodies and autoimmune diseases (AID), especially autoimmune thyroiditis and inflammatory bowel disease. Despite the fact that the strong association between TS and AID is well known and has been widely studied, the underlying immunopathogenic mechanism remains partially unexplained. Recent studies have displayed how TS patients do not show an excess of immunogenic risk markers. This is evocative for a higher responsibility of X-chromosome abnormalities in the development of AID, and particularly of X-genes involved in immune response. For instance, the long arm of the X chromosome hosts a MHC-locus, so the loss of that region may lead to a deficiency in immune regulation. Currently no firm guidelines for diagnosis exist. In conclusion, TS is a condition associated with a number of autoimmune manifestations. Individuals with TS need life-long medical attention. As a consequence of these findings, early diagnosis and regular screening for potential associated autoimmune conditions are essential in the medical follow-up of TS patients. PMID:22154619

  4. Control of Toll-like receptor-mediated T cell-independent type 1 antibody responses by the inducible nuclear protein IκB-ζ.

    Science.gov (United States)

    Hanihara-Tatsuzawa, Fumito; Miura, Hanae; Kobayashi, Shuhei; Isagawa, Takayuki; Okuma, Atsushi; Manabe, Ichiro; MaruYama, Takashi

    2014-11-01

    Antibody responses have been classified as being either T cell-dependent or T cell-independent (TI). TI antibody responses are further classified as being either type 1 (TI-1) or type 2 (TI-2), depending on their requirement for B cell-mediated antigen receptor signaling. Although the mechanistic basis of antibody responses has been studied extensively, it remains unclear whether different antibody responses share similarities in their transcriptional regulation. Here, we show that mice deficient in IκB-ζ, specifically in their B cells, have impaired TI-1 antibody responses but normal T cell-dependent and TI-2 antibody responses. The absence of IκB-ζ in B cells also impaired proliferation triggered by Toll-like receptor (TLR) activation, plasma cell differentiation, and class switch recombination (CSR). Mechanistically, IκB-ζ-deficient B cells could not induce TLR-mediated induction of activation-induced cytidine deaminase (AID), a class-switch DNA recombinase. Retroviral transduction of AID in IκB-ζ-deficient B cells restored CSR activity. Furthermore, acetylation of histone H3 in the vicinity of the transcription start site of the gene that encodes AID was reduced in IκB-ζ-deficient B cells relative to IκB-ζ-expressing B cells. These results indicate that IκB-ζ regulates TLR-mediated CSR by inducing AID. Moreover, IκB-ζ defines differences in the transcriptional regulation of different antibody responses. PMID:25124037

  5. The Peptide Vaccine Combined with Prior Immunization of a Conventional Diphtheria-Tetanus Toxoid Vaccine Induced Amyloid β Binding Antibodies on Cynomolgus Monkeys and Guinea Pigs

    Directory of Open Access Journals (Sweden)

    Akira Yano

    2015-01-01

    Full Text Available The reduction of brain amyloid beta (Aβ peptides by anti-Aβ antibodies is one of the possible therapies for Alzheimer’s disease. We previously reported that the Aβ peptide vaccine including the T-cell epitope of diphtheria-tetanus combined toxoid (DT induced anti-Aβ antibodies, and the prior immunization with conventional DT vaccine enhanced the immunogenicity of the peptide. Cynomolgus monkeys were given the peptide vaccine subcutaneously in combination with the prior DT vaccination. Vaccination with a similar regimen was also performed on guinea pigs. The peptide vaccine induced anti-Aβ antibodies in cynomolgus monkeys and guinea pigs without chemical adjuvants, and excessive immune responses were not observed. Those antibodies could preferentially recognize Aβ40, and Aβ42 compared to Aβ fibrils. The levels of serum anti-Aβ antibodies and plasma Aβ peptides increased in both animals and decreased the brain Aβ40 level of guinea pigs. The peptide vaccine could induce a similar binding profile of anti-Aβ antibodies in cynomolgus monkeys and guinea pigs. The peptide vaccination could be expected to reduce the brain Aβ peptides and their toxic effects via clearance of Aβ peptides by generated antibodies.

  6. Low fasting serum triglyceride level as a precocious marker of autoimmune disorders.

    Science.gov (United States)

    Iannello, Silvia; Cavaleri, Antonina; Milazzo, Paolina; Cantarella, Santi; Belfiore, Francesco

    2003-08-01

    The authors recently reported the occurrence of low fasting serum triglyceride (TG) and high free fatty acid (FFA) levels in idiopathic pulmonary fibrosis. TG estimation in diverse groups of patients with autoimmune disease or hyperactive immune response confirmed the occurrence of a similar decrease of TG. In some patients, serum FFA level was also evaluated. TG value in lean and obese patients was compared with that in lean (n = 108) and obese (n = 208) control subjects without autoimmune disease. In patients affected by autoimmune chronic thyroiditis with enhanced concentration of antithyroglobulin antibodies and without thyroidal failure (n = 24), lean and obese patients had reduced TG (-69/%, P autoimmune diseases (scleroderma, APECED [autoimmune polyendocrinopathy, candidiasis, and ectodermal dystrophy], urticaria or urticarial vasculitis, Reiter or Sjogren syndromes, ulcerative colitis or Crohn's disease, multiple sclerosis or Guillain-Barré syndrome) (n = 14), decreased TG was also observed both in the lean and obese subjects (-59%, P autoimmunity or immune system hyperreactivity. PMID:14600656

  7. Challenges in interpretation of thyroid function tests in pregnant women with autoimmune thyroid disease

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, Ulla; Bliddal, Sofie; Rasmussen, Åse Krogh; Boas, Malene; Hilsted, Linda; Main, Katharina

    2011-01-01

    Physiological changes during gestation are important to be aware of in measurement and interpretation of thyroid function tests in women with autoimmune thyroid diseases. Thyroid autoimmune activity is decreasing in pregnancy. Measurement of serum TSH is the first-line screening variable for thyr....... Measurement of antithyroperoxidase and/or TSH receptor antibodies adds to the differential diagnosis of autoimmune and nonautoimmune thyroid diseases.......Physiological changes during gestation are important to be aware of in measurement and interpretation of thyroid function tests in women with autoimmune thyroid diseases. Thyroid autoimmune activity is decreasing in pregnancy. Measurement of serum TSH is the first-line screening variable for...... thyroid dysfunction also in pregnancy. However, using serum TSH for control of treatment of maternal thyroid autoimmunity infers a risk for compromised foetal development. Peripheral thyroid hormone values are highly different among laboratories, and there is a need for laboratory-specific gestational age...

  8. A pilot study comparing the development of EIAV Env-specific antibodies induced by DNA/recombinant vaccinia-vectored vaccines and an attenuated Chinese EIAV vaccine.

    Science.gov (United States)

    Meng, Qinglai; Lin, Yuezhi; Ma, Jian; Ma, Yan; Zhao, Liping; Li, Shenwei; Yang, Kai; Zhou, Jianhua; Shen, Rongxian; Zhang, Xiaoyan; Shao, Yiming

    2012-12-01

    Data from successful attenuated lentiviral vaccine studies indicate that fully mature Env-specific antibodies characterized by high titer, high avidity, and the predominant recognition of conformational epitopes are associated with protective efficacy. Although vaccination with a DNA prime/recombinant vaccinia-vectored vaccine boost strategy has been found to be effective in some trials with non-human primate/simian/human immunodeficiency virus (SHIV) models, it remains unclear whether this vaccination strategy could elicit mature equine infectious anemia virus (EIAV) Env-specific antibodies, thus protecting vaccinated horses against EIAV infection. Therefore, in this pilot study we vaccinated horses using a strategy based on DNA prime/recombinant Tiantan vaccinia (rTTV)-vectored vaccines encoding EIAV env and gag genes, and observed the development of Env-specific antibodies, neutralizing antibodies, and p26-specific antibodies. Vaccination with DNA induced low titer, low avidity, and the predominant recognition of linear epitopes by Env-specific antibodies, which was enhanced by boosting vaccinations with rTTV vaccines. However, the maturation levels of Env-specific antibodies induced by the DNA/rTTV vaccines were significantly lower than those induced by the attenuated vaccine EIAV(FDDV). Additionally, DNA/rTTV vaccines did not elicit broadly neutralizing antibodies. After challenge with a virulent EIAV strain, all of the vaccinees and control horses died from EIAV disease. These data indicate that the regimen of DNA prime/rTTV vaccine boost did not induce mature Env-specific antibodies, which might have contributed to immune protection failure. PMID:23171359

  9. Suppression of Aggrus/podoplanin-induced platelet aggregation and pulmonary metastasis by a single-chain antibody variable region fragment

    International Nuclear Information System (INIS)

    Almost all highly metastatic tumor cells possess high platelet aggregating abilities, thereby form large tumor cell-platelet aggregates in the microvasculature. Embolization of tumor cells in the microvasculature is considered to be the first step in metastasis to distant organs. We previously identified the platelet aggregation-inducing factor expressed on the surfaces of highly metastatic tumor cells and named as Aggrus. Aggrus was observed to be identical to the marker protein podoplanin (alternative names, T1α, OTS-8, and others). Aggrus is frequently overexpressed in several types of tumors and enhances platelet aggregation by interacting with the platelet receptor C-type lectin-like receptor 2 (CLEC-2). Here, we generated a novel single-chain antibody variable region fragment (scFv) by linking the variable regions of heavy and light chains of the neutralizing anti-human Aggrus monoclonal antibody MS-1 with a flexible peptide linker. Unfortunately, the generated KM10 scFv failed to suppress Aggrus-induced platelet aggregation in vitro. Therefore, we performed phage display screening and finally obtained a high-affinity scFv, K-11. K-11 scFv was able to suppress Aggrus-induced platelet aggregation in vitro. Moreover, K-11 scFv prevented the formation of pulmonary metastasis in vivo. These results suggest that K-11 scFv may be useful as metastasis inhibitory scFv and is expected to aid in the development of preclinical and clinical examinations of Aggrus-targeted cancer therapies

  10. Amplification of rabies virus-induced stimulation of human T-cell lines and clones by antigen-specific antibodies.

    OpenAIRE

    Celis, E; Wiktor, T J; Dietzschold, B.; Koprowski, H

    1985-01-01

    The effect of antigen-specific antibodies on the response of human T-cell lines and clones to rabies virus was studied. Plasmas from rabies-immune vaccine recipients, but not those from nonimmune individuals, enhanced the proliferative response of rabies-reactive T cells to whole inactivated virus or to the purified glycoprotein and nucleocapsid from the rabies virion. Rabies-immune plasma also increased the antigen-induced production of gamma interferon by the rabies-specific T-cell lines. E...

  11. Recombinant Outer Capsid Glycoprotein (VP7 of Rotavirus Expressed in Insect Cells Induces Neutralizing Antibodies in Rabbits

    Directory of Open Access Journals (Sweden)

    H Keyvani

    2012-04-01

    Full Text Available Background:Rotaviruses cause diarrhea in infants and young children worldwide. Rotavirus outer capsid protein, VP7 is major neutralizing antigen that is important component of subunit vaccine to prevent rotavirus infection.Many efforts have been done to produce recombinant VP7 that maintain native characteristics.We used baculovirus expression system to produce rotavirus VP7 protein and to study its immunogenicity. Methods: Simian rotavirus SA11 full-length VP7 ORF was cloned into a cloning plasmid and then the cloned gene was inserted into the linear DNA of baculovirus Autographa californica Nuclear Polyhedrosis Virus (AcNPV downstream of the polyhedrin promoter by in vitro recombination reactions. The expressed VP7 in the insect cells was recognized by rabbit hyperimmune serum raised against SA11 rotavirus by Immunofluorescence and western blotting assays. Rabbits were immunized subcutaneously by cell extracts expressing VP7 protein. Results: Reactivity with anti-rotavirus antibody suggested that expressed VP7 protein had native antigenic determinants.Injection of recombinant VP7 in rabbits elicited the production of serum antibodies,which were able to recognize VP7 protein from SA11 rotavirus by Western blotting test and neutralized SA11 rotavirus in cell culture.Conclusion: Recombinant outer capsid glycoprotein (VP7 of rotavirus expressed in insect cells induces neutralizing antibodies in rabbits and may be a candidate of rotavirus vaccine.

  12. Reduction of enterotoxin induced fluid accumulation in ileal loops of neonatal calves with anti-F5 fimbriae recombinant antibody.

    Science.gov (United States)

    Sahagun-Ruiz, Alfredo; Velazquez, Leticia V; Bhaskaran, Shoba; Jay, Chris M; Morales-Salinas, E; Rathore, Keerti; Wagner, Gale G; Waghela, Suryakant D

    2015-12-01

    Neonatal calf colibacillosis caused by enterotoxigenic Escherichia coli (ETEC) is an economically significant problem in most parts of the world. The most common ETEC found in calves express the F5 (K99) fimbriae, which are necessary for the attachment of the bacteria to the ganglioside receptors on enterocytes. It is known that prevention of ETEC F5(+) adhesion to its ganglioside receptors with specific antibodies protects calves from colibacillosis. Previously we have described the development and characterization of a mouse recombinant antibody fragment (moRAb) that prevents F5 fimbrial protein induced agglutination of horse red blood cells (HRBC), which exhibit the same gangloside receptor for F5 fimbriae. Here we demonstrate that this recombinant antibody fragment inhibits in vitro the attachment of ETEC F5(+) bacteria to HRBC as well as isolated calf enterocytes, and in vivo it decreases fluid accumulation in intestinal loops of calves. Thus, correct oral administration of this anti-F5 moRAb may serve as an immunoprophylactic for cost effective control of colibacillosis in calves. PMID:26521056

  13. Haploinsufficiency of activation-induced deaminase for antibody diversification and chromosome translocations both in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Isora V Sernández

    Full Text Available The humoral immune response critically relies on the secondary diversification of antibodies. This diversification takes places through somatic remodelling of the antibody genes by two molecular mechanisms, Class Switch Recombination (CSR and Somatic Hypermutation (SHM. The enzyme Activation Induced Cytidine Deaminase (AID initiates both SHM and CSR by deaminating cytosine residues on the DNA of immunoglobulin genes. While crucial for immunity, AID-catalysed deamination is also the triggering event for the generation of lymphomagenic chromosome translocations. To address whether restricting the levels of AID expression in vivo contributes to the regulation of its function, we analysed mice harbouring a single copy of the AID gene (AID(+/-. AID(+/- mice express roughly 50% of normal AID levels, and display a mild hyperplasia, reminiscent of AID deficient mice and humans. Moreover, we found that AID(+/- cells have an impaired competence for CSR and SHM, which indicates that AID gene dose is limiting for its physiologic function. We next evaluated the impact of AID reduction in AID(+/- mice on the generation of chromosome translocations. Our results show that the frequency of AID-promoted c-myc/IgH translocations is reduced in AID(+/- mice, both in vivo and in vitro. Therefore, AID is haploinsufficient for antibody diversification and chromosome translocations. These findings suggest that limiting the physiologic levels of AID expression can be a regulatory mechanism that ensures an optimal balance between immune proficiency and genome integrity.

  14. Propylthiouracil induced anti-neutrophil cytoplasmic antibody-associated vasculitis with bone marrow plasmacytosis andgranulocytopenia

    Institute of Scientific and Technical Information of China (English)

    Abdullah Ozkok

    2009-01-01

    @@ Antithyroid drugs are molecules known as thionamides that inhibit thyroid hormone synthesis by interfering with thyroid peroxidase mediated iodination of tyrosine residues in thyroglobulin. These extensively used drugs are associated with a variety of well-known side effects such as anti-neutrophil cytoplasmic antibody (ANCA)-positive vasctilitis, granulocytopenia and aplastic anemia.

  15. Immune antibodies and helminth products promote CXCR2-dependent repair of parasite-induced injury

    Science.gov (United States)

    Helminth parasites cause massive damage when migrating through host tissues, thus making rapid tissue repair imperative to prevent bleeding and bacterial dissemination. We observed that mice lacking antibodies (AID-/-) or activating Fc receptors (FcR'-/-) displayed impaired intestinal repair followi...

  16. Vaccine-induced cross-genotype reactive neutralizing antibodies against hepatitis C virus

    DEFF Research Database (Denmark)

    Meunier, Jean-Christophe; Gottwein, Judith M; Houghton, Michael; Russell, Rodney S; Emerson, Suzanne U; Bukh, Jens; Purcell, Robert H

    2011-01-01

    We detected cross-reactive neutralizing antibodies (NtAb) against hepatitis C virus (HCV) in chimpanzees vaccinated with HCV-1 (genotype 1a) recombinant E1/E2 envelope glycoproteins. Five vaccinated chimpanzees, protected following HCV-1 challenge, were initially studied using the heterologous H77...

  17. Vaccine-Induced Antibodies that Neutralize Group 1 and Group 2 Influenza A Viruses.

    Science.gov (United States)

    Joyce, M Gordon; Wheatley, Adam K; Thomas, Paul V; Chuang, Gwo-Yu; Soto, Cinque; Bailer, Robert T; Druz, Aliaksandr; Georgiev, Ivelin S; Gillespie, Rebecca A; Kanekiyo, Masaru; Kong, Wing-Pui; Leung, Kwanyee; Narpala, Sandeep N; Prabhakaran, Madhu S; Yang, Eun Sung; Zhang, Baoshan; Zhang, Yi; Asokan, Mangaiarkarasi; Boyington, Jeffrey C; Bylund, Tatsiana; Darko, Sam; Lees, Christopher R; Ransier, Amy; Shen, Chen-Hsiang; Wang, Lingshu; Whittle, James R; Wu, Xueling; Yassine, Hadi M; Santos, Celia; Matsuoka, Yumiko; Tsybovsky, Yaroslav; Baxa, Ulrich; Mullikin, James C; Subbarao, Kanta; Douek, Daniel C; Graham, Barney S; Koup, Richard A; Ledgerwood, Julie E; Roederer, Mario; Shapiro, Lawrence; Kwong, Peter D; Mascola, John R; McDermott, Adrian B

    2016-07-28

    Antibodies capable of neutralizing divergent influenza A viruses could form the basis of a universal vaccine. Here, from subjects enrolled in an H5N1 DNA/MIV-prime-boost influenza vaccine trial, we sorted hemagglutinin cross-reactive memory B cells and identified three antibody classes, each capable of neutralizing diverse subtypes of group 1 and group 2 influenza A viruses. Co-crystal structures with hemagglutinin revealed that each class utilized characteristic germline genes and convergent sequence motifs to recognize overlapping epitopes in the hemagglutinin stem. All six analyzed subjects had sequences from at least one multidonor class, and-in half the subjects-multidonor-class sequences were recovered from >40% of cross-reactive B cells. By contrast, these multidonor-class sequences were rare in published antibody datasets. Vaccination with a divergent hemagglutinin can thus increase the frequency of B cells encoding broad influenza A-neutralizing antibodies. We propose the sequence signature-quantified prevalence of these B cells as a metric to guide universal influenza A immunization strategies. PMID:27453470

  18. Opsonization of Treponema pallidum is mediated by immunoglobulin G antibodies induced only by pathogenic treponemes.

    OpenAIRE

    Shaffer, J M; Baker-Zander, S A; Lukehart, S A

    1993-01-01

    Rabbit antisera to Leptospira interrogans, Borrelia hermsii, and Treponema phagedenis biotype Reiter, reactive to shared spirochetal antigens, failed to enhance phagocytosis of Treponema pallidum by macrophages, while immunoglobulin G to Treponema pallidum subsp. pertenue and Treponema paraluiscuniculi promoted phagocytosis. Opsonic antibodies are directed to pathogen-restricted, not shared spirochetal, antigens.

  19. Cytokines and Cytokine Profiles in Human Autoimmune Diseases and Animal Models of Autoimmunity

    Directory of Open Access Journals (Sweden)

    Manfred Kunz

    2009-01-01

    Full Text Available The precise pathomechanisms of human autoimmune diseases are still poorly understood. However, a deepened understanding of these is urgently needed to improve disease prevention and early detection and guide more specific treatment approaches. In recent years, many new genes and signalling pathways involved in autoimmunity with often overlapping patterns between different disease entities have been detected. Major contributions were made by experiments using DNA microarray technology, which has been used for the analysis of gene expression patterns in chronic inflammatory and autoimmune diseases, among which were rheumatoid arthritis, systemic lupus erythematosus, psoriasis, systemic sclerosis, multiple sclerosis, and type-1 diabetes. In systemic lupus erythematosus, a so-called interferon signature has been identified. In psoriasis, researchers found a particular immune signalling cluster. Moreover the identification of a new subset of inflammatory T cells, so-called Th17 T cells, secreting interleukin (IL-17 as one of their major cytokines and the identification of the IL-23/IL-17 axis of inflammation regulation, have significantly improved our understanding of autoimmune diseases. Since a plethora of new treatment approaches using antibodies or small molecule inhibitors specifically targeting cytokines, cellular receptors, or signalling mechanisms has emerged in recent years, more individualized treatment for affected patients may be within reach in the future.

  20. Tic disorders and obsessive-compulsive disorder: is autoimmunity involved?

    Science.gov (United States)

    Hoekstra, Pieter J; Minderaa, Ruud B

    2005-12-01

    The precise cause of tic disorders and paediatric obsessive-compulsive disorder (OCD) is unknown. In addition to genetic factors, autoimmunity may play a role, possibly as a sequela of preceding streptococcal throat infections in susceptible children. Here we review the most recent findings, from July 2003 onwards, with regard to a possible relationship between tics/OCD and autoimmunity. Evidence about an intriguing correlation between streptococcal infections and tic disorders and OCD is accumulating. Specific criteria have been outlined for paediatric autoimmune disorders associated with streptococcal infections (PANDAS), but autoimmunity may also be involved in tic disorders and/or OCD in general. Anti-basal ganglia auto-antibodies are an important potential indicator of autoimmunity. Although the lack of a standardized methodology makes comparisons of findings difficult, new data has emerged pointing to the possible involvement of specific auto-antigens. Earlier findings of increased D8/17 B cell expression as a putative susceptibility marker could not be replicated, possibly due to instability of the D8/17-binding antibody. Although PANDAS patients have been reported to improve after therapeutic plasma exchange, and antibiotics may prevent symptom exacerbations, immune-based treatments should not be routinely given. In future studies, demonstrating the pathogenetic significance of anti-basal ganglia antibodies in animals is a major challenge to draw any firm conclusions about a role for autoimmunity. Future longitudinal studies should be aimed at assessing the precise relationship between symptom exacerbations, infections, and immune parameters, possibly along with gene expression profiles. PMID:16401548

  1. [Polyglandular autoimmune syndromes : An overview].

    Science.gov (United States)

    Komminoth, P

    2016-05-01

    Polyglandular autoimmune syndromes (PGAS), also known as autoimmune polyendocrinopathy syndromes (APS), are a heterogeneous group of rare, genetically caused diseases of the immune system which lead to inflammatory damage of various endocrine glands resulting in malfunctions. In addition, autoimmune diseases of non-endocrine organs may also be found. Early diagnosis of PGAS is often overlooked because of heterogeneous symptoms and the progressive occurrence of the individual diseases. The two most important forms of PGAS are the juvenile and adult types. The juvenile type (PGAS type 1) is caused by mutations in the autoimmune regulator (AIRE) gene on chromosome 21, exhibits geographic variations in incidence and is defined by the combination of mucocutaneous candidiasis, Addison's disease and hypoparathyroidism. In addition, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome and other autoimmune diseases can also occur. The adult form of PGAS (PGAS type 2) is a multigenetic disorder associated with some HLA haplotypes, is more common than the juvenile type, shows female predominance and exhibits the combination of type 1 diabetes, autoimmune thyroid disease, Addison's disease and other autoimmune disorders. The histological alterations in affected organs of PGAS patients are similar to findings in sporadically occurring autoimmune diseases of these organs but there are no pathognomic fine tissue findings. If patients exhibit autoimmune changes in two different endocrine glands or if there are indications of several autoimmune disorders from the patient history, it is important to consider PGAS and inform the clinicians of this suspicion. PMID:27099223

  2. Autoimmune disease: A role for new anti-viral therapies?

    Science.gov (United States)

    Dreyfus, David H

    2011-12-01

    Many chronic human diseases may have an underlying autoimmune mechanism. In this review, the author presents a case of autoimmune CIU (chronic idiopathic urticaria) in stable remission after therapy with a retroviral integrase inhibitor, raltegravir (Isentress). Previous reports located using the search terms "autoimmunity" and "anti-viral" and related topics in the pubmed data-base are reviewed suggesting that novel anti-viral agents such as retroviral integrase inhibitors, gene silencing therapies and eventually vaccines may provide new options for anti-viral therapy of autoimmune diseases. Cited epidemiologic and experimental evidence suggests that increased replication of epigenomic viral pathogens such as Epstein-Barr Virus (EBV) in chronic human autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus Erythematosus (SLE), and multiple sclerosis (MS) may activate endogenous human retroviruses (HERV) as a pathologic mechanism. Memory B cells are the reservoir of infection of EBV and also express endogenous retroviruses, thus depletion of memory b-lymphocytes by monoclonal antibodies (Rituximab) may have therapeutic anti-viral effects in addition to effects on B-lymphocyte presentation of both EBV and HERV superantigens. Other novel anti-viral therapies of chronic autoimmune diseases, such as retroviral integrase inhibitors, could be effective, although not without risk. PMID:21871974

  3. High-throughput pseudovirion-based neutralization assay for analysis of natural and vaccine-induced antibodies against human papillomaviruses.

    Directory of Open Access Journals (Sweden)

    Peter Sehr

    Full Text Available A highly sensitive, automated, purely add-on, high-throughput pseudovirion-based neutralization assay (HT-PBNA with excellent repeatability and run-to-run reproducibility was developed for human papillomavirus types (HPV 16, 18, 31, 45, 52, 58 and bovine papillomavirus type 1. Preparation of 384 well assay plates with serially diluted sera and the actual cell-based assay are separated in time, therefore batches of up to one hundred assay plates can be processed sequentially. A mean coefficient of variation (CV of 13% was obtained for anti-HPV 16 and HPV 18 titers for a standard serum tested in a total of 58 repeats on individual plates in seven independent runs. Natural antibody response was analyzed in 35 sera from patients with HPV 16 DNA positive cervical intraepithelial neoplasia grade 2+ lesions. The new HT-PBNA is based on Gaussia luciferase with increased sensitivity compared to the previously described manual PBNA (manPBNA based on secreted alkaline phosphatase as reporter. Titers obtained with HT-PBNA were generally higher than titers obtained with the manPBNA. A good linear correlation (R(2 = 0.7 was found between HT-PBNA titers and anti-HPV 16 L1 antibody-levels determined by a Luminex bead-based GST-capture assay for these 35 sera and a Kappa-value of 0.72, with only 3 discordant sera in the low titer range. In addition to natural low titer antibody responses the high sensitivity of the HT-PBNA also allows detection of cross-neutralizing antibodies induced by commercial HPV L1-vaccines and experimental L2-vaccines. When analyzing the WHO international standards for HPV 16 and 18 we determined an analytical sensitivity of 0.864 and 1.105 mIU, respectively.

  4. Age impact on autoimmune thyroid disease in females

    Science.gov (United States)

    Stoian, Dana; Craciunescu, Mihalea; Timar, Romulus; Schiller, Adalbert; Pater, Liana; Craina, Marius

    2013-10-01

    Thyroid autoimmune disease, a widespread phenomenon in female population, impairs thyroid function during pregnancy. Identifying cases, which will develop hypothyroidism during pregnancy, is crucial in the follow-up process. The study group comprised 108 females, with ages between 20-40 years; with known inactive autoimmune thyroid disease, before pregnancy that became pregnant in the study follow-up period. They were monitored by means of clinical, hormonal and immunological assays. Supplemental therapy with thyroid hormones was used, where needed. Maternal age and level of anti-thyroid antibodies were used to predict thyroid functional impairment.

  5. [Autoimmune thyroiditis and thyroid cancer].

    Science.gov (United States)

    Krátký, Jan; Jiskra, Jan

    2015-10-01

    Association between autoimmune thyroiditis (CLT) and thyroid cancer remains not clear. Although both diseases often occur simultaneously in histological samples, it is not yet clear whether CLT can be regarded as a risk factor for thyroid malignancy. This review focus on the known epidemiological and molecular genetics links between both diseases. Most studies have shown a significant association between thyroid cancer and positive antibodies to thyroglobulin and histological evidence of CLT, as well. Both disorders share some risk factors (greater incidence in women, in areas with adequate supply of iodine and in patients after radiotherapy of the neck) and molecular genetics linkage. For example: RET/PTC rearrangements could be more often found in carcinomas associated with CLT, but this mutation could be found in benign lesions such as CLT, as well. CLT seems to be a positive prognostic factor in patients with differentiated thyroid cancer. It is associated with less invasive forms of tumor, lower occurrence of infiltrated lymphatic nodes and a lower risk of recurrence. PMID:26486481

  6. Long-term follow-up of seven patients with ophthalmopathy not associated with thyroid autoimmunity: heterogeneity of autoimmune ophthalmopathy

    Directory of Open Access Journals (Sweden)

    McCorquodale T

    2012-07-01

    Full Text Available Tom McCorquodale,1 Hooshang Lahooti,1 Bamini Gopinath,2 Jack R Wall11Department of Medicine, Nepean Clinical School, the University of Sydney, Penrith, NSW, Australia; 2Centre for Vision Research, the University of Sydney, Westmead Hospital, Westmead, NSW, AustraliaBackground: Ophthalmopathy is the most common extrathyroidal manifestation of Graves' disease. However, in approximately 5% of cases this autoimmune eye disorder occurs in the apparent absence of Graves' hyperthyroidism: the so-called euthyroid Graves' disease (EGD.Methods: Seven patients with EGD were followed for evidence of thyroid and orbital autoimmunity, for up to 10 years. Calsequestrin and collagen XIII antibodies were measured by enzyme linked immunosorbent assay (ELISA, and TSH-receptor (TSH-r antibodies were measured as TSH-r-binding antibody (TRAb and thyroid-stimulating immunoglobulin (TSI. Eye signs were characterized and quantified as clinical activity score (CAS, NOSPECS classes, Nunery types 1 and 2, and margin-reflex distance (MRD.Results: Calsequestrin antibodies were detected on at least one occasion in three of the seven patients and collagen XIII antibodies were detected one or more times in five patients. In one patient with isolated congestive ophthalmopathy who was studied intensely, collagen XIII antibodies were initially positive and then became negative as the eye disease stabilized, while antibodies targeting calsequestrin were always negative. TRAb was not detected in any patient, but TSI was detected in three patients on one occasion each. Ultrasound abnormalities were found in four of the six patients for whom this was carried out, but there was no clear evidence for thyroiditis in any of these patients. For comparison, 13 patients were studied with typical Graves' ophthalmopathy. There were no significant differences compared to EGD in respect to the prevalence of positive calsequestrin or collagen XIII antibodies, but these patients included more

  7. Experimental autoimmune glomerulonephritis induced by anti-glomerular basement membrane antibody. II. Effects of injecting heterologous, homologous, or autologous glomerular basement membranes and complete Freund's adjuvant into sheep.

    OpenAIRE

    Steblay, R. W.; Rudofsky, U H

    1983-01-01

    The effects of injecting human, rabbit, rat, or single-kidney homologous glomerular basement membrane (GBM) or autologous GBM, each in complete Freund's adjuvant (CFA), into 15- to 18-month-old sheep are compared. All sheep receiving heterologous GBM and 3 of 6 sheep receiving homologous GBM had anti-GBM nephritis, but such sheep did not bind autoantibodies or have Goodpasturelike lesions in their lungs. Sheep given injections of human GBM had autoantibodies to antigenic determinants shared b...

  8. Is autoimmune hepatitis a frequent finding among HCV patients with intense interface hepatitis?

    Institute of Scientific and Technical Information of China (English)

    Rosilene; G; Badiani; Vitória; Becker; Renata; M; Perez; Carla; AL; Matos; Lara; B; Lemos; Valéria; P; Lanzoni; Luis; Eduardo; C; Andrade; Alessandra; Dellavance; Antonio; Eduardo; B; Silva; Maria; Lucia; G; Ferraz

    2010-01-01

    AIM:To evaluate the overlap of autoimmune hepatitis in hepatitis C virus(HCV)-infected patients with intense interface hepatitis.METHODS:Among 1759 patients with hepatitis C submitted to liver biopsy,92(5.2%) presented intense interface hepatitis.These patients were evaluated regarding the presence of antinuclear antibody(ANA),anti-smooth muscle antibody(SMA) and anti-liver/kidney microsomal antibody(LKM-1),levels of γ-globulin and histological findings related to autoimmune hepatitis(plasma cell infiltrate...

  9. Protective antibody and CD8+ T-cell responses to the Plasmodium falciparum circumsporozoite protein induced by a nanoparticle vaccine.

    Directory of Open Access Journals (Sweden)

    Stephen A Kaba

    Full Text Available BACKGROUND: The worldwide burden of malaria remains a major public health problem due, in part, to the lack of an effective vaccine against the Plasmodium falciparum parasite. An effective vaccine will most likely require the induction of antigen specific CD8(+ and CD4(+ T-cells as well as long-lasting antibody responses all working in concert to eliminate the infection. We report here the effective modification of a self-assembling protein nanoparticle (SAPN vaccine previously proven effective in control of a P. berghei infection in a rodent model to now present B- and T-cell epitopes of the human malaria parasite P. falciparum in a platform capable of being used in human subjects. METHODOLOGY/PRINCIPAL FINDINGS: To establish the basis for a SAPN-based vaccine, B- and CD8(+ T-cell epitopes from the P. falciparum circumsporozoite protein (PfCSP and the universal CD4 T-helper epitope PADRE were engineered into a versatile small protein (∼125 amino acids that self-assembles into a spherical nanoparticle repetitively displaying the selected epitopes. P. falciparum epitope specific immune responses were evaluated in mice using a transgenic P. berghei malaria parasite of mice expressing the human malaria full-length P. falciparum circumsporozoite protein (Tg-Pb/PfCSP. We show that SAPN constructs, delivered in saline, can induce high-titer, long-lasting (1 year protective antibody and poly-functional (IFNγ(+, IL-2(+ long-lived central memory CD8(+ T-cells. Furthermore, we demonstrated that these Ab or CD8(+ T-cells can independently provide sterile protection against a lethal challenge of the transgenic parasites. CONCLUSION: The SAPN construct induces long-lasting antibody and cellular immune responses to epitope specific sequences of the P. falciparum circumsporozoite protein (PfCSP and prevents infection in mice by a transgenic P. berghei parasite displaying the full length PfCSP.

  10. Immunisation with recombinant PfEMP1 domains elicits functional rosette-inhibiting and phagocytosis-inducing antibodies to Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    Ashfaq Ghumra

    Full Text Available BACKGROUND: Rosetting is a Plasmodium falciparum virulence factor implicated in the pathogenesis of life-threatening malaria. Rosetting occurs when parasite-derived P. falciparum Erythrocyte Membrane Protein One (PfEMP1 on the surface of infected erythrocytes binds to human receptors on uninfected erythrocytes. PfEMP1 is a possible target for a vaccine to induce antibodies to inhibit rosetting and prevent severe malaria. METHODOLOGY/FINDINGS: We examined the vaccine potential of the six extracellular domains of a rosette-mediating PfEMP1 variant (ITvar9/R29var1 from the R29 parasite strain by immunizing rabbits with recombinant proteins expressed in E. coli. Antibodies raised to each domain were tested for surface fluorescence with live infected erythrocytes, rosette inhibition and phagocytosis-induction. Antibodies to all PfEMP1 domains recognized the surface of live infected erythrocytes down to low concentrations (0.02-1.56 µg/ml of total IgG. Antibodies to all PfEMP1 domains except for the second Duffy-Binding-Like region inhibited rosetting (50% inhibitory concentration 0.04-4 µg/ml and were able to opsonize and induce phagocytosis of infected erythrocytes at low concentrations (1.56-6.25 µg/ml. Antibodies to the N-terminal region (NTS-DBL1α were the most effective in all assays. All antibodies were specific for the R29 parasite strain, and showed no functional activity against five other rosetting strains. CONCLUSIONS/SIGNIFICANCE: These results are encouraging for vaccine development as they show that potent antibodies can be generated to recombinant PfEMP1 domains that will inhibit rosetting and induce phagocytosis of infected erythrocytes. However, further work is needed on rosetting mechanisms and cross-reactivity in field isolates to define a set of PfEMP1 variants that could induce functional antibodies against a broad range of P. falciparum rosetting parasites.

  11. Intranasal Delivery of Group B Meningococcal Native Outer Membrane Vesicle Vaccine Induces Local Mucosal and Serum Bactericidal Antibody Responses in Rabbits

    OpenAIRE

    Shoemaker, David R.; Saunders, Nancy B.; Brandt, Brenda L.; Moran, E. Ellen; LaClair, Andrew D.; Zollinger, Wendell D.

    2005-01-01

    We have previously shown that intranasal immunization of mice with meningococcal native outer membrane vesicles (NOMV) induces both a good local mucosal antibody response and a good systemic bactericidal antibody response. However, in the intranasal mouse model, some of the NOMV entered the lung and caused an acute granulocytic response. We therefore developed an alternate animal model using the rabbit. This model reduces the probability of lung involvement and more closely mimics intranasal ...

  12. Metabolic requirements for hormone-induced resistance to antibody-complement mediated killing of tumor cells

    International Nuclear Information System (INIS)

    Line-1 guinea pig hepatoma cells are susceptible to killing by anti-Forssman IgM antibody plus guinea pig complement (GPC). When these tumor cells are incubated with insulin, epinephrine, hydrocortisone, or prednisolone, the cells show a marked reduction in their susceptibility to antibody-C-mediated killing. If the ability of the cells to synthesize DNA, RNA, and protein is impaired by pretreatment with metabolic inhibitors, x-irradiation, or culture in nutrient-deficient media, the hormones are no longer effective in rendering the cells resistant to killing. If only DNA synthesis is impaired, but not RNA and protein synthesis, the hormones are effective. The inability of cells inhibited in their macromolecular synthesis to be rendered resistant to killing after hormone treatment is not due to an inability of the cells to bind hormone

  13. Update on autoimmune hepatitis

    Institute of Scientific and Technical Information of China (English)

    Andreas Teufel; Peter R Galle; Stephan Kanzler

    2009-01-01

    Autoimmune hepatitis (AIH) is a necroinflammatory liver disease of unknown etiology that occurs in children and adults of all ages. Characteristics are its autoimmune features, hyperglobulinemia (IgG), and the presence of circulating autoantibodies, as well as a response to immunosuppressant drugs. Current treatment consists of prednisone and azathioprine and in most patients this disease has become very treatable. Over the past 2 years, a couple of new insights into the genetic aspects, clinical course and treatment of AIH have been reported, which will be the focus of this review. In particular, we concentrate on genome-wide microsatellite analysis, a novel mouse model of AIH, the evaluation of a large AIH cohort for overlap syndromes,suggested novel criteria for the diagnosis of AIH, and the latest studies on treatment of AIH with budenoside and mycophenolate mofetil.

  14. How does the recombinant human interferon beta induce antibodies in immune tolerant mice?

    OpenAIRE

    Kijanka, G.M.

    2013-01-01

    Therapeutic proteins revolutionized the treatment of severe diseases like multiple sclerosis, diabetes, haemophilia and many more. Unfortunately, their usage is often limited due to the formation of anti drug antibodies (ADAs), which may block the activity of these protein drugs and may lead to immune-related side effects. In order to better understand the mechanism underlying the formation of ADAs we performed a series of experiments in immune tolerant transgenic mice. These mice express a s...

  15. Streptococcus pneumoniae-Induced Inhibition of Rat Ependymal Cilia Is Attenuated by Antipneumolysin Antibody

    OpenAIRE

    Hirst, Robert A; Mohammed, Bashir J.; Mitchell, Timothy J.; Andrew, Peter W.; O'Callaghan, Christopher

    2004-01-01

    Ciliated ependymal cells line the ventricular surfaces and aqueducts of the brain. In ex vivo experiments, pneumolysin caused rapid inhibition of the ependymal ciliary beat frequency and caused ependymal cell disruption. Wild-type pneumococci and pneumococci deficient in pneumolysin caused ciliary slowing, but penicillin lysis of wild-type, not pneumolysin-deficient, pneumococci increased the extent of ciliary inhibition. This effect was abolished by antipneumolysin antibody. Ependymal ciliar...

  16. Y-Hydroxyphosphonate inducing single-chain antibodies capable of catalyzing soman hydrolysis

    Institute of Scientific and Technical Information of China (English)

    王字玲; 荣康泰; 杨日芳; 恽榴红

    2000-01-01

    A γ-hydroxyphosphonate P6 (O1-methyl-O2-(1, 2, 2-trimethylpropyl)-2-hydroxy-5-nitro-phenyl methylphosphonic acid) which is proposed to be an analog of the transition state in hydrolysis of soman was synthesized. Artificial antigens were obtained by conjugating P6 to the carrier proteins BSA (bovine serum albumin) and LPH (Limulus polyphenus hemocyanin). Mice were immunized with P6-LPH and recombinant single-chain antibody phage display library was constructed. After 4 rounds of panning against P6-BSA and competitive inhibition enzyme immunoassay, more than 70 strains of phage antibodies capable of binding soman were obtained and 11 of them can accelerate the hydrolysis reaction of soman. One of them (EP6) was studied further. Soluble single-chain antibody was prepared and purification was performed by gel filtration and ion exchange chromatography. The kinetic experiment was carried out showing that the turnover number kcatt= 198 min-1 and the rate enhancement kcatkuncat = 122 419. When 0.16 mg · mL-1

  17. MDSC in Autoimmunity

    OpenAIRE

    Cripps, James G.; Gorham, James D.

    2011-01-01

    Myeloid derived suppressor cells (MDSC) were first described nearly two decades ago. Until recently, however, descriptions of MDSC populations were found almost exclusively in animal models of cancer or in cancer patients. Over the last few years, an increasing number of reports have been published describing populations of myeloid cells with MDSC-like properties in murine models of autoimmune disease. In contrast to the proposed deleterious role of MDSC in cancer - where these cells likely i...

  18. Easily obtainable clinical features increase the diagnostic accuracy for later autoimmune diabetes in adults. An evidence based report

    NARCIS (Netherlands)

    Lutgens, M.W.M.D.; Meijer, M.; Peeters, B.; Poulsen, M.N.F.; Rutten, M.J.; Bots, M.L.; Heijden, van der G.J.M.G.; Soedamah-Muthu, S.S.

    2008-01-01

    Background Latent autoimmune diabetes in adults (LADA) represents a subgroup of diabetes mellitus. LADA is characterised by adult-onset diabetes and circulating autoimmune antibodies. LADA patients may need a different therapeutic approach than the usual type 2 diabetes mellitus. When LADA is inadeq

  19. Peptide immunotherapy in experimental autoimmune encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Stephen M Anderton

    2015-06-01

    Full Text Available We now have potent drugs available to treat the inflammatory component of multiple sclerosis (MS. However, not all patients respond, the drugs are not curative, and the associated risks to beneficial immune surveillance are considerable. A more desirable approach is to specifically target those comparatively rare T lymphocytes that are orchestrating the autoimmune attack. Using the autoantigen itself to instill immune tolerance in those cells remains a holy grail of immunotherapy. Peptide immunotherapy (PIT is highly effective at silencing autoimmune responses in experimental autoimmune encephalomyelitis (EAE, and clinical trials of PIT are underway in MS. This review discusses the current paradigms for PIT-induced tolerance in naïve T cells. It highlights the need for better understanding of the mode of action of PIT upon memory and effector T cells that are responsible for driving/sustaining ongoing autoimmune pathology. Recent studies in EAEsuggest genetic and epigenetic changes in these pathogenic T-cell populations in response to PIT. Finally, future challenges to effective translation of PIT to the clinic are considered.

  20. Etiopathogenesis of Insulin Autoimmunity

    Directory of Open Access Journals (Sweden)

    Norio Kanatsuna

    2012-01-01

    Full Text Available Autoimmunity against pancreatic islet beta cells is strongly associated with proinsulin, insulin, or both. The insulin autoreactivity is particularly pronounced in children with young age at onset of type 1 diabetes. Possible mechanisms for (proinsulin autoimmunity may involve beta-cell destruction resulting in proinsulin peptide presentation on HLA-DR-DQ Class II molecules in pancreatic draining lymphnodes. Recent data on proinsulin peptide binding to type 1 diabetes-associated HLA-DQ2 and -DQ8 is reviewed and illustrated by molecular modeling. The importance of the cellular immune reaction involving cytotoxic CD8-positive T cells to kill beta cells through Class I MHC is discussed along with speculations of the possible role of B lymphocytes in presenting the proinsulin autoantigen over and over again through insulin-carrying insulin autoantibodies. In contrast to autoantibodies against other islet autoantigens such as GAD65, IA-2, and ZnT8 transporters, it has not been possible yet to standardize the insulin autoantibody test. As islet autoantibodies predict type 1 diabetes, it is imperative to clarify the mechanisms of insulin autoimmunity.

  1. Antinuclear antibody panel

    Science.gov (United States)

    ... blood may be due to: Chronic liver disease Collagen vascular disease Drug-induced lupus erythematosus Myositis (inflammatory muscle disease) ... Saunders; 2011:chap 51. Read More Antibody Arthritis Collagen vascular disease Drug-induced lupus erythematosus Liver disease Scleroderma Systemic ...

  2. CD8+ T-Cell Deficiency, Epstein-Barr Virus Infection, Vitamin D Deficiency, and Steps to Autoimmunity: A Unifying Hypothesis

    Directory of Open Access Journals (Sweden)

    Michael P. Pender

    2012-01-01

    Full Text Available CD8+ T-cell deficiency is a feature of many chronic autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, dermatomyositis, primary biliary cirrhosis, primary sclerosing cholangitis, ulcerative colitis, Crohn's disease, psoriasis, vitiligo, bullous pemphigoid, alopecia areata, idiopathic dilated cardiomyopathy, type 1 diabetes mellitus, Graves' disease, Hashimoto's thyroiditis, myasthenia gravis, IgA nephropathy, membranous nephropathy, and pernicious anaemia. It also occurs in healthy blood relatives of patients with autoimmune diseases, suggesting it is genetically determined. Here it is proposed that this CD8+ T-cell deficiency underlies the development of chronic autoimmune diseases by impairing CD8+ T-cell control of Epstein-Barr virus (EBV infection, with the result that EBV-infected autoreactive B cells accumulate in the target organ where they produce pathogenic autoantibodies and provide costimulatory survival signals to autoreactive T cells which would otherwise die in the target organ by activation-induced apoptosis. Autoimmunity is postulated to evolve in the following steps: (1 CD8+ T-cell deficiency, (2 primary EBV infection, (3 decreased CD8+ T-cell control of EBV, (4 increased EBV load and increased anti-EBV antibodies, (5 EBV infection in the target organ, (6 clonal expansion of EBV-infected autoreactive B cells in the target organ, (7 infiltration of autoreactive T cells into the target organ, and (8 development of ectopic lymphoid follicles in the target organ. It is also proposed that deprivation of sunlight and vitamin D at higher latitudes facilitates the development of autoimmune diseases by aggravating the CD8+ T-cell deficiency and thereby further impairing control of EBV. The hypothesis makes predictions which can be tested, including the prevention and successful treatment of chronic autoimmune diseases by controlling EBV infection.

  3. Fluorescence Adherence Inhibition Assay: A Novel Functional Assessment of Blocking Virus Attachment by Vaccine-Induced Antibodies.

    Science.gov (United States)

    Asati, Atul; Kachurina, Olga; Karol, Alex; Dhir, Vipra; Nguyen, Michael; Parkhill, Robert; Kouiavskaia, Diana; Chumakov, Konstantin; Warren, William; Kachurin, Anatoly

    2016-01-01

    Neutralizing antibodies induced by vaccination or natural infection play a critically important role in protection against the viral diseases. In general, neutralization of the viral infection occurs via two major pathways: pre- and post-attachment modes, the first being the most important for such infections as influenza and polio, the latter being significant for filoviruses. Neutralizing capacity of antibodies is typically evaluated by virus neutralization assays that assess reduction of viral infectivity to the target cells in the presence of functional antibodies. Plaque reduction neutralization test, microneutralization and immunofluorescent assays are often used as gold standard virus neutralization assays. However, these methods are associated with several important prerequisites such as use of live virus requiring safety precautions, tedious evaluation procedure and long assessment time. Hence, there is a need for a robust, inexpensive high throughput functional assay that can be performed rapidly using inactivated virus, without extensive safety precautions. Herein, we report a novel high throughput Fluorescence Adherence Inhibition assay (fADI) using inactivated virus labeled with fluorescent secondary antibodies virus and Vero cells or erythrocytes as targets. It requires only few hours to assess pre-attachment neutralizing capacity of donor sera. fADI assay was tested successfully on donors immunized with polio, yellow fever and influenza vaccines. To further simplify and improve the throughput of the assay, we have developed a mathematical approach for calculating the 50% titers from a single sample dilution, without the need to analyze multi-point titration curves. Assessment of pre- and post-vaccination human sera from subjects immunized with IPOL®, YF-VAX® and 2013-2014 Fluzone® vaccines demonstrated high efficiency of the assay. The results correlated very well with microneutralization assay performed independently by the FDA Center of

  4. Autoimmune thyroid disease and other non-endocrine autoimmune diseases

    OpenAIRE

    Todorović-Đilas Ljiljana; Ičin Tijana; Novaković-Paro Jovanka; Bajkin Ivana

    2011-01-01

    Introduction, Autoimmune diseases are chronic conditions initiated by the loss of immunological tolerance to self-antigens. They constitute heterogeneous group of disorders, in which multiple alterations in the immune system result in a spectrum of syndromes that either target specific organs or affect the body systematically. Recent epidemiological studies have shown a possible shift of one autoimmune disease to another or the fact that more than one autoimmune disease may coexist in a...

  5. Nitrosative Stress and Nitrated Proteins in Trichloroethene-Mediated Autoimmunity

    OpenAIRE

    Gangduo Wang; Jianling Wang; Xuemei Luo; Shakeel Ansari, G. A.; M Firoze Khan

    2014-01-01

    Exposure to trichloroethene (TCE), a ubiquitous environmental contaminant, has been linked to a variety of autoimmune diseases (ADs) including SLE, scleroderma and hepatitis. Mechanisms involved in the pathogenesis of ADs are largely unknown. Earlier studies from our laboratory in MRL+/+ mice suggested the contribution of oxidative/nitrosative stress in TCE-induced autoimmunity, and N-acetylcysteine (NAC) supplementation provided protection by attenuating oxidative stress. This study was unde...

  6. Mast Cells Contribute to Peripheral Tolerance and Attenuate Autoimmune Vasculitis

    OpenAIRE

    Gan, Poh-Yi; Summers, Shaun A.; Ooi, Joshua D.; O’Sullivan, Kim M.; Tan, Diana S.Y.; Muljadi, Ruth C.M.; Odobasic, Dragana; Kitching, A. Richard; Holdsworth, Stephen R.

    2012-01-01

    Mast cells contribute to the modulation of the immune response, but their role in autoimmune renal disease is not well understood. Here, we induced autoimmunity resulting in focal necrotizing GN by immunizing wild-type or mast cell-deficient (KitW-sh/W-sh) mice with myeloperoxidase. Mast cell-deficient mice exhibited more antimyeloperoxidase CD4+ T cells, enhanced dermal delayed-type hypersensitivity responses to myeloperoxidase, and more severe focal necrotizing GN. Furthermore, the lymph no...

  7. Bioluminescence in vivo imaging of autoimmune encephalomyelitis predicts disease

    OpenAIRE

    Steinman Lawrence; Ho Peggy; Luo Jian; Wyss-Coray Tony

    2008-01-01

    Abstract Background Experimental autoimmune encephalomyelitis is a widely used animal model to understand not only multiple sclerosis but also basic principles of immunity. The disease is scored typically by observing signs of paralysis, which do not always correspond with pathological changes. Methods Experimental autoimmune encephalomyelitis was induced in transgenic mice expressing an injury responsive luciferase reporter in astrocytes (GFAP-luc). Bioluminescence in the brain and spinal co...

  8. AUTOIMMUNE DISEASE DURING PREGNANCY AND THE MICROCHIMERISM LEGACY OF PREGNANCY

    OpenAIRE

    Kristina M Adams Waldorf; Nelson, J. Lee

    2008-01-01

    Pregnancy has both short-term effects and long-term consequences. For women who have an autoimmune disease and subsequently become pregnant, pregnancy can induce amelioration of the mother’s disease, such as in rheumatoid arthritis, while exacerbating or having no effect on other autoimmune diseases like systemic lupus erythematosus. That pregnancy also leaves a long-term legacy has recently become apparent by the discovery that bi-directional cell trafficking results in persistence of fetal ...

  9. Clinical features and management of autoimmune hepatitis

    OpenAIRE

    2008-01-01

    Autoimmune hepatitis (AIH) is a chronic hepatitis of unknown etiology which can progress to cirrhosis. Its clinical manifestations are highly variable and sometimes follow a fluctuating course. Diagnosis is based on characteristic histologic, clinical, biochemical and serological findings. Anti-inflammatory/immunosuppressive treatment frequently induces remission but long-term maintenance therapy is often required. Liver transplantation is generally successful in patients with decompensated c...

  10. Chronic calorie restriction attenuates experimental autoimmune encephalomyelitis

    OpenAIRE

    Piccio, Laura; Stark, Jennifer L.; Cross, Anne H.

    2008-01-01

    Calorie restriction (CR) prevents many age-associated diseases and prolongs the lifespan. CR induces multiple metabolic and physiologic modifications, including anti-inflammatory, antioxidant, and neuroprotective effects that may be beneficial in multiple sclerosis (MS). The present studies sought to determine whether CR or increased calorie intake alters the course of experimental autoimmune encephalomyelitis (EAE), the leading animal model for MS. SJL and C57BL/6 mice were subjected to 40% ...

  11. High Dose Cyclophosphamide Treatment for Autoimmune Disorders

    OpenAIRE

    Brodsky, Robert A.

    2002-01-01

    High-dose cyclophosphamide (200 mg/kg) was initially developed as a conditioning regimen for allogeneic bone marrow transplantation. Recently, high-dose cyclophosphamide without bone marrow transplantation has been employed as a method to induce durable treatment-free remissions in severe aplastic anemia and a variety of other severe autoimmune disorders. The premise underlying this approach is that high-dose cyclophosphamide is maximally immunosuppressive, but not myeloablative. Early hemato...

  12. Clinical features and management of autoimmune hepatitis

    Institute of Scientific and Technical Information of China (English)

    Edward L Krawitt

    2008-01-01

    Autoimmune hepatitis (AIH) is a chronic hepatitis of unknown etiology which can progress to cirrhosis.Its clinical manifestations are highly variable and sometimes follow a fluctuating course.Diagnosis is based on characteristic histologic,clinical,biochemical and serological findings. Anti-inflammatory/immunosuppressive treatment frequently induces remission but long-term maintenance therapy is often required. Liver transplantation is generally successful in patients with decompensated cirrhosis unresponsive to or intolerant of medical therapy.

  13. Antigen and substrate withdrawal in the management of autoimmune thrombotic disorders.

    Science.gov (United States)

    Cines, Douglas B; McCrae, Keith R; Zheng, X Long; Sachais, Bruce S; Luning Prak, Eline T; Siegel, Don L

    2012-11-15

    Prevailing approaches to manage autoimmune thrombotic disorders, such as heparin-induced thrombocytopenia, antiphospholipid syndrome and thrombotic thrombocytopenic purpura, include immunosuppression and systemic anticoagulation, though neither provides optimal outcome for many patients. A different approach is suggested by the concurrence of autoantibodies and their antigenic targets in the absence of clinical disease, such as platelet factor 4 in heparin-induced thrombocytopenia and β(2)-glycoprotein-I (β(2)GPI) in antiphospholipid syndrome. The presence of autoantibodies in the absence of disease suggests that conformational changes or other alterations in endogenous protein autoantigens are required for recognition by pathogenic autoantibodies. In thrombotic thrombocytopenic purpura, the clinical impact of ADAMTS13 deficiency caused by autoantibodies likely depends on the balance between residual antigen, that is, enzyme activity, and demand imposed by local genesis of ultralarge multimers of von Willebrand factor. A corollary of these concepts is that disrupting platelet factor 4 and β(2)GPI conformation (or ultralarge multimer of von Willebrand factor oligomerization or function) might provide a disease-targeted approach to prevent thrombosis without systemic anticoagulation or immunosuppression. Validation of this approach requires a deeper understanding of how seemingly normal host proteins become antigenic or undergo changes that increase antibody avidity, and how they can be altered to retain adaptive functions while shedding epitopes prone to elicit harmful autoimmunity. PMID:22966172

  14. Juvenile autoimmune hepatitis: Spectrum of the disease

    Institute of Scientific and Technical Information of China (English)

    Giuseppe; Maggiore; Silvia; Nastasio; Marco; Sciveres

    2014-01-01

    Juvenile autoimmune hepatitis(JAIH) is a progressive inflammatory liver disease, affecting mainly young girls, from infancy to late adolescence, characterized by active liver damage, as shown by high serum activity of aminotransferases, by elevated immunoglobulin G levels, high titers of serum non organ-specific andorgan-specific autoantibodies, and by interface hepatitis on liver biopsy. It is a multifactorial disease of unknown etiology in which environmental factors act as a trigger in genetically predisposed individuals. Two types of JAIH are identified according to the autoan-tibody panel detected at diagnosis: AIH-1, characterized by the presence of anti-smooth muscle antibody and/or antinuclear antibody and AIH-2, by anti-liver-kidney microsomal antibody type 1 and/or by the presence of anti-liver cytosol type 1 antibody. Epidemiological distribution, genetic markers, clinical presentation and pattern of serum cytokines differentiate the two types of AIH suggesting possible pathogenetic mechanisms. The most effective therapy for AIH is pharmacological suppression of the immune response. Treatment should be started as soon as the diagnosis is made to avoid severe liver damage and progression of fibrosis. The aim of this review is to outline the most significant and peculiar features of JAIH, based largely on our own personal database and on a review of current literature.

  15. Autoimmune liver serology: Current diagnostic and clinical challenges

    Directory of Open Access Journals (Sweden)

    Dimitrios P Bogdanos, Pietro Invernizzi, Ian R Mackay, Diego Vergani

    2008-06-01

    Full Text Available Liver-related autoantibodies are crucial for the correct diagnosis and classification of autoimmune liver diseases (AiLD, namely autoimmune hepatitis types 1 and 2 (AIH-1 and 2, primary biliary cirrhosis (PBC, and the sclerosing cholangitis variants in adults and children. AIH-1 is specified by anti-nuclear antibody (ANA and smooth muscle antibody (SMA. AIH-2 is specified by antibody to liver kidney microsomal antigen type-1 (anti-LKM1 and anti-liver cytosol type 1 (anti-LC1. SMA, ANA and anti-LKM antibodies can be present in de-novo AIH following liver transplantation. PBC is specified by antimitochondrial antibodies (AMA reacting with enzymes of the 2-oxo-acid dehydrogenase complexes (chiefly pyruvate dehydrogenase complex E2 subunit and disease-specific ANA mainly reacting with nuclear pore gp210 and nuclear body sp100. Sclerosing cholangitis presents as at least two variants, first the classical primary sclerosing cholangitis (PSC mostly affecting adult men wherein the only (and non-specific reactivity is an atypical perinuclear antineutrophil cytoplasmic antibody (p-ANCA, also termed perinuclear anti-neutrophil nuclear antibodies (p-ANNA and second the childhood disease called autoimmune sclerosing cholangitis (ASC with serological features resembling those of type 1 AIH. Liver diagnostic serology is a fast-expanding area of investigation as new purified and recombinant autoantigens, and automated technologies such as ELISAs and bead assays, become available to complement (or even compete with traditional immunofluorescence procedures. We survey for the first time global trends in quality assurance impacting as it does on (1 manufacturers/purveyors of kits and reagents, (2 diagnostic service laboratories that fulfill clinicians’ requirements, and (3 the end-user, the physician providing patient care, who must properly interpret test results in the overall clinical context.

  16. Autoimmune liver serology: Current diagnostic and clinical challenges

    Institute of Scientific and Technical Information of China (English)

    Dimitrios P Bogdanos; Pietro Invernizzi; Ian R Mackay; Diego Vergani

    2008-01-01

    Liver-related autoantibodies are crucial for the correct diagnosis and classification of autoimmune liver diseases (AiLD), namely autoimmune hepatitis types 1 and 2 (AIH-1 and 2), primary biliary cirrhosis (PBC),and the sclerosing cholangitis variants in adults and children.AIH-1 is specified by anti-nuclear antibody (ANA) and smooth muscle antibody (SMA). AIH-2 is specified by antibody to liver kidney microsomal antigen type-1 (anti-LKM1) and anti-liver cytosol type 1 (anti-LC1).SMA,ANA and anti-LKM antibodies can be present in de-novo AIH following liver transplantation.PBC is specified by antimitochondrial antibodies (AMA) reacting with enzymes of the 2-oxo-acid dehydrogenase complexes (chiefly pyruvate dehydrogenase complex E2 subunit) and disease-specific ANA mainly reacting with nuclear pore gp210 and nuclear body sp100. Sclerosing cholangitis presents as at least two variants,first the classical primary sclerosing cholangitis (PSC) mostly affecting adult men wherein the only (and nonspecific) reactivity is an atypical perinuclear antineutrophil cytoplasmic antibody (p-ANCA),also termed perinuclear anti-neutrophil nuclear antibodies (p-ANNA) and second the childhood disease called autoimmune sclerosing cholangitis (ASC) with serological features resembling those of type 1 AIH.Liver diagnostic serology is a fast-expanding area of investigation as new purified and recombinant autoantigens,and automated technologies such as ELISAs and bead assays,become available to complement (or even compete with) traditional immunofluorescence procedures.We survey for the first time global trends in quality assurance impacting as it does on (1) manufacturers/purveyors of kits and reagents,(2) diagnostic service laboratories that fulfill clinicians'requirements, and (3) the end-user,the physician providing patient care,who must properly interpret test results in the overall clinical context.

  17. Concurrent autoimmune hepatitis and grave′s disease in Hepatitis C during pegylated Interferon α-2a and ribavirin therapy

    OpenAIRE

    Trikudanathan, Guru V.; Imad Ahmad; Israel, Jonathan L

    2011-01-01

    Classical interferon-α has been shown to be associated with the development of a variety of autoimmune disorders. A 34-year-old white woman with chronic hepatitis C virus infection who was treated with pegylated interferon α-2a and ribavirin, developed Grave's disease and autoimmune hepatitis (AIH) at 32 and 44 weeks, respectively, following initiation of the therapy. The diagnosis of AIH was made based on the new development of anti-smooth muscle antibodies, anti-mitochondrial antibodies, an...

  18. Autoimmune myasthenia gravis.

    Science.gov (United States)

    Jayawant, Sandeep; Parr, Jeremy; Vincent, Angela

    2013-01-01

    Myasthenia gravis in children can be generalized or ocular, and associated with antibodies to acetylcholine receptors or muscle-specific kinase, but it can be negative for those antibodies (seronegative). It needs to be distinguished from congenital myasthenic syndromes and other neuromuscular diseases. In the perinatal period, transient neonatal myasthenia and arthrogryposis multiplex congenita, due to maternal antibodies, need to be considered. Juvenile myasthenia is similar in presentation and treatment to that in adults. Here we present guidelines for recognition, diagnosis, and treatment. PMID:23622368

  19. Induction of autoimmune disease by radiation exposure. Analysis of molecular structure of myeloperoxidase in neutrophil

    International Nuclear Information System (INIS)

    Recently, antineutrophil cytoplasmic antibody (ANCA) that is one of autoimmune antibodies has been paid attention since the antibody was found in patients with articular rheumatism. Molecular structure of myeloperoxidase (MPO), which has been regarded as the antigen of ANCA was investigated in this study. Peripheral neutrophil was exposed to γ-ray at 10 and 30 Gy followed by addition of cytochalasin B. The extracellular and intracellular activities of MPO were determined to estimate the effects of the radiation. Moreover, MPO released to the culture medium was purified from the crude extract of the medium and investigated by Western blot analysis to confirm the occurrence of molecular cleavage in MPO. The releasing activity of MPO was decreased by γ-ray exposure at a dose ranging from 0.1 to 1.0 Gy and it tended to increase with 10 or 30 Gy. On the other hand, the activity of the released enzyme was increased by exposure at 0.1-3.0 Gy and became the normal level with 10 or 30 Gy. There were no changes in the SDS-PAGE pattern for the proteins from neutrophils. Western blotting revealed that 30 kDa fragment was included in the proteins released from neutrophils exposed to 0.1-0.3 Gy. The evidence that a low dose exposure induced such fragmentation of MPO molecule would be utilized to evaluate the effects of low-dose radiation. These results suggested that the MPO molecule fragmented by radiation exposure is highly reactive with the autoantibody in neutrophils, but correlation between MPO and its ANCA- related autoimmune disease has not yet demonstrated. (M.N.)

  20. AUTOIMMUNE CYTOPENIAS IN CHRONIC LYMPHOCYTIC LEUKEMIA, FACTS AND MYTHS

    Directory of Open Access Journals (Sweden)

    Pavankumar Tandra

    2013-11-01

    Full Text Available CLL has been defined as presence of more than 5000 small mature appearing monoclonal B lymphocytes with a specific immunophenotype in peripheral blood. It is a well-known fact that CLL is associated with autoimmune cytopenias. CLL cells are CD5+ B lymphocytes, and usually are not the “guilty” cells which produce autoantibodies. T cell defect is another characteristic of CLL and the total number of T cells is increased, and there is inversion of the CD4/CD8 ratio. Autoimmune hemolytic anemia (AIHA is the most common autoimmune complication of CLL and has been reported in 10-25% of CLL patients. However, the stage-adjusted estimated rate of AIHA in CLL is about 5%. Conversely, CLL is three times more common in patients who present with AIHA. Direct agglutinin test (DAT is positive in 7-14% of CLL patients but AIHA may also occur in DAT negative patients. Autoimmune thrombocytopenia (AIT is the second most common complication of CLL and has been reported in 2-3% of patients. DAT is positive in AIT but presence of antiplatelet antibodies is neither diagnostic nor reliable. Autoimmune neutropenia (AIN and pure red cell aplasia (PRCA are very rare complications of CLL and like other autoimmune complications of CLL may occur at any clinical stage. It is believed that most case reports of AIN and PRCA in CLL actually belong to large granular lymphocytic leukemia (LGL. Non-hematologic autoimmune complications of CLL including cold agglutinin disease (CAD, paraneoplastic pemphigus (PNP, acquired angioedema, and anti-myelin associated globulin are rare. Before starting any treatment, clinicians should distinguish between autoimmune cytopenias and massive bone marrow infiltration since autoimmune complications of CLL are not necessarily equal to advanced disease with poor prognosis. According to IWCLL guideline, steroids are the mainstay of treatment of simple autoimmunity. Intravenous immunoglobulin (IVIg, cyclosporine, and rituximab are used in

  1. Serum autoantibodies and the diagnosis of type-1 autoimmune hepatitis in Italy: a reappraisal at the light of hepatitis C virus infection.

    OpenAIRE

    Cassani, F; Muratori, L; Manotti, P; Lenzi, M; FUSCONI, M.; G. Ballardini; Selleri, L; Volta, U; Zauli, D; Miniero, R

    1992-01-01

    Antinuclear antibodies with the homogeneous pattern (ANA-H) and smooth muscle antibodies with antiactin specificity (SMA-AA) are regarded as the serum markers of type-1 autoimmune chronic hepatitis. Their diagnostic relevance, however, has been questioned recently after the detection of signs of hepatitis C virus infection in autoimmune chronic hepatitis patients. To further evaluate this point, antihepatitis C virus antibodies were sought by two second generation assays (ELISA 2 and RIBA 2) ...

  2. Clinical aspects of indirect immunofluorescence for autoimmune diseases.

    Science.gov (United States)

    Ghanadan, Alireza; Saghazadeh, Amene; Jahanzad, Issa; Rezaei, Nima

    2015-05-01

    Because the most common term used in conversations considering autoimmunity is autoantibodies, it is well-expected that the indirect immunofluorescence assay, which detects antibodies directed against various antigens, is one of our most impressive techniques for investigating autoimmune diseases (AIDs). Roughly speaking, the current literature corroborates that this immunopathologic investigation means that autoantibodies detection makes a considerable contribution to both diagnostic and prognostic aspects of AIDs in the clinical setting. However, it varies between different AIDs, autoantibodies, ethnicities or detection methodologies. Directly focusing on the indirect immunofluorescence assay, we present evidence to support this multidimensional variation regarding the subject via reviewing briefly the best-investigated autoantibodies in the well-documented AIDs, including vasculitis, inflammatory bowel disease, scleroderma, autoimmune hepatitis, primary biliary cirrhosis, systemic lupus erythematosus and Sjögren's syndrome. PMID:25786676

  3. Autoimmune diagnostics: the technology, the strategy and the clinical governance.

    Science.gov (United States)

    Bizzaro, Nicola; Tozzoli, Renato; Villalta, Danilo

    2015-02-01

    In recent years, there has been a profound change in autoimmune diagnostics. From long, tiring and inaccurate manual methods, the art of diagnostics has turned to modern, rapid and automated technology. New antibody tests have been developed, and almost all autoimmune diseases now have some specific diagnostic markers. The current need to make the most of available economic and human resources has led to the production of diagnostic algorithms and guidelines designated for optimal strategic use of the tests and to increase the diagnostic appropriateness. An important role in this scenario was assumed by the laboratory autoimmunologist, whose task is not only to govern the analytical phase, but also to help clinicians in correctly choosing the most suitable test for each clinical situation and provide consultancy support. In this review, we summarize recent advances in technology, describe the diagnostic strategies and highlight the current role of the laboratory autoimmunologist in the clinical governance of autoimmune diagnostics. PMID:25398640

  4. Thyroid Antibodies

    Science.gov (United States)

    ... be limited. Home Visit Global Sites Search Help? Thyroid Antibodies Share this page: Was this page helpful? Also known as: Thyroid Autoantibodies; Antithyroid Antibodies; Antimicrosomal Antibody; Thyroid Microsomal Antibody; ...

  5. Flagellin induces antibody responses through a TLR5- and inflammasome-independent pathway1

    OpenAIRE

    López-Yglesias, Américo Harry; Zhao, Xiaodan; Ellen K Quarles; Lai, Marvin A.; VandenBos, Tim; Strong, Roland K.; Smith, Kelly D.

    2014-01-01

    Flagellin is a potent immunogen that activates the innate immune system via TLR5 and Naip5/6, and generates strong T and B cell responses. The adaptor protein MyD88 is critical for signaling by TLR5, as well as IL-1 and IL-18 receptors, major downstream mediators of the Naip5/6 Nlrc4-inflammasome. Herein we define roles of known flagellin receptors and MyD88 in antibody responses generated towards flagellin. We used mice genetically deficient in flagellin recognition pathways to characterize ...

  6. Study of proton spin-lattice relaxation variation induced by paramagnetic antibodies

    International Nuclear Information System (INIS)

    A murine anti-human melanoma monoclonal antibody fragment was labeled with gadolinium and its proton relaxation efficiency compared to controls at frequencies ranging from 2 to 300 MHz. Relaxation time variations were about 30-40% in 10-15 microM solutions. The labeled fragment showed proton relaxation enhancement relative to free gadolinium, while preserving its immunoreactivity. A tentative labeling of a melanoma pellet by means of the fragment, just at the borderline of a minimum expected T1 variation, gave no detectable difference

  7. Persistence of Yellow Fever vaccine-induced antibodies after cord blood stem cell transplant.

    Science.gov (United States)

    Avelino-Silva, Vivian Iida; Freire, Marcos da Silva; Rocha, Vanderson; Rodrigues, Celso Arrais; Novis, Yana Sarkis; Sabino, Ester C; Kallas, Esper Georges

    2016-04-01

    We report the case of a cord blood haematopoietic stem cell transplant recipient who was vaccinated for Yellow Fever (YF) 7 days before initiating chemotherapy and had persistent YF antibodies more than 3 years after vaccination. Since the stem cell donor was never exposed to wild YF or to the YF vaccine, and our patient was not exposed to YF or revaccinated, this finding strongly suggests the persistence of recipient immunity. We briefly discuss potential consequences of incomplete elimination of recipient's leukocytes following existing haematopoietic cancer treatments. PMID:26618995

  8. Evaluation of the effects of dexamethasone-induced stress on levels of natural antibodies in immunized laying hens.

    Science.gov (United States)

    Cecchini, Stefano; Rossetti, Michele; Tomaso, Francesco Di; Caputo, Anna Rocchina

    2016-09-01

    Natural antibodies (NAb) are an important humoral component of innate immunity, playing a pivotal role as first line of defence against pathogens even without prior antigen-specific activation or antigen-driven selection. The levels of NAb in plasma of young laying hens were explored in more detail and identified 2,4,6-trinitrophenyl bovine serum albumin (TNP-BSA), as the non-self antigen showing the highest levels of IgΥ- and IgM-NAb. Subsequently, the relation between specific antibody (SpAb) levels and NAb levels, and the effect of dexamethasone (DEX)-induced stress on the acquired Ab response and on NAb levels were examined. According to obtained results, the affinity of NAb and SpAb, measured using the thiocyanate elution method, resulted higher in SpAb than in NAb. After stress induction, IgM-NAb and SpAb levels showed a transient decrease, whereas the levels of IgΥ-NAb were not changed. Moreover, statistical analysis showed positive correlations between IgΥ- and IgM-NAb levels and between IgM-NAb and SpAb levels that are lost as stress has been induced, whereas no correlation was observed between IgΥ-NAb and SpAb levels, neither before nor after the DEX-administration. This indicates that IgM-NAb assessment could be a valid tool to estimate the potential of the acquired Ab response and that the dexamethasone-induced stress condition causes depression of IgM-NAb levels and the acquired Ab response, but it has no evaluable effects on IgΥ-NAb levels. PMID:27436442

  9. Autoimmune Thyroid Diseases in Children

    OpenAIRE

    Francesca Crea; Carla Bizzarri; Marco Cappa

    2011-01-01

    The two major autoimmune thyroid diseases (ATDs) include Graves' disease (GD) and autoimmune thyroiditis (AT); both of which are characterized by infiltration of the thyroid by T and B cells reactive to thyroid antigens, by the production of thyroid autoantibodies and by abnormal thyroid function (hyperthyroidism in GD and hypothyroidism in AT). While the exact etiology of thyroid autoimmunity is not known, it is believed to develop when a combination of genetic susceptibility and environment...

  10. IFN-γ licenses CD11b(+) cells to induce progression of systemic lupus erythematosus.

    Science.gov (United States)

    Shaabani, Namir; Honke, Nadine; Dolff, Sebastian; Görg, Boris; Khairnar, Vishal; Merches, Katja; Duhan, Vikas; Metzger, Sabine; Recher, Mike; Barthuber, Carmen; Hardt, Cornelia; Proksch, Peter; Häussinger, Dieter; Witzke, Oliver; Lang, Philipp A; Lang, Karl S

    2015-08-01

    Autoantibodies are a hallmark of autoimmune diseases, such as rheumatoid arthritis, autoimmune hepatitis, and systemic lupus erythematosus (SLE). High titers of anti-nuclear antibodies are used as surrogate marker for SLE, however their contribution to pathogenesis remains unclear. Using murine model of SLE and human samples, we studied the effect of immune stimulation on relapsing of SLE. Although autoantibodies bound to target cells in vivo, only additional activation of CD8(+) T cells converted this silent autoimmunity into overt disease. In mice as well as in humans CD8(+) T cells derived IFN-γ enhanced expression of Fc-receptors on CD11b(+) cells. High expression of Fc-receptors allowed CD11b(+) cells to bind to antibody covered target cells and to destroy them in vivo. We found that autoantibodies induce clinically relevant disease when adaptive immunity, specific for disease non-related antigen, is activated. PMID:26094774

  11. Occurrence and properties of antibodies against virus-associated transformation proteins in radiation-induced osteosarcomas in mice

    International Nuclear Information System (INIS)

    In this thesis it was looked if there is an immunresponse against such viral oncogene products in mice with radiation-induced osteosarcomas. Sera from mice with transplantable radiation-induced osteosacomas showed strong cytotoxicity against cells from a Moloney sarcoma virus-induced tumor and to a smaller extent also against FBJ osteosarcoma virus-transformed nonproducer cells. The cytotoxic activity was bound to the IgM fraction of the sera. Immunprecipitation of 35S-methionine labelled virus- or radiation-transformed cells with cytotoxic sera showed on PAGE two proteins of molecular weights (m.w.) of about 50-55 kD. A protein of about 38 kD was expressed only in transformed cells whereas another protein of about 43 kD was seen in all cells except in uninfected muscle cells of adult mice. In order to further characterize the nature of these antigens immunprecipitates with unlabelled cells were tested in a protein kinase assay with gamma 32P ATP and analysed on PAGE. Phosphorylation of proteins occured predominantly of more than 70 kD m.w., of about 68 kD, 50-55 kD and to a lesser extent also of about 32, 34 and 39 kD. The phosphorylation site of the proteins was at serine and threonine residues. These results indicate that mice with radiation-induced osteosarkomas develop antibodies against 'in vivo' and 'in vitro'-sarcoma virus transformed cells. (orig./MG)

  12. Effects of antibodies induced by a conjugate vaccine on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone absorptive transport, metabolism, and proliferation of human lung cells.

    Science.gov (United States)

    De Buck, Stefan S; Schellenberger, Mario T; Ensch, Corinne; Muller, Claude P

    2010-08-01

    One of the most abundant and potent lung carcinogen is the nicotine-derived tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The monoclonal antibody P9D5 induced with a NNK-conjugate vaccine was used to investigate the ability of NNK-specific antibodies to modulate NNK-induced adverse effects as well as its absorptive transport and metabolism in two lung cancer cell lines (Calu-3 and NCI-H82). Transport experiments in Calu-3 cells with a 50-fold molar excess of apical P9D5 increased the recovery of coadministered apical NNK, with a concomitant decrease in NNK transepithelial transport of more than 50% compared to controls. In contrast, basolateral P9D5 did neither influence transepithelial transport of NNK nor its disappearance from the apical compartment. Calu-3 cells were also found to reduce NNK to NNAL and a 65-fold molar excess of NNK-specific antibody inhibited this metabolic conversion by 46 and 54% compared to irrelevant control antibody after 48 and 72 hr, respectively. The biological relevance of NNK redistribution by antibody was demonstrated by reversion of NNK-induced cell proliferation in NCI-H82 cells. Repartitioning of tobacco carcinogens by antibody may reduce their early effective peak concentrations in susceptible target organs and thus relieve overloaded local DNA repair mechanisms and diminish carcinogen-induced cell proliferation. These in vitro data therefore suggest that a prophylactic antibody response may be associated with a reduced risk of cancer. PMID:19960439

  13. Enhanced Innate Inflammation Induced by Anti-BTLA Antibody in Dual Insult Model of Hemorrhagic Shock/Sepsis.

    Science.gov (United States)

    Cheng, Tingting; Bai, Jianwen; Chung, Chun-Shiang; Chen, Yaping; Biron, Bethany M; Ayala, Alfred

    2016-01-01

    Sepsis following hemorrhagic shock is a common clinical condition, in which innate immune system suffers from severe suppression. B and T lymphocyte attenuator (BTLA) is an immune-regulatory coinhibitory receptor expressed not only on adaptive, but also on innate immune cells. Our previous data showed that BTLA gene deficient mice were protected from septic mortality when compared with wild-type control C57BL/6 mice. Here, we extended our study by treating C57BL/6 mice with an anti-BTLA monoclonal antibody (clone 6A6; reported to have the ability to neutralize or agonize/potentiate BTLA signaling) in a mouse model of hemorrhagic shock (Hem) followed by sepsis induced by cecal ligation and puncture (CLP); positing initially that if BTLA engagement was neutralized, like gene deficiency, an anti-BTLA mAb would have the similar effects on the inflammatory response/morbidity in these mice after such insults. Here, we report that BTLA expression is elevated on innate immune cells after Hem/CLP. However, anti-BTLA antibody treatment increased cytokine (TNF-α, IL-12, IL-10)/chemokine (KC, MIP-2, MCP-1) levels and inflammatory cells (neutrophils, macrophages, dendritic cells) recruitment in the peritoneal cavity, which in turn aggravated organ injury and elevated these animals' mortality in Hem/CLP. When compared with the protective effects of our previous study using BTLA gene deficient mice in a model of lethal septic challenge, we further confirmed BTLA's contribution to enhanced innate cell recruitment, elevated IL-10 levels, and reduced survival, and that engagement of antibody with BTLA potentiates/exacerbates the pathophysiology in Hem/sepsis. PMID:26674453

  14. Lack of specific association between gastric autoimmunity hallmarks and clinical presentations of atrophic body gastritis

    Institute of Scientific and Technical Information of China (English)

    Bruno Annibale; Edith Lahner; Riccardo Negrini; Flavia Baccini; Cesare Bordi; Bruno Monarca; Gianfranco Delle Fave

    2005-01-01

    AIM: To investigate the possible relationships between gastric autoimmune phenomena and clinical presentations of this disorder, in consecutive atrophic body gastritis patients.METHODS: A total of 140 atrophic body gastritis patients,diagnosed as consecutive outpatients presenting with macrocytic or iron deficiency anemia, or longstanding dyspepsia underwent gastroscopy with antral and body biopsies, assay of intrinsic factor, parietal cells and Helicobacter pylori(H pylori) antibodies. Gastritis was assessed according to Sydney System.RESULTS: Parietal cell antibodies were equally distributed in all clinical presentations, whereas the positivity of intrinsic factor antibodies (49/140, 35%) was significantly higher in pernicious anemia patients (49.2%) than in iron deficiency (21.1%) and dyspeptic patients (27.8%). No specific pattern of autoantibodies was related to the clinical presentations of atrophic body gastritis. A positive correlation was obtained between the body atrophy score and the intrinsic factor antibody levels (r = 0.2216,P = 0.0085). Associated autoimmune diseases were present in 25/140 (17.9%) patients, but the prevalence of autoimmune diseases was comparable, irrespective of the clinical presentations.CONCLUSION: The so-called hallmarks of gastric autoimmunity, particularly in intrinsic factor antibody cannot be usefully employed in defining an autoimmune pattern in the clinical presentations of ABG.

  15. Psychiatric manifestations of autoimmune diseases – diagnostic and therapeutic problems [Zaburzenia psychiczne w chorobach autoimmunologicznych – problemy diagnostyczno-terapeutyczne

    Directory of Open Access Journals (Sweden)

    Celińska-Löwenhoff, Magdalena

    2012-12-01

    Full Text Available In autoimmune diseases, also called connective tissue diseases, many systems and organs are involved, including the central, peripheral and autonomic nervous system. The frequency of neurological and neuropsychiatric manifestations varies in certain autoimmune diseases. One of the most common causes of these symptoms are vascular pathologies, including inflammatory and thrombotic, immunologic and atherosclerotic changes. Neuropsychiatric complications may present as a single symptom or might form a syndrome. In a particular patient, a syndrome might change its form in time, presenting itself as a different syndrome. Quite a lot of these symptoms are not a result of a disease itself but its treatment, metabolic abnormalities, arterial hypertension or infection. Steroids play a particular role in the induction of these complications.The role of increasingly used biological agents is uncertain. The most frequent psychiatric manifestations of the connective tissue diseases are: benign behavioural changes, emotional instability and sleep impairment. Neuropsychiatric symptoms are most frequently seen in systemic lupus erythematosus (up to 80% of these patients, particularly with the co-existent antiphospholipidsyndrome. Psychoses with or without seizures are included in the diagnostic criteria of the disease. A separate clinical problem is an induction of a synthesis of autoantiobodies by some drugs, including psychiatric drugs. These antibodies induce clinical symptoms of an autoimmune disease only in some patients, most frequently the symptoms of lupus erythematous, co called: drug induced lupus, including arthralgia, myalgia, fever, skin lesions and serositis. The diagnosis and treatment of psychiatric complications of autoimmune diseases is quite complicated. It is extremely important to distinguish whether a particular symptom is primary to the disease itself or secondary to its treatment. The most important recommendations are treatment of the

  16. P15: The expression of Tc17 cells in thymoma accompany with autoimmune diseases or autoimmune disorders

    Science.gov (United States)

    Zhang, Peng

    2015-01-01

    Background Thymoma is thymic epithelial cell tumor. Studies have shown that thymoma associated with autoimmune disorders and possible mechanisms of autoimmune diseases is the central immune tolerance and peripheral tolerance obstacles have resulted in the breaking of the autoimmune response activation and immune tolerance. Tc17 cells and Th17 cells have been shown play an important role in tumor and autoimmune diseases’ development process. This study test the distribution of Tc17cells in thymoma and the expression of RORγt in thymus of thymoma patients with myasthenia gravis (MG) or other autoimmune diseases, the frequency of Th17/Tc17 in PBMCs, to explore the expression of Th17/Tc17 cells in thymoma accompany with autoimmune diseases or autoimmune disorders. Methods In this study, grouped as follows: (I) thymoma non gravis group (Tm groups); (II) thymoma with MG group thymoma with MG (MG group); (III) thymoma with MG associated with other autoimmune diseases group or anti- nuclear antibodies abnormal elevation of the group (AD group), to analyze the basic differences between the groups. In this study, we examined the RT-PCR to detect RORγt in the thymoma tissue, immunohistochemical double staining method to detect Tc17 cells expression and localization in the thymoma tissue distribution expression Th17/Tc17 in PBMCs by flow cytometry [Interleukin (IL)-17-producing CD8+ cells as Thl7 cells and IL-17-producing CD4+ cells as Tcl7 cells], analysis of differential expression of three in each group thymoma; and explore of Th17/Tc17 expression. Results (I) Tm groups and AD group serum CD8+ cells was statistically significant (PTc17 cells in MG/AD group was significantly higher than that in Tm, was statistically significant (PTc17 cells have risen trend in Tm groups and MG/AD group. Conclusions (I) CD8+ cells, CD4+/CD8+ T ratio, immunoglobulin, CRP and complement C3 levels can be used as indicators of evaluation of the role of the immune status of patients with

  17. A TRANSIENT DRUG INDUCED LUPUS ERYTHEMATOSUS- LIKE ALLERGIC DRUG REACTION WITH MULTIPLE ANTIBODIES

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    Ana Maria Abreu Velez

    2013-10-01

    Full Text Available Drug reactions may mimic several dermatoses, including lupus erythematosus. We present an 80 year old female patient on multiple medications, who presented with blisters on her hands and arms for two weeks, which then generalized to the rest of her body. The patient was evaluated by a dermatologist, and biopsies for hematoxylin and eosin (H&E examination, as well as for direct immunofluorescence (DIF and immunohistochemistry (IHC were performed. The H&E biopsy examination revealed a mild, superficial, perivascular dermal infiltrate of lymphocytes, histiocytes and abundant eosinophils; neutrophils were rare. No vasculitis was noted. DIF revealed positive basement membrane (BMZ staining, primarily with patchy Complement/C3c and fibrinogen; in addition, strong reactivity to dermal blood vessel was appreciated. Antibodies to cell junction-like structures were also noted in the epidermis and dermis with these two antibodies. IHC using similar immunoglobulins and complement components showed similar patterns. We observed that contrary to lupus erythematosus, neither IgG nor IgM were positive at the BMZ.

  18. Effector Regulatory T Cells Reflect the Equilibrium between Antitumor Immunity and Autoimmunity in Adult T-cell Leukemia.

    Science.gov (United States)

    Ureshino, Hiroshi; Shindo, Takero; Nishikawa, Hiroyoshi; Watanabe, Nobukazu; Watanabe, Eri; Satoh, Natsuko; Kitaura, Kazutaka; Kitamura, Hiroaki; Doi, Kazuko; Nagase, Kotaro; Kimura, Hiromi; Samukawa, Makoto; Kusunoki, Susumu; Miyahara, Masaharu; Shin-I, Tadasu; Suzuki, Ryuji; Sakaguchi, Shimon; Kimura, Shinya

    2016-08-01

    The regulatory T cells (Treg) with the most potent immunosuppressive activity are the effector Tregs (eTreg) with a CD45RA(-)Foxp3(++)CCR4(+) phenotype. Adult T-cell leukemia (ATL) cells often share the Treg phenotype and also express CCR4. Although mogamulizumab, a monoclonal antibody to CCR4, shows marked antitumor effects against ATL and peripheral T-cell lymphoma, concerns have been raised that it may induce severe autoimmune immunopathology by depleting eTregs. Here, we present case reports for two patients with ATL who responded to mogamulizumab but developed a severe skin rash and autoimmune brainstem encephalitis. Deep sequencing of the T-cell receptor revealed that ATL cells and naturally occurring Tregs within the cell population with a Treg phenotype can be clearly distinguished according to CADM1 expression. The onset of skin rash and brainstem encephalitis was coincident with eTreg depletion from the peripheral blood, whereas ATL relapses were coincident with eTreg recovery. These results imply that eTreg numbers in the peripheral blood sensitively reflect the equilibrium between antitumor immunity and autoimmunity, and that mogamulizumab might suppress ATL until the eTreg population recovers. Close monitoring of eTreg numbers is crucial if we are to provide immunomodulatory treatments that target malignancy without severe adverse events. Cancer Immunol Res; 4(8); 644-9. ©2016 AACR. PMID:27215229

  19. A simple nonradioactive method for the determination of the binding affinities of antibodies induced by hapten bioconjugates for drugs of abuse.

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    Torres, Oscar B; Antoline, Joshua F G; Li, Fuying; Jalah, Rashmi; Jacobson, Arthur E; Rice, Kenner C; Alving, Carl R; Matyas, Gary R

    2016-02-01

    The accurate analytical measurement of binding affinities of polyclonal antibody in sera to heroin, 6-acetylmorphine (6-AM), and morphine has been a challenging task. A simple nonradioactive method that uses deuterium-labeled drug tracers and equilibrium dialysis (ED) combined with ultra performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) to measure the apparent dissociation constant (K d) of antibodies to 6-AM and morphine is described. The method can readily detect antibodies with K d in the low nanomolar range. Since heroin is rapidly degraded in sera, esterase inhibitors were included in the assay, greatly reducing heroin hydrolysis. MS/MS detection directly measured the heroin in the assay after overnight ED, thereby allowing the quantitation of % bound heroin in lieu of K d as an alternative measurement to assess heroin binding to polyclonal antibody sera. This is the first report that utilizes a solution-based assay to quantify heroin-antibody binding without being confounded by the presence of 6-AM and morphine and to measure K d of polyclonal antibody to 6-AM. Hapten surrogates 6-AcMorHap, 6-PrOxyHap, MorHap, DiAmHap, and DiPrOxyHap coupled to tetanus toxoid (TT) were used to generate high affinity antibodies to heroin, 6-AM, and morphine. In comparison to competition ED-UPLC/MS/MS which gave K d values in the nanomolar range, the commonly used competition enzyme-linked immunosorbent assay (ELISA) measured the 50% inhibition concentration (IC50) values in the micromolar range. Despite the differences in K d and IC50 values, similar trends in affinities of hapten antibodies to heroin, 6-AM, and morphine were observed by both methods. Competition ED-UPLC/MS/MS revealed that among the five TT-hapten bioconjugates, TT-6-AcMorHap and TT-6-PrOxyHap induced antibodies that bound heroin, 6-AM, and morphine. In contrast, TT-MorHap induced antibodies that poorly bound heroin, while TT-DiAmHap and TT-DiPrOxyHap induced antibodies either did not

  20. LEVELS OF BRAIN-SPECIFIC S-100B PROTEIN, SPECIFIC ANTIBODIES AND CYTOKINE PROFILE IN THE PATIENTS WITH ALCOHOL-INDUCED DELIRIUM STATES

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    N. N. Tsybikov

    2008-01-01

    Full Text Available Abstract. Present article deals with our results concerning brain-specific S-100B protein levels, anti-S-100B autoantibodies of IgM and IgG classes, like as cytokine profiles of blood serum and cerebrospinal fluid in the patients with alcohol-induced delirium state. The results obtained provide an evidence of association between alcoholic psychosis and destruction of brain tissue, development of autoimmune reactions and altered cytokine status, thus, probably, resulting into disintegration of immune and neuroendocrine systems.