Sample records for antibody induced autoimmunity

  1. Pregnancy Induced Autoimmune Warm Antibodies Hemolytic Anemia: A Case Report. (United States)

    Laužikienė, D; Ramašauskaitė, D; Lūža, T; Lenkutienė, R


    Background: Autoimmune haemolytic anaemia (AIHA), caused primarily by pregnancy, is poorly described in the literature. There is especially little information on coping with cases that are not responsive to glucocorticoid treatment, monitoring a fetal condition, and identifying fetal haemolytic anaemia as early as possible. Case: A case of pregnancy-induced autoimmune haemolytic anaemia is reported with major problems in differential diagnosis, treatment and the risks posed to both the mother and the fetus. The anaemia went into spontaneous remission of the disease several weeks after delivery. Conclusion: Autoimmune haemolytic anaemia is rarely reported in literature, but can be dangerous for both fetus and mother. It therefore should be described and discussed among obstetricians and gynaecologists, and the etiopathogenesis should be further studied.

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


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


    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 ...

  3. Antiphospholipid antibody syndrome and autoimmune diseases. (United States)

    Ostrowski, Rochella A; Robinson, John A


    The arbitrary division between antiphospholipid antibody syndrome and secondary antiphospholipid antibody syndrome has not proven useful. Antiphospholipid antibodies in the absence of antiphospholipid antibody syndrome often occur as epiphenomena in many autoimmune diseases. They are very common in systemic lupus erythematosus. Antiphospholipid antibody syndrome is a significant comorbidity in lupus but is uncommon in Sjögren's syndrome, rheumatoid arthritis, scleroderma, and systemic vasculitis. Evidence is growing that antiphospholipid antibodies may have a pathogenic role in pulmonary hypertension and accelerated atherosclerosis of autoimmune diseases.

  4. Presence of Autoimmune Antibody in Chikungunya Infection

    Directory of Open Access Journals (Sweden)

    Wirach Maek-a-nantawat


    Full Text Available Chikungunya infection has recently re-emerged as an important arthropod-borne disease in Thailand. Recently, Southern Thailand was identified as a potentially endemic area for the chikungunya virus. Here, we report a case of severe musculoskeletal complication, presenting with muscle weakness and swelling of the limbs. During the investigation to exclude autoimmune muscular inflammation, high titers of antinuclear antibody were detected. This is the report of autoimmunity detection associated with an arbovirus infection. The symptoms can mimic autoimmune polymyositis disease, and the condition requires close monitoring before deciding to embark upon prolonged specific treatment with immunomodulators.

  5. Autoimmune encephalitis: Clinical diagnosis versus antibody confirmation

    Directory of Open Access Journals (Sweden)

    Asha Caroline Cyril


    Full Text Available Context: Autoimmune encephalitis is a heterogeneous disorder which is being diagnosed with increasing frequency. The diagnosis of these disorders is based on the detection of autoantibodies and characteristic clinical profiles. Aims: We aimed to study the antibody profile in encephalitis patients with suspected autoimmune etiology presenting to a tertiary care center. Settings and Design: The subjects were selected by screening all patients with clinical profile suggesting autoimmune encephalitis admitted in the neuromedical intensive care unit (ICU of a tertiary care center in South India. Materials and Methods: Patients who fulfilled modified Zuliani et al.′s, criteria for autoimmune encephalitis were identified during the period December 2009-June 2013. Blood samples from these subjects were screened for six neuronal antibodies. Statistical analysis used: Chi-square test was applied to compare the antibody positive and negative patients. Results: Out of 1,227 patients screened, 39 subjects (14 males: 25 females were identified with a mean age of 15.95 years and 19 cases were assessed in the acute and 20 in the convalescent phase of the illness. Seizure (87.8 % was the most common presenting symptom; status epilepticus occurred in 23 (60.5% patients during the course of the illness. Fourteen (35.9% patients were N-methyl-D-aspartate receptor (NMDAR antibody-positive and all were negative for the other antibodies tested. Conclusions: One-third of patients presenting with acute noninfective encephalitis would be positive for NMDAR antibodies with the remaining two-thirds with clinically suspected autoimmune encephalitis being antibody-negative. There are few markers in the clinical and investigative profiles to distinguish antibody-positive and -negative patients.

  6. 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


    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.

  7. [Autoimmune hepatitis induced by isotretionine]. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Maria Segni


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

  9. Autoimmune/Inflammatory Syndrome Induced by Adjuvants and Thyroid Autoimmunity (United States)

    Watad, Abdulla; David, Paula; Brown, Stav; Shoenfeld, Yehuda


    The autoimmune/inflammatory syndrome induced by adjuvants (ASIA), presented by Shoenfeld and Agmon-Levin in 2011, is an entity that incorporates diverse autoimmune conditions induced by the exposure to various adjuvants. Adjuvants are agents that entail the capability to induce immune reactions. Adjuvants are found in many vaccines and used mainly to increase the response to vaccination in the general population. Silicone has also been reported to be able to induce diverse immune reactions. Clinical cases and series of heterogeneous autoimmune conditions including systemic sclerosis, systemic lupus erythematosus, and rheumatoid arthritis have been reported to be induced by several adjuvants. However, only a small number of cases of autoimmune thyroid disorder have been included under the umbrella of ASIA syndrome. Indeed, clinical cases of Hashimoto’s thyroiditis and/or subacute thyroiditis were observed after the exposure to vaccines as well as silicone implantation. In our review, we aimed to summarize the current knowledge on ASIA syndrome presented as endocrinopathies, focusing on autoimmune thyroid disorders associated with the various adjuvants. PMID:28167927

  10. Propylthiouracil-induced autoimmune disease

    Directory of Open Access Journals (Sweden)

    Santosh Paiaulla


    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. Strategies for Treating Autoimmune Disease With Monoclonal Antibodies


    Wofsy, David


    There is no safe and reliable therapy for most serious autoimmune diseases, such as systemic lupus erythematosus. Severe cases usually require treatment with corticosteroids or cytotoxic drugs or both, which frequently provide inadequate disease control and can cause serious complications. These therapies are not restricted in their effects to cells of the immune system, but rather have a broad range of toxic effects on cells throughout the body. The development of monoclonal antibodies has l...

  12. Delineating liver events in trichloroethylene-induced autoimmune hepatitis. (United States)

    Gilbert, Kathleen M; Przybyla, Beata; Pumford, Neil R; Han, Tao; Fuscoe, James; Schnackenberg, Laura K; Holland, Ricky D; Doss, Jason C; Macmillan-Crow, Lee Ann; Blossom, Sarah J


    Exposure to the environmental pollutant trichloroethylene (TCE) has been linked to autoimmune disease development in humans. Chronic (32-week) low-level exposure to TCE has been shown to promote autoimmune hepatitis in association with CD4(+) T cell activation in autoimmune-prone MRL+/+ mice. MRL+/+ mice are usually thought of as a model of systemic lupus rather than an organ-specific disease such as autoimmune hepatitis. Consequently, the present study examined gene expression and metabolites to delineate the liver events that skewed the autoimmune response toward that organ in TCE-treated mice. Female MRL+/+ mice were treated with 0.5 mg/mL TCE in their drinking water. The results showed that TCE-induced autoimmune hepatitis could be detected in as little as 26 weeks. TCE exposure also generated a time-dependent increase in the number of antibodies specific for liver proteins. The gene expression correlated with the metabolite analysis to show that TCE upregulated the methionine/homocysteine pathway in the liver after 26 weeks of exposure. The results also showed that TCE exposure altered the expression of selective hepatic genes associated with immunity and inflammation. On the basis of these results, future mechanistic studies will focus on how alterations in genes associated with immunity and inflammation, in conjunction with protein alterations in the liver, promote liver immunogenicity in TCE-treated MRL+/+ mice.

  13. The crossroads between cancer immunity and autoimmunity: antibodies to self antigens. (United States)

    Benvenuto, Monica; Mattera, Rosanna; Masuelli, Laura; Tresoldi, Ilaria; Giganti, Maria Gabriella; Frajese, Giovanni Vanni; Manzari, Vittorio; Modesti, Andrea; Bei, Roberto


    The production of autoantibodies to self antigens is dependent on the failure of immune tolerance. Cancer cells express antigens which elicit a spontaneous immune response in cancer patients. The repertoire of autoantibodies found in cancer patients partly covers that of patients with autoimmune diseases. Biological activities of autoantibodies to self antigens may induce paraneoplastic syndromes which reflect the attempt of cancer patients to counteract tumor growth. Autoantibodies with similar specificities may have different effects in cancer and autoimmune disease patients due to different immunological microenvironments. Tregs dysfunction has been observed in patients with paraneoplastic syndromes and/or with autoimmune diseases, while the increase of Tregs has been associated with poor cancer patients prognosis. Novel therapies have employed antibodies against Tregs immune-checkpoint receptors with the aim to boost immune response in cancer patients. The presence of autoantibodies to tumors antigens has also been investigated as a marker for cancer detection and cancer patients prognosis. This report reviews the current knowledge on the analysis and meaning of autoantibodies to self antigens detected in cancer and autoimmune disease patients.

  14. Heparin-Induced Thrombocytopenia Antibody Test (United States)

    ... Global Sites Search Help? Heparin-induced Thrombocytopenia PF4 Antibody Share this page: Was this page helpful? Also known as: Heparin-PF4 Antibody; HIT Antibody; HIT PF4 Antibody; Heparin Induced Antibody; ...

  15. Glutamate receptor antibodies in neurological diseases: anti-AMPA-GluR3 antibodies, anti-NMDA-NR1 antibodies, anti-NMDA-NR2A/B antibodies, anti-mGluR1 antibodies or anti-mGluR5 antibodies are present in subpopulations of patients with either: epilepsy, encephalitis, cerebellar ataxia, systemic lupus erythematosus (SLE) and neuropsychiatric SLE, Sjogren's syndrome, schizophrenia, mania or stroke. These autoimmune anti-glutamate receptor antibodies can bind neurons in few brain regions, activate glutamate receptors, decrease glutamate receptor's expression, impair glutamate-induced signaling and function, activate blood brain barrier endothelial cells, kill neurons, damage the brain, induce behavioral/psychiatric/cognitive abnormalities and ataxia in animal models, and can be removed or silenced in some patients by immunotherapy. (United States)

    Levite, Mia


    Glutamate is the major excitatory neurotransmitter of the Central Nervous System (CNS), and it is crucially needed for numerous key neuronal functions. Yet, excess glutamate causes massive neuronal death and brain damage by excitotoxicity--detrimental over activation of glutamate receptors. Glutamate-mediated excitotoxicity is the main pathological process taking place in many types of acute and chronic CNS diseases and injuries. In recent years, it became clear that not only excess glutamate can cause massive brain damage, but that several types of anti-glutamate receptor antibodies, that are present in the serum and CSF of subpopulations of patients with a kaleidoscope of human neurological diseases, can undoubtedly do so too, by inducing several very potent pathological effects in the CNS. Collectively, the family of anti-glutamate receptor autoimmune antibodies seem to be the most widespread, potent, dangerous and interesting anti-brain autoimmune antibodies discovered up to now. This impression stems from taking together the presence of various types of anti-glutamate receptor antibodies in a kaleidoscope of human neurological and autoimmune diseases, their high levels in the CNS due to intrathecal production, their multiple pathological effects in the brain, and the unique and diverse mechanisms of action by which they can affect glutamate receptors, signaling and effects, and subsequently impair neuronal signaling and induce brain damage. The two main families of autoimmune anti-glutamate receptor antibodies that were already found in patients with neurological and/or autoimmune diseases, and that were already shown to be detrimental to the CNS, include the antibodies directed against ionotorpic glutamate receptors: the anti-AMPA-GluR3 antibodies, anti-NMDA-NR1 antibodies and anti-NMDA-NR2 antibodies, and the antibodies directed against Metabotropic glutamate receptors: the anti-mGluR1 antibodies and the anti-mGluR5 antibodies. Each type of these anti

  16. Reactivity of anti-thyroid antibodies to thyroglobulin tryptic fragments: comparison of autoimmune and non-autoimmune thyroid diseases

    Directory of Open Access Journals (Sweden)

    Boechat L.H.B.


    Full Text Available Studies concerning the antigenicity of thyroglobulin fragments allow the characterization of the epitopes but do not consider the role of heavier antigenic fragments that could result in vivo from the action of endoproteases. Here we assess the relative importance of the fragments obtained from thyroglobulin by limited proteolysis with trypsin and compare by immunoblotting their reactivity to serum from patients with autoimmune (Graves' disease and Hashimoto's thyroiditis and non-autoimmune (subacute thyroiditis disease. The results showed no difference in frequency of recognition of any peptide by sera from patients with autoimmune thyroiditis. In contrast, sera from patients with subacute thyroiditis reacted more frequently with a peptide of 80 kDa. These results suggest the presence of antibody subpopulations directed at fragments produced in vivo by enzymatic cleavage of thyroglobulin. This fragment and antibodies to it may represent markers for subacute thyroiditis.

  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;


    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....


    Directory of Open Access Journals (Sweden)

    Luca Laurenti


    Full Text Available Autoimmune cytopenias are a frequent complication in CLL, occuring in approximately 5-10% of the patients. The most common manifestation is autoimmune haemolytic anaemia, followed by immune thrombocytopaenia and only rarely pure red blood cell aplasia or autoimmune granulocytopaenia. Initial treatment is as for the idiopathic autoimmune cytopenias, with most patients responding to conventional corticosteroid therapy. Patients not responding after 4–6 weeks of conventional therapy should be considered for alternative immunosuppression, monoclonal antibody therapy or splenectomy.   While randomized trials demonstrating the benefit of rituximab in CLL-related autoimmune diseases are still lacking, there are considerable data in the literature that provide evidence for its effectiveness. The monoclonal antibody alemtuzumab also displays considerable activity against both the malignant disease and the autoimmune complication in patients with CLL, although at the expense of greater toxicity. A number of new monoclonal antibodies, such as ofatumumab, GA-101, lumiliximab, TRU-016, epratuzumab, and galiximab, are currently investigated in CLL and their activity in CLL-related autoimmune cytopenias should be evaluated in future studies.

  19. Evaluation of Incidence and Clinical Features of Antibody-Associated Autoimmune Encephalitis Mimicking Dementia

    Directory of Open Access Journals (Sweden)

    Arzu Çoban


    Full Text Available Background. Anti-neuronal autoimmunity may cause cognitive impairment that meets the criteria for dementia. Objective. Our aim was to detect the incidence and clinical features of autoimmune encephalitis imitating clinical findings of primary dementia disorders and to delineate the validity of anti-neuronal antibody screening in dementia patients. Methods. Fifty consecutive patients fulfilling the clinical criteria for primary dementia, 130 control patients, and 50 healthy controls were included. Their sera were investigated for several ion channel and glutamic acid decarboxylase (GAD antibodies by a cell-based assay, radioimmunoassay, and ELISA, as required. Results. Sixteen patients satisfying dementia criteria had atypical findings or findings suggestive of autoimmune encephalitis. N-methyl-D-aspartate receptor (NMDAR antibody was detected in a patient with dementia, Parkinsonism, and REM sleep behavior disorder (RBD fulfilling the criteria for dementia with Lewy bodies (DLB. One control patient with bipolar disease displayed low anti-GAD antibody levels. Conclusions. Our study showed for the first time the presence of parkinsonism and RBD in an anti-NMDAR encephalitis patient mimicking DLB. Although autoimmune encephalitis patients may occasionally present with cognitive decline, most dementia patients do not exhibit anti-neuronal antibodies, suggesting that routine analysis of these antibodies in dementia is not mandatory, even though they display atypical features.

  20. Therapeutic antibodies that target inflammatory cytokines in autoimmune diseases. (United States)

    Lai, Yuping; Dong, Chen


    Inflammatory cytokines are key regulators of immune responses. Persistent and excessive production of inflammatory cytokines underscores the development of autoimmune diseases. Therefore, neutralizing inflammatory cytokines or antagonizing their receptor function is considered as a useful therapeutic strategy to treat autoimmune diseases. To achieve the success of such a strategy, understanding of the complex actions of these cytokines and cytokine networks is required. In this review we focus on four inflammatory cytokines--tumor necrosis factor α (TNFα), interleukin-6 (IL-6), IL-23 and IL-17--and dissect how the dysregulation of these cytokines regulates autoimmune diseases. On the basis of pre-clinical and clinical data, we specifically discuss the therapeutic rationale for targeting these cytokines and describe the potential adverse effects.

  1. Atorvastatin-induced necrotizing autoimmune myositis (United States)

    Troyanov, Yves; Landon-Cardinal, Océane; Fritzler, Marvin J.; Ferreira, José; Targoff, Ira N.; Rich, Eric; Goulet, Michelle; Goulet, Jean-Richard; Bourré-Tessier, Josiane; Robitaille, Yves; Drouin, Julie; Albert, Alexandra; Senécal, Jean-Luc


    Abstract The general aim of this study was to evaluate the disease spectrum in patients presenting with a pure polymyositis (pPM) phenotype. Specific objectives were to characterize clinical features, autoantibodies (aAbs), and membrane attack complex (MAC) in muscle biopsies of patients with treatment-responsive, statin-exposed necrotizing autoimmune myositis (NAM). Patients from the Centre hospitalier de l’Université de Montréal autoimmune myositis (AIM) Cohort with a pPM phenotype, response to immunosuppression, and follow-up ≥3 years were included. Of 17 consecutive patients with pPM, 14 patients had a NAM, of whom 12 were previously exposed to atorvastatin (mean 38.8 months). These 12 patients were therefore suspected of atorvastatin-induced AIM (atorAIM) and selected for study. All had aAbs to 3-hydroxy-3-methylglutaryl coenzyme A reductase, and none had overlap aAbs, aAbs to signal recognition particle, or cancer. Three stages of myopathy were recognized: stage 1 (isolated serum creatine kinase [CK] elevation), stage 2 (CK elevation, normal strength, and abnormal electromyogram [EMG]), and stage 3 (CK elevation, proximal weakness, and abnormal EMG). At diagnosis, 10/12 (83%) patients had stage 3 myopathy (mean CK elevation: 7247 U/L). The presenting mode was stage 1 in 6 patients (50%) (mean CK elevation: 1540 U/L), all of whom progressed to stage 3 (mean delay: 37 months) despite atorvastatin discontinuation. MAC deposition was observed in all muscle biopsies (isolated sarcolemmal deposition on non-necrotic fibers, isolated granular deposition on endomysial capillaries, or mixed pattern). Oral corticosteroids alone failed to normalize CKs and induce remission. Ten patients (83%) received intravenous immune globulin (IVIG) as part of an induction regimen. Of 10 patients with ≥1 year remission on stable maintenance therapy, IVIG was needed in 50%, either with methotrexate (MTX) monotherapy or combination immunosuppression. In the remaining

  2. Primary antiphospholipid antibody syndrome and autoimmune haemolytic anaemia--a rare combination. (United States)

    Suhail, Saera; Baig, Muhammad Shakil; Humail, Syed Mujahid; Riaz, Amir


    Primary Antiphospholipid Antibody Syndrome (PAPS) and Autoimmune haemolytic anemia (AIHA) is a very rare combination. Antiphospholipid Antibody Syndrome (APS) with underlying SLE, however, has a well documented association with Coomb's positive Auoimmune Haemolytic Anaemia. We describe a young girl with PAPS presenting with deep venous thrombosis, livedo reticularis and features of AIHA. The patient was refractory to treatment for 5 years however, her condition improved dramatically with anticoagulants, corticosteroid therapy and the addition of hydroxychloroquine and azathioprin. We have also discussed hydroxychloroquine therapy in PAPS which is not yet fully established and the probability of this patient developing other autoimmune disorders in future.

  3. Lymphocyte Activation Gene-3 (LAG-3 negatively regulates environmentally-induced autoimmunity.

    Directory of Open Access Journals (Sweden)

    Vibha Jha

    Full Text Available Environmental factors including drugs, mineral oils and heavy metals such as lead, gold and mercury are triggers of autoimmune diseases in animal models or even in occupationally exposed humans. After exposure to subtoxic levels of mercury (Hg, genetically susceptible strains of mice develop an autoimmune disease characterized by the production of highly specific anti-nucleolar autoantibodies, hyperglobulinemia and nephritis. However, mice can be tolerized to the disease by a single low dose administration of Hg. Lymphocyte Activation Gene-3 (LAG-3 is a CD4-related, MHC-class II binding molecule expressed on activated T cells and NK cells which maintains lymphocyte homeostatic balance via various inhibitory mechanisms. In our model, administration of anti-LAG-3 monoclonal antibody broke tolerance to Hg resulting in autoantibody production and an increase in serum IgE level. In addition, LAG-3-deficient B6.SJL mice not only had increased susceptibility to Hg-induced autoimmunity but were also unresponsive to tolerance induction. Conversely, adoptive transfer of wild-type CD4(+ T cells was able to partially rescue LAG-3-deficient mice from the autoimmune disease. Further, in LAG-3-deficient mice, mercury elicited higher amounts of IL-6, IL-4 and IFN-γ, cytokines known to play a critical role in mercury-induced autoimmunity. Therefore, we conclude that LAG-3 exerts an important regulatory effect on autoimmunity elicited by a common environmental pollutant.

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

    Directory of Open Access Journals (Sweden)

    Meha Goyal


    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.

  5. Budesonide induces complete remission in autoimmune hepatitis

    Institute of Scientific and Technical Information of China (English)

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


    AIM: Prednisone and azathioprine represent the standard treatment for autoimmune hepatitis (AIH). However, only 65% of the patients enter complete histological remission. Recently, budesonide (BUD) was reported to be a promising alternative. In this study we assessed the efficacy and safety of BUD in AIH.METHODS: Eighteen patients (12 women, 6 men; mean age 45.4±21 years) with AIH were treated with BUD (Budenofalk(R)) 3 mg thrice daily and followed up for at least 24 wk. Seven patients also had features of primary biliary cirrhosis (n = 5) or primary sclerosing cholangitis (n = 2). Advanced liver fibrosis or cirrhosis was present in 6 patients.RESULTS: Fifteen (83%) patients had a complete clinical and biochemical remission. Ten patients, including five with acute hepatitis, were given BUD as first-line therapy, of which seven enter remission. Three patients,two with liver cirrhosis, did not improve. All patients with second-line therapy experienced long-term remission.A histological remission was also seen in three patients.Clinically relevant BUD-induced side effects were recorded only in patients with liver cirrhosis (n = 4).CONCLUSION: BUD is effective in remission induction in the majority of our patients with AIH. Side effects and treatment failure was mainly observed in patients with liver cirrhosis.

  6. 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;


    prevalence than the controls: NISAb: 17% vs 0% (P Hashimoto's thyroiditis (HT) had NISAb, (P ...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...

  7. 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;


    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 ...

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

    Directory of Open Access Journals (Sweden)

    Arkachaisri Thaschawee


    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

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

    Institute of Scientific and Technical Information of China (English)

    Jian Zhang; Xuemei Xu; Yong Liu


    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.

  10. A Unique Case of Autoimmune Retinopathy Associated with Anti-Alpha-Enolase Antibodies

    Directory of Open Access Journals (Sweden)

    Paul A. Kurz


    Full Text Available Background. We report a case of autoimmune retinopathy associated with anti-alpha-enolase antibodies with unique manifestations. Methods. A case report. Results. A 30-year-old male experienced recurrent, primarily peripheral visual field disturbances and minimal photopsia, with interval symptom resolution. Fundus changes subsequently developed in areas corresponding to the previous visual field symptoms. Electroretinogram showed bilaterally symmetric abnormalities of light-adapted responses and suggested loss of photoreceptor function. Only anti-alpha-enolase antibodies were detected on Western blot. Our patient noted cutaneous symptoms at the time of both episodes of visual symptoms, but not in the interim. Biomicroscopy revealed subtle small reddish spots in areas of the peripheral retina corresponding to the areas of the patient’s visual field where he noted symptoms. To our knowledge these reddish spots have not been reported in autoimmune retinopathy and may clinically support in vitro and in vivo evidence that anti-alpha-enolase antibodies may target photoreceptors. Conclusions. Our patient demonstrates some unique features adding to the known characteristics of autoimmune retinopathy associated with anti-alpha-enolase antibodies. As more cases are reported, further understanding of the features and pathophysiology of this rare condition will hopefully be elucidated.

  11. A novel thymoma-associated autoimmune disease: Anti-PIT-1 antibody syndrome (United States)

    Bando, Hironori; Iguchi, Genzo; Okimura, Yasuhiko; Odake, Yukiko; Yoshida, Kenichi; Matsumoto, Ryusaku; Suda, Kentaro; Nishizawa, Hitoshi; Fukuoka, Hidenori; Mokubo, Atsuko; Tojo, Katsuyoshi; Maniwa, Yoshimasa; Ogawa, Wataru; Takahashi, Yutaka


    Anti-PIT-1 antibody syndrome has recently been reported and characterized by acquired growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH) deficiencies associated with autoimmunity to a pituitary specific transcription factor PIT-1, which plays an essential role in GH-, PRL-, and TSH-producing cells. Although circulating anti-PIT-1 antibody and PIT-1-reactive cytotoxic T cells (CTLs) were detected in the patients, the pathophysiology and precise mechanisms for the autoimmunity remain unclarified. During the follow up, thymoma was diagnosed in all 3 cases with anti-PIT-1 antibody syndrome. Immunohistochemical analysis revealed that PIT-1 was strongly expressed in neoplastic cortical thymic epithelial cells. Importantly, after thymectomy, the titer of anti-PIT-1 antibody decreased and reactivity of CTLs toward PIT-1 diminished. These data strongly suggest that the aberrant expression of PIT-1 in the thymoma plays a causal role in the development of this syndrome. Thus, we define that this syndrome is a novel thymoma-associated autoimmune disease. PMID:28216655

  12. The role of rituximab in adults with warm antibody autoimmune hemolytic anemia. (United States)

    Dierickx, Daan; Kentos, Alain; Delannoy, André


    Warm antibody hemolytic anemia is the most common form of autoimmune hemolytic anemia. When therapy is needed, corticosteroids remain the cornerstone of initial treatment but are able to cure only a minority of patients (hemolytic anemia in adults, although no prospective study convincingly supports this attitude. A recent randomized study strongly suggests that in first-line treatment, rituximab combined with steroids is superior to monotherapy with steroids. If this finding is confirmed, rituximab will emerge as a major component of the management of warm antibody hemolytic anemia not only after relapse but as soon as treatment is needed.

  13. An elderly 'kawara' craftsman with acute kidney injury and haemoptysis: a case of silica-induced autoimmunity. (United States)

    Matsui, Satoshi; Tsuji, Hiroko; Ono, Shinji


    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-induced, silicon-induced or silica-induced autoimmunity. The patient had been exposed to silica for > 40 years. The environmental aetiology of autoimmune diseases should be considered in cases that show atypical epidemiology and serology.

  14. Toxin-Induced Autoimmune Hepatitis Caused by Raw Cashew Nuts (United States)

    Stueck, Ashley; Bansal, Meena


    A 64-year-old man with no past medical history presented with abnormally elevated liver enzymes 1 year after developing a diffuse rash thought to be related to eating large quantities of raw cashew nuts. Liver biopsy was performed, which revealed features concerning for drug- or toxin-induced autoimmune hepatitis. The patient began treatment with azathioprine and prednisone, and liver enzymes normalized. We describe a unique case of a toxin-induced autoimmune hepatitis precipitated not by a drug or dietary supplement but by a food product.

  15. Severe autoimmune hemolytic anemia associated with IgM warm auto-antibodies in primary Sjögren's syndrome. (United States)

    Shinoda, Koichiro; Taki, Hirofumi; Hounoki, Hiroyuki; Ogawa, Reina; Sugiyama, Eiji; Tobe, Kazuyuki


    Primary Sjögren's syndrome is an autoimmune disorder involving mainly salivary and lachrymal glands. However, many extraglandular symptoms have also been reported. Although leucocytopenia and lymphocytopenia are frequently observed in hematological disorders, autoimmune hemolytic anemia is rarely reported. We experienced a case of primary Sjögren's syndrome developing severe autoimmune hemolytic anemia. The patient's red blood cells showed spontaneous agglutination in saline at room temperature, and immunoglobulin M (IgM) was detected on the surface of red blood cells by flow cytometry, indicating that autoimmune hemolytic anemia was caused by warm reactive IgM antibodies. Immediate corticosteroid therapy resulted in a dramatic recovery. We report a first case of severe autoimmune hemolytic anemia caused by warm reactive IgM antibodies in primary Sjögren's syndrome.


    AUTOIMMUNITY AS A POSSIBLE MECHANISM OF PROLACTIN-INDUCED PROSTATITIS. RW Luebke, CB Copeland, and LR Bishop. US EPA, Research Triangle Park, NCStoker et al. reported inflammation of the lateral prostate (LP) lobes in 120 day old Wistar rats after manipulation of prolac...

  17. Diagnosis and classification of drug-induced autoimmunity (DIA). (United States)

    Xiao, Xiao; Chang, Christopher


    Since sulfadiazine associated lupus-like symptoms were first described in 1945, certain drugs have been reported to interfere with the immune system and induce a series of autoimmune diseases (named drug-induced autoimmunity, DIA), exemplified by systemic lupus erythematosus (SLE). Among the drugs, procainamide and hydralazine are considered to be associated with the highest risk for developing lupus, while quinidine has a moderate risk, and all other drugs have low or very low risk. More recently, drug-induced lupus has been associated with the use of newer biological modulators, such as tumor necrosis factor (TNF)-alpha inhibitors and cytokines. In addition to lupus, other major autoimmune diseases, including vasculitis and arthritis, have also been associated with drugs. Because resolution of symptoms generally occurs after cessation of the offending drugs, early diagnosis is crucial for treatment strategy and improvement of prognosis. Unfortunately, it is difficult to establish standardized criteria for DIA diagnosis. Diagnosis of DIA requires identification of a temporal relationship between drug administration and the onset of symptoms, but the relative risk with respect to dose and duration for each drug has rarely been determined. DIA is affected by multiple genetic and environmental factors, leading to difficulties in establishing a list of global clinical features that are characteristic of most or all DIA patients. Moreover, the distinction between authentic DIA and unmasking of a latent autoimmune disease also poses challenges. In this review, we summarize the highly variable clinical features and laboratory findings of DIA, with an emphasis on the diagnostic criteria.

  18. A case of autoimmune epilepsy associated with anti-leucine-rich glioma inactivated subunit 1 antibodies manifesting electrical shock-like sensations and transparent sadness

    Directory of Open Access Journals (Sweden)

    Yoshiko Murata


    Full Text Available Autoimmune epilepsy is an isolated phenotype of autoimmune encephalitis, which may be suspected in patients with unexplained adult-onset seizure disorders or resistance to antiepileptic drugs (AEDs. Antibodies against leucine-rich glioma inactivated subunit 1 of the voltage-gated potassium channel (VGKC complex, recently termed anti-LGI-1 antibodies, are one of the causes of autoimmune epilepsies. Bizarre symptoms with extremely short duration and high frequency are clues to the possible presence of autoimmune epilepsy with anti-LGI-1 antibodies. Precise diagnosis is important because autoimmune epilepsy is treatable and the prognosis can be predicted.

  19. A case of autoimmune epilepsy associated with anti-leucine-rich glioma inactivated subunit 1 antibodies manifesting electrical shock-like sensations and transparent sadness. (United States)

    Murata, Yoshiko; Watanabe, Osamu; Taniguchi, Go; Sone, Daichi; Fujioka, Mao; Okazaki, Mitsutoshi; Nakagawa, Eiji; Watanabe, Yutaka; Watanabe, Masako


    Autoimmune epilepsy is an isolated phenotype of autoimmune encephalitis, which may be suspected in patients with unexplained adult-onset seizure disorders or resistance to antiepileptic drugs (AEDs). Antibodies against leucine-rich glioma inactivated subunit 1 of the voltage-gated potassium channel (VGKC) complex, recently termed anti-LGI-1 antibodies, are one of the causes of autoimmune epilepsies. Bizarre symptoms with extremely short duration and high frequency are clues to the possible presence of autoimmune epilepsy with anti-LGI-1 antibodies. Precise diagnosis is important because autoimmune epilepsy is treatable and the prognosis can be predicted.

  20. Evidence of Borrelia autoimmunity-induced component of Lyme carditis and arthritis. (United States)

    Raveche, Elizabeth S; Schutzer, Steven E; Fernandes, Helen; Bateman, Helen; McCarthy, Brian A; Nickell, Steven P; Cunningham, Madeleine W


    We investigated the possibility that manifestations of Lyme disease in certain hosts, such as arthritis and carditis, may be autoimmunity mediated due to molecular mimicry between the bacterium Borrelia burgdorferi and self-components. We first compared amino acid sequences of Streptococcus pyogenes M protein, a known inducer of antibodies that are cross-reactive with myosin, and B. burgdorferi and found significant homologies with OspA protein. We found that S. pyogenes M5-specific antibodies and sera from B. burgdorferi-infected mice reacted with both myosin and B. burgdorferi proteins by Western blots and enzyme-linked immunosorbent assay. To investigate the relationship between self-reactivity and the response to B. burgdorferi, NZB mice, models of autoimmunity, were infected. NZB mice infected with B. burgdorferi developed higher degrees of joint swelling and higher anti-B. burgdorferi immunoglobulin M cross-reactive responses than other strains with identical major histocompatibility complex (DBA/2 and BALB/c). These studies reveal immunological cross-reactivity and suggest that B. burgdorferi may share common epitopes which mimic self-proteins. These implications could be important for certain autoimmunity-susceptible individuals or animals who become infected with B. burgdorferi.

  1. 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


    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.

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

    Directory of Open Access Journals (Sweden)

    Ija Talja


    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.

  3. Detection of antiplatelet antibody in serum and on megakaryocytes of dogs with autoimmune thrombocytopenia. (United States)

    Joshi, B C; Jain, N C


    Blood and bone marrow samples from 13 thrombocytopenic dogs were examined to determine whether immunologic thrombocytopenia existed. Antiplatelet antibody was detected in serum of 8 of the dogs by platelet factor 3 test or its modification. Moderate to strong immunofluorescence of megakaryocytes was noticed in bone marrow smears stained with rabbit anticanine globulin conjugated with fluorescin isothiocyanate. Negative results were obtained with serum and bone marrow samples collected from 6 of the dogs during therapy for autoimmune thrombocytopenia. Clinical and laboratory findings varied in individual patients with circulating antiplatelet antibodies. Thrombocytopenia was present in all the dogs, with platelet counts ranging from less than 3,000 to 20,000/mu1 of blood. Signs of bleeding in tissues and body cavities were present in all dogs, but anemia was evidenced in only 3 dogs. Differential leukocyte counts were variable. Morphologic abnormalities such as vacuolation and reduced or absence of granulation of the cytoplasm and nuclear fragmentation were seen in some megakaryocytes.

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

    DEFF Research Database (Denmark)

    Thygesen, P; Hougen, H P; Christensen, H B;


    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 gly...

  5. LINGO-1 antibody ameliorates myelin impairment and spatial memory deficits in experimental autoimmune encephalomyelitis mice. (United States)

    Sun, Jun-Jun; Ren, Qing-Guo; Xu, Lin; Zhang, Zhi-Jun


    More than 50% of multiple sclerosis patients develop cognitive impairment. However, the underlying mechanisms are still unclear, and there is no effective treatment. LINGO-1 (LRR and Ig domain containing NOGO receptor interacting protein 1) has been identified as an inhibitor of oligodendrocyte differentiation and myelination. Using the experimental autoimmune encephalomyelitis (EAE) mouse model, we assessed cognitive function at early and late stages of EAE, determined brain expression of myelin basic protein (MBP) and investigated whether the LINGO-1 antibody could restore deficits in learning and memory and ameliorate any loss of MBP. We found that deficits in learning and memory occurred in late EAE and identified decreased expression of MBP in the parahippocampal cortex (PHC) and fimbria-fornix. Moreover, the LINGO-1 antibody significantly improved learning and memory in EAE and partially restored MBP in PHC. Furthermore, the LINGO-1 antibody activated the AKT/mTOR signaling pathway regulating myelin growth. Our results suggest that demyelination in the PHC and fimbria-fornix might contribute to cognitive deficits and the LINGO-1 antibody could ameliorate these deficits by promoting myelin growth in the PHC. Our research demonstrates that LINGO-1 antagonism may be an effective approach to the treatment of the cognitive impairment of multiple sclerosis patients.

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

    Directory of Open Access Journals (Sweden)

    Etxagibel Aitziber


    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.

  7. Pertinence of kappa and lambda recombinant antibodies directed against thyroid peroxidase in thyroid autoimmune disease. (United States)

    Bresson, D; Chardès, T; Chapal, N; Bès, C; Cerutti, M; Devauchelle, G; Bouanani, M; Mani, J C; Péraldi-Roux, S


    Forty-one single-chain variable region fragments (scFvs) directed against thyroid peroxidase (TPO) were obtained by phage display libraries constructed from thyroid-infiltrating B cells of Graves' disease patients. Among these scFvs, 24.4% used a Vkappa light chain whereas 75.6% shows a light chain of Vlamda origin. Study of light chain gene usage in the TPO antibody repertoire demonstrated a dominance of the Vkappa 1-39 and Vlambda 1-51 genes. Thyroid peroxidase probing of overlapping peptides covering the amino acid sequences of anti-TPO T2/kappa and T13/lambda variable regions demonstrated a more restricted antigen recognition on T13/lambda than on T2/kappa. These two recombinant antibodies, expressed as whole IgG1 in the baculovirus/insect cell system, inhibited the binding to TPO of serum TPO autoantibodies whatever the light chain. Our study indicates that lambda as well as kappa light chain usage are found in the TPO antibody repertoire of thyroid-infiltrating B cells and are pertinent in the pathogenesis of autoimmune thyroid disease.

  8. Thyroid Antibodies, Autoimmunity and Cognitive Decline: Is There a Population-Based Link

    Directory of Open Access Journals (Sweden)

    Kate Napthali


    Full Text Available Background: Autoimmunity is considered an uncommon but under-recognised cause of cognitive decline. Methods: Serum samples from 3,253 randomly selected subjects enrolled in the Hunter Community Study, aged 55-85 years, were assayed for thyrotropin stimulatory hormone, anti-thyroid peroxidase antibodies (TPO-Ab, anti-nuclear antibodies (ANA and extractable nuclear antigens (ENA. Cognitive function was assessed using the Audio Recorded Cognitive Screen (ARCS tool. Results: TPO-Ab were found in 8.4% and ANA in 27.9% of the study population, of whom 3% had positive ENA findings. No relationship was found between the ARCS score and either TPO-Ab (coefficient = 0.133; 95% CI -0.20, 0.82, p = 0.616, ANA at a low (coefficient = 1.01; 95% CI -2.58, 0.55, p = 0.203 or a high titre (coefficient = -0.65; 95% CI -2.59, 1.28, p = 0.508, or ENA antibodies (coefficient = 5.12; 95% CI -0.53, 10.77; p = 0.076. Conclusions: Autoantibody findings are common in an aging population and are not associated with cognitive decline.

  9. Hydralazine Induced Lupus Syndrome Presenting with Recurrent Pericardial Effusion and a Negative Antinuclear Antibody


    Praneet Iyer; Ahmed Dirweesh; Ritika Zijoo


    Drug induced lupus erythematosus (DIL or DILE) is an autoimmune disorder caused by chronic use of certain drugs. We report a unique case of hydralazine induced lupus syndrome (HILS) with a negative antinuclear antibody in a female patient who was on hydralazine for a period of 1.5–2 years and developed recurrent pericardial effusion as a result of it. Initially her condition was managed with a pericardial window. The recurrence of a massive pericardial effusion necessitated a right hemiperica...

  10. Vitiligo: How do oxidative stress-induced autoantigens trigger autoimmunity? (United States)

    Xie, Heng; Zhou, Fubo; Liu, Ling; Zhu, Guannan; Li, Qiang; Li, Chunying; Gao, Tianwen


    Vitiligo is a common depigmentation disorder characterized by a loss of functional melanocytes and melanin from epidermis, in which the autoantigens and subsequent autoimmunity caused by oxidative stress play significant roles according to hypotheses. Various factors lead to reactive oxygen species (ROS) overproduction in the melanocytes of vitiligo: the exogenous and endogenous stimuli that cause ROS production, low levels of enzymatic and non-enzymatic antioxidants, disturbed antioxidant pathways and polymorphisms of ROS-associated genes. These factors synergistically contribute to the accumulation of ROS in melanocytes, finally leading to melanocyte damage and the production of autoantigens through the following ways: apoptosis, accumulation of misfolded peptides and cytokines induced by endoplasmic reticulum stress as well as the sustained unfolded protein response, and an 'eat me' signal for phagocytic cells triggered by calreticulin. Subsequently, autoantigens presentation and dendritic cells maturation occurred mediated by the release of antigen-containing exosomes, adenosine triphosphate and melanosomal autophagy. With the involvement of inducible heat shock protein 70, cellular immunity targeting autoantigens takes the essential place in the destruction of melanocytes, which eventually results in vitiligo. Several treatments, such as narrow band ultraviolet, quercetin and α-melanophore-stimulating hormone, are reported to be able to lower ROS thereby achieving repigmentation in vitiligo. In therapies targeting autoimmunity, restore of regulatory T cells is absorbing attention, in which narrow band ultraviolet also plays a role.

  11. Prevention of experimental autoimmune encephalomyelitis by antibodies against α4βl integrin (United States)

    Yednock, Ted A.; Cannon, Catherine; Fritz, Lawrence C.; Sanchez-Madrid, Francisco; Steinman, Lawrence; Karin, Nathan


    EXPERIMENTAL autoimmune encephalomyelitis (EAE) is an inflammatory condition of the central nervous system with similarities to multiple sclerosis1,2. In both diseases, circulating leukocytes penetrate the blood-brain barrier and damage myelin, resulting in impaired nerve conduction and paralysis3-5. We sought to identify the adhesion receptors that mediate the attachment of circulating leukocytes to inflamed brain endothelium in EAE, because this interaction is the first step in leukocyte entry into the central nervous system. Using an in vitro adhesion assay on tissue sections, we found that lymphocytes and monocytes bound selectively to inflamed EAE brain vessels. Binding was inhibited by antibodies against the integrin molecule α4βl, but not by antibodies against numerous other adhesion receptors. When tested in vivo, anti-α4 integrin effectively prevented the accumulation of leukocytes in the central nervous system and the development of EAE. Thus, therapies designed to interfere with α4βl integrin may be useful in treating inflammatory diseases of the central nervous system, such as multiple sclerosis.

  12. Pregnancy may favour the development of severe autoimmune central diabetes insipidus in women with vasopressin cell antibodies: description of two cases. (United States)

    Bellastella, Giuseppe; Bizzarro, Antonio; Aitella, Ernesto; Barrasso, Mariluce; Cozzolino, Domenico; Di Martino, Sergio; Esposito, Katherine; De Bellis, Annamaria


    Recently, an increased incidence of central diabetes insipidus (CDI) in pregnancy, and less frequently in the post partum period, has been reported, most probably favoured by some conditions occurring in pregnancy. This study was aimed at investigating the influence of pregnancy on a pre-existing potential/subclinical hypothalamic autoimmunity. We studied the longitudinal behaviour of arginine-vasopressin cell antibodies (AVPcAbs) and post-pituitary function in two young women with a positive history of autoimmune disease and presence of AVPcAbs, but without clinical CDI, and who became pregnant 5 and 7 months after our first observation. The behaviour of post-pituitary function and AVPcAbs (by immunofluorescence) was evaluated at baseline, during pregnancy and for 2 years after delivery. AVPcAbs, present at low/middle titres at baseline in both patients, showed a titre increase during pregnancy in one patient and after delivery in the other patient, with development of clinically overt CDI. Therapy with 1-deamino-8-d-arginine vasopressin (DDAVP) caused a prompt clinical remission. After a first unsuccessful attempt of withdrawal, the therapy was definitively stopped at the 6th and the 7th month of post partum period respectively, when AVPcAbs disappeared, accompanied by post-pituitary function recovery, persisting until the end of the follow-up. The determination of AVPcAbs is advisable in patients with autoimmune diseases planning their pregnancy, because they could be considered good predictive markers of gestational or post partum autoimmune CDI. The monitoring of AVPcAb titres and post-pituitary function during pregnancy in these patients may allow for an early diagnosis and an early replacement therapy, which could induce the disappearance of these antibodies with consequent complete remission of CDI.

  13. Ebola virus infection induces autoimmunity against dsDNA and HSP60 (United States)

    Fausther-Bovendo, H.; Qiu, X.; McCorrister, S.; Westmacott, G.; Sandstrom, P.; Castilletti, C.; Di Caro, A.; Ippolito, G.; Kobinger, G. P.


    Ebola virus (EBOV) survivors are affected by a variety of serious illnesses of unknown origin for years after viral clearance from the circulation. Identifying the causes of these persistent illnesses is paramount to develop appropriate therapeutic protocols. In this study, using mouse and non-human primates which survived EBOV challenge, ELISA, western blot, mass spectrometry and flow cytometry were used to screen for autoantibodies, identify their main targets, investigate the mechanism behind their induction and monitor autoantibodies accumulation in various tissues. In infected mice and NHP, polyclonal B cell activation and autoantigens secretion induced autoantibodies against dsDNA and heat shock protein 60 as well as antibody accumulation in tissues associated with long-term clinical manifestations in humans. Finally, the presence of these autoantibodies was confirmed in human EBOV survivors. Overall, this study supports the concept that autoimmunity is a causative parameter that contributes to the various illnesses observed in EBOV survivors. PMID:28181533

  14. Diagnostic value of antithyroid peroxidase antibody for incidental autoimmune thyroiditis based on histopathologic results. (United States)

    Rho, Myung Ho; Kim, Dong Wook; Hong, Hyun Pyo; Park, Young Mi; Kwon, Min Jeong; Jung, Soo Jin; Kim, Young Wook; Kang, Taewoo


    Detection of antithyroid peroxidase antibody (TPOAb) is widely used in the diagnosis of autoimmune thyroiditis (AIT), but no research has evaluated the diagnostic accuracy of TPOAb detection using histopathologic reference standards. To fill this research gap, this study assessed the diagnostic accuracy of detection of TPOAb and that of other serological markers in asymptomatic patients who had been diagnosed with AIT by histopathologic analysis after thyroid surgery. After review of patient records, 598 patients who had undergone thyroid nodule surgery were enrolled for examination for thyroid parenchyma by a pathologist and classification into no co-existing lymphocytic thyroiditis, Hashimoto thyroiditis, or non-Hashimoto type of lymphocytic thyroiditis (NHLT). The correlation between patient serological data and thyroid parenchyma pathology was analyzed. Statistically significant differences (P lymphocytic thyroiditis and no co-existing lymphocytic thyroiditis groups regarding thyroid-stimulating hormone (TSH) and TPOAb levels. And, TPOAb titer was significantly associated with the degree of inflammation. An abnormal TPOAb titer was found in 86 of the 598 patients (14.4 %) and the specificity of TPOAb detection for AIT diagnosis was found to be 96.9 %. The prevalence of Hashimoto thyroiditis and NHLT in the 560 papillary thyroid cancer (PTC) patients was found to be 7.9 and 17.9 %, respectively. The results indicate that TPOAb titer is associated with the degree of thyroid inflammation and that detection of TPOAb is a very specific means of diagnosing AIT. The results also indicate that the incidence of AIT and PTC coexistence is relatively high.

  15. [Autoimmune hepatitis]. (United States)

    Ostojić, Rajko


    Autoimmune hepatitis is an unresolving, hepatocellular inflammation of unknown cause that is characterized by the presence of periportal hepatitis on histologic examination, tissue autoantibodies in serum, and hypergammaglobulinemia. By international consensus, the designation autoimmune hepatitis has replaced alternative terms for the condition. Three types of autoimmune hepatitis have been proposed based on immunoserologic findings. Type 1 autoimmune hepatitis is characterized by the presence of antinuclear antibodies (ANA) or smooth muscle antibodies (SMA) (or both) in serum. Seventy percent of patients with type 1 of autoimmune hepatitis are women. This type is the most common form and accounts for at least 80% of cases. Type 2 is characterized by the presence of antibodies to liver-kidney microsome type 1 (anti-LKM1) in serum. Patients with this type of autoimmune hepatitis are predominantly children. Type 3 autoimmune hepatitis is characterized by the presence of antibodies to soluble liver antigen (anti-SLA) in serum. There are no individual features that are pathognomonic of autoimmune hepatitis, and its diagnosis requires the confident exclusion of other conditions. The large majority of patients show satisfactory response to corticosteroid (usually prednisone or prednisolone) therapy. For the past 30 years it has been customary to add azathioprine as a "steroid sparing" agent to allow lower doses of steroids to be used and remission, once achieved, can be sustained in many patients with azathioprine alone after steroid withdrawal. Patients with autoimmune hepatitis who have decompensated during or after corticosteroid therapy are candidates for liver transplantation.

  16. An HIV gp120-CD4 Immunogen Does Not Elicit Autoimmune Antibody Responses in Cynomolgus Macaques. (United States)

    Schwartz, Jennifer A; Prado, Ilia; Misamore, Johnathan; Weiss, Deborah; Francis, Jesse; Pal, Ranajit; Huaman, Maria; Cristillo, Anthony; Lewis, George K; Gallo, Robert C; DeVico, Anthony L; Fouts, Timothy R


    are unlikely to elicit autoimmune antibody responses, supporting the advancement of gp120-CD4 complex-based antigens, such as FLSC, into clinical testing.

  17. Monoclonal antibodies in human organ transplantation and auto-immune diseases. (United States)

    Wijdenes, J; Roy, C; Morel-Fourrier, B; Racadot, E


    The usefulness of monoclonal antibodies (mAbs) in the transplantation field has become evident over the last couple of years. Different mAbs have been used as a prophylactic treatment after transplantation, in a therapeutic way against acute organ rejection and new diagnostic tools to predict clinical rejection immerge. One can even hope that with humanised mAbs or human mAbs obtained by repertoire cloning the formation of human anti-mouse antibodies will be solved although on the one hand this appeared not to be a big problem and on the other hand anti-idiotypic antibodies can still be expected. However, the most puzzling question is how the mAbs modulates the immuno-response and this not only in organ rejection but also in auto-immune diseases. Only one out of many CD25 mAbs with seemingly similar epitope recognition can be used in therapeutical treatment of acute Graft versus Host Disease. The same mAb is not, however, very efficient in the prophylactic treatment of kidney transplantation without association of suboptimal doses of cyclosporin A. Another example is a CD4 mAb which is efficient in the treatment of polyarthritis with no side effects but which provokes transient but clear side effects when used in psoriasis or multiple sclerosis patients. A second CD4 mAb with high inhibitory activity in several bioassays compared to the first CD4 mAb has no beneficial effect at all on polyarthritis. Also the question why there is a percentage of "no response" patients among apparently identical "good response" patients remains unanswered. However it becomes clear from these experiences that: 1) mAbs recognizing a similar epitope and being of the same isotype will not automatically have the same effect in therapy. 2) side effects may be depending of the disease treated. 3) the activities of mAbs in bioassays and even animal models very often do not reflect the in vivo situation in human. 4) efficiency of the treatment with mAbs can be increased by a better

  18. Transplacental transmission of antibodies to tubular basement membrane in guinea-pigs with autoimmune tubulointerstitial nephritis. (United States)

    Albini, B; Milgrom, M; Noble, B; Albini, C; Ossi, E; Andres, G A


    The offspring of female guinea-pigs with tubulo-interstitial nephritis were studied for possible passive transfer of disease. Whereas no immune deposits were seen on or before day 30 of gestation, IgG was detected in the tubular basement membrane (TBM) of fetuses at and after day 44. Serum of offspring contained antibodies to TBM, albeit in much lower titres than found in circulation of the mother guinea-pigs. No histopathological changes were seen in fetal kidneys. Thus, autoantibodies induced by heteroimmunization of pregnant guinea-pigs may be transmitted to offspring in the last third of the gestation period and can bind to fetal TBM. However, this transfer of antibodies does not cause disease.

  19. A role for plasma cell targeting agents in immune tolerance induction in autoimmune disease and antibody responses to therapeutic proteins. (United States)

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


    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Koh, Chang Soon [Seoul National University College of Medicine, Seoul (Korea, Republic of)


    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 T{sub 3},T{sub 4} and free T{sub 4}, index but low gamma{sup 2} 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 {sup 131}I 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

  1. The sphingosine 1-phosphate receptor modulator FTY720 prevents iodide-induced autoimmune thyroiditis in non-obese diabetic mice. (United States)

    Morohoshi, Kazuki; Osone, Michiko; Yoshida, Katsumi; Nakagawa, Yoshinori; Hoshikawa, Saeko; Ozaki, Hiroshi; Takahashi, Yurie; Ito, Sadayoshi; Mori, Kouki


    FTY720 is an immunomodulator that alters migration and homing of lymphocytes via sphingosine 1-phosphate receptors. This compound has been shown to be effective in suppressing autoimmune diseases in experimental and clinical settings. In the present study, we tested whether FTY720 prevented autoimmune thyroiditis in iodide-treated non-obese diabetic (NOD) mice, a model of Hashimoto's thyroiditis (HT) in humans. Mice were given 0.05% iodide water for 8 weeks, and this treatment effectively induced thyroiditis. Iodide-treated mice were injected intraperitoneally with either saline or FTY720 during the iodide treatment. FTY720 clearly suppressed the development of thyroiditis and reduced serum anti-thyroglobulin antibody levels. The number of circulating lymphocytes and spleen cells including CD4(+) T cells, CD8(+) T cells, and CD4(+)Foxp3(+) T cells was decreased in FTY720-treated mice. Our results indicate that FTY720 has immunomodulatory effects on iodide-induced autoimmune thyroiditis in NOD mice and may be a potential candidate for use in the prevention of HT.

  2. Experimental autoimmune prostatitis induces microglial activation in the spinal cord (United States)

    Wong, Larry; Done, Joseph D.; Schaeffer, Anthony J.; Thumbikat, Praveen


    Background The pathogenesis of chronic prostatitis/chronic pelvic pain syndrome is unknown and factors including the host’s immune response and the nervous system have been attributed to the development of CP/CPPS. We previously demonstrated that mast cells and chemokines such as CCL2 and CCL3 play an important role in mediating prostatitis. Here, we examined the role of neuroinflammation and microglia in the CNS in the development of chronic pelvic pain. Methods Experimental autoimmune prostatitis (EAP) was induced using a subcutaneous injection of rat prostate antigen. Sacral spinal cord tissue (segments S4–S5) was isolated and utilized for immunofluorescence or QRT-PCR analysis. Tactile allodynia was measured at baseline and at various points during EAP using Von Frey fibers as a function for pelvic pain. EAP mice were treated with minocycline after 30 days of prostatitis to test the efficacy of microglial inhibition on pelvic pain. Results Prostatitis induced the expansion and activation of microglia and the development of inflammation in the spinal cord as determined by increased expression levels of CCL3, IL-1β, Iba1, and ERK1/2 phosphorylation. Microglial activation in mice with prostatitis resulted in increased expression of P2X4R and elevated levels of BDNF, two molecular markers associated with chronic pain. Pharmacological inhibition of microglia alleviated pain in mice with prostatitis and resulted in decreased expression of IL-1β, P2X4R, and BDNF. Conclusion Our data shows that prostatitis leads to inflammation in the spinal cord and the activation and expansion of microglia, mechanisms that may contribute to the development and maintenance of chronic pelvic pain. PMID:25263093

  3. Inactivation of T cell receptor peptide-specific CD4 regulatory T cells induces chronic experimental autoimmune encephalomyelitis (EAE). (United States)

    Kumar, V; Stellrecht, K; Sercarz, E


    T cell receptor (TCR)-recognizing regulatory cells, induced after vaccination with self-reactive T cells or TCR peptides, have been shown to prevent autoimmunity. We have asked whether this regulation is involved in the maintenance of peripheral tolerance to myelin basic protein (MBP) in an autoimmune disease model, experimental autoimmune encephalomyelitis (EAE). Antigen-induced EAE in (SJL x B10.PL)F1 mice is transient in that most animals recover permanently from the disease. Most of the initial encephalitogenic T cells recognize MBP Ac1-9 and predominantly use the TCR V beta 8.2 gene segment. In mice recovering from MBP-induced EAE, regulatory CD4+ T cells (Treg) specific for a single immunodominant TCR peptide B5 (76-101) from framework region 3 of the V beta 8.2 chain, become primed. We have earlier shown that cloned B5-reactive Treg can specifically downregulate responses to Ac1-9 and also protect mice from EAE. These CD4 Treg clones predominantly use the TCR V beta 14 or V beta 3 gene segments. Here we have directly tested whether deletion/blocking of the Treg from the peripheral repertoire affects the spontaneous recovery from EAE. Treatment of F1 mice with appropriate V beta-specific monoclonal antibodies resulted in an increase in the severity and duration of the disease; even relapses were seen in one-third to one-half of the Treg-deleted mice. Interestingly, chronic disease in treated mice appears to be due to the presence of Ac1-9-specific T cells. Thus, once self-tolerance to MBP is broken by immunization with the antigen in strong adjuvant, TCR peptide-specific CD4 Treg cells participate in reestablishing peripheral tolerance. Thus, a failure to generate Treg may be implicated in chronic autoimmune conditions.

  4. Autoimmune epilepsy. (United States)

    Greco, Antonio; Rizzo, Maria Ida; De Virgilio, Armando; Conte, Michela; Gallo, Andrea; Attanasio, Giuseppe; Ruoppolo, Giovanni; de Vincentiis, Marco


    Despite the fact that epilepsy is the third most common chronic brain disorder, relatively little is known about the processes leading to the generation of seizures. Accumulating data support an autoimmune basis in patients with antiepileptic drug-resistant seizures. Besides, recent studies show that epilepsy and autoimmune disease frequently co-occur. Autoimmune epilepsy is increasingly recognized in the spectrum of neurological disorders characterized by detection of neural autoantibodies in serum or spinal fluid and responsiveness to immunotherapy. An autoimmune cause is suspected based on frequent or medically intractable seizures and the presence of at least one neural antibody, inflammatory changes indicated in serum or spinal fluid or on MRI, or a personal or family history of autoimmunity. It is essential that an autoimmune etiology be considered in the initial differential diagnosis of new onset epilepsy, because early immunotherapy assures an optimal outcome for the patient.

  5. 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.

  6. Hydralazine Induced Lupus Syndrome Presenting with Recurrent Pericardial Effusion and a Negative Antinuclear Antibody

    Directory of Open Access Journals (Sweden)

    Praneet Iyer


    Full Text Available Drug induced lupus erythematosus (DIL or DILE is an autoimmune disorder caused by chronic use of certain drugs. We report a unique case of hydralazine induced lupus syndrome (HILS with a negative antinuclear antibody in a female patient who was on hydralazine for a period of 1.5–2 years and developed recurrent pericardial effusion as a result of it. Initially her condition was managed with a pericardial window. The recurrence of a massive pericardial effusion necessitated a right hemipericardiectomy. After hydralazine was stopped, she never had any further episodes of pericardial effusion or tamponade.

  7. Hydralazine Induced Lupus Syndrome Presenting with Recurrent Pericardial Effusion and a Negative Antinuclear Antibody (United States)

    Iyer, Praneet; Zijoo, Ritika


    Drug induced lupus erythematosus (DIL or DILE) is an autoimmune disorder caused by chronic use of certain drugs. We report a unique case of hydralazine induced lupus syndrome (HILS) with a negative antinuclear antibody in a female patient who was on hydralazine for a period of 1.5–2 years and developed recurrent pericardial effusion as a result of it. Initially her condition was managed with a pericardial window. The recurrence of a massive pericardial effusion necessitated a right hemipericardiectomy. After hydralazine was stopped, she never had any further episodes of pericardial effusion or tamponade. PMID:28194293

  8. 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


    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.

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

    Institute of Scientific and Technical Information of China (English)


    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

  10. Autoimmune hemolytic anemia induced by anti-PD-1 therapy in metastatic melanoma. (United States)

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


    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.

  11. A unique combination of autoimmune limbic encephalitis, type 1 diabetes, and Stiff person syndrome associated with GAD-65 antibody. (United States)

    Sharma, Chandra Mohan; Pandey, Rajendra Kumar; Kumawat, Banshi Lal; Khandelwal, Dinesh; Gandhi, Pankaj


    Antibodies to GAD-65 have been implicated in the pathogenesis of type 1 diabetes, limbic encephalitis and Stiff person syndrome, however these diseases rarely occur concurrently. We intend to present a rare case of 35 year old female who was recently diagnosed as having type 1 diabetes presented with 1½ month history of recurrent seizures, subacute onset gait ataxia, dysathria, psychiatric disturbance and cognitive decline. No tumor was found on imaging and the classic paraneoplastic panel was negative. Cerebrospinal fluid and blood was positive for GAD-65 antibodies. Patient showed significant improvement with immunomodulatory therapy. Association of GAD-65 antibodies has been found with various disorders including type 1 diabetes, limbic encephalitis, Stiff person syndrome, cerebellar ataxia and palatal myoclonus. This case presents with unique combination of type 1 diabetes, Stiff person syndrome and limbic encephalitis associated with GAD-65 antibodies that is responsive to immunotherapy. It also highlights the emerging concept of autoimmunity in the causation of various disorders and there associations.

  12. Novel autoimmune phenomena induced in vivo by a new DNA binding protein Nuc: a study on MRL/n mice. (United States)

    Kanai, Y; Takeda, O; Kanai, Y; Miura, K; Kurosawa, Y


    We previously purified a 55 kDa protein that preferentially expands anti-DNA antibody production both in vitro and in vivo across the H-2 barrier from culture supernatants of KML1-7 cells, cloned from a lupus-prone MRL/lpr mouse. By using the purified protein, termed nucleobindin (Nuc), we cloned cDNA and produced recombinant(r) Nuc in Escherichia coli. To elucidate the function of rNuc in vivo, we initially injected intraperitoneally 5 micrograms of rNuc without adjuvant into female MRL/n mice at 8 weeks of age and continued injection twice a week. As early as 5 weeks after administration, all mice treated showed an increase in IgG anti-double stranded (ds) DNA antibodies accompanied by IgG hypergammaglobulinemia (HG). Of particular interest was that these mice also produced anti-U1RNP antibodies and rheumatoid factor (RF) of IgG class, but not anti-Sm antibodies. Histopathologically, hypercellularity with occasional crescents in the glomeruli was observed, but evidence for lupus nephritis was lacking, indicating that some factors other than Nuc are necessary for the development of a lupus syndrome observed in MRL/lpr mice. Similar administration of lipopolysaccharide into MRL/n mice failed to induce autoantibodies except for a slight increase in serum IgG, suggesting that these autoimmune responses are not due simply to polyclonal B-cell activation. The presence of rNuc will give us a clue for further understanding of autoimmunity.

  13. Cruzipain induces autoimmune response against skeletal muscle and tissue damage in mice. (United States)

    Giordanengo, L; Fretes, R; Díaz, H; Cano, R; Bacile, A; Vottero-Cima, E; Gea, S


    The goal of the current study was to investigate whether cruzipain, a major Trypanosoma cruzi antigen, is able to induce in mice an autoimmune response and skeletal muscle damage. We demonstrate that immunization with cruzipain triggers immunoglobulin G antibody binding to a 210-kDa antigen from a syngeneic skeletal muscle extract. The absorption of immune sera with purified myosin completely eliminated this reactivity, confirming that the protein identified is really myosin. We also found that spleen cells from immunized mice proliferated in response to a skeletal muscle extract rich in myosin and to purified myosin. Cells from control mice did not proliferate against any of the antigens tested. In addition, we observed an increase in plasma creatine kinase activity, a biochemical marker of muscle damage. Histological studies showed inflammatory infiltrates and myopathic changes in skeletal muscle of immunized animals. Electromyographic studies of these mice revealed changes such as are found in inflammatory or necrotic myopathy. Altogether, our results suggest that this experimental model provides strong evidence for a pathogenic role of anticruzipain immune response in the development of muscle tissue damage.

  14. Clearance of a monoclonal anti-DNA antibody following administration of DNA in normal and autoimmune mice

    Energy Technology Data Exchange (ETDEWEB)

    Jones, F.S.; Pisetsky, D.S.; Kurlander, R.J.


    To study the assembly of DNA-anti-DNA complexes in vivo, we have measured the clearance from blood and organ localization of a murine IgG2a monoclonal anti-DNA antibody, called 6/0, following the infusion of DNA intravenously or intraperitoneally. Intraperitoneal DNA caused a profound acceleration of 6/0 anti-DNA clearance that was dose dependent and demonstrable after the infusion of as little as 1.9 microgram per gram of body weight of single-stranded DNA. The antibody was cleared primarily in the liver without increased deposition in the kidney. Intraperitoneal infusions of DNA also accelerated the clearance of 6/0 in autoimmune MRL-lpr/lpr mice. In contrast, intravenous DNA given in comparable doses caused only a slight increase in 6/0 antibody clearance; this accelerated clearance was seen only at low antigen doses and only during the first 10 min following DNA infusion. Using double-radiolabeling techniques, 6/0 and Cl.18, an IgG2ak myeloma protein without anti-DNA activity, were found to disappear from blood at a comparable rate in both B6D2 mice and MRL-lpr/lpr mice. These results suggest that the DNA-anti-DNA immune complexes can form in vivo but that this process is profoundly affected by the manner in which DNA enters the circulation. In addition, the results suggest that DNA-dependent clearance is not a major pathway for anti-DNA metabolism in normal or at least one strain of autoimmune mice.

  15. Antibodies to Liposomes, Phospholipids, and Cholesterol, Implications for Autoimmunity, Atherosclerosis and Aging (United States)


    from Fogler et al., 1987). Based on the above observations, it may now be con- cluded that antibodies to at least one phospholipid (phos...suspension culture, but binding rapidly occurred when the cells were allowed to become adherent to a plastic dish (Fig. 3) ( Fogler et al., 1987). Antibody...lipid bilayers. Antibodies to Uposomes, Phosphoilpids, and Cholesterol /49 REFERENCES Alving, BM, Banerji, B, Fogler , WE, Alving, CR (1987). Lupus

  16. Inactivation of T cell receptor peptide-specific CD4 regulatory T cells induces chronic experimental autoimmune encephalomyelitis (EAE)



    T cell receptor (TCR)-recognizing regulatory cells, induced after vaccination with self-reactive T cells or TCR peptides, have been shown to prevent autoimmunity. We have asked whether this regulation is involved in the maintenance of peripheral tolerance to myelin basic protein (MBP) in an autoimmune disease model, experimental autoimmune encephalomyelitis (EAE). Antigen-induced EAE in (SJL x B10.PL)F1 mice is transient in that most animals recover permanently from the disease. Most of the i...

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

    Directory of Open Access Journals (Sweden)

    Hasegawa Akira


    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.

  18. Research Advances in Drug-induced Autoimmune Disordersw%药物诱导性自身免疫性疾病的研究进展

    Institute of Scientific and Technical Information of China (English)



    药物诱导性自身免疫性疾病是长期用药引发的一种不良反应,其作用机制因药物种类不同而不同.但最终会因机体丧失对自身抗原的免疫耐受而产生自身抗体.认识原发性和药物诱导性自身免疫反应,将有助于提高对这些疾病机制的理解.并且通过分析药物诱导性自身免疫性疾病的发病机制,为药物不良反应的预防以及临床治疗提供帮助.%Drug-induced autoimmune disease is an adverse effect caused by the long-term use of drug. The mechanisma of actions depend the properties of drugs. The auto-antibodies are produced due to the loss of immune tolerance to the auto-antigens. The understanding of primary and drug-induced autoimmune response helps to improve the study of the pathogenesis of drug-induced autoimmune disease. The analysis.f pathogenesis of drug-in-duced autoimmune disease helps to improve the prevention and treatment of adverse drug reactions.

  19. Alpha-Methyldopa-Induced Autoimmune Hemolytic Anemia in the Third Trimester of Pregnancy

    Directory of Open Access Journals (Sweden)

    Charalampos Grigoriadis


    Full Text Available Alpha-methyldopa has been demonstrated to be safe for use during pregnancy and is now used to treat gestational hypertension. In pregnancy, alpha-methyldopa-induced autoimmune hemolytic anemia does not have typical features and the severity of symptoms ranges from mild fatigue to dyspnea, respiratory failure, and death if left untreated. A case of alpha-methyldopa-induced autoimmune hemolytic anemia in a 36-year-old gravida 2, para 1 woman at 37+6 weeks of gestation is reported herein along with the differential diagnostic procedure and the potential risks to the mother and the fetus.

  20. Inebilizumab, a B Cell-Depleting Anti-CD19 Antibody for the Treatment of Autoimmune Neurological Diseases: Insights from Preclinical Studies

    Directory of Open Access Journals (Sweden)

    Ding Chen


    Full Text Available Exaggerated or inappropriate responses by B cells are an important feature in many types of autoimmune neurological diseases. The recent success of B-cell depletion in the treatment of multiple sclerosis (MS has stimulated the development of novel B-cell-targeting therapies with the potential for improved efficacy. CD19 has emerged as a promising target for the depletion of B cells as well as CD19-positive plasmablasts and plasma cells. Inebilizumab (MEDI-551, an anti-CD19 antibody with enhanced antibody-dependent cell-mediated cytotoxicity against B cells, is currently being evaluated in MS and neuromyelitis optica. This review discusses the role of B cells in autoimmune neurological disorders, summarizes the development of inebilizumab, and analyzes the recent results for inebilizumab treatment in an autoimmune encephalitis mouse model. The novel insights obtained from these preclinical studies can potentially guide future investigation of inebilizumab in patients.

  1. A role for muscarinic receptors in neutrophil extracellular trap formation and levamisole-induced autoimmunity (United States)

    Carmona-Rivera, Carmelo; Purmalek, Monica M.; Moore, Erica; Waldman, Meryl; Walter, Peter J.; Garraffo, H. Martin; Phillips, Karran A.; Preston, Kenzie L.; Graf, Jonathan; Grayson, Peter C.


    Levamisole, an anthelmintic drug with cholinergic properties, has been implicated in cases of drug-induced vasculitis when added to cocaine for profit purposes. Neutrophil extracellular trap (NET) formation is a cell death mechanism characterized by extrusion of chromatin decorated with granule proteins. Aberrant NET formation and degradation have been implicated in idiopathic autoimmune diseases that share features with levamisole-induced autoimmunity as well as in drug-induced autoimmunity. This study’s objective was to determine how levamisole modulates neutrophil biology and its putative effects on the vasculature. Murine and human neutrophils exposed to levamisole demonstrated enhanced NET formation through engagement of muscarinic subtype 3 receptor. Levamisole-induced NETosis required activation of Akt and the RAF/MEK/ERK pathway, ROS induction through the nicotinamide adenine dinucleotide phosphate oxidase, and peptidylarginine deiminase activation. Sera from two cohorts of patients actively using levamisole-adulterated cocaine displayed autoantibodies against NET components. Cutaneous biopsy material obtained from individuals exposed to levamisole suggests that neutrophils produce NETs in areas of vasculitic inflammation and thrombosis. NETs generated by levamisole were toxic to endothelial cells and impaired endothelium-dependent vasorelaxation. Stimulation of muscarinic receptors on neutrophils by cholinergic agonists may contribute to the pathophysiology observed in drug-induced autoimmunity through the induction of inflammatory responses and neutrophil-induced vascular damage. PMID:28194438

  2. A role for muscarinic receptors in neutrophil extracellular trap formation and levamisole-induced autoimmunity. (United States)

    Carmona-Rivera, Carmelo; Purmalek, Monica M; Moore, Erica; Waldman, Meryl; Walter, Peter J; Garraffo, H Martin; Phillips, Karran A; Preston, Kenzie L; Graf, Jonathan; Kaplan, Mariana J; Grayson, Peter C


    Levamisole, an anthelmintic drug with cholinergic properties, has been implicated in cases of drug-induced vasculitis when added to cocaine for profit purposes. Neutrophil extracellular trap (NET) formation is a cell death mechanism characterized by extrusion of chromatin decorated with granule proteins. Aberrant NET formation and degradation have been implicated in idiopathic autoimmune diseases that share features with levamisole-induced autoimmunity as well as in drug-induced autoimmunity. This study's objective was to determine how levamisole modulates neutrophil biology and its putative effects on the vasculature. Murine and human neutrophils exposed to levamisole demonstrated enhanced NET formation through engagement of muscarinic subtype 3 receptor. Levamisole-induced NETosis required activation of Akt and the RAF/MEK/ERK pathway, ROS induction through the nicotinamide adenine dinucleotide phosphate oxidase, and peptidylarginine deiminase activation. Sera from two cohorts of patients actively using levamisole-adulterated cocaine displayed autoantibodies against NET components. Cutaneous biopsy material obtained from individuals exposed to levamisole suggests that neutrophils produce NETs in areas of vasculitic inflammation and thrombosis. NETs generated by levamisole were toxic to endothelial cells and impaired endothelium-dependent vasorelaxation. Stimulation of muscarinic receptors on neutrophils by cholinergic agonists may contribute to the pathophysiology observed in drug-induced autoimmunity through the induction of inflammatory responses and neutrophil-induced vascular damage.

  3. Autoimmune disease

    Institute of Scientific and Technical Information of China (English)


    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

  4. 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


    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.

  5. [Autoimmunity factor in chronic gastritis: incidence of antiparietal cell antibodies and their relation to antral histology and basal blood gastrins]. (United States)

    Schraier, M; Katz, S; Pest, S; Chiocca, J C; Costa, J A


    In 118 patients with histological proven chronic gastritis, was performed a study of seric antibodies against parietal cells (ACCP), following the indirect inmuno-fluorescence method. The results were positives in 36 cases (30%). Four positives cases were found in 40 normal controls (10%), two of them were compensated diabetics, one have the thyrohyoid Hashimoto's disease, and the remainder, brother of a patient with chronic gastritis, was a positive ACCP. A major positiveness (44.4%) was obtained in 9 cases of gastric atrophy than in 65 cases with atrophic gastritis (32%) and in 44 cases of superficial gastritis (25%); although due to the few cases of gastric atrophy regarding other histological types, conclusions cannot be obtained about the incidence of ACCP and histological variety of chronic gastritis. If we do group the patients according to their acid secretory debit, 53 achlorhydric patients had a positiveness of ACCP of 45%, while over 63 with decreased secretory capability, only 18.4%, was positive. The distribution by age groups, shows a major incidence of ACCP about the 4th and 5th decade of life. Thirty seven patients with chronic atrophic gastritis and achlorhydria, and seven with chronic superficial gastritis and hypochlorhydria, besides the antibodies study were on a basal dosage of gastrinemia and antral endoscopic biopsy, finding out that, achlorhydric patients (15 on 19) with normal or slightly altered antrus, have gastrinemia (222 +/- 123 Pgo/oo) and the majority of patients with normal gastrinemia (32 +/- 16 pgo/oo) have more important antral lesions. The ratio between antral histology and ACCP in auto--immune gastritis (Type A), conciliates only partially with the observation by Strickland et al., as only 52.4% of achlorhydric patients and ACCP have a normal antrus or al least with mild lesions. Our results suggest the possibility of that on auto--immune gastritis could act other pathogenic factors of antral lesion.

  6. Premature Ovarian Failure Syndrome May Be Induced by Autoimmune Reactions to Zona Pellucida Proteins

    Directory of Open Access Journals (Sweden)

    Koyama K


    Full Text Available Autoimmunity is thought to be involved in pathogenesis of the premature ovarian failure (POF causing infertility. The zona pellucida (ZP, an extracellular matrix surrounding the oocyte, is considered to be pathogenic among autoantigens, because many contraceptive vaccine research has shown that anti-ZP antibodies impair ovarian function in animal experiments. In this article we describe the importance of ZP in oocyte growth and the possible effects of anti-ZP antibodies on ovarian failure. Clinical experiments were conducted to detect anti-ZP antibodies in POF patients by dot immunoassay and immunofluorescent staining method. Also, as an animal model experiment, we examined whether or not peptide ZP antigens of same-species amino acid sequences could produce autoantibodies reactive to ZP. The results showed that antibodies were produced by immunisation with the antigens and histological examination revealed that the number of growing follicles was considerably reduced. These results conclusively indicated that self-ZP protein is a possible pathogenic antigen for autoimmunity causing POF.

  7. Prevalence and clinical significance of nonorgan specific antibodies in patients with autoimmune thyroiditis as predictor markers for rheumatic diseases (United States)

    Elnady, Basant M.; Kamal, Naglaa M.; Shaker, Raneyah H.M.; Soliman, Amal F.; Hasan, Waleed A.; Alghamdi, Hamed A.; Algethami, Mohammed M.; Jajah, Mohamed Bilal


    Abstract Autoimmune diseases are considered the 3rd leading cause of morbidity and mortality in the industrialized countries. Autoimmune thyroid diseases (ATDs) are associated with high prevalence of nonorgan-specific autoantibodies, such as antinuclear antibodies (ANA), antidouble-stranded deoxyribonucleic acid (anti-dsDNA), antiextractable-nuclear antigens (anti-ENAs), rheumatoid factor (RF), and anticyclic-citrullinated peptides (anti-CCP) whose clinical significance is unknown. We aimed to assess the prevalence of various nonorgan-specific autoantibodies in patients with ATD, and to investigate the possible association between these autoantibodies and occurrence of rheumatic diseases and, if these autoantibodies could be considered as predictor markers for autoimmune rheumatic diseases in the future. This study had 2 phases: phase 1; in which 61 ATD patients free from rheumatic manifestations were assessed for the presence of these nonorgan-specific autoantibodies against healthy 61 control group, followed by 2nd phase longitudinal clinical follow-up in which cases are monitored systematically to establish occurrence and progression of any rheumatic disease in association to these autoantibodies with its influences and prognosis. Regarding ATD patients, ANA, anti-dsDNA, Anti-ENA, and RF were present in a percentage of (50.8%), (18%), (21.3%), and (34.4%), respectively, with statistically significance difference (P < 0.5) rather than controls. Nearly one third of the studied group (32.8%) developed the rheumatic diseases, over 2 years follow-up. It was obvious that those with positive anti-dsDNA had higher risk (2.45 times) to develop rheumatic diseases than those without. There was a statistically significant positive linear relationship between occurrence of disease in months and (age, anti-dsDNA, anti-CCP, RF, and duration of thyroiditis). Anti-dsDNA and RF are the most significant predictors (P < 0.0001). ATD is more associated with rheumatic

  8. Autoimmune Hemolytic Anemia. (United States)

    Liebman, Howard A; Weitz, Ilene C


    Autoimmune hemolytic anemia is an acquired autoimmune disorder resulting in the production of antibodies directed against red blood cell antigens causing shortened erythrocyte survival. The disorders can present as a primary disorder (idiopathic) or secondary to other autoimmune disorders, malignancies, or infections. Treatment involves immune modulation with corticosteroids and other agents.

  9. Preventing intense false positive and negative reactions attributed to the principle of ELISA to re-investigate antibody studies in autoimmune diseases. (United States)

    Terato, Kuniaki; Do, Christopher T; Cutler, Dawn; Waritani, Takaki; Shionoya, Hiroshi


    To study the possible involvement of potential environmental pathogens in the pathogenesis of autoimmune diseases, it is essential to investigate antibody responses to a variety of environmental agents and autologous components. However, none of the conventional ELISA buffers can prevent the false positive and negative reactions attributed to its principal, which utilizes the high binding affinity of proteins to plastic surfaces. The aims of this study are to reveal all types of non-specific reactions associated with conventional buffer systems, and to re-investigate antibody responses to potential environmental pathogenic and autologous antigens in patients with autoimmune diseases using a newly developed buffer system "ChonBlock™" by ELISA. Compared to conventional buffers, the new buffer was highly effective in reducing the most intense false positive reaction caused by hydrophobic binding of immunoglobulin in sample specimens to plastic surfaces, "background (BG) noise reaction", and other non-specific reactions without interfering with antigen-antibody reactions. Applying this buffer, we found that IgG antibody responses to Escherichia coli O111:B4, E. coli lipopolysaccharide (LPS) and peptidoglycan polysaccharide (PG-PS) were significantly lower or tended to be lower in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), whereas IgA antibody responses to these antigens were equal or tended to be higher compared to normal controls. As a consequence, the IgA/IgG antibody ratios against these agents were significantly higher in patients with RA and SLE, except for Crohn's disease, which showed significantly higher IgG responses to these antigens. To assay antibodies in human sera, it is indispensable to eliminate false positive and negative reactions by using an appropriate buffer system, and to include antigen non-coated blank wells to determine BG noise reactions of invidual samples. Finally, based on our preliminary analysis in

  10. Myelin sheaths and autoimmune response induced by myelin proteins and alphaviruses. I. Physicochemical background. (United States)

    Sedzik, Jan


    Myelin proteins of the central and peripheral nervous system range from very hydrophilic to extremely hydrophobic proteins. Their biological function and involvement in various clinically defined neurological diseases are well documented. In this review the myelin proteins will be compared with proteins of alphaviruses with emphasis on Semliki Forest Virus (strain pSP6-SFV4), to elucidate better the multiple function and the potential role in several neurological diseases. The main purpose of this review is to assist neuroscientists, neurochemists, neurologists, and other interested scientists in developing a better understanding on the information relating to myelin proteins referred in autoimmune diseases. Therefore, this review is focused on simple physiochemical background of proteins and structural aspect, which may be involved in autoimmunity. It is very unusual that few different a.a. sequences (epitops) induce indeed the same autoimmune reaction.

  11. Autoimmune hepatitis. (United States)

    Heneghan, Michael A; Yeoman, Andrew D; Verma, Sumita; Smith, Alastair D; Longhi, Maria Serena


    Autoimmune hepatitis is a disease of the hepatic parenchyma that can present in acute or chronic forms. In common with many autoimmune diseases, autoimmune hepatitis is associated with non-organ-specific antibodies in the context of hepatic autoimmunity. This dichotomy has made definition of a unifying hypothesis in the pathophysiology of the disease difficult, although data from the past 8 years have drawn attention to the role of regulatory T cells. Several triggers have been identified, and the disease arises in genetically susceptible individuals. Clinical and biochemical remission is achievable in up to 85% of cases. For the remaining patients, alternative immunosuppression strategies are an option. Liver transplantation provides an excellent outcome for patients with acute liver failure or complications of end-stage liver disease, including hepatocellular carcinoma. Variant or overlapping syndromes are worthy of consideration when unexpected disease features arise.

  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.


    Institute of Scientific and Technical Information of China (English)

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


    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

  14. Complement-fixing properties of antinuclear antibodies distinguish drug-induced lupus from systemic lupus erythematosus. (United States)

    Rubin, R L; Teodorescu, M; Beutner, E H; Plunkett, R W


    The immunofluorescence antinuclear antibody (ANA) test has been widely used to monitor autoimmune disease, but its value for diagnostic purposes is compromised by low specificity and high prevalence in disease-free individuals. The capacity of autoantibodies to fix serum complement proteins when bound to antigen is an important effector function because this property is associated with acute and chronic inflammatory processes. The current study evaluates the complement-fixing properties of antinuclear antibodies (CANA) in three well-defined and clinically-related patient groups: systemic lupus erythematosus (SLE), drug-induced lupus (DIL) and drug-induced autoimmunity (DIA). Of 20 patients diagnosed with SLE, 90% displayed complement-fixing ANA while this feature was present in only two of 18 patients with DIL and no patients with DIA without associated disease even though the mean ANA titres were similar among these patient groups. CANA was significantly correlated with anti-Sm activity. Because SLE but not DIL or DIA can be a life-threatening disease associated with complement consumption in vivo, these results demonstrate that measurement of CANA is a diagnostically useful tool and may have immunopathologic implications.

  15. The epidemiologic evidence linking autoimmune diseases and psychosis. (United States)

    Benros, Michael E; Eaton, William W; Mortensen, Preben B


    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, there is some evidence of associations of psychosis with a family history of autoimmune disorders and vice versa. Additionally, several autoimmune diseases, individually and in aggregate, have been identified as raising the risk for psychotic disorders in longitudinal studies. The associations have been suspected to be caused by inflammation or brain-reactive antibodies associated with the autoimmune diseases. However, the associations could also be caused by shared genetic factors or common etiologic components such as infections. Infections can induce the development of autoimmune diseases and autoantibodies, possibly affecting the brain. Autoimmune diseases and brain-reactive antibodies should be considered by clinicians in the treatment of individuals with psychotic symptoms, and even if the association is not causal, treatment would probably still improve quality of life and survival.

  16. Evaluation of epitopes specificity of antibodies to thyroid peroxidase in autoimmune thyroid disorders

    Directory of Open Access Journals (Sweden)

    A V Subkov


    Full Text Available The problem of the human antithyroid peroxidase autoantibodies epitopes heterogeneity diagnosed in case of Graves' disease and Hashimoto's thyroiditis has been researched using monoclonal antibodies to thyroid peroxidase. It was shown, that in the competition for the binding sites of thyroid peroxidase and autoantibodies taken from patients with Graves' disease and Hashimoto's thyroiditis sera participate 8 mAb to epitopes 1, 70, 82, 88, 2, 3, 77 and 79. The maxima of the binding inhibition has been marked for the conformation epitope mAb 3: in case of Graves' disease it amounts to 60.3 ± 12.7%, in case of Hashimoto's thyroiditis – 61.8 ± 32.2%. Moreover the level of the binding inhibition did not depend on the concentration of Ab to thyroid peroxidase in the sera of patient with Graves' as opposed to the serum of patients with Hashimoto's thyroiditis. Autoantibodies in the serum of the patientswith Hashimoto's thyroiditis inhibited the binding of mAb to epitope 77 much more effectively, than in the serum of the patients with: 36.3 ± 17.2 and 54.3 ± 9.6% (p ≤ 0.05.The obtained results represented the specific reaction of the autoantibodies to the certain thyroid peroxidase molecular patterns which corresponds to the literature data. It is possible to assume that the further research of the competitive interactions with other autoantibodies to monoclonal antibodies, not included in this trial, and widening of the different thyroid diseased patients' serum palette can expose new immunodominant thyroid peroxidase molecular patterns, forming antibodies for different diseases, and enable the development of diagnostics and control of the thyroid functions and applied therapy.

  17. Rituximab induces sustained reduction of pathogenic B cells in patients with peripheral nervous system autoimmunity (United States)

    Maurer, Michael A.; Rakocevic, Goran; Leung, Carol S.; Quast, Isaak; Lukačišin, Martin; Goebels, Norbert; Münz, Christian; Wardemann, Hedda; Dalakas, Marinos; Lünemann, Jan D.


    The B cell–depleting IgG1 monoclonal antibody rituximab can persistently suppress disease progression in some patients with autoimmune diseases. However, the mechanism underlying these long-term beneficial effects has remained unclear. Here, we evaluated Ig gene usage in patients with anti–myelin-associated glycoprotein (anti-MAG) neuropathy, an autoimmune disease of the peripheral nervous system that is mediated by IgM autoantibodies binding to MAG antigen. Patients with anti-MAG neuropathy showed substantial clonal expansions of blood IgM memory B cells that recognized MAG antigen. The group of patients showing no clinical improvement after rituximab therapy were distinguished from clinical responders by a higher load of clonal IgM memory B cell expansions before and after therapy, by persistence of clonal expansions despite efficient peripheral B cell depletion, and by a lack of substantial changes in somatic hypermutation frequencies of IgM memory B cells. We infer from these data that the effectiveness of rituximab therapy depends on efficient depletion of noncirculating B cells and is associated with qualitative immunological changes that indicate reconfiguration of B cell memory through sustained reduction of autoreactive clonal expansions. These findings support the continued development of B cell–depleting therapies for autoimmune diseases. PMID:22426210

  18. Structural characterization and optimization of antibody-selected phage library mimotopes of an antigen associated with autoimmune recurrent thrombosis. (United States)

    Sem, D S; Baker, B L; Victoria, E J; Jones, D S; Marquis, D; Yu, L; Parks, J; Coutts, S M


    The presence of high titers of anti-cardiolipin antibodies (ACA's) of autoimmune origin, which are known to bind to plasma beta2-glycoprotein I (aka apolipoprotein H), correlates clinically with autoimmune recurrent thrombosis. Soluble beta2-glycoprotein I binds to solid-phase ACA (immobilized on a surface plasmon resonance chip) with a Kd of 1.4 microM, but if the reactants are reversed and beta2-glycoprotein I is on the solid-phase support, then the Kd is 52 nM. This 27-fold difference in affinity reflects the avidity/entropic advantage obtained for an antibody binding to an antigen that is made multivalent because it is attached to a solid phase. A mimotope of this antigen, selected from a phage display peptide library screen with an ACA, has been shown to bind to solid-phase ACA as a phage, using surface plasmon resonance. This peptide is representative of the motif from 37 peptides obtained in a previously reported phage library screen with this ACA (1). A synthetic version of this peptide, referred to as P4, has the sequence: A1G2P3C4I5L6L7A8R9D10R11C12P13G14, and binds to its selecting antibody with a Kd of 42 nM. NMR data indicate that proline-13 is present in both cis and trans configurations, and that these two geometries dramatically affect the overall tertiary structure of the molecule. The peptide lacking this proline binds severalfold better to the ACA, consistent with at least one of these structures having low affinity for binding ACA. Replacement of the arginine-9 position with a proline decreases binding affinity to ACA 10-fold. Another phage library-selected peptide has a proline in position 9, but also has a leucine in position 5, instead of isoleucine. Since its affinity for ACA is nearly as good as that for peptide P4, the phage library screening must have selected for a non-beta-branched amino acid in this position to compensate for the adverse effects of the arginine-9 to proline-9 substitution. The solution structure of a modified version

  19. Evaluation of the LIAISON ANA screen assay for antinuclear antibody testing in autoimmune diseases. (United States)

    Ghillani, P; Rouquette, A M; Desgruelles, C; Hauguel, N; Le Pendeven, C; Piette, J C; Musset, L


    Antinuclear antibodies (ANA) are widely detected by immunofluorescence on HEp-2 cells in patients with connective tissue diseases and other pathological conditions. We evaluated the first-automated chemiluminescence immunoassay for the detection of ANA (LIAISON ANA screen, DiaSorin). This study was carried out simultaneously in two laboratories by testing 327 patient samples with clinically defined connective diseases, 273 routine samples for ANA screening, and 300 blood donors. A total of 268 out of 337 IIF-positive sera were positive with LIAISON ANA screen (79.5% of agreement) and 240 out of 263 IIF-negative sera were negative with LIAISON ANA screen (91.2% of agreement). After resolution of discrepant results, the concordance reached, respectively, 94.9% and 98.8%. The specificity was 99.3% and the sensitivity was 94%. Unlike results obtained by other ANA screening assays, we observed acceptable sensitivity and specificity. Despite the presence of HEp-2 cell extract, we failed to detect some antibodies as antinucleolar, antinuclear envelope, and antiproliferating cell nuclear antigen. This automated assay allows quick process to results and exhibits satisfactory sensitivity for the detection of the main ANA specificities of connective tissue diseases.

  20. Celiac Anti-Type 2 Transglutaminase Antibodies Induce Phosphoproteome Modification in Intestinal Epithelial Caco-2 Cells (United States)

    Marabotti, Anna; Lepretti, Marilena; Salzano, Anna Maria; Scaloni, Andrea; Vitale, Monica; Zambrano, Nicola; Sblattero, Daniele; Esposito, Carla


    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 identified in this study

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

    Directory of Open Access Journals (Sweden)

    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

  2. Myelin-reactive antibodies initiate T cell-mediated CNS autoimmune disease by opsonization of endogenous antigen. (United States)

    Kinzel, Silke; Lehmann-Horn, Klaus; Torke, Sebastian; Häusler, Darius; Winkler, Anne; Stadelmann, Christine; Payne, Natalie; Feldmann, Linda; Saiz, Albert; Reindl, Markus; Lalive, Patrice H; Bernard, Claude C; Brück, Wolfgang; Weber, Martin S


    In the pathogenesis of central nervous system (CNS) demyelinating disorders, antigen-specific B cells are implicated to act as potent antigen-presenting cells (APC), eliciting waves of inflammatory CNS infiltration. Here, we provide the first evidence that CNS-reactive antibodies (Ab) are similarly capable of initiating an encephalitogenic immune response by targeting endogenous CNS antigen to otherwise inert myeloid APC. In a transgenic mouse model, constitutive production of Ab against myelin oligodendrocyte glycoprotein (MOG) was sufficient to promote spontaneous experimental autoimmune encephalomyelitis (EAE) in the absence of B cells, when mice endogenously contained MOG-recognizing T cells. Adoptive transfer studies corroborated that anti-MOG Ab triggered activation and expansion of peripheral MOG-specific T cells in an Fc-dependent manner, subsequently causing EAE. To evaluate the underlying mechanism, anti-MOG Ab were added to a co-culture of myeloid APC and MOG-specific T cells. At otherwise undetected concentrations, anti-MOG Ab enabled Fc-mediated APC recognition of intact MOG; internalized, processed and presented MOG activated naïve T cells to differentiate in an encephalitogenic manner. In a series of translational experiments, anti-MOG Ab from two patients with an acute flare of CNS inflammation likewise facilitated detection of human MOG. Jointly, these observations highlight Ab-mediated opsonization of endogenous CNS auto-antigen as a novel disease- and/or relapse-triggering mechanism in CNS demyelinating disorders.

  3. 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


    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.

  4. Early Detection of T cell Transfer-induced Autoimmune Colitis by In Vivo Imaging System


    Yu-Ling Chen; Yi-Ting Chen; Cheng-Feng Lo; Ching-I Hsieh; Shang-Yi Chiu; Chang-Yen Wu; Yu-Shan Yeh; Shu-Hsuan Hung; Po-Hao Cheng; Yu-Hsuan Su; Si-Tse Jiang; Hsian-Jean Chin; Yu-Chia Su


    Inflammatory bowel disease is a chronic and progressive inflammatory intestinal disease that includes two major types, namely ulcerative colitis and Crohn’s disease (CD). CD is characterized by intestinal epithelial hyperplasia and inflammatory cell infiltration. Transfer of CD25−CD45RBhiCD4+ (naïve) T cells into immunodeficiency mice induces autoimmune colitis with pathological lesions similar to CD and loss of body weight 4 weeks after cell transfer. However, weight loss neither has suffici...

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

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


    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.

  6. Microarray Analysis of Antibodies Induced with Synthetic Antitumor Vaccines: Specificity against Diverse Mucin Core Structures. (United States)

    Pett, Christian; Cai, Hui; Liu, Jia; Palitzsch, Björn; Schorlemer, Manuel; Hartmann, Sebastian; Stergiou, Natascha; Lu, Mengji; Kunz, Horst; Schmitt, Edgar; Westerlind, Ulrika


    Glycoprotein research is pivotal for vaccine development and biomarker discovery. Many successful methodologies for reliably increasing the antigenicity toward tumor-associated glycopeptide structures have been reported. Deeper insights into the quality and specificity of the raised polyclonal, humoral reactions are often not addressed, despite the fact that an immunological memory, which produces antibodies with cross-reactivity to epitopes exposed on healthy cells, may cause autoimmune diseases. In the current work, three MUC1 antitumor vaccine candidates conjugated with different immune stimulants are evaluated immunologically. For assessment of the influence of the immune stimulant on antibody recognition, a comprehensive library of mucin 1 glycopeptides (>100 entries) is synthesized and employed in antibody microarray profiling; these range from small tumor-associated glycans (TN , STN , and T-antigen structures) to heavily extended O-glycan core structures (type-1 and type-2 elongated core 1-3 tri-, tetra-, and hexasaccharides) glycosylated in variable density at the five different sites of the MUC1 tandem repeat. This is one of the most extensive glycopeptide libraries ever made through total synthesis. On tumor cells, the core 2 β-1,6-N-acetylglucosaminyltransferase-1 (C2GlcNAcT-1) is down-regulated, resulting in lower amounts of the branched core 2 structures, which favor formation of linear core 1 or core 3 structures, and in particular, truncated tumor-associated antigen structures. The core 2 structures are commonly found on healthy cells and the elucidation of antibody cross-reactivity to such epitopes may predict the tumor-selectivity and safety of synthetic vaccines. With the extended mucin core structures in hand, antibody cross-reactivity toward the branched core 2 glycopeptide epitopes is explored. It is observed that the induced antibodies recognize MUC1 peptides with very high glycosylation site specificity. The nature of the

  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


    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. A Distinct Class of Antibodies May Be an Indicator of Gray Matter Autoimmunity in Early and Established Relapsing Remitting Multiple Sclerosis Patients

    Directory of Open Access Journals (Sweden)

    Ann J. Ligocki


    Full Text Available * These authors contributed equally to the work in this manuscript.We have previously identified a distinct class of antibodies expressed by B cells in the cerebrospinal fluid (CSF of early and established relapsing remitting multiple sclerosis (RRMS patients that is not observed in healthy donors. These antibodies contain a unique pattern of mutations in six codons along VH4 antibody genes that we termed the antibody gene signature (AGS. In fact, patients who have such B cells in their CSF are identified as either having RRMS or developing RRMS in the future. As mutations in antibody genes increase antibody affinity for particular antigens, the goal for this study was to investigate whether AGS+ antibodies bind to brain tissue antigens. Single B cells were isolated from the CSF of 10 patients with early or established RRMS. We chose 32 of these B cells that expressed antibodies enriched for the AGS for further study. We generated monoclonal full-length recombinant human antibodies (rhAbs and used both immunological assays and immunohistochemistry to investigate the capacity of these AGS+ rhAbs to bind brain tissue antigens. AGS+ rhAbs did not recognize myelin tracts in the corpus callosum. Instead, AGS+ rhAbs recognized neuronal nuclei and/or astrocytes, which are prevalent in the cortical gray matter. This pattern was unique to the AGS+ antibodies from early and established RRMS patients, as AGS+ antibodies from an early neuromyelitis optica patient did not display the same reactivity. Prevalence of CSF-derived B cells expressing AGS+ antibodies that bind to these cell types may be an indicator of gray matter-directed autoimmunity in early and established RRMS patients.

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

    DEFF Research Database (Denmark)

    Espejo, C.; Penkowa, Milena; Saez-Torres, I.


    Neuroinflammation, neuronal degeneration, regeneration, monoclonal antibodies, multiple schlerosis......Neuroinflammation, neuronal degeneration, regeneration, monoclonal antibodies, multiple schlerosis...

  10. Pregnancy outcomes in patients with autoimmune diseases and anti-Ro/SSA antibodies. (United States)

    Brucato, Antonio; Cimaz, Rolando; Caporali, Roberto; Ramoni, Véronique; Buyon, Jill


    Anti-Ro/SSA antibodies are associated with neonatal lupus (congenital heart block (CHB), neonatal transient skin rash, hematological and hepatic abnormalities), but do not negatively affects other gestational outcomes, and the general outcome of these pregnancies is now good, when followed by experienced multidisciplinary teams. The prevalence of CHB, defined as an atrioventricular block diagnosed in utero, at birth, or within the neonatal period (0-27 days after birth), in the offspring of an anti-Ro/SSA-positive women is 1-2%, of neonatal lupus rash around 10-20%, while laboratory abnormalities in asymptomatic babies can be detected in up to 27% of cases. The risk of recurrence of CHB is ten times higher. Most of the mothers are asymptomatic at delivery and are identified only by the birth of an affected child. Half of these asymptomatic women develop symptoms of a rheumatic disease, most commonly arthralgias and xerophtalmia, but few develop lupus nephritis. A standard therapy for CHB is still matter of investigation, although fluorinated corticosteroids have been reported to be effective for associated cardiomyopathy. Serial echocardiograms and obstetric sonograms, performed at least every 1-2 weeks starting from the 16th week of gestational age, are recommended in anti-Ro/SSA-positive pregnant women to detect early fetal abnormalities that might be a target of preventive therapy.

  11. Antibody responses to mycobacterial and self heat shock protein 65 in autoimmune arthritis: epitope specificity and implication in pathogenesis. (United States)

    Kim, Hong Ro; Kim, Eugene Y; Cerny, Jan; Moudgil, Kamal D


    Many autoimmune diseases are believed to involve primarily T cell-mediated effector mechanisms. There is increasing realization, however, that Abs may also play a vital role in the propagation of T cell-driven disorders. In this study, on the rat adjuvant-induced arthritis (AA) model of human rheumatoid arthritis, we examined the characteristics of serum Ab response to mycobacterial heat shock protein (hsp) 65 (Bhsp65), self (rat) hsp65 (Rhsp65), and linear peptides spanning these two molecules. The AA-resistant WKY (RT.1(l)) rat responded to the heat-killed Mycobacterium tuberculosis immunization with a rapid burst of Abs to both Bhsp65 and Rhsp65. These Abs reacted with numerous peptide epitopes; however, this response was reduced to a few epitopes with time. On the contrary, the susceptible Lewis (RT.1(l)) rat developed a relatively lower Ab response to Bhsp65, and Abs to Rhsp65 did not appear until the recovery from the disease. The Ab response in Lewis rats diversified with progression of AA, and there was an intriguing overlap between the repertoire of Bhsp65-reactive B and T cells during the recovery phase of AA. Nonetheless, subsets of the repertoire of the late Abs in both rat strains became focused on the same epitope regions of Bhsp65 and Rhsp65. The functional relevance of these Abs was evident from the results showing that sera from recovery phase Lewis or WKY rats, but not that of naive rats, afforded protection against subsequent AA. These results are of significance in further understanding of the role of humoral immunity in the pathogenesis of autoimmune arthritis.

  12. Familial clustering of juvenile thyroid autoimmunity: higher risk is conferred by human leukocyte antigen DR3-DQ2 and thyroid peroxidase antibody status in fathers. (United States)

    Segni, Maria; Pani, Michael A; Pasquino, Anna Maria; Badenhoop, Klaus


    Thyroid autoimmunity is one of the most common immune disorders in females, and its polygenic background remains to be elucidated. The human leukocyte antigen (HLA) DQ region of chromosome 6 has been shown to confer susceptibility to thyroid autoimmune disease. The aim of our present investigation was to determine whether the transmission of high risk HLA DQ to patients with thyroid autoimmunity differs when transmission is from fathers as opposed to when transmission is from mothers. We studied 91 juvenile patients with chronic lymphocytic thyroiditis (68 females and 23 males; mean age, 10.5 +/- 3.9 yr), 12 patients with Graves' disease (all females; mean age, 8.8 +/- 4.0 yr), 53 healthy siblings, and their parents for thyroid function, antibodies, ultrasound, and DNA typing for HLA DQ susceptibility alleles. We observed an increased rate of transmission for the DQA1*0501-DQB1*0201 (DQ2) haplotype [35 of 53 transmitted (66%); P = 0.02]. This allele was preferentially transmitted by fathers [21 of 27 (78%); P < 0.004], whereas the maternal DQ2 haplotypes were not transmitted more often than expected. Subsequently, families were stratified as follows according to the parental thyroid peroxidase antibody (TPOAb) status: no parent, only mothers, only fathers, and both parents positive. There was no significant maternal transmission disequilibrium in any subset, but the paternal HLA DQ2 was preferentially transmitted [11 of 14 cases (79%); P = 0.03] in the group of TPOAb-positive mothers, and we observed a similar trend in the group of TPOAb- positive fathers (P = 0.08). Also, the portion of offspring affected by Graves' disease was significantly higher in TPOAb-positive than in TPOAb-negative fathers (P < 0.02). In conclusion, our findings demonstrate a significant effect of paternal HLA DQ alleles as well as antibody status on susceptibility to thyroid autoimmune disease in juvenile patients.

  13. High throughput screening for antibody induced complement-dependent cytotoxicity in early antibody discovery using homogeneous macroconfocal fluorescence imaging

    NARCIS (Netherlands)

    Gerritsen, Arnout F.; Bosch, Martijn; de Weers, Michel; van de Winkel, Jan G. J.; Parren, Paul W. H. I.


    Complement-dependent cytotoxicity (CDC) represents an important Fc-mediated effector function of antibodies and is a quality often sought in candidates for therapeutic antibody development in cancer. Antibodies inducing potent CDC are relatively rare as the ability to induce CDC is strongly dependen

  14. Therapeutic Targeting of CD6 in Autoimmune Diseases: A Review of Cuban Clinical Studies with the Antibodies IOR-T1 and Itolizumab. (United States)

    Hernández, Patricia; Moreno, Ernesto; Aira, Lazaro E; Rodríguez, Pedro C


    The CD6 molecule is a pan T cell marker involved in T cell regulation. Although CD6 expression has been correlated with human autoimmune diseases, only a few therapeutic approaches are exploring this molecule as target in the clinic. The biological functions and mechanisms of actions of CD6 have not been definitively established. It is probable that this molecule plays a dual role as a modulator of intracellular signaling. Itolizumab is a humanized monoclonal antibody specific for human CD6, developed at the Center of Molecular Immunology in Havana, Cuba. Its parent murine antibody, the IOR-T1 mAb, had been obtained in the 80's at the Institute of Oncology and Radiology, also in Havana. This article provides an overview of the clinical data obtained in Cuban patients with autoimmune diseases who have been treated with IOR-T1 mAb or itolizumab. Furthermore, we discuss the possible mechanism of action of itolizumab basing the analysis on recent site mutagenesis and structural data, which, contrary to previous interpretations, points to a steric blocking of the CD6-CD166 interaction in the cellular context. Overall, the conducted clinical studies have demonstrated that itolizumab has favorable clinical effects and a safety profile when used as monotherapy in patients with rheumatoid arthritis and psoriasis. So far, in vitro and in vivo evidences indicate that itolizumab has immunomodulatory and anti-inflammatory effects. Hence, itolizumab represents a new therapeutic option for autoimmune diseases such as rheumatoid arthritis and psoriasis.

  15. 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;


    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...

  16. Predictive value of antinuclear antibodies in autoimmune diseases classified by clinical criteria: Analytical study in a specialized health institute, one year follow-up (United States)

    Soto, María Elena; Hernández-Becerril, Nidia; Perez-Chiney, Ada Claudia; Hernández-Rizo, Alfredo; Telich-Tarriba, José Eduardo; Juárez-Orozco, Luis Eduardo; Melendez, Gabriela; Bojalil, Rafael


    Introduction: Determination of antinuclear antibodies (ANA) by indirect immunofluorescence (IIF) is usually the initial test for the diagnosis of systemic rheumatic diseases (SRD). Assigning predictive values to positive and negative results of the test is vital because lack of knowledge about ANAs and their usefulness in classification criteria of SRD leads to inappropriate use. Methods: Retrospective study, ANA tests requested by different specialties, correlation to patients' final diagnosis. Results: The prevalence of autoimmune disease was relatively low in our population yielding a low PPV and a high NPV for the ANA test. 40% of the patients had no clinical criteria applied prior to test. Coexistence of two or more autoimmune disorders affects prevalence and predictive values. Conclusion: Application of the test after careful evaluation for clinical criteria remarkably improves the positive likelihood ratio for the diagnosis. PMID:26623249

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

    Directory of Open Access Journals (Sweden)

    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

  18. Drug-induced autoimmune liver disease: A diagnostic dilemma of an increasingly reported disease. (United States)

    Castiella, Agustin; Zapata, Eva; Lucena, M Isabel; Andrade, Raúl J


    The aetiology of autoimmune hepatitis (AIH) is uncertain but the disease can be triggered in susceptible patients by external factors such as viruses or drugs. AIH usually develops in individuals with a genetic background mainly consisting of some risk alleles of the major histocompatibility complex (HLA). Many drugs have been linked to AIH phenotypes, which sometimes persist after drug discontinuation, suggesting that they awaken latent autoimmunity. At least three clinical scenarios have been proposed that refers to drug- induced autoimmune liver disease (DIAILD): AIH with drug-induced liver injury (DILI); drug induced-AIH (DI-AIH); and immune mediated DILI (IM-DILI). In addition, there are instances showing mixed features of DI-AIH and IM-DILI, as well as DILI cases with positive autoantibodies. Histologically distinguishing DILI from AIH remains a challenge. Even more challenging is the differentiation of AIH from DI-AIH mainly relying in histological features; however, a detailed standardised histologic evaluation of large cohorts of AIH and DI-AIH patients would probably render more subtle features that could be of help in the differential diagnosis between both entities. Growing information on the relationship of drugs and AIH is being available, being drugs like statins and biologic agents more frequently involved in cases of DIAILD. In addition, there is some evidence on the fact that patients diagnosed with DIAILD may have had a previous episode of hepatotoxicity. Further collaborative studies in DIAILD will strengthen the knowledge and understanding of this intriguing and complex disorder which might represent different phenotypes across the spectrum of disease.

  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. Prospective investigation of pituitary functions in patients with acute infectious meningitis: is acute meningitis induced pituitary dysfunction associated with autoimmunity? (United States)

    Tanriverdi, F; De Bellis, A; Teksahin, H; Alp, E; Bizzarro, A; Sinisi, A A; Bellastella, G; Paglionico, V A; Bellastella, A; Unluhizarci, K; Doganay, M; Kelestimur, F


    Previous case reports and retrospective studies suggest that pituitary dysfunction may occur after acute bacterial or viral meningitis. In this prospective study we assessed the pituitary functions, lipid profile and anthropometric measures in adults with acute bacterial or viral meningitis. Moreover, in order to investigate whether autoimmune mechanisms could play a role in the pathogenesis of acute meningitis-induced hypopituitarism we also investigated the anti-pituitary antibodies (APA) and anti-hypothalamus antibodies (AHA) prospectively. Sixteen patients (10 males, 6 females; mean ± SD age 40.9 ± 15.9) with acute infectious meningitis were included and the patients were evaluated in the acute phase, and at 6 and 12 months after the acute meningitis. In the acute phase 18.7% of the patients had GH deficiency, 12.5% had ACTH and FSH/LH deficiencies. At 12 months after acute meningitis 6 of 14 patients (42.8%) had GH deficiency, 1 of 14 patients (7.1%) had ACTH and FSH/LH deficiencies. Two of 14 patients (14.3%) had combined hormone deficiencies and four patients (28.6%) had isolated hormone deficiencies at 12 months. Four of 9 (44.4%) hormone deficiencies at 6 months were recovered at 12 months, and 3 of 8 (37.5%) hormone deficiencies at 12 months were new-onset hormone deficiencies. At 12 months there were significant negative correlations between IGF-I level vs. LDL-C, and IGF-I level vs. total cholesterol. The frequency of AHA and APA positivity was substantially high, ranging from 35 to 50% of the patients throughout the 12 months period. However there were no significant correlations between AHA or APA positivity and hypopituitarism. The risk of hypopituitarism, GH deficiency in particular, is substantially high in the acute phase, after 6 and 12 months of the acute infectious meningitis. Moreover we found that 6th month after meningitis is too early to make a decision for pituitary dysfunction and these patients should be screened for at least 12 months

  1. [Autoimmune Associated Encephalitis and Dementia]. (United States)

    Watanabe, Osamu


    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.

  2. 药源性自身免疫性疾病%Drug-induced Autoimmunity

    Institute of Scientific and Technical Information of China (English)

    李洪波; 林玲


    自从1945年首次报道磺胺嘧啶引起狼疮样症状至今,越来越多的药物被报道能影响人体免疫系统从而诱发自身免疫性疾病,药源性自身免疫性疾病(drug-induced autoimmunity, DIA)的关注度越来越高,但目前DIA的致病机制尚未完全阐明,尚未制定一个合适的诊断标准,治疗和预防也缺乏系统的循证医学证据。本文就 DIA的一般临床特征、致病机制、实验室检查特点、诊断、预防和治疗进行综合。%Since sulfadiazine associated lupus-like symptoms were first described in 1945, more and more drugs have been reported to interfere with the immune system and induce a series of autoimmune diseases ( named drug-induced autoimmunity, DIA ) . However, the pathogenesis of DIA has not been fully clarified, and the standardized criteria for DIA diagnosis has not been established, and it is also lack of systematic research on its treatment and prevention. In this review, we summarize the clinical features, pathogenesis, laboratory findings, diagnosis, prevention and treatment of DIA.

  3. Hapten-Induced Contact Hypersensitivity, Autoimmune Reactions, and Tumor Regression: Plausibility of Mediating Antitumor Immunity

    Directory of Open Access Journals (Sweden)

    Dan A. Erkes


    Full Text Available Haptens are small molecule irritants that bind to proteins and elicit an immune response. Haptens have been commonly used to study allergic contact dermatitis (ACD using animal contact hypersensitivity (CHS models. However, extensive research into contact hypersensitivity has offered a confusing and intriguing mechanism of allergic reactions occurring in the skin. The abilities of haptens to induce such reactions have been frequently utilized to study the mechanisms of inflammatory bowel disease (IBD to induce autoimmune-like responses such as autoimmune hemolytic anemia and to elicit viral wart and tumor regression. Hapten-induced tumor regression has been studied since the mid-1900s and relies on four major concepts: (1 ex vivo haptenation, (2 in situ haptenation, (3 epifocal hapten application, and (4 antigen-hapten conjugate injection. Each of these approaches elicits unique responses in mice and humans. The present review attempts to provide a critical appraisal of the hapten-mediated tumor treatments and offers insights for future development of the field.

  4. Heterogeneous antigen recognition behavior of induced polyspecific antibodies. (United States)

    Dimitrov, Jordan D; Planchais, Cyril; Kang, Jonghoon; Pashov, Anastas; Vassilev, Tchavdar L; Kaveri, Srinivas V; Lacroix-Desmazes, Sebastien


    Polyspecific antibodies represent a significant fraction of the antibody repertoires in healthy animals and humans. Interestingly, certain antibodies only acquire a polyspecific antigen-binding behavior after exposure to protein-modifying conditions, such as those found at inflammation sites, or used in small- and large-scale immunoglobulin purification. This phenomenon is referred to as "criptic polyspecificity". In the present study, we compare the potential of different chemical agents to induce IgG polyspecificity. Depending on the treatment used, quantitative and qualitative differences in the recognition of individual antigens from a standard panel were observed. Antibodies with cryptic polyspecificity utilized common mechanisms for the recognition of structurally unrelated antigens when exposed to a particular inductor of polyspecificity. Our study contributes to the understanding of the mechanisms underlying the cryptic polyspecificity.

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

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


    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.

  6. Flavivirus-induced antibody cross-reactivity. (United States)

    Mansfield, Karen L; Horton, Daniel L; Johnson, Nicholas; Li, Li; Barrett, Alan D T; Smith, Derek J; Galbraith, Sareen E; Solomon, Tom; Fooks, Anthony R


    Dengue viruses (DENV) cause countless human deaths each year, whilst West Nile virus (WNV) has re-emerged as an important human pathogen. There are currently no WNV or DENV vaccines licensed for human use, yet vaccines exist against other flaviviruses. To investigate flavivirus cross-reactivity, sera from a human cohort with a history of vaccination against tick-borne encephalitis virus (TBEV), Japanese encephalitis virus (JEV) and yellow fever virus (YFV) were tested for antibodies by plaque reduction neutralization test. Neutralization of louping ill virus (LIV) occurred, but no significant neutralization of Murray Valley encephalitis virus was observed. Sera from some individuals vaccinated against TBEV and JEV neutralized WNV, which was enhanced by YFV vaccination in some recipients. Similarly, some individuals neutralized DENV-2, but this was not significantly influenced by YFV vaccination. Antigenic cartography techniques were used to generate a geometric illustration of the neutralization titres of selected sera against WNV, TBEV, JEV, LIV, YFV and DENV-2. This demonstrated the individual variation in antibody responses. Most sera had detectable titres against LIV and some had titres against WNV and DENV-2. Generally, LIV titres were similar to titres against TBEV, confirming the close antigenic relationship between TBEV and LIV. JEV was also antigenically closer to TBEV than WNV, using these sera. The use of sera from individuals vaccinated against multiple pathogens is unique relative to previous applications of antigenic cartography techniques. It is evident from these data that notable differences exist between amino acid sequence identity and mapped antigenic relationships within the family Flaviviridae.

  7. Comparison of antibody repertoires produced by HIV-1 infection, other chronic and acute infections, and systemic autoimmune disease.

    Directory of Open Access Journals (Sweden)

    Felix Breden

    Full Text Available BACKGROUND: Antibodies (Abs produced during HIV-1 infection rarely neutralize a broad range of viral isolates; only eight broadly-neutralizing (bNt monoclonal (MAbs have been isolated. Yet, to be effective, an HIV-1 vaccine may have to elicit the essential features of these MAbs. The V genes of all of these bNt MAbs are highly somatically mutated, and the V(H genes of five of them encode a long (≥ 20 aa third complementarity-determining region (CDR-H3. This led us to question whether long CDR-H3s and high levels of somatic mutation (SM are a preferred feature of anti-HIV bNt MAbs, or if other adaptive immune responses elicit them in general. METHODOLOGY AND PRINCIPAL FINDINGS: We assembled a V(H-gene sequence database from over 700 human MAbs of known antigen specificity isolated from chronic (viral infections (ChI, acute (bacterial and viral infections (AcI, and systemic autoimmune diseases (SAD, and compared their CDR-H3 length, number of SMs and germline V(H-gene usage. We found that anti-HIV Abs, regardless of their neutralization breadth, tended to have long CDR-H3s and high numbers of SMs. However, these features were also common among Abs associated with other chronic viral infections. In contrast, Abs from acute viral infections (but not bacterial infections tended to have relatively short CDR-H3s and a low number of SMs, whereas SAD Abs were generally intermediate in CDR-H3 length and number of SMs. Analysis of V(H gene usage showed that ChI Abs also tended to favor distal germline V(H-genes (particularly V(H1-69, especially in Abs bearing long CDR-H3s. CONCLUSIONS AND SIGNIFICANCE: The striking difference between the Abs produced during chronic vs. acute viral infection suggests that Abs bearing long CDR-H3s, high levels of SM and V(H1-69 gene usage may be preferentially selected during persistent infection.

  8. Anti-Glutamic Acid Decarboxylase Antibody-Associated Ataxia as an Extrahepatic Autoimmune Manifestation of Hepatitis C Infection: A Case Report

    Directory of Open Access Journals (Sweden)

    Amer Awad


    Full Text Available Extrahepatic immunological manifestations of hepatitis C virus (HCV are well described. In addition, antiglutamic acid decarboxylase (GAD antibody-associated cerebellar ataxia is well-established entity. However, there have been no reports in the literature of anti-GAD antibody-associated ataxia as an extrahepatic manifestation of HCV infection. We report the case of a young woman with chronic hepatitis C virus and multiple extrahepatic autoimmune diseases including Sjögren syndrome and pernicious anemia who presented with subacute midline cerebellar syndrome and was found to have positive antiglutamic acid decarboxylase (GAD antibody in the serum and cerebrospinal fluid. An extensive diagnostic workup to rule out neoplastic growths was negative, suggesting the diagnosis of nonparaneoplastic antiglutamic acid decarboxylase antibody-associated cerebellar ataxia as an additional extrahepatic manifestation of hepatitis C virus infection. The patient failed to respond to high-dose steroids and intravenous immunoglobulin. Treatment with the monoclonal antibody rituximab stabilized the disease. We postulate that anti-GAD associated ataxia could be an extrahepatic manifestation of HCV infection.

  9. Anti-glutamic Acid decarboxylase antibody-associated ataxia as an extrahepatic autoimmune manifestation of hepatitis C infection: a case report. (United States)

    Awad, Amer; Stüve, Olaf; Mayo, Marlyn; Alkawadri, Rafeed; Estephan, Bachir


    Extrahepatic immunological manifestations of hepatitis C virus (HCV) are well described. In addition, antiglutamic acid decarboxylase (GAD) antibody-associated cerebellar ataxia is well-established entity. However, there have been no reports in the literature of anti-GAD antibody-associated ataxia as an extrahepatic manifestation of HCV infection. We report the case of a young woman with chronic hepatitis C virus and multiple extrahepatic autoimmune diseases including Sjögren syndrome and pernicious anemia who presented with subacute midline cerebellar syndrome and was found to have positive antiglutamic acid decarboxylase (GAD) antibody in the serum and cerebrospinal fluid. An extensive diagnostic workup to rule out neoplastic growths was negative, suggesting the diagnosis of nonparaneoplastic antiglutamic acid decarboxylase antibody-associated cerebellar ataxia as an additional extrahepatic manifestation of hepatitis C virus infection. The patient failed to respond to high-dose steroids and intravenous immunoglobulin. Treatment with the monoclonal antibody rituximab stabilized the disease. We postulate that anti-GAD associated ataxia could be an extrahepatic manifestation of HCV infection.

  10. Perspectives on autoimmunity

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, I.R.


    The contents of this book are: HLA and Autoimmunity; Self-Recognition and Symmetry in the Immune System; Immunology of Insulin Dependent Diabetes Mellitus; Multiple Sclerosis; Autoimmunity and Immune Pathological Aspects of Virus Disease; Analyses of the Idiotypes and Ligand Binding Characteristics of Human Monoclonal Autoantibodies to DNA: Do We Understand Better Systemic Lupus Erythematosus. Autoimmunity and Rheumatic Fever; Autoimmune Arthritis Induced by Immunization to Mycobacterial Antigens; and The Interaction Between Genetic Factors and Micro-Organisms in Ankylosing Spondylitis: Facts and Fiction.

  11. 狼疮肾炎患者血清自身抗体检测及意义%Clinical significance of autoimmune antibody in patients with lupus nephritis

    Institute of Scientific and Technical Information of China (English)

    王丽; 王琳


    Objective To investigate the clinical significance autoimmune antibody in patients with lupus nephritis(LN).Methods ELISA assay was performed to examine anti-C1q antibody and anti-nucleus antibody;immunoblot assay was performed to examine anti-dsDNA antibody,anti-nucleosome antibody and anti-Sm antibody in sera of 38 patients with LN and 22 patients of system lupus erythemalosus without renal damage.Standard methods were uaed for laboratory testing.Results The positive rate of anti-C1q antibody,anti-dsDNA antibody,anti-nucleosome antibody,anti-Sm antibody and anti-nucleus antibody were significantly higher in LN than in controls(P<0.01).AntiC1q antibody and anti-nucleus antibody were significantty higher in LN than in controls(P<0.01,P<0.05).Serum levels of anti-C1q antibody was positively correlated with SLEDAI score and the level of anti-nucleus antibody,but was negatively oorrelated with C3、 C4.Conclusion Anti-C1q antibody,anti-dsDNA antibody,anti-nucleosome antibody and anti-nucleus antibody are suggested to play a role in the pathogenesis of LN and can be used as diagnostic tools and disease activity markers.%目的 探讨狼疮肾炎(LN)患者血清自身抗体检测的临床意义.方法 检测60例系统性红斑狼疮(SLE)患者血清抗Clq抗体、ANA抗体、抗dsDNA、核小体、抗-Sm抗体,并依据有无狼疮肾炎分为狼疮肾炎组(A组)38例和无狼疮肾炎的SLE对照组(B组)22例.结果 A组抗C1q、dsDNA、核小体、抗-Sm和ANA抗体阳性率显著高于B组(均P<0.01),血清中抗C1q抗体水平分别与SLEDAI评分、抗ANA水平呈显著正相关(均P<0.01);与补体C3、C4含量呈显著负相关(P<0.01).结论 抗C1q抗体、dsDNA、核小体和ANA是反映SLE患者并发肾脏损害的重要指标,在LN诊断和判定活动性方面有重要作用.

  12. Measurement of anti-DFS70 antibodies in patients with ANA-associated autoimmune rheumatic diseases suspicion is cost-effective. (United States)

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


    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.

  13. Diagnosis and classification of autoimmune orchitis. (United States)

    Silva, C A; Cocuzza, M; Carvalho, J F; Bonfá, E


    Autoimmune orchitis is characterized by testis inflammation and the presence of specific antisperm antibodies (ASA). It is classified in two categories. Primary autoimmune orchitis is defined by infertility and asymptomatic orchitis associated with ASA (100%) directed to the basement membrane or seminiferous tubules in infertile men, without any systemic disease and usually asymptomatic. Secondary autoimmune orchitis is characterized by symptomatic orchitis and/or testicular vasculiti`s associated with a systemic autoimmune disease, particularly vasculitis. These patients typically demonstrate testicular pain, erythema and/or swelling. ASA in secondary autoimmune orchitis have been reported in up to 50% of patients, especially in systemic lupus erythematosus patients. The pathogenesis of primary as well as secondary autoimmune orchitis is still unknown. Although the etiology is likely to be multifactorial, testicular inflammation, infection or trauma may induce T cell response with pro-inflammatory cytokine production with a consequent blood-testis-barrier permeability alteration, ASA production and apoptosis of spermatocytes and spermatids. ASA is known to cause immobilization and/or agglutination of spermatozoa, which may block sperm-egg interaction resulting in infertility. Assisted reproduction has been used as an efficient option in primary cases and immunosuppressive therapy for secondary autoimmune orchitis, although there is no double-blind, randomized trial to confirm the efficacy of any treatment regimens for these conditions.

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

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


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

  15. 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


    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.

  16. 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


    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.

  17. In type 1 diabetes a subset of anti-coxsackievirus B4 antibodies recognize autoantigens and induce apoptosis of pancreatic beta cells.

    Directory of Open Access Journals (Sweden)

    Caterina Bason

    Full Text Available Type 1 diabetes is characterized by autoimmune destruction of pancreatic beta cells. The role played by autoantibodies directed against beta cells antigens in the pathogenesis of the disease is still unclear. Coxsackievirus B infection has been linked to the onset of type 1 diabetes; however its precise role has not been elucidated yet. To clarify these issues, we screened a random peptide library with sera obtained from 58 patients with recent onset type 1 diabetes, before insulin therapy. We identified an immunodominant peptide recognized by the majority of individual patients'sera, that shares homology with Coxsackievirus B4 VP1 protein and with beta-cell specific autoantigens such as phogrin, phosphofructokinase and voltage-gated L-type calcium channels known to regulate beta cell apoptosis. Antibodies against the peptide affinity-purified from patients' sera, recognized the viral protein and autoantigens; moreover, such antibodies induced apoptosis of the beta cells upon binding the L-type calcium channels expressed on the beta cell surface, suggesting a calcium dependent mechanism. Our results provide evidence that in autoimmune diabetes a subset of anti-Coxsackievirus antibodies are able to induce apoptosis of pancreatic beta cells which is considered the most critical and final step in the development of autoimmune diabetes without which clinical manifestations do not occur.

  18. Involvement of brain-derived neurotrophic factor (BDNF) in MP4-induced autoimmune encephalomyelitis. (United States)

    Javeri, Sita; Rodi, Michael; Tary-Lehmann, Magdalena; Lehmann, Paul V; Addicks, Klaus; Kuerten, Stefanie


    The role of brain-derived neurotrophic factor (BDNF) in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) is still unclear. Here we investigate the clinical course, CNS histopathology and peripheral antigen-specific immunity in MP4-induced EAE of BDNF (-/+) mice. We demonstrate that these mice displayed less severe disease compared to BDNF (+/+) mice, reflected by decreased inflammation and demyelination. In correspondence to diminished frequencies of T and B cells in CNS infiltrates, the peripheral MP4-specific T(H)1/T(H)17 response was attenuated in BDNF (-/+), but not in wild-type animals. In contrast, immunization with ovalbumin triggered similar frequencies of IFN-γ- and IL-17-secreting T cells in both groups. The cytokine secretion and proliferative activity upon mitogen stimulation did not reveal any global defect of T cell function in BDNF (-/+) mice. By influencing the antigen-specific immune response in autoimmune encephalomyelitis, BDNF may support and maintain the disease in ways that go beyond its alleged neuroprotective role.

  19. Helminth-induced Ly6Chi monocyte-derived alternatively activated macrophages suppress experimental autoimmune encephalomyelitis (United States)

    Terrazas, Cesar; de Dios Ruiz-Rosado, Juan; Amici, Stephanie A.; Jablonski, Kyle A.; Martinez-Saucedo, Diana; Webb, Lindsay M.; Cortado, Hanna; Robledo-Avila, Frank; Oghumu, Steve; Satoskar, Abhay R.; Rodriguez-Sosa, Miriam; Terrazas, Luis I.; Guerau-de-Arellano, Mireia; Partida-Sánchez, Santiago


    Helminths cause chronic infections and affect the immune response to unrelated inflammatory diseases. Although helminths have been used therapeutically to ameliorate inflammatory conditions, their anti-inflammatory properties are poorly understood. Alternatively activated macrophages (AAMϕs) have been suggested as the anti-inflammatory effector cells during helminth infections. Here, we define the origin of AAMϕs during infection with Taenia crassiceps, and their disease-modulating activity on the Experimental Autoimmune Encephalomyelitis (EAE). Our data show two distinct populations of AAMϕs, based on the expression of PD-L1 and PD-L2 molecules, resulting upon T. crassiceps infection. Adoptive transfer of Ly6C+ monocytes gave rise to PD-L1+/PD-L2+, but not PD-L1+/PD-L2− cells in T. crassiceps-infected mice, demonstrating that the PD-L1+/PD-L2+ subpopulation of AAMϕs originates from blood monocytes. Furthermore, adoptive transfer of PD-L1+/PD-L2+ AAMϕs into EAE induced mice reduced disease incidence, delayed disease onset, and diminished the clinical disability, indicating the critical role of these cells in the regulation of autoimmune disorders. PMID:28094319

  20. 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.


    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 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.

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

    DEFF Research Database (Denmark)

    Astakhova, Irina Kira


    of the monoclonal human autoantibody is achieved. It makes the novel "clickable" LNA/DNA complexes a very promising tool in molecular diagnostics of both nucleic acids and autoantibodies against DNA. The latter are produced under several autoimmune conditions including antiphospholipide syndrome and systemic lupus...

  2. Autoimmunity-Basics and link with periodontal disease. (United States)

    Kaur, Gagandeep; Mohindra, Kanika; Singla, Shifali


    Autoimmune reactions reflect an imbalance between effector and regulatory immune responses, typically develop through stages of initiation and propagation, and often show phases of resolution (indicated by clinical remissions) and exacerbations (indicated by symptomatic flares). The fundamental underlying mechanism of autoimmunity is defective elimination and/or control of self-reactive lymphocytes. Periodontal diseases are characterized by inflammatory conditions that directly affect teeth-supporting structures, which are the major cause of tooth loss. Several studies have demonstrated the involvement of autoimmune responses in periodontal disease. Evidence of involvement of immunopathology has been reported in periodontal disease. Bacteria in the dental plaque induce antibody formation. Autoreactive T-cells, natural killer cells, ANCA, heat shock proteins, autoantibodies, and genetic factors are reported to have an important role in the autoimmune component of periodontal disease. The present review describes the involvement of autoimmune responses in periodontal diseases and also the mechanisms underlying these responses.

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


    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.

  4. 自身抗体检测在自身免疫性疾病中的价值%Detective value of autoimmune antibodies in autoimmune diseases

    Institute of Scientific and Technical Information of China (English)

    覃仕锋; 李春美


    目的:探讨ENA(抗可提取性核抗原抗体)、ANA(抗核抗体)和抗ds-DNA抗体(双链DNA抗体)在AID患者中的相关性及敏感性。方法:分析2013年2月至2014年4月在我院接受治疗的AID患者的临床资料。检测入组患者的ENA、ANA、抗ds-DNA抗体表达情况。比较男性、女性的自身抗体阳性情况差异,并探讨不同荧光模式的ANA对应的ENA各项阳性情况以及ANA表达与ENA、抗ds-DNA表达相关性。结果:本研究共纳入研究对象180例,其中男性患者67例,女性患者113例。女性患者的ANA(χ2=12.23,P<0.01)、抗ds-DNA阳性率(χ2=5.906,P=0.015)均显著高于男性。 nRNP、ss-A阳性标本中的颗粒型ANA比例最高,而Scl-70阳性标本中均质型ANA比例最高;ANA阳性标本的ENA阳性率(χ2=6.406,P=0.011)、抗ds-DNA阳性率(χ2=43.49,P<0.01)显著高于ANA阴性的标本。结论:男性自身抗体阳性率明显低于女性,颗粒型在ANA核型中占据比较高的比率,抗ds-DNA和ENA的阳性检出率与ANA阳性率有着一定的关系。%Objective:To study the sensitivity and correlation between ANA,ENA and anti ds-DNA antibody in the patients with AID.Methods:Clinical data of patients with AID received treatment at our hospital from February 2013 to January 2014 was retro-spectively analyzed.The antibody expressions of ENA, ANA, anti ds-DNA antibody of the patients were detected.The autoantibody positive differences between the males and females were compared.The positive situation of ENA correspond to different fluorescent patterns of ANA and the correlation between the expression of ANA and the expressions of ENA,anti ds-DNA antibody were both dis-cussed.The relationship between the expression of ANA and the expression of ENA,dsDNA was also discussed.Results:A total of 180 patients were retrospective analyzed,including 67 males and 113 females.The positive rates of ANA,anti ds

  5. Autoimmune autonomic disorders. (United States)

    Mckeon, Andrew; Benarroch, Eduardo E


    Autoimmune autonomic disorders occur because of an immune response directed against sympathetic, parasympathetic, and enteric ganglia, autonomic nerves, or central autonomic pathways. In general, peripheral autoimmune disorders manifest with either generalized or restricted autonomic failure, whereas central autoimmune disorders manifest primarily with autonomic hyperactivity. Some autonomic disorders are generalized, and others are limited in their anatomic extent, e.g., isolated gastrointestinal dysmotility. Historically, these disorders were poorly recognized, and thought to be neurodegenerative. Over the last 20 years a number of autoantibody biomarkers have been discovered that have enabled the identification of certain patients as having an autoimmune basis for either autonomic failure or hyperactivity. Peripheral autoimmune autonomic disorders include autoimmune autonomic ganglionopathy (AAG), paraneoplastic autonomic neuropathy, and acute autonomic and sensory neuropathy. AAG manifests with acute or subacute onset of generalized or selective autonomic failure. Antibody targeting the α3 subunit of the ganglionic-type nicotinic acetylcholine receptor (α3gAChR) is detected in approximately 50% of cases of AAG. Some other disorders are characterized immunologically by paraneoplastic antibodies with a high positive predictive value for cancer, such as antineuronal nuclear antibody, type 1 (ANNA-1: anti-Hu); others still are seronegative. Recognition of an autoimmune basis for autonomic disorders is important, as their manifestations are disabling, may reflect an underlying neoplasm, and have the potential to improve with a combination of symptomatic and immune therapies.

  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


    Context: The 1-year postpartum period is often accompanied by increased risk for thyroid disease. Objective: The objective of the study was to investigate the role of reproductive risk factors in the development of autoimmune overt hypothyroidism in the years after the 1-year postpartum period....... 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...

  7. 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


    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.

  8. Autoimmune hepatitis

    Directory of Open Access Journals (Sweden)

    F Motamed


    Full Text Available Autoimmune hepatitis is (AIH is a chronic hepatitis that occurs in children and adults of all ages. It is characterized by immunologic and autoimmune features, including circulating auto antibodies and high serum globulin concentrations. It was first described in the 1950s by term of chronic active hepatitis. It has 2 types with different auto antibodies. Diagnosis is based upon serologic and histologic findings and exclusion of other forms of chronic liver disease.   A scoring system should be used in assessment based upon: 1 Auto anti bodie titer 2 Serum IgG level  3 Liver histology 4 Absence of viral and other causes of hepatitis. Clear indications for treatment: 1   rise of aminotrasferases 2   clinical symptoms of liver disease 3   histological features in liver biopsy 4   Children with AIH initial treatment involve glucocorticoid with or without azathioprine. For patients with fulminant hepatitis liver transplantation, should be kept in mind.   Remission is defined by: 1   Resolution of symptoms 2   Normalization of serum trasaminases 3   Normalization of serum bilirubin and gamma globuline levels. 4   Improvement in liver histology 5   Treatment is continued for at least 2-5 years, glucocorticoids are with drawn first, by tapering over six weeks. Azathioprine will be with drawn.  

  9. Pathophysiology of autoimmune polyneuropathies. (United States)

    Dalakas, Marinos C


    The most common autoimmune neuropathies include the acute inflammatory polyneuropathy [the Guillain-Barré Syndrome(s)]; chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN) and IgM anti-MAG-antibody mediated paraproteinemic neuropathy. These neuropathies occur when immunologic tolerance to peripheral nerve components (myelin, Schwann cell, axon, and motor or ganglionic neurons) is lost. Based on the immunopathologic similarities with experimental allergic neuritis induced after immunization with nerve proteins, disease transfer experiments with the patients' serum or with intraneural injections, and immunocytochemical studies on the patients' nerves, it appears that both cellular and humoral factors, either independently or in concert with each other, play a role in the cause of these neuropathies. Although in some of them there is direct evidence for autoimmune reactivity mediated by specific antibodies or autoreactive T lymphocytes, in others the underlying immune-mediated mechanisms have not been fully elucidated, in spite of good response to immunotherapies. The review highlights the factors associated with breaking the T-cell tolerance, the T-cell activation and costimulatory molecules, the immunoregulatory T-cells and relevant cytokines and the antibodies against peripheral nerve glycolipids or glycoproteins that seem to be of pathogenic relevance. Antigens in the nodal, paranodal and juxtaparanodal regions are discussed as potentially critical targets in explaining conduction failure and rapid recovery. Based on the immunopathologic network believed to play a fundamental role in the pathogenesis of these neuropathies, future therapeutic directions are highlighted using new biological agents against T-cells, cytokines, B-cells, transmigration and transduction molecules.

  10. Decreased RORC-dependent silencing of prostaglandin receptor EP2 induces autoimmune Th17 cells. (United States)

    Kofler, David M; Marson, Alexander; Dominguez-Villar, Margarita; Xiao, Sheng; Kuchroo, Vijay K; Hafler, David A


    Prostaglandin E2 (PGE2) promotes Th17 expansion while otherwise inhibiting other CD4+ T cell subsets. Here, we identified a PGE2-dependent pathway that induces pathogenic Th17 cells in autoimmune disease and is regulated by the transcription factor RORC. Compared with other CD4+ cell types from healthy subjects, there is a surprising lack of the prostaglandin receptor EP2 on Th17 cells; therefore, we examined the hypothesis that RORγt, which is highly expressed in Th17 cells, mediates EP2 downregulation. Chromatin immunoprecipitation followed by DNA sequencing revealed that RORγt binds directly to Ptger2 (the gene encoding EP2 receptor) in Th17 cells isolated from WT mice. In Th17 cells isolated from humans, RORC repressed EP2 by directly silencing PTGER2 transcription, and knock down of RORC restored EP2 expression in Th17 cells. Compared with Th17 cells from healthy individuals, Th17 cells from patients with MS exhibited reduced RORC binding to the PTGER2 promoter region, resulting in higher EP2 levels and increased expression of IFN-γ and GM-CSF. Finally, overexpression of EP2 in Th17 cells from healthy individuals induced a specific program of inflammatory gene transcription that produced a pathogenic Th17 cell phenotype. These findings reveal that RORC directly regulates the effects of PGE2 on Th17 cells, and dysfunction of this pathway induces a pathogenic Th17 cell phenotype.

  11. Autoimmunity against laminins. (United States)

    Florea, Florina; Koch, Manuel; Hashimoto, Takashi; Sitaru, Cassian


    Laminins are ubiquitous constituents of the basement membranes with major architectural and functional role as supported by the fact that absence or mutations of laminins lead to either lethal or severely impairing phenotypes. Besides genetic defects, laminins are involved in a wide range of human diseases including cancer, infections, and inflammatory diseases, as well as autoimmune disorders. A growing body of evidence implicates several laminin chains as autoantigens in blistering skin diseases, collagenoses, vasculitis, or post-infectious autoimmunity. The current paper reviews the existing knowledge on autoimmunity against laminins referring to both experimental and clinical data, and on therapeutic implications of anti-laminin antibodies. Further investigation of relevant laminin epitopes in pathogenic autoimmunity would facilitate the development of appropriate diagnostic tools for thorough characterization of patients' antibody specificities and should decisively contribute to designing more specific therapeutic interventions.

  12. Vitamin D supplementation reduces thyroid peroxidase antibody levels in patients with autoimmune thyroid disease: An open-labeled randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Sandeep Chaudhary


    Full Text Available Background and Aims: Although Vitamin D deficiency has been linked to autoimmune thyroid disorders (AITD, the impact of Vitamin D supplementation on thyroid autoimmunity is not known. This study aimed to evaluate the impact of Vitamin D supplementation on thyroid autoimmunity (thyroid peroxidase antibody [TPO-Ab] titers in patients with newly diagnosed AITD in a randomized controlled trial. Materials and Methods: One hundred two patients with newly diagnosed AITD (TPO-Ab > 34 kIU/L and/or sonographic evidence of thyroiditis patients were randomized into Group-1 (intervention group and Group-2 (control group. Group-1 received cholecalciferol 60,000 IU weekly and calcium 500 mg/day for 8 weeks; Group-2 received calcium 500 mg/day for 8 weeks. Responders were defined as ≥25% fall in TPO-Ab titers. Individuals with at least 3-month follow-up were analyzed. Trial is registered at (CTRI/2015/04/005713. Results: Data from 100 AITD patients (68 with thyroid stimulating hormone [TSH] ≤10 mIU/L, 32 with TSH > 10 mIU/L, 93% having Vitamin D insufficiency, were analyzed. TPO-Ab titers were highest among patients in the lowest 25-hydroxyvitamin D quartile (P = 0.084. At 3 months follow-up, there was significant fall in TPO-Ab in Group-1 (−46.73% as compared to Group-2 (−16.6% (P = 0.028. Sixty-eight percentage patients in Group-1 were responders compared to 44% in Group-2 (P = 0.015. Kaplan–Meier analysis revealed significantly higher response rate in Group-1 (P = 0.012. Significantly greater reduction in TPO-Ab titers was observed in AITD with TSH ≤ 10 mIU/L compared to TSH > 10 mIU/L. Cox regression revealed Group-1 followed by TPO-Ab and free tetraiodothyronine levels to be a good predictor of response to therapy (P = 0.042, 0.069, and 0.074, respectively. Conclusion: Vitamin D supplementation in AITD may have a beneficial effect on autoimmunity as evidence by significant reductions in TPO-Ab titers.

  13. Lithium associated autoimmune thyroiditis.


    Shimizu, M; Hirokawa, M.; T. Manabe; Shimozuma, K; Sonoo, H; Harada, T.


    A case of autoimmune thyroiditis after long term treatment with lithium is described in a 29 year old Japanese woman with manic depression. Positive serum antithyroglobulin and antimicrosomal antibodies, diffuse goitre, and microscopic chronic thyroiditis, as well as the clinical history of long term lithium treatment were suggestive of lithium associated autoimmune thyroiditis. Microscopically, there was a mild degree of interstitial fibrosis and a moderate degree of lymphocytic infiltration...

  14. Identification of anti-CD98 antibody mimotopes for inducing antibodies with antitumor activity by mimotope immunization. (United States)

    Saito, Misa; Kondo, Masahiro; Ohshima, Motohiro; Deguchi, Kazuki; Hayashi, Hideki; Inoue, Kazuyuki; Tsuji, Daiki; Masuko, Takashi; Itoh, Kunihiko


    A mimotope is an antibody-epitope-mimicking peptide retrieved from a phage display random peptide library. Immunization with antitumor antibody-derived mimotopes is promising for inducing antitumor immunity in hosts. In this study, we isolated linear and constrained mimotopes from HBJ127, a tumor-suppressing anti-CD98 heavy chain mAb, and determined their abilities for induction of antitumor activity equal to that of the parent antibody. We detected elevated levels of antipeptide responses, but failed to detect reactivity against native CD98-expressing HeLa cells in sera of immunized mice. Phage display panning and selection of mimotope-immunized mouse spleen-derived antibody Fab library showed that HeLa cell-reactive Fabs were successfully retrieved from the library. This finding indicates that native antigen-reactive Fab clones represented an undetectable minor population in mimotope-induced antibody repertoire. Functional and structural analysis of retrieved Fab clones revealed that they were almost identical to the parent antibody. From these results, we confirmed that mimotope immunization was promising for retrieving antitumor antibodies equivalent to the parent antibody, although the co-administration of adjuvant compounds such as T-cell epitope peptides and Toll-like receptor 4 agonist peptides is likely to be necessary for inducing stronger antitumor immunity than mimotope injection alone.

  15. Antibody (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 ...

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

    DEFF Research Database (Denmark)

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


    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...

  17. Antinuclear Antibody-Positive Ticlopidine-Induced Hepatitis

    Directory of Open Access Journals (Sweden)

    Sander Jo Veldhuyzen van Zanten


    Full Text Available Ticlopidine hydrochloride has been shown to reduce the risk of first or recurrent stroke in patients who have experienced a transient ischemic attack, reversible ischemic neurological deficit, recurrent stroke or first stroke. Severe liver dysfunction is a contraindication for its use. Increase in liver enzymes has been reported with use of this drug, but jaundice is rare. A case of severe ticlopidine-induced hepatitis that was associated with a marked increase in antinuclear antibody (ANA levels is reported. Physicians prescribing ticlopidine hydrochloride should be aware that a potentially severe acute hepatitis associated with ANA positivity can occur. The drug should be discontinued if signs of liver dysfunction occur.

  18. Orthotopic liver transplantation after successful treatment with anti-CD20 monoclonal antibody (rituximab) for severe steroid-resistant autoimmune hemolytic anemia: a case report. (United States)

    Annicchiarico, B E; Siciliano, M; Avolio, A W; Agnes, S; Bombardieri, G


    Chronic hepatitis C virus (HCV) infection has been associated with a wide number of immunologic disorders, ranging from clinically silent laboratory abnormalities (eg, autoantibody positivity) to severe systemic diseases (eg, cryoglobulinemic vasculitis). Autoimmune hemolytic anemia (AIHA), due to the production of antibodies against erythrocyte membrane antigens, is an uncommon extrahepatic manifestation in the setting of chronic hepatitis C. Herein we have reported the case of a 57-year-old woman with decompensated HCV-related cirrhosis awaiting orthotopic liver transplantation (OLT) who experienced severe AIHA. After 1 month of treatment with prednisone (1 mg/kg body weight/d), there was no significant amelioration of anemia. Rituximab, an anti-CD20 monoclonal antibody that depletes B-lymphocytes reducing serum immunoglobulins, was initiated (375 mg/m(2) IV, weekly for 4 weeks) with a prompt, sustained increase in hemoglobin. The drug was well tolerated; it did not interfere with the course of the liver disease. Thirty-one months after rituximab therapy with resolution of AIHA, the patient successfully underwent OLT using immunosuppression with tacrolimus and low-dose steroids. The patient was discharged on postoperative day 36. No infectious event occurred in the postoperative period. At 18 months follow-up after OLT, there has been no infectious or hematological event. Our experience supported the safety of rituximab use in patients with advanced HCV-related liver disease before OLT.

  19. Thyroid Antibodies (United States)

    ... e.g., at regular intervals after thyroid cancer treatment) Thyroid stimulating hormone receptor antibody, Thyroid Stimulating Immunoglobulin TRAb, TSHR Ab, TSI Graves disease When a person has symptoms of hyperthyroidism If a pregnant woman has a known autoimmune ...

  20. Autoimmune movement disorders. (United States)

    Mckeon, Andrew; Vincent, Angela


    Autoimmune movement disorders encapsulate a large and diverse group of neurologic disorders occurring either in isolation or accompanying more diffuse autoimmune encephalitic illnesses. The full range of movement phenomena has been described and, as they often occur in adults, many of the presentations can mimic neurodegenerative disorders, such as Huntington disease. Disorders may be ataxic, hypokinetic (parkinsonism), or hyperkinetic (myoclonus, chorea, tics, and other dyskinetic disorders). The autoantibody targets are diverse and include neuronal surface proteins such as leucine-rich, glioma-inactivated 1 (LGI1) and glycine receptors, as well as antibodies (such as intracellular antigens) that are markers of a central nervous system process mediated by CD8+ cytotoxic T cells. However, there are two conditions, stiff-person syndrome (also known as stiff-man syndrome) and progressive encephalomyelitis with rigidity and myoclonus (PERM), that are always autoimmune movement disorders. In some instances (such as Purkinje cell cytoplasmic antibody-1 (PCA-1) autoimmunity), antibodies detected in serum and cerebrospinal fluid can be indicative of a paraneoplastic cause, and may direct the cancer search. In other instances (such as 65kDa isoform of glutamic acid decarboxylase (GAD65) autoimmunity), a paraneoplastic cause is very unlikely, and early treatment with immunotherapy may promote improvement or recovery. Here we describe the different types of movement disorder and the clinical features and antibodies associated with them, and discuss treatment.


    Institute of Scientific and Technical Information of China (English)

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


    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.

  2. Celiac anti-type 2 transglutaminase antibodies induce differential effects in fibroblasts from celiac disease patients and from healthy subjects. (United States)

    Paolella, Gaetana; Lepretti, Marilena; Barone, Maria Vittoria; Nanayakkara, Merlin; Di Zenzo, Marina; Sblattero, Daniele; Auricchio, Salvatore; Esposito, Carla; Caputo, Ivana


    Type 2 transglutaminase (TG2) has an important pathogenic role in celiac disease (CD), an inflammatory intestinal disease that is caused by the ingestion of gluten-containing cereals. Indeed, TG2 deamidates specific gliadin peptides, thus enhancing their immunogenicity. Moreover, the transamidating activity seems to provoke an autoimmune response, where TG2 is the main autoantigen. Many studies have highlighted a possible pathogenetic role of anti-TG2 antibodies, because they modulate TG2 enzymatic activity and they can interact with cell-surface TG2, triggering a wide range of intracellular responses. Autoantibodies also alter the uptake of the alpha-gliadin peptide 31-43 (p31-43), responsible of the innate immune response in CD, thus partially protecting cells from p31-43 damaging effects in an intestinal cell line. Here, we investigated whether anti-TG2 antibodies protect cells from p31-43-induced damage in a CD model consisting of primary dermal fibroblasts. We found that the antibodies specifically reduced the uptake of p31-43 by fibroblasts derived from healthy subjects but not in those derived from CD patients. Analyses of TG2 expression and enzymatic activity did not reveal any significant difference between fibroblasts from healthy and celiac subjects, suggesting that other features related to TG2 may be responsible of such different behaviors, e.g., trafficking or subcellular distribution. Our findings are in line with the concept that a "celiac cellular phenotype" exists and that TG2 may contribute to this phenotype. Moreover, they suggest that the autoimmune response to TG2, which alone may damage the celiac mucosa, also fails in its protective role in celiac cells.

  3. Necroptosis in spontaneously-mutated hematopoietic cells induces autoimmune bone marrow failure in mice (United States)

    Xin, Junping; Breslin, Peter; Wei, Wei; Li, Jing; Gutierrez, Rafael; Cannova, Joseph; Ni, Allen; Ng, Grace; Schmidt, Rachel; Chen, Haiyan; Parini, Vamsi; Kuo, Paul C.; Kini, Ameet R.; Stiff, Patrick; Zhu, Jiang; Zhang, Jiwang


    Acquired aplastic anemia is an autoimmune-mediated bone marrow failure syndrome. The mechanism by which such an autoimmune reaction is initiated is unknown. Whether and how the genetic lesions detected in patients cause autoimmune bone marrow failure have not yet been determined. We found that mice with spontaneous deletion of the TGFβ-activated kinase-1 gene in a small subset of hematopoietic cells developed bone marrow failure which resembled the clinical manifestations of acquired aplastic anemia patients. Bone marrow failure in such mice could be reversed by depletion of CD4+ T lymphocytes or blocked by knockout of interferon-γ, suggesting a Th1-cell-mediated autoimmune mechanism. The onset and progression of bone marrow failure in such mice were significantly accelerated by the inactivation of tumor necrosis factor-α signaling. Tumor necrosis factor-α restricts autoimmune bone marrow failure by inhibiting type-1 T-cell responses and maintaining the function of myeloid-derived suppressor cells. Furthermore, we determined that necroptosis among a small subset of mutant hematopoietic cells is the cause of autoimmune bone marrow failure because such bone marrow failure can be prevented by deletion of receptor interacting protein kinase-3. Our study suggests a novel mechanism to explain the pathogenesis of autoimmune bone marrow failure. PMID:27634200

  4. Postinflammation stage of autoimmune orchitis induced by immunization with syngeneic testicular germ cells alone in mice. (United States)

    Naito, Munekazu; Hirai, Shuichi; Terayama, Hayato; Qu, Ning; Kuerban, Maimaiti; Musha, Muhetaerjiang; Kitaoka, Miyuki; Ogawa, Yuki; Itoh, Masahiro


    We previously established an immunological infertility model, experimental autoimmune orchitis (EAO), which can be induced by two subcutaneous injections of viable syngeneic testicular germ cells on days 0 and 14 in mice without using any adjuvant. In this EAO model, CD4+ T-cell-dependent lymphocytic infiltration and immune deposits were found with spermatogenic disturbance on day 120. However, the late stage of EAO (= postactive inflammation stage on day 365) has not yet been investigated. Therefore, we investigated the histopathological characteristics of the late stage. The results revealed that the lymphocytic infiltration finally resolved; however, the seminiferous epithelium persistently showed maturation arrest and the Sertoli cell-only feature. In the seminiferous tubules showing maturation arrest, both proliferation and apoptosis of germ cells had occurred simultaneously. It was also noted that there were deposits of immunoglobulin G and the third component of complement on the thickened basement membrane of seminiferous tubules in the late stage of EAO. These results indicate that histopathology after active inflammation in EAO comprises persistent damage to the seminiferous epithelium and may resemble the histopathology of "idiopathic disturbance of spermatogenesis" in man.

  5. Neuropathology of autoimmune encephalitides. (United States)

    Bauer, Jan; Bien, Christian G


    In recent years a large number of antibody-associated or antibody-defined encephalitides have been discovered. These conditions are often referred to as autoimmune encephalitides. The clinical features include prominent epileptic seizures, cognitive and psychiatric disturbance. These encephalitides can be divided in those with antibodies against intracellular antigens and those with antibodies against surface antigens. The discovery of new antibodies against targets on the surface of neurons is especially interesting since patients with such antibodies can be successfully treated immunologically. This chapter focuses on the pathology and the pathogenetic mechanisms involved in these encephalitides and discusses some of the questions that are raised in this exciting new field. It is important to realise, however, that because of the use of antibodies to diagnose the patients, and their improvement with treatment, there are relatively few biopsy or postmortem reports, limiting the neuropathological data and conclusions that can be drawn. For this reason we especially focus on the most frequent autoimmune encephalitides, those with antibodies to the NMDA receptor and with antibodies to the known protein components of the VGKC complex. Analysis of these encephalitides show completely different pathogenic mechanisms. In VGKC complex encephalitis, antibodies seem to bind to their target and activate complement, leading to destruction and loss of neurons. On the other hand, in NMDAR encephalitis, complement activation and neuronal degeneration seems to be largely absent. Instead, binding of antibodies leads to a decrease of NMDA receptors resulting in a hypofunction. This hypofunction offers an explanation for some of the clinical features such as psychosis and episodic memory impairment, but not for the frequent seizures. Thus, additional analysis of the few human brain specimens present and the use of specific animal models are needed to further understand the effects

  6. Erythropoietin: a potent inducer of peripheral immuno/inflammatory modulation in autoimmune EAE.

    Directory of Open Access Journals (Sweden)

    RuiRong Yuan

    Full Text Available BACKGROUND: Beneficial effects of short-term erythropoietin (EPO therapy have been demonstrated in several animal models of acute neurologic injury, including experimental autoimmune encephalomyelitis (EAE--the animal model of multiple sclerosis. We have found that EPO treatment substantially reduces the acute clinical paralysis seen in EAE mice and this improvement is accompanied by a large reduction in the mononuclear cell infiltration and downregulation of glial MHC class II expression within the inflamed CNS. Other reports have recently indicated that peripherally generated anti-inflammatory CD4(+Foxp3(+ regulatory T cells (Tregs and the IL17-producing CD4+ T helper cell (Th17 subpopulations play key antagonistic roles in EAE pathogenesis. However, no information regarding the effects of EPO therapy on the behavior of the general mononuclear-lymphocyte population, Tregs or Th17 cells in EAE has emerged. METHODS AND FINDINGS: We first determined in vivo that EPO therapy markedly suppressed MOG specific T cell proliferation and sharply reduced the number of reactive dendritic cells (CD11c positive in EAE lymph nodes during both inductive and later symptomatic phases of MOG(35-55 induced EAE. We then determined the effect in vivo of EPO on numbers of peripheral Treg cells and Th17 cells. We found that EPO treatment modulated immune balance in both the periphery and the inflamed spinal cord by promoting a large expansion in Treg cells, inhibiting Th17 polarization and abrogating proliferation of the antigen presenting dendritic cell population. Finally we utilized tissue culture assays to show that exposure to EPO in vitro similarly downregulated MOG-specific T cell proliferation and also greatly suppressed T cell production of pro-inflammatory cytokines. CONCLUSIONS: Taken together, our findings reveal an important new locus whereby EPO induces substantial long-term tissue protection in the host through signaling to several critical subsets of

  7. Bioinformatics analysis of the factors controlling type I IFN gene expression in autoimmune disease and virus-induced immunity

    Directory of Open Access Journals (Sweden)

    Di eFeng


    Full Text Available Patients with systemic lupus erythematosus (SLE and Sjögren's syndrome (SS display increased levels of type I IFN-induced genes. Plasmacytoid dendritic cells (PDCs are natural interferon producing cells and considered to be a primary source of IFN-α in these two diseases. Differential expression patterns of type I IFN inducible transcripts can be found in different immune cell subsets and in patients with both active and inactive autoimmune disease. A type I IFN gene signature generally consists of three groups of IFN-induced genes - those regulated in response to virus-induced type I IFN, those regulated by the IFN-induced mitogen-activated protein kinase/extracellular-regulated kinase (MAPK/ERK pathway, and those by the IFN-induced phosphoinositide-3 kinase (PI-3K pathway. These three groups of type I IFN-regulated genes control important cellular processes such as apoptosis, survival, adhesion, and chemotaxis, that when dysregulated, contribute to autoimmunity. With the recent generation of large datasets in the public domain from next-generation sequencing and DNA microarray experiments, one can perform detailed analyses of cell type-specific gene signatures as well as identify distinct transcription factors that differentially regulate these gene signatures. We have performed bioinformatics analysis of data in the public domain and experimental data from our lab to gain insight into the regulation of type I IFN gene expression. We have found that the genetic landscape of the IFNA and IFNB genes are occupied by transcription factors, such as insulators CTCF and cohesin, that negatively regulate transcription, as well as IRF5 and IRF7, that positively and distinctly regulate IFNA subtypes. A detailed understanding of the factors controlling type I IFN gene transcription will significantly aid in the identification and development of new therapeutic strategies targeting the IFN pathway in autoimmune disease.

  8. B cells as therapeutic targets in autoimmune neurological disorders. (United States)

    Dalakas, Marinos C


    B cells have a fundamental role in the pathogenesis of various autoimmune neurological disorders, not only as precursors of antibody-producing cells, but also as important regulators of the T-cell activation process through their participation in antigen presentation, cytokine production, and formation of ectopic germinal centers in the intermeningeal spaces. Two B-cell trophic factors-BAFF (B-cell-activating factor) and APRIL (a proliferation-inducing ligand)-and their receptors are strongly upregulated in many immunological disorders of the CNS and PNS, and these molecules contribute to clonal expansion of B cells in situ. The availability of monoclonal antibodies or fusion proteins against B-cell surface molecules and trophic factors provides a rational approach to the treatment of autoimmune neurological diseases. This article reviews the role of B cells in autoimmune neurological disorders and summarizes the experience to date with rituximab, a B-cell-depleting monoclonal antibody against CD20, for the treatment of relapsing-remitting multiple sclerosis, autoimmune neuropathies, neuromyelitis optica, paraneoplastic neurological disorders, myasthenia gravis, and inflammatory myopathies. It is expected that ongoing controlled trials will establish the efficacy and long-term safety profile of anti-B-cell agents in several autoimmune neurological disorders, as well as exploring the possibility of a safe and synergistic effect with other immunosuppressants or immunomodulators.

  9. The possible link between elevated serum levels of epithelial cell-derived neutrophil- activating peptide-78 (ENA-78/CXCL5) and autoimmunity in autistic children


    Mostafa, Gehan Ahmed; AL-Ayadhi, Laila Yousef


    Background In autoimmune disorders, the underlying pathogenic mechanism is the formation of antigen-antibody complexes which trigger an inflammatory response by inducing the infiltration of neutrophils. Epithelial cell-derived neutrophil-activating peptide-78 (ENA-78) is a chemokine that recruits and activates neutrophils, thus it could play a pathogenic role in inflammation and autoimmune disorders. Some autistic children have elevated levels of brain specific auto-antibodies. We are the fir...

  10. HIV-1 envelope glycoprotein immunogens to induce broadly neutralizing antibodies. (United States)

    Sliepen, Kwinten; Sanders, Rogier W


    The long pursuit for a vaccine against human immunodeficiency virus 1 (HIV-1) has recently been boosted by a number of exciting developments. An HIV-1 subunit vaccine ideally should elicit potent broadly neutralizing antibodies (bNAbs), but raising bNAbs by vaccination has proved extremely difficult because of the characteristics of the HIV-1 envelope glycoprotein complex (Env). However, the isolation of bNAbs from HIV-1-infected patients demonstrates that the human humoral immune system is capable of making such antibodies. Therefore, a focus of HIV-1 vaccinology is the elicitation of bNAbs by engineered immunogens and by using vaccination strategies aimed at mimicking the bNAb maturation pathways in HIV-infected patients. Important clues can also be taken from the successful subunit vaccines against hepatitis B virus and human papillomavirus. Here, we review the different types of HIV-1 immunogens and vaccination strategies that are being explored in the search for an HIV-1 vaccine that induces bNAbs.

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

    Directory of Open Access Journals (Sweden)

    Nanna Siegmann


    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.

  12. Generation and characterization of integration-free induced pluripotent stem cells from patients with autoimmune disease. (United States)

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


    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.

  13. Autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA syndrome) in commercial sheep. (United States)

    Luján, Lluís; Pérez, Marta; Salazar, Eider; Álvarez, Neila; Gimeno, Marina; Pinczowski, Pedro; Irusta, Silvia; Santamaría, Jesús; Insausti, Nerea; Cortés, Yerzol; Figueras, Luis; Cuartielles, Isabel; Vila, Miguel; Fantova, Enrique; Chapullé, José Luis Gracia


    We describe a form of the autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA syndrome) in commercial sheep, linked to the repetitive inoculation of aluminum-containing adjuvants through vaccination. The syndrome shows an acute phase that affects less than 0.5% of animals in a given herd, it appears 2-6 days after an adjuvant-containing inoculation and it is characterized by an acute neurological episode with low response to external stimuli and acute meningoencephalitis, most animals apparently recovering afterward. The chronic phase is seen in a higher proportion of flocks, it can follow the acute phase, and it is triggered by external stimuli, mostly low temperatures. The chronic phase begins with an excitatory phase, followed by weakness, extreme cachexia, tetraplegia and death. Gross lesions are related to a cachectic process with muscular atrophy, and microscopic lesions are mostly linked to a neurodegenerative process in both dorsal and ventral column of the gray matter of the spinal cord. Experimental reproduction of ovine ASIA in a small group of repeatedly vaccinated animals was successful. Detection of Al(III) in tissues indicated the presence of aluminum in the nervous tissue of experimental animals. The present report is the first description of a new sheep syndrome (ovine ASIA syndrome) linked to multiple, repetitive vaccination and that can have devastating consequences as it happened after the compulsory vaccination against bluetongue in 2008. The ovine ASIA syndrome can be used as a model of other similar diseases affecting both human and animals. A major research effort is needed in order to understand its complex pathogenesis.

  14. Cancer-associated retinopathy: an autoimmune retinopathy

    Directory of Open Access Journals (Sweden)

    Nurbuanto Tradjutrisno


    Full Text Available Cancer-associated retinopathy (CAR is a paraneoplastic syndrome most commonly associated with small-cell carcinoma of the lung, but also less frequently reported in patients with breast, endometrial, and other cancers. A paraneoplastic syndrome (PNS is a secondary organ dysfunction occurring in a cancer patient at a site that is anatomically remote from the tumor. PNS is not due to a direct effect of the tumor itself or its metastases but caused by other mechanisms, commonly autoimmune mechanisms develop when malignant tumors express proteins, paraneoplastic antigens (PNA, which are normally present only in neurons. One retinal antigen implicated in the autoimmune mechanism of CAR is recoverin, a 23 kDa photoreceptor-specific calcium-binding protein modulating the activity of photoreceptor guanylyl cyclase. The anti-recoverin antibodies induced by the primary tumor may on contact with intraretinal recoverin initiate a photoreceptor degeneration and trigger photoreceptor death by apoptosis, thus causing blindness. Other circulating antibodies directed against a 46 kDa protein identified as retinol enolase and a 60 kDa retinal protein have been demonstrated in patients with clinically diagnosed CAR syndrome. In certain patients no specific antibody has been identified. This suggests that the CAR syndrome includes an heterogenous group of autoimmune conditions directed against various retinal proteins.

  15. Cold antibody autoimmune hemolytic anemia and lymphoproliferative disorders: a retrospective study of 20 patients including clinical, hematological, and molecular findings. (United States)

    Arthold, Cathrin; Skrabs, Cathrin; Mitterbauer-Hohendanner, Gerlinde; Thalhammer, Renate; Simonitsch-Klupp, Ingrid; Panzer, Simon; Valent, Peter; Lechner, Klaus; Jäger, Ulrich; Sillaber, Christian


    A total of 20 patients with cold antibody hemolytic anemia were evaluated in a retrospective study of them, 15 had a monoclonal gammopathy of unknown significance (MGUS): 14 with MGUS of immunoglobulin M (IgM) subtype and 1 with immunoglobulin G subtype. One patient had smoldering Waldenström's macroglobulinemia, but four patients had no monoclonal protein and no evidence of lymphoma. However, in three of these patients, we were able to demonstrate a (mono-)clonal rearrangement of their immunoglobulin heavy and/or light chains. Of the 20 patients, 5 had IgHV34 nucleotide sequence indicating that the antibody was directed against the "I" antigen. Two patients exhibited a progressive increase of IgM over time, however without increasing hemolytic activity. Moreover, in two patients with long-term follow-up, we were able to correlate recurrent hemolytic activity with low environmental temperatures. Among four patients treated with rituximab, all four responded to treatment. However, treatment effect was only transient in all of them.

  16. A Rationally Designed TNF-α Epitope-Scaffold Immunogen Induces Sustained Antibody Response and Alleviates Collagen-Induced Arthritis in Mice (United States)

    Zhang, Li; Wang, Jin; Xu, Aizhang; Zhong, Conghao; Lu, Wuguang; Deng, Li; Li, Rongxiu


    The TNF-α biological inhibitors have significantly improved the clinical outcomes of many autoimmune diseases, in particular rheumatoid arthritis. However, the practical uses are limited due to high costs and the risk of anti-drug antibody responses. Attempts to develop anti-TNF-α vaccines have generated encouraging data in animal models, however, data from clinical trials have not met expectations. In present study, we designed a TNF-α epitope-scaffold immunogen DTNF7 using the transmembrane domain of diphtheria toxin, named DTT as a scaffold. Molecular dynamics simulation shows that the grafted TNF-α epitope is entirely surface-exposed and presented in a native-like conformation while the rigid helical structure of DTT is minimally perturbed, thereby rendering the immunogen highly stable. Immunization of mice with alum formulated DTNF7 induced humoral responses against native TNF-α, and the antibody titer was sustained for more than 6 months, which supports a role of the universal CD4 T cell epitopes of DTT in breaking self-immune tolerance. In a mouse model of rheumatoid arthritis, DTNF7-alum vaccination markedly delayed the onset of collagen-induced arthritis, and reduced incidence as well as clinical score. DTT is presumed safe as an epitope carrier because a catalytic inactive mutant of diphtheria toxin, CRM197 has good clinical safety records as an active vaccine component. Taken all together, we show that DTT-based epitope vaccine is a promising strategy for prevention and treatment of autoimmune diseases. PMID:27658047

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

    Directory of Open Access Journals (Sweden)

    Huseyin Gursoy


    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.

  18. Treatment of severe refractory autoimmune hemolytic anemia in B-cell chronic lymphocytic leukemia with alemtuzumab (humanized CD52 monoclonal antibody). (United States)

    Karlsson, C; Hansson, L; Celsing, F; Lundin, J


    Progressive B-cell chronic lymphocytic leukemia (B-CLL) is often complicated by autoimmune hemolytic anemia (AIHA), which in some cases may be refractory to conventional therapy such as corticosteroids, rituximab and splenectomy. We report here on 5 patients (median age 66 years, range 59-69) with advanced B-CLL, all of whom developed severe transfusion-dependent AIHA resistant to conventional therapy and received subcutaneous (SC) or intravenous (IV) alemtuzumab, a humanized monoclonal antibody that targets the CD52 antigen as salvage treatment for AIHA. Alemtuzumab was well tolerated with only minor 'first dose' reactions. All 5 patients responded with a >or=2.0 g/dl rise in hemoglobin (Hb) concentration, in the absence of further transfusions, after a median time of 5 weeks (range 4-7), and the mean Hb increased from 7.2 g/dl at baseline to 11.9 g/dl at end of treatment. All patients remained stable, without further AIHA episodes, after a median follow-up time of 12 months with a mean Hb of 12.5 g/dl (range 12.2-12.9). For patients with severe, refractory CLL-related AIHA, who have not previously responded to conventional therapy, alemtuzumab is an effective agent.

  19. A critical question for HIV vaccine development: Which antibodies to induce?


    Zolla-Pazner, Susan


    A vaccine against HIV-1 must prevent infection against genetically diverse virus strains. Two approaches are currently being pursued to elicit antibody-mediated protection: vaccines that induce potent and broadly reactive neutralizing antibodies (bnAbs) or vaccines that induce “conventional antibodies,” which are less potent and broadly neutralizing in comparison. Although bnAbs may provide the greatest level of protection, their structural and genetic characteristics make their elicitation t...

  20. 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;


    antibodies (mAb) on day 8 postimmunization. Clinical scoring and both histological and immunohistochemical studies were undertaken for all groups. We hereby show that treatment with anti-IFN-gamma mAb worsened the disease course of 129Sv wild-type mice. However, it decreased the mean daily score in IFN......-gamma R(-/-) 129Sv and the incidence of the disease down to 50% in C57Bl/6x129Sv IFN-gamma R(-/-) mice. Moreover, after anti-IFN-gamma mAb treatment, oxidative stress levels, metallothionein I and II antioxidant protein expression, and apoptoticneuronal death were increased in wild-type mice while...... decreased in IFN-gamma R(-/-) mice. These results suggest a putative alternative mechanism of action of this cytokine that works independent of its receptor....

  1. Anti-tissue transglutaminase antibodies (IgA and IgG in both Crohn's disease and autoimmune diabetes Anticuerpos (IgA e IgG antitransglutaminasa tisular en la enfermedad de Crohn y diabetes autoinmune

    Directory of Open Access Journals (Sweden)

    Virgínia Lúcia Ribeiro-Cabral


    Full Text Available Objective: a strong association has been observed between celiac disease, generally its silent clinical form, and autoimmune disorders. A potential correlation with inflammatory bowel disease has also been suggested. Anti-tissue transglutaminase antibodies have been detected in Crohn's disease. We investigated the prevalence of celiac disease in patients with autoimmune diabetes and in Crohn's disease patients and also evaluated the correlation between anti-transglutaminase antibody positivity and the clinical status of these diseases. Methods: anti-tissue transglutaminase and anti-endomysium antibodies were assessed by enzyme-linked immunosorbent assay and indirect immunofluorescence, respectively. Upper digestive endoscopy and duodenal biopsy were indicated for cases with positive serology. Results: anti-transglutaminase antibodies were detected in five diabetic patients (prevalence of 11.1%, only one serum sample was positive for IgG isotypes. Nine of thirty-three patients with Crohn's disease had low positive levels for IgA anti-transglutaminase. Anti-endomysium antibodies were detected only in celiac patients. Celiac disease was confirmed in all diabetic patients submitted to duodenal biopsies who presented both anti-transglutaminase and anti-endomisyum antibodies positivity. In Crohn's disease, its clinical status and the diagnosis of celiac disease were not associated with positive anti-transglutaminase result. Conclusions: the prevalence of celiac disease was high in diabetic patients. Anti-tissue transglutaminase antibodies were sensitive and specific markers of celiac disease in this diabetic group, while these antibodies were of limited value for celiac disease screening in patients with Crohn's disease.

  2. Preparation of Europium Induced Conformation—specific anti—calmodulin Monoclonal Antibody

    Institute of Scientific and Technical Information of China (English)

    WeiGuoLI; ChaoQI; 等


    Monoclonal antibody technique was employed to detect the conformational difference of CaM induced by metal ions. A trivalent europium ion induced conformation-specific anti-calmodulin monoclonal antibody was successfully prepared with europium-saturated calmodulin as antigen.

  3. Preparation of Europium Induced Conformation-specific anti-calmodulin Monoclonal Antibody

    Institute of Scientific and Technical Information of China (English)


    Monoclonal antibody technique was employed to detect the conformational difference of CaM induced by metal ions. A trivalent europium ion induced conformation-specific anti-calmodulin monoclonal antibody was successfully prepared with europium-saturated calmodulin as antigen.

  4. Role of Complement in Autoimmune Hemolytic Anemia


    Berentsen, Sigbjørn


    Summary The classification of autoimmune hemolytic anemias and the complement system are reviewed. In autoimmune hemolytic anemia of the warm antibody type, complement-mediated cell lysis is clinically relevant in a proportion of the patients but is hardly essential for hemolysis in most patients. Cold antibody-mediated autoimmune hemolytic anemias (primary cold agglutinin disease, secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria) are entirely complement-mediated disorder...

  5. 多种自身抗体联合检测对自身免疫性肝病的诊断价值%Diagnosis value of multiple autoimmune antibody detection in autoimmune liver diseases

    Institute of Scientific and Technical Information of China (English)

    任妹; 廖永强; 彭可君; 孟芳; 俞丹菁


    目的:分析各种肝病患者多种自身抗体的检出率,探讨其对自身免疫性肝病(autoimmune liver diseases,ALD)的诊断价值.方法:根据临床诊断将患者分为ALD组(n=96)、病毒性肝炎组(n=135,包括75例乙型肝炎,65例丙型肝炎),另取62例健康体检者作为健康对照组(n=62);其中,ALD组又分为自身免疫性肝炎组(AIH组,n=36)、原发性胆汁性肝硬化组(PBC组,n=58)、原发性硬化性胆管炎组(PSC组,n=2).用间接免疫荧光法检测上述各组的抗核抗体(antinuclear antibodies,ANA)、抗平滑肌抗体(anti-smooth muscle antibodies,ASMA)、抗线粒体抗体(antimitochondrial ant-ibodies,AMA);用Western印迹法检测抗肝肾微粒体Ⅰ型抗体(anti liver-kidney microsomal antibody Type 1,LKM-1)和抗线粒体Ⅱ型抗体(subtype of AMA,AMA-M2)、抗可溶性肝抗原/胰抗原抗体(soluble liver antigen/liver pancreas,SLA/LP)、抗肝细胞溶质抗原Ⅰ型抗体(antihepatocyte cytosol antigen Type 1,LC-1).结果:AIH组ANA阳性率(69.4%)和PBC组ANA阳性率(87.9%)显著高于病毒性肝炎组(37.3%)和健康对照组(4.8%)(均P<0.01);AIH组ASMA,LKM-1,SLA/LP,LC-1阳性率(44.4%,11.1%,2.8%,8.3%)显著高于病毒性肝炎组(1.3%,1.7%,0,0)和健康对照组(均P<0.01);PBC组AMA-M2阳性率(91.3%)显著高于病毒性肝炎组(1.3%)和健康对照组(0)(均P<0.01).结论:联合检测ANA,ASMA,LKM-1,SLA/LP,LC-1和AMA-M2等自身抗体可提高ALD诊断的灵敏性和特异性,且对ALD分型、诊疗具有重要意义.

  6. Long-Lived Plasma Cells in Autoimmunity: Lessons from B-Cell Depleting Therapy



    A large number of autoimmune diseases are treated with rituximab, an antibody against CD20 that depletes most of the B cells in the organism. The response to this treatment depends largely on the disease and the type of lymphoid cells involved in the autoimmune process. We recently reported that B-cell depletion in immune thrombocytopenia induced the appearance of pathogenic long-lived plasma cells in the spleen, which were not present before treatment or in non-autoimmune conditions. The spl...

  7. Coeliac disease in 2013: new insights in dietary-gluten-induced autoimmunity. (United States)

    Kaukinen, Katri; Mäki, Markku


    Coeliac disease comprises intolerance against dietary wheat, rye and barley gluten and is one of the most common food-related life-long disorders in Western countries. In 2013, new knowledge of the clinical diversity of coeliac disease and further details about the autoimmune aspects of this disorder have emerged.

  8. Maturation, reactivity and therapy induced changes of memory T-cells in rheumatic autoimmune diseases

    NARCIS (Netherlands)

    Fritsch, R.D.E.


    This thesis covers different aspects of CD4+T-cells (maturational pathway, auto-reactive potential and differential reaction to glucocorticoid-therapy) in two auto-immune diseases: systemic lupus erythematosus (SLE) and Rheumatoid arthritis (RA). Immunological memory is important for an adequate res

  9. [The role of hereditary and environmental factors in autoimmune thyroid diseases]. (United States)

    Balázs, Csaba


    Autoimmune thyroid diseases are the most common organ-specific autoimmune disorders affecting 5% to 10% of the population in Western countries. The clinical presentation varies from hyperthyroidism in Graves' disease to hypothyroidism in Hashimoto's thyroiditis. While the exact etiology of thyroid autoimmunity is not known, the interaction between genetic susceptibility and environmental factors appears to be of fundamental importance to initiate the process of thyroid autoimmunity. The identified autoimmune thyroid disease susceptibility genes include immune-modulating genes, such as the major histocompatibility complex, and thyroid-specific genes, including TSH receptor, thyroglobulin and thyroid peroxidase. The majority of the anti-TSH-receptor antibodies have a stimulating capacity and are responsible for hyperthyroidism. The anti-thyroglobulin- and anti-thyroid peroxidase antibodies belonging to the catalytic type of antibodies destroy the thyrocytes resulting in hypothyroidism. The appearance of anti-thyroid peroxidase antibodies precedes the induction of thyroiditis and the manifestation of hypothyroidism. The molecular analysis of thyroglobulin gene polymorphism is important in the mechanism of autoimmune thyroiditis. The autoantigen presentation by major histocompatibility complex molecules is a key point of the autoimmune mechanism. It has been shown that a HLA-DR variant containing arginine at position 74 of the DRβ1 chain confers a strong genetic susceptibility to autoimmune thyroid diseases, Graves' disease and Hashimoto's thyroiditis, while glutamine at position DRβ1-74 is protective. Human thyroglobulin 2098 peptide represents a strong and specific DRβ1-Arg74 binder, while a non-binding control peptide, thyroglobulin 2766 fails to induce this response. Moreover, thyroglobulin 2098 stimulated T-cells from individuals who were positive for thyroglobulin antibodies, demonstrating that thyroglobulin 2098 is an immunogenic peptide capable of being

  10. Autoimmune hepatitis induced by nitrofurantoin. The importance of the autoantibodies for an early diagnosis of immune disease. (United States)

    Sherigar, Jagannath M; Fazio, Richard; Zuang, Minsheng; Arsura, Edward


    Nitrofurantoin has been in use since 1953 as an effective agent for the prevention of recurrent urinary tract infection. It is associated with a wide range of adverse drug reactions. Chronic active hepatitis has increasingly been observed and many cases have been reported with case fatalities. We present a case of nitrofurantoin induced chronic active hepatitis and briefly review the serology and clinico pathological features of 57 similar cases reported in English literature. The consistent presence of antinuclear antibody, anti smooth muscle antibody, elevated immunoglobulin and pathological feature suggests an immunologic mechanism. Complete recovery is possible in most cases if medication is discontinued in time. Steroids may play a role in management if no improvement occurs despite discontinuation of medication. We suggest all patients who are on prolonged nitrofurantoin therapy be followed up with anti nuclear antibody, anti smooth muscle antibody, serum immunoglobulin and hepatic panel every three months.

  11. Autoimmune hepatitis induced by nitrofurantoin. The importance of the autoantibodies for an early diagnosis of immune disease

    Directory of Open Access Journals (Sweden)

    Jagannath M. Sherigar


    Full Text Available Nitrofurantoin has been in use since 1953 as an effective agent for the prevention of recurrent urinary tract infection. It is associated with a wide range of adverse drug reactions. Chronic active hepatitis has increasingly been observed and many cases have been reported with case fatalities. We present a case of nitrofurantoin induced chronic active hepatitis and briefly review the serology and clinico pathological features of 57 similar cases reported in English literature. The consistent presence of antinuclear antibody, anti smooth muscle antibody, elevated immunoglobulin and pathological feature suggests an immunologic mechanism. Complete recovery is possible in most cases if medication is discontinued in time. Steroids may play a role in management if no improvement occurs despite discontinuation of medication. We suggest all patients who are on prolonged nitrofurantoin therapy be followed up with anti nuclear antibody, anti smooth muscle antibody, serum immunoglobulin and hepatic panel every three months.

  12. Ezrin, maspin, peroxiredoxin 2, and heat shock protein 27: potential targets of a streptococcal-induced autoimmune response in psoriasis. (United States)

    Besgen, Petra; Trommler, Paul; Vollmer, Sigrid; Prinz, Joerg Christoph


    Psoriasis is an HLA-Cw6-associated T cell-mediated autoimmune disease of the skin that is often triggered by streptococcal angina. To identify keratinocyte proteins, which may become psoriatic autoantigens as the result of an immune response against streptococci, rabbits were immunized with heat-killed Streptococcus pyogenes. Streptococcal immunization induced Ab formation against various human keratinocyte proteins. Sera from psoriasis patients reacted against several of these proteins as well. Common serologic reactivities of rabbits and patients included the proteins ezrin, maspin, peroxiredoxin 2 (PRDX2), heat shock protein (hsp)27, and keratin 6. When used for stimulation of blood lymphocytes, ezrin, maspin, PRDX2, and hsp27 induced increased T cell activation in psoriasis patients, which was particularly evident for HLA-Cw6(+) individuals. Ag-specific T cell lines generated with these proteins consisted predominantly of CD8(+) T cells and used TCR beta-chain rearrangements, which were highly homologous to those expanded within the corresponding skin lesion. Several immunodominant epitopes on the different proteins could be defined according to sequence alignments with the whole genome of S. pyogenes. Our data indicate that maspin, ezrin, PRDX2, hsp27, and potentially keratin 6 could act as autoantigens of a streptococcal-induced autoimmune response and represent targets of the exaggerated T cell response in psoriasis. Additionally, ezrin and hsp27 might constitute antigenic links between psoriasis and inflammatory bowel disease, uveitis, or arteriosclerosis, which are clinically associated.

  13. Galectin-3 in autoimmunity and autoimmune diseases. (United States)

    de Oliveira, Felipe L; Gatto, Mariele; Bassi, Nicola; Luisetto, Roberto; Ghirardello, Anna; Punzi, Leonardo; Doria, Andrea


    Galectin-3 (gal-3) is a β-galactoside-binding lectin, which regulates cell-cell and extracellular interactions during self/non-self-antigen recognition and cellular activation, proliferation, differentiation, migration and apoptosis. It plays a significant role in cellular and tissue pathophysiology by organizing niches that drive inflammation and immune responses. Gal-3 has some therapeutic potential in several diseases, including chronic inflammatory disorders, cancer and autoimmune diseases. Gal-3 exerts a broad spectrum of functions which differs according to its intra- or extracellular localization. Recombinant gal-3 strategy has been used to identify potential mode of action of gal-3; however, exogenous gal-3 may not reproduce the functions of the endogenous gal-3. Notably, gal-3 induces monocyte-macrophage differentiation, interferes with dendritic cell fate decision, regulates apoptosis on T lymphocytes and inhibits B-lymphocyte differentiation into immunoglobulin secreting plasma cells. Considering the influence of these cell populations in the pathogenesis of several autoimmune diseases, gal-3 seems to play a role in development of autoimmunity. Gal-3 has been suggested as a potential therapeutic agent in patients affected with some autoimmune disorders. However, the precise role of gal-3 in driving the inflammatory process in autoimmune or immune-mediated disorders remains elusive. Here, we reviewed the involvement of gal-3 in cellular and tissue events during autoimmune and immune-mediated inflammatory diseases.

  14. Autoimmunity in 2013. (United States)

    Selmi, Carlo


    The peer-reviewed publications in the field of autoimmunity published in 2013 represented a significant proportion of immunology articles and grew since the previous year to indicate that more immune-mediated phenomena may recognize an autoimmune mechanism and illustrated by osteoarthritis and atherosclerosis. As a result, our understanding of the mechanisms of autoimmunity is becoming the paradigm for translational research in which the progress in disease pathogenesis for both tolerance breakdown and inflammation perpetuation is rapidly followed by new treatment approaches and clinical management changes. The similarities across the autoimmune disease spectrum outnumber differences, particularly when treatments are compared. Indeed, the therapeutics of autoimmune diseases are based on a growing armamentarium that currently includes monoclonal antibodies and small molecules which act by targeting molecular markers or intracellular mediators with high specificity. Among the over 100 conditions considered as autoimmune, the common grounds are well illustrated by the data reported for systemic lupus erythematosus and rheumatoid arthritis or by the plethora of studies on Th17 cells and biomarkers, particularly serum autoantibodies. Further, we are particularly intrigued by studies on the genomics, epigenetics, and microRNA at different stages of disease development or on the safe and effective use of abatacept acting on the costimulation of T and B cells in rheumatoid arthritis. We are convinced that the data published in 2013 represent a promising background for future developments that will exponentially impact the work of laboratory and clinical scientists over the next years.

  15. Anti-PD-L1 atezolizumab-Induced Autoimmune Diabetes: a Case Report and Review of the Literature. (United States)

    Hickmott, Laura; De La Peña, Hugo; Turner, Helen; Ahmed, Fathelrahman; Protheroe, Andrew; Grossman, Ashley; Gupta, Avinash


    Programmed cell death-1 and programmed death ligand 1 (PD-1/PD-L1) inhibitors trigger an immune-mediated anti-tumour response by promoting the activation of cytotoxic T lymphocytes. Although proven to be highly effective in the treatment of several malignancies they can induce significant immune-related adverse events (irAEs) including endocrinopathies, most commonly hypophysitis and thyroid dysfunction, and rarely autoimmune diabetes. Here we present the first case report of a patient with a primary diagnosis of urothelial cancer developing PD-L1 inhibitor-induced autoimmune diabetes. A euglycemic 57 year old male presented to clinic with dehydration after the fifth cycle of treatment with the novel PD-L1 inhibitor atezolizumab. Blood tests demonstrated rapid onset hyperglycaemia (BM 24 mmol/L), ketosis and a low C-peptide level (0.65 ng/mL) confirming the diagnosis of type 1 diabetes. He responded well to insulin therapy and was discharged with stable blood glucose levels. Due to the widening use of PD-1/PD-L1 inhibitors in cancer treatment clinicians need to be aware of this rare yet treatable irAE. Given the morbidity and mortality associated with undiagnosed autoimmune diabetes we recommend routine HbA1c and plasma glucose testing in all patients prior to and during treatment with PD-1/PD-L1 inhibitors until more evidence has accumulated on identifying those patients with a pre-treatment risk of such irAEs.

  16. Autoimmunity in visual loss. (United States)

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


    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

  17. The role of autoimmunity in premature ovarian failure

    Directory of Open Access Journals (Sweden)

    Mahbod Ebrahimi


    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.

  18. [Non-autoimmune thyroiditis]. (United States)

    Rizzo, Leonardo F L; Mana, Daniela L; Bruno, Oscar D


    The term thyroiditis comprises a group of thyroid diseases characterized by the presence of inflammation, including autoimmune and non-autoimmune entities. It may manifest as an acute illness with severe thyroid pain (subacute thyroiditis and infectious thyroiditis), and conditions in which the inflammation is not clinically evident evolving without pain and presenting primarily thyroid dysfunction and/or goiter (drug-induced thyroiditis and Riedel thyroiditis). The aim of this review is to provide an updated approach on non-autoimmune thyroiditis and its clinical, diagnostic and therapeutic aspects.

  19. Evaluation on the detection of anti-nuclear antibody and anti-soluble nuclearantigen antibody for the diagnosis of autoimmune disease%ANA和ENA检测在自身免疫性疾病中的应用评价

    Institute of Scientific and Technical Information of China (English)

    陆慧琦; 李畅; 叶伟民; 杨洁; 何铭珺; 韩焕兴


    To evaluating the sensitivity and correlation on anti-nuclear antibody(ANA) and anti-soluble nuclear antigen antibody (ENA) in the diagnosis of autoimmune disease(AID ), the results of auto-antibody detection in serum were retrospectively analyzed for patients visited at Changzheng hospital from Jan, 2007 to Oct, 2009, among which 224 cases were patients with AID and 325 cases were patients with non-autoimmune diseases. For all these patients, the indirect immunofluorescene(IIF)assay based on the cultured human epidermoid carcinoma cells( Hep-2 cell/liver and immunoblot assay were used to detect ANA and ENA respectively. It was demonstrated that 4 different patterns were formed by using these two kinds of detection methods, i.e. ANA+/ENA+、 ANA-/ENA-、 ANA+/ENA- and ANA-/ENA+ respectively. Positive rate of ANA and ENA (63.4% vs 58. 5%) in AID was significantly higher than that of non-AID (16.9% vs 25.2%). Expect in with MCTD and SLE, there were no correlation between ANA and ENA. The ANA-IIF assay appears to be a time-consuming procedure and difficult to standardize owing to subjective interpretation of results. Acting as a screening experimental method, the sensitivity of ANA is higher than that of ENA. Nevertheless. the combined use of both methods would increase the sensitivity and reliability of testing.%探讨抗核抗体和抗可溶性核抗原抗体的不同检测方法对自身免疫性疾病诊断的指导意义.回顾性分析2007年1月至2009年10月间在长征医院就诊的患者血清自身抗体的检测结果,549位患者,其中自身免疫病患者224例,非自身免疫病325例,所有患者血清同时检测ANA和ENA.以Hep-2细胞/肝组织为基质的间接免疫荧光法检测ANA,免疫印迹法检测ENA.两种检测方法产生4种检出模式:ANA+/ENA+、ANA-/ENA-、ANA+/ENA-和ANA-/ENA+.前两种模式共占检测的62.84%.ANA和ENA在自身免疫病患者中的阳性率(63.4%和58.5%)显著高于非自免病患者(16.9%和25

  20. The lactic acid bacterium Pediococcus acidilactici suppresses autoimmune encephalomyelitis by inducing IL-10-producing regulatory T cells.

    Directory of Open Access Journals (Sweden)

    Kazushiro Takata

    Full Text Available BACKGROUND: Certain intestinal microflora are thought to regulate the systemic immune response. Lactic acid bacteria are one of the most studied bacteria in terms of their beneficial effects on health and autoimmune diseases; one of which is Multiple sclerosis (MS which affects the central nervous system. We investigated whether the lactic acid bacterium Pediococcus acidilactici, which comprises human commensal bacteria, has beneficial effects on experimental autoimmune encephalomyelitis (EAE, an animal model of MS. METHODOLOGY/PRINCIPAL FINDINGS: P. acidilactici R037 was orally administered to EAE mice to investigate the effects of R037. R037 treatment suppressed clinical EAE severity as prophylaxis and therapy. The antigen-specific production of inflammatory cytokines was inhibited in R037-treated mice. A significant increase in the number of CD4(+ Interleukin (IL-10-producing cells was observed in the mesenteric lymph nodes (MLNs and spleens isolated from R037-treated naive mice, while no increase was observed in the number of these cells in the lamina propria. Because only a slight increase in the CD4(+Foxp3(+ cells was observed in MLNs, R037 may primarily induce Foxp3(- IL10-producing T regulatory type 1 (Tr1 cells in MLNs, which contribute to the beneficial effect of R037 on EAE. CONCLUSIONS/SIGNIFICANCE: An orally administered single strain of P. acidilactici R037 ameliorates EAE by inducing IL10-producing Tr1 cells. Our findings indicate the therapeutic potential of the oral administration of R037 for treating multiple sclerosis.

  1. Vaccine-induced antibody responses in relation to season

    NARCIS (Netherlands)

    Termorshuizen F; Sleijffers A; Hof S van den; Melker H de; Garssen J; Boland GJ; Hattum J van; Gruijl FR de; Loveren H van; LPI


    The effect of season on the antibody response after Hepatitis B (HB), Measles and Rubella vaccination in humans was investigated. In view of the immunosuppressive effects of ultraviolet radiation (UVR), especially the B-waveband (UVB), it was hypothesised that a lower antibody response after vaccina

  2. Prevalence and Gene Characteristics of Antibodies with Cofactor-induced HIV-1 Specificity* (United States)

    Lecerf, Maxime; Scheel, Tobias; Pashov, Anastas D.; Jarossay, Annaelle; Ohayon, Delphine; Planchais, Cyril; Mesnage, Stephane; Berek, Claudia; Kaveri, Srinivas V.; Lacroix-Desmazes, Sébastien; Dimitrov, Jordan D.


    The healthy immune repertoire contains a fraction of antibodies that bind to various biologically relevant cofactors, including heme. Interaction of heme with some antibodies results in induction of new antigen binding specificities and acquisition of binding polyreactivity. In vivo, extracellular heme is released as a result of hemolysis or tissue damage; hence the post-translational acquisition of novel antigen specificities might play an important role in the diversification of the immunoglobulin repertoire and host defense. Here, we demonstrate that seronegative immune repertoires contain antibodies that gain reactivity to HIV-1 gp120 upon exposure to heme. Furthermore, a panel of human recombinant antibodies was cloned from different B cell subpopulations, and the prevalence of antibodies with cofactor-induced specificity for gp120 was determined. Our data reveal that upon exposure to heme, ∼24% of antibodies acquired binding specificity for divergent strains of HIV-1 gp120. Sequence analyses reveal that heme-sensitive antibodies do not differ in their repertoire of variable region genes and in most of the molecular features of their antigen-binding sites from antibodies that do not change their antigen binding specificity. However, antibodies with cofactor-induced gp120 specificity possess significantly lower numbers of somatic mutations in their variable region genes. This study contributes to the understanding of the significance of cofactor-binding antibodies in immunoglobulin repertoires and of the influence that the tissue microenvironment might have in shaping adaptive immune responses. PMID:25564611

  3. Autoimmune diseases induced by TNF-targeted therapies: analysis of 233 cases. (United States)

    Ramos-Casals, Manuel; Brito-Zerón, Pilar; Muñoz, Sandra; Soria, Natalia; Galiana, Diana; Bertolaccini, Laura; Cuadrado, Maria-Jose; Khamashta, Munther A


    Tumor necrosis factor (TNF)-targeted therapies are increasingly used for a rapidly expanding number of rheumatic and autoimmune diseases. With this use and longer follow-up periods of treatment, there are a growing number of reports of the development of autoimmune processes related to anti-TNF agents. We have analyzed the clinical characteristics, outcomes, and patterns of association with the different anti-TNF agents used in all reports of autoimmune diseases developing after TNF-targeted therapy found through a MEDLINE search of articles published between January 1990 and December 2006. We identified 233 cases of autoimmune diseases (vasculitis in 113, lupus in 92, interstitial lung diseases in 24, and other diseases in 4) secondary to TNF-targeted therapies in 226 patients. The anti-TNF agents were administered for rheumatoid arthritis (RA) in 187 (83%) patients, Crohn disease in 17, ankylosing spondylitis in 7, psoriatic arthritis in 6, juvenile RA in 5, and other diseases in 3. The anti-TNF agents administered were infliximab in 105 patients, etanercept in 96, adalimumab in 21, and other anti-TNF agents in 3. We found 92 reported cases of lupus following anti-TNF therapy (infliximab in 40 cases, etanercept in 37, and adalimumab in 15). Nearly half the cases fulfilled 4 or more classification criteria for systemic lupus erythematosus (SLE), which fell to one-third after discarding preexisting lupus-like features. One hundred thirteen patients developed vasculitis after receiving anti-TNF agents (etanercept in 59 cases, infliximab in 47, adalimumab in 5, and other agents in 2). Leukocytoclastic vasculitis was the most frequent type of vasculitis, and purpura was the most frequent cutaneous lesion. A significant finding was that one-quarter of patients with vasculitis related to anti-TNF agents had extracutaneous involvement. Twenty-four cases of interstitial lung disease associated with the use of anti-TNF agents were reported. In these patients, 2 specific

  4. 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:


    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

  5. Detection of antinuclear and antilaminin antibodies in autistic children who received thimerosal-containing vaccines. (United States)

    Singh, Vijendra K; Rivas, Wyatt H


    Autism, a neurodevelopmental disorder, may involve autoimmune pathogenesis. Since mercury is potentially a risk factor for autoimmunity, we conducted a study of mercury-induced antinuclear and antilaminin antibodies in autistic and normal children who had been pre-administered with thimerosal-containing vaccines. Laboratory analysis by different immunoassays showed that the serum level of these two autoimmune markers did not significantly differ between autistic and normal children. This finding suggests that the mercury as in thimerosal-containing vaccines is likely not related to autoimmune phenomenon in autism.

  6. Epigenetics of the antibody response. (United States)

    Li, Guideng; Zan, Hong; Xu, Zhenming; Casali, Paolo


    Epigenetic marks, such as DNA methylation, histone post-translational modifications and miRNAs, are induced in B cells by the same stimuli that drive the antibody response. They play major roles in regulating somatic hypermutation (SHM), class switch DNA recombination (CSR), and differentiation to plasma cells or long-lived memory B cells. Histone modifications target the CSR and, possibly, SHM machinery to the immunoglobulin locus; they together with DNA methylation and miRNAs modulate the expression of critical elements of that machinery, such as activation-induced cytidine deaminase (AID), as well as factors central to plasma cell differentiation, such as B lymphocyte-induced maturation protein-1 (Blimp-1). These inducible B cell-intrinsic epigenetic marks instruct the maturation of antibody responses. Their dysregulation plays an important role in aberrant antibody responses to foreign antigens, such as those of microbial pathogens, and self-antigens, such as those targeted in autoimmunity, and B cell neoplasia.

  7. Biologics-induced autoimmune renal disorders in chronic inflammatory rheumatic diseases: systematic literature review and analysis of a monocentric cohort. (United States)

    Piga, Matteo; Chessa, Elisabetta; Ibba, Valentina; Mura, Valentina; Floris, Alberto; Cauli, Alberto; Mathieu, Alessandro


    The use of biologic drugs has been linked with the paradoxical development of systemic and organ specific autoimmune processes. The aim of this study was to describe the features of biologics-induced autoimmune renal disorders (AIRD) through a systematic review and a cohort study of 707 adult patients affected with Rheumatoid Arthritis (RA), Ankylosing Spondylitis (SA) and Psoriatic Arthritis (PsA). The literature search identified 2687 articles of which 21 were considered relevant for the present study, accounting for 26 case reports. The cohort analysis retrieved 3 cases. According to clinical manifestations and kidney histology the identified AIRD cases were classified as: a) glomerulonephritis associated with systemic vasculitis (GNSV), b) glomerulonephritis in lupus-like syndrome (GNLS), c) isolated autoimmune renal disorders (IARD). Twenty-two out of 29 cases with AIRD were reported in patients affected by RA, 5 in AS and 2 in PsA. The biologic drug most frequently associated with development of AIRD was Etanercept (15 cases, 51.7%), followed by Adalimumab (9 cases, 31.0%) and Infliximab (3 cases, 10.3%) while Tocilizumab and Abatacept were reported in 1 case (3.4%) for each. Thirteen out of 29 (44.8%) cases were classified as affected by IARD, 12 (41.3%) as GNSV and 4 (13.9%) as GNLS. Worse prognosis was associated with GNSV and lack of biologic withdrawal. Although rare, AIRD may be life-threatening and may lead to renal failure and death. If AIRD occurs, biologic drugs must be stopped and patient should be treated according to clinical manifestations and kidney biopsy findings.

  8. Vaccines, adjuvants and autoimmunity. (United States)

    Guimarães, Luísa Eça; Baker, Britain; Perricone, Carlo; Shoenfeld, Yehuda


    Vaccines and autoimmunity are linked fields. Vaccine efficacy is based on whether host immune response against an antigen can elicit a memory T-cell response over time. Although the described side effects thus far have been mostly transient and acute, vaccines are able to elicit the immune system towards an autoimmune reaction. The diagnosis of a definite autoimmune disease and the occurrence of fatal outcome post-vaccination have been less frequently reported. Since vaccines are given to previously healthy hosts, who may have never developed the disease had they not been immunized, adverse events should be carefully accessed and evaluated even if they represent a limited number of occurrences. In this review of the literature, there is evidence of vaccine-induced autoimmunity and adjuvant-induced autoimmunity in both experimental models as well as human patients. Adjuvants and infectious agents may exert their immune-enhancing effects through various functional activities, encompassed by the adjuvant effect. These mechanisms are shared by different conditions triggered by adjuvants leading to the autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome). In conclusion, there are several case reports of autoimmune diseases following vaccines, however, due to the limited number of cases, the different classifications of symptoms and the long latency period of the diseases, every attempt for an epidemiological study has so far failed to deliver a connection. Despite this, efforts to unveil the connection between the triggering of the immune system by adjuvants and the development of autoimmune conditions should be undertaken. Vaccinomics is a field that may bring to light novel customized, personalized treatment approaches in the future.

  9. The expression of apoptotic gene PDCD5 and anti-nucleic antibody spectrum in autoimmune diseases%凋亡基因PDCD5及抗核抗体谱在自身免疫病中的表达

    Institute of Scientific and Technical Information of China (English)

    李婉红; 徐友文; 黄海东; 缪蕾蕾; 陈琪


    Objective:To investigate the expressions of PDCD5 and anti - nucleic antibodies spectrum in autoimmune diseases. Methods: Using the method of enzyme - linked immunosorbent assay ( ELISA) , the serum levels of PDCD5 and anti -nucleic antibodies from 117 autoimmune disease patients and 32 healthy people were detected. Results: Anti -nucleic antibodies spectrum were detected from 117 autoimmune disease patients, antibodies had changes with different degrees. SSA was highest, total positive rate was 76. 9%. In the SLE patients, the positive rates of SSA, SSA (Ro52) , dsDNA were 81% , 51% , 51%. In the SS patients, the positive rates of SSA, SSB were 88% , 75% , but in healthy people, the anti - nucleic antibodies were not found. The expressions of PDCD5 in peripheral blood of autoimmune disease patients significantly increased compared to those of the controls ( P < 0.05). In SLE patients, the expressions of PDCD5 were the highest than others. Conclusion: PDCD5 might play a role in the pathogenesis of autoimmune disease. ENA antibody spectrum had prompting significance autoimmune disease.%目的:通过检测PDCD5及抗核抗体谱在自身免疫性疾病中的表达.方法:应用酶联免疫吸附法(ELISA法)对117例自身免疫病患者及32例正常人外周血PDCD5表达和抗核抗体谱检测,观察二者在自身免疫性疾病中的相关性.结果:117例自身免疫性疾病患者抗核多肽抗体谱中,抗核抗体有不同程度的变化,SSA阳性率最高,总阳性率为76.9%.在诊断为SLE的患者中SSA、SSA (R052)、dsDNA的阳性率较高,分别为81%、51%、51%.在SS患者中SSA、SSB的阳性率较高分别为88%、75%,健康对照组未检出抗核抗体.自身免疫患者与健康对照组外周血PDCD5含量比较显示对照组与SLE、RA、ITP、SS患者的PDCD5含量存在显著性差异(P<0.05),且在SLE患者中PDCD5含量最高.结论:自身免疫病患者PDCD5存在着异常表达,抗核抗体谱检测对自身免疫病有一定的提示作用.

  10. Claudin-1 induced sealing of blood–brain barrier tight junctions ameliorates chronic experimental autoimmune encephalomyelitis


    Pfeiffer, Friederike; Schäfer, Julia; Lyck, Ruth; Makrides, Victoria; Brunner, Sarah; Schaeren-Wiemers, Nicole; Deutsch, Urban; ENGELHARDT, Britta


    In experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS), loss of the blood–brain barrier (BBB) tight junction (TJ) protein claudin-3 correlates with immune cell infiltration into the CNS and BBB leakiness. Here we show that sealing BBB TJs by ectopic tetracycline-regulated expression of the TJ protein claudin-1 in Tie-2 tTA//TRE-claudin-1 double transgenic C57BL/6 mice had no influence on immune cell trafficking across the BBB during EAE and furthermore...

  11. Autoimmune hepatitis (United States)

    ... PA: Elsevier Saunders; 2010:chap 88. Read More Autoimmune disorders Chronic thyroiditis (Hashimoto disease) Cirrhosis Glomerulonephritis Hemolytic anemia Liver cancer - hepatocellular carcinoma Mesenteric venous thrombosis Type ...

  12. Clinical application of antinuclear antibodies in autoimmune diseases%抗核抗体检测在自身免疫性疾病的临床应用

    Institute of Scientific and Technical Information of China (English)

    苏娜; 刘晓玲; 窦存瑞


    Objective To discuss the clinical significance of anti-nuclear antibody (ANA) in treatment of autoimmune diseases (AID). Methods 2055 patients up to the diagnosis standards were selected. The ANA in serum of patients was measured by indirect immunofluorescence. The positive rate, karyotype and titer of ANA were analyzed in the above AID. Results The titer of ANA in AID patients group was 1:80 while 1 :160 in the control group. ANA positive rate of AID patients group was 80%, and its difference with control group had statistical significance (P <0.01). The highest rate was in systemic lupus erythematosus (SLE) patients. Fluorescence patterns of ANA statistics were spot-type based for SLE, drying syndrome, rheumatoid arthritis patients. The homogenous and the nuclear core spots were mainly for autoimmune hepatitis patients. Conclusion The positive rate and titer of ANA are different among various AID patients. More attention should be paid to the titer value of ANA in the ANA test. Because more and more types of ANA fluorescence patterns are found, and different models represent different fluorescent target antigen. In particular, some special fluorescent models play an important role in the diagnosis of AID.%目的 探讨抗核抗体(ANA)在自身免疫性疾病(AID)中的临床意义.方法 选取符合AID诊断标准的患者2055例,采用间接免疫荧光法对患者血清标本进行ANA检测,分析ANA的阳性率、核型及滴度的变化.结果 ANA滴度AID患者以1:160为主,对照组以1:80为主.AID检测患者中,ANA阳性率为80%,与对照组比较有显著性差异(P<0.01),以系统性红斑狼疮的ANA阳性率为最高.ANA荧光模型结果系统性红斑狼疮、干燥综合症、类风湿关节炎患者以斑点型为主,自身免疫性肝炎患者以核均质型及核斑点性为主.结论 不同AID患者检测ANA阳性率和滴度有差异,检测ANA应重视ANA滴度的价值.ANA荧光模型种类较多,不同的荧光模型表示不同的

  13. Nonstandard drugs and feasible new interventions for autoimmune hepatitis: part II. (United States)

    Czaja, Albert J


    Molecular, cellular, and genetic interventions are now feasible for autoimmune hepatitis because of improved understanding of pathogenic mechanisms, advances in recombinant technology, and previous successes in animal models and humans with other immune-mediated inflammatory diseases. Non-mitogenic monoclonal antibodies to CD3 promote apoptosis of cytotoxic T lymphocytes, inhibit production of pro-inflammatory cytokines, improve the function of regulatory T cells, and induce a durable remission in mouse models and humans with autoimmune diabetes. Monoclonal antibodies to CD20 deplete B lymphocytes, modify antibody-dependent and cell-mediated cytotoxic pathways, enhance regulatory T cell function, and improve isolated cases of autoimmune hepatitis with B-cell disorders. Recombinant cytotoxic T lymphocyte antigen-4 fused with immunoglobulin can block the second co-stimulatory signal required for lymphocyte activation, and it has been licensed for use in rheumatoid arthritis but not tried in autoimmune hepatitis. Other considerations on the distant horizon are monoclonal antibodies against inhibitory receptors on regulatory T cells, adoptive transfer of fresh regulatory T cells, tailored glycolipids that strengthen the immunosuppressive activity of natural killer T cells, small inhibitory ribonucleic acid molecules that silence promoter genes supporting disease activity, and mesenchymal stem cell transplantation to re-constitute immune homeostasis and support the damaged liver. Development of these feasible new interventions for autoimmune hepatitis requires therapeutic animal models, societal support, and a collaborative network of investigators to conduct rigorous clinical trials.

  14. Spontaneous germinal centers and autoimmunity. (United States)

    Domeier, Phillip P; Schell, Stephanie L; Rahman, Ziaur S M


    Germinal centers (GCs) are dynamic microenvironments that form in the secondary lymphoid organs and generate somatically mutated high-affinity antibodies necessary to establish an effective humoral immune response. Tight regulation of GC responses is critical for maintaining self-tolerance. GCs can arise in the absence of purposeful immunization or overt infection (called spontaneous GCs, Spt-GCs). In autoimmune-prone mice and patients with autoimmune disease, aberrant regulation of Spt-GCs is thought to promote the development of somatically mutated pathogenic autoantibodies and the subsequent development of autoimmunity. The mechanisms that control the formation of Spt-GCs and promote systemic autoimmune diseases remain an open question and the focus of ongoing studies. Here, we discuss the most current studies on the role of Spt-GCs in autoimmunity.

  15. 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.

  16. Vaccines and autoimmunity. (United States)

    De Martino, M; Chiappini, E; Galli, L


    Vaccines have eradicated or controlled many infectious diseases, saving each year millions of lives and quality of life of many other millions of people. In spite of the success of vaccines over the last two centuries, parents (and also some health care workers) gloss over the devastating consequences of diseases, which are now avoided thanks to vaccines, and direct their attention to possible negative effects of immunization. Three immunological objections are raised: vaccines cause antigenic overload, natural immunity is safer and better than vaccine-induced immunity, and vaccines induce autoimmunity. The last point is examined in this review. Theoretically, vaccines could trigger autoimmunity by means of cytokine production, anti-idiotypic network, expression of human histocompatibility leukocyte antigens, modification of surface antigens and induction of novel antigens, molecular mimicry, bystander activation, epitope spreading, and polyclonal activation of B cells. There is strong evidence that none of these mechanisms is really effective in causing autoimmune diseases. Vaccines are not a source of autoimmune diseases. By contrast, absolute evidence exists that infectious agents can trigger autoimmune mechanisms and that they do cause autoimmune diseases.

  17. Autoimmunity and Asbestos Exposure

    Directory of Open Access Journals (Sweden)

    Jean C. Pfau


    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.

  18. Autoimmune gastritis: Pathologist's viewpoint. (United States)

    Coati, Irene; Fassan, Matteo; Farinati, Fabio; Graham, David Y; Genta, Robert M; Rugge, Massimo


    Western countries are seeing a constant decline in the incidence of Helicobacter pylori-associated gastritis, coupled with a rising epidemiological and clinical impact of autoimmune gastritis. This latter gastropathy is due to autoimmune aggression targeting parietal cells through a complex interaction of auto-antibodies against the parietal cell proton pump and intrinsic factor, and sensitized T cells. Given the specific target of this aggression, autoimmune gastritis is typically restricted to the gastric corpus-fundus mucosa. In advanced cases, the oxyntic epithelia are replaced by atrophic (and metaplastic) mucosa, creating the phenotypic background in which both gastric neuroendocrine tumors and (intestinal-type) adenocarcinomas may develop. Despite improvements in our understanding of the phenotypic changes or cascades occurring in this autoimmune setting, no reliable biomarkers are available for identifying patients at higher risk of developing a gastric neoplasm. The standardization of autoimmune gastritis histology reports and classifications in diagnostic practice is a prerequisite for implementing definitive secondary prevention strategies based on multidisciplinary diagnostic approaches integrating endoscopy, serology, histology and molecular profiling.

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

    Directory of Open Access Journals (Sweden)

    Taha Rashid


    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.

  20. [Drug-induced exacerbation of hypoaldosteronism in autoimmune polyglandular syndrome type 2]. (United States)

    Krysiak, Robert; Okopień, Bogusław


    Hypoaldosteronism is a clinical condition resulting from inadequate stimulation of aIdosterone secretion (hyporeninemic hypoaIdosteronism), defects in adrenal synthesis of aldosterone (hyperreninemic hypoaldosteronism), or resistance to the peripheral action of this hormone (pseudohypoaldosteronism). The disease is characterized by a wide spectrum of clinical manifestations, ranging from asymptomatic hyperkalemia to life-threatening volume depletion, and, if unrecognized and untreated, it increases morbidity and mortality rates. In this paper, we report a case of a woman diagnosed with autoimmune polyglandular syndrome type 2. As a consequence of adrenal cortex destruction, the patient developed subclinical hypoaldosteronism which was effectively treated with small doses of fludrocortisone. Two and fours years later, she required ibuprofen and atenolol treatment and each of these treatments was accompanied by a transient deterioration in mineralocorticoid activity which resolved after drug withdrawal. This case shows for the first time that drugs reducing plasma renin activity may unmask subclinical hypoaldosteronism in subjects with autoimmune polyglandular syndromes, and that they should be avoided in patients with even small disturbances in the hormonal function of the zona glomerulosa.

  1. Different levels of thyroid autoimmune antibody in four kinds of thyroid diseases%甲状腺自身免疫抗体在四种甲状腺疾病中水平差异的研究

    Institute of Scientific and Technical Information of China (English)

    马建宏; 莫巧璇; 严永智; 陈晓丽; 梁雪冰


    目的::观察自身免疫抗体甲状腺球蛋白抗体( TGAb)、抗甲状腺过氧化物酶抗体( TPOAb)和促甲状腺素受体抗体( TRAb)在4种甲状腺疾病中的水平差异。方法:将2012年1月至2014年6月在佛山市中医院内分泌科门诊就诊的506例4种甲状腺疾病患者作为研究对象,定量检测患者血液中TGAb、TPOAb和TRAb抗体水平。结果:桥本甲状腺炎患者血液中TGAb和TPOAb值、阳性率最高,分别为1439.0 IU/mL、87.7%和427.5 IU/mL、97.7%;Graves病患者血液中TRAb值和阳性率最高,为34.44 IU/L和100%;单纯性甲状腺肿及亚急性甲状腺炎患者血液中,甲状腺自身免疫抗体也有不同程度的升高。4种甲状腺疾病患者TGAb、TPOAb和TRAb抗体水平两两比较,除了亚急性甲状腺炎与桥本甲状腺炎患者的TRAb水平外,差异均有统计学意义( P<0.05)。结论:甲状腺自身免疫抗体TGAb、TPOAb和TRAb水平在不同甲状腺疾病中存在差异,结合分析对于甲状腺疾病尤其是自身免疫性甲状腺疾病具有重要的诊断价值。%Objective:To determine the different levels of the thyroid autoimmune antibodies, including thyroglobulin antibody (TGAb) and antithyroid peroxidase antibody (TPOAb) and thyroid stimulating hormone receptor antibody ( TRAb) in four kinds of thyroid diseases. Methods:A total of 506 patients with four kinds of thyroid diseases, who were hospitalized in Department of Endocrinology, Foshan Hospital of Traditional Chinese Medicine between January 2012 and June 2014, were included as the subjects in the study. The levels of plasma TGAb, TPOAb and TRAb antibodies in all patients were quantitatively determined. Results: The values and positive rates of plasma TGAb and TPOAb in patients with Hashimoto thyroiditis were the highest, which were 1439.0IU/ml, 87.7% and 427.5IU/ml, 97.7%, respectively. The plasma TRAb value and positive rate were the highest in patients with Graves, which

  2. Prevalence of antinuclear antibodies in 3 groups of healthy individuals: blood donors, hospital personnel, and relatives of patients with autoimmune diseases. (United States)

    Marin, Guadalupe G; Cardiel, Mario H; Cornejo, Horacio; Viveros, Martha E


    Antinuclear antibodies (ANA) are frequently found in healthy populations. To define the prevalence, pattern, and titer of ANA in different groups of the healthy Mexican population, we studied 304 individuals, classified into 3 groups: 104 blood donors, 100 hospital personnel working at The State General Hospital, which included doctors, laboratory technicians, and nurses; and 100 relatives of patient diagnosed either with systemic lupus erythematosus or rheumatoid arthritis, all of them apparently healthy at the time of study. We determined ANA using immunofluorescence microscopy performed on HEp-2 cells. Fluorescence was detected in 165 serum samples (54.3%). The most frequent pattern was the speckled (50.3%). The most frequent dilution was 1:40 (35.4%), followed by 1:80 (13.4%), 1:160 (3.2%), and 1:320 (1.3%).Regarding the results by study group, we found a trend toward higher ANA levels in group 2 (hospital personnel), compared with group 1 (blood donors) and group 3 (relatives of patients), a trend also reflected by the increasing frequency of serum titers of 1:80 and higher (P = 0.074). According to occupation, medical doctors showed a higher incidence of speckled pattern when compared with other occupations (P = 0.022). Medical doctors (n = 75) showed also higher titers of this particular pattern (P = 0.03). In group 3, relatives of patients with systemic lupus erythematosus showed the speckled pattern more frequently than relatives of patients with rheumatoid arthritis, in low titers (P = 0.017). We suggest that ANA tests showing speckled pattern should be at a 1:160 titer or higher to be considered positive; other patterns such as homogeneous, peripheral, or centromeric might be considered positive even at low titers (

  3. Type 1 diabetes associated autoimmunity. (United States)

    Kahaly, George J; Hansen, Martin P


    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.

  4. Autoimmune myelopathies. (United States)

    Flanagan, Eoin P


    Autoimmune myelopathies are a heterogeneous group of immune-mediated spinal cord disorders with a broad differential diagnosis. They encompass myelopathies with an immune attack on the spinal cord (e.g., aquaporin-4-IgG (AQP4-IgG) seropositive neuromyelitis optica (NMO) and its spectrum disorders (NMOSD)), myelopathies occurring with systemic autoimmune disorders (which may also be due to coexisting NMO/NMOSD), paraneoplastic autoimmune myelopathies, postinfectious autoimmune myelopathies (e.g., acute disseminated encephalomyelitis), and myelopathies thought to be immune-related (e.g., multiple sclerosis and spinal cord sarcoidosis). Spine magnetic resonance imaging is extremely useful in the evaluation of autoimmune myelopathies as the location of signal change, length of the lesion, gadolinium enhancement pattern, and evolution over time narrow the differential diagnosis considerably. The recent discovery of multiple novel neural-specific autoantibodies accompanying autoimmune myelopathies has improved their classification. These autoantibodies may be pathogenic (e.g., AQP4-IgG) or nonpathogenic and more reflective of a cytotoxic T-cell-mediated autoimmune response (collapsin response mediator protein-5(CRMP5)-IgG). The presence of an autoantibody may help guide cancer search, assist treatment decisions, and predict outcome/relapse. With paraneoplastic myelopathies the initial goal is detection and treatment of the underlying cancer. The aim of immunotherapy in all autoimmune myelopathies is to maximize reversibility, maintain benefits (while preventing relapse), and minimize side effects.

  5. Novel Immunotherapies for Autoimmune Hepatitis. (United States)

    Cassim, Shamir; Bilodeau, Marc; Vincent, Catherine; Lapierre, Pascal


    Autoimmune hepatitis (AIH) is a multifactorial autoimmune disease of unknown pathogenesis, characterized by a loss of immunological tolerance against liver autoantigens resulting in the progressive destruction of the hepatic parenchyma. Current treatments are based on non-specific immunosuppressive drugs. Although tremendous progress has been made using specific biological agents in other inflammatory diseases, progress has been slow to come for AIH patients. While current treatments are successful in the majority of patients, treatment discontinuation is difficult to achieve, and relapses are frequent. Lifelong immunosuppression is not without risks, especially in the pediatric population; 4% of patient with type 1 AIH will eventually develop hepatocellular carcinoma with a 2.9% probability after 10 years of treatment. Therefore, future treatments should aim to restore tolerance to hepatic autoantigens and induce long-term remission. Promising new immunotherapies have been tested in experimental models of AIH including T and B cell depletion and regulatory CD4(+) T cells infusion. Clinical studies on limited numbers of patients have also shown encouraging results using B-cell-depleting (rituximab) and anti-TNF-α (infliximab) antibodies. A better understanding of key molecular targets in AIH combined with effective site-specific immunotherapies could lead to long-term remission without blanket immunosuppression and with minimal deleterious side effects.

  6. Novel Immunotherapies for Autoimmune Hepatitis (United States)

    Cassim, Shamir; Bilodeau, Marc; Vincent, Catherine; Lapierre, Pascal


    Autoimmune hepatitis (AIH) is a multifactorial autoimmune disease of unknown pathogenesis, characterized by a loss of immunological tolerance against liver autoantigens resulting in the progressive destruction of the hepatic parenchyma. Current treatments are based on non-specific immunosuppressive drugs. Although tremendous progress has been made using specific biological agents in other inflammatory diseases, progress has been slow to come for AIH patients. While current treatments are successful in the majority of patients, treatment discontinuation is difficult to achieve, and relapses are frequent. Lifelong immunosuppression is not without risks, especially in the pediatric population; 4% of patient with type 1 AIH will eventually develop hepatocellular carcinoma with a 2.9% probability after 10 years of treatment. Therefore, future treatments should aim to restore tolerance to hepatic autoantigens and induce long-term remission. Promising new immunotherapies have been tested in experimental models of AIH including T and B cell depletion and regulatory CD4+ T cells infusion. Clinical studies on limited numbers of patients have also shown encouraging results using B-cell-depleting (rituximab) and anti-TNF-α (infliximab) antibodies. A better understanding of key molecular targets in AIH combined with effective site-specific immunotherapies could lead to long-term remission without blanket immunosuppression and with minimal deleterious side effects. PMID:28184367

  7. LINGO-1 antagonist promotes spinal cord remyelination and axonal integrity in MOG-induced experimental autoimmune encephalomyelitis. (United States)

    Mi, Sha; Hu, Bing; Hahm, Kyungmin; Luo, Yi; Kam Hui, Edward Sai; Yuan, Qiuju; Wong, Wai Man; Wang, Li; Su, Huanxing; Chu, Tak-Ho; Guo, Jiasong; Zhang, Wenming; So, Kwok-Fai; Pepinsky, Blake; Shao, Zhaohui; Graff, Christilyn; Garber, Ellen; Jung, Vincent; Wu, Ed Xuekui; Wu, Wutian


    Demyelinating diseases, such as multiple sclerosis, are characterized by the loss of the myelin sheath around neurons, owing to inflammation and gliosis in the central nervous system (CNS). Current treatments therefore target anti-inflammatory mechanisms to impede or slow disease progression. The identification of a means to enhance axon myelination would present new therapeutic approaches to inhibit and possibly reverse disease progression. Previously, LRR and Ig domain-containing, Nogo receptor-interacting protein (LINGO-1) has been identified as an in vitro and in vivo negative regulator of oligodendrocyte differentiation and myelination. Here we show that loss of LINGO-1 function by Lingo1 gene knockout or by treatment with an antibody antagonist of LINGO-1 function leads to functional recovery from experimental autoimmune encephalomyelitis. This is reflected biologically by improved axonal integrity, as confirmed by magnetic resonance diffusion tensor imaging, and by newly formed myelin sheaths, as determined by electron microscopy. Antagonism of LINGO-1 or its pathway is therefore a promising approach for the treatment of demyelinating diseases of the CNS.

  8. 药物诱导自身免疫性肝炎的研究进展%Progress in research of drug-induced autoimmune hepatitis

    Institute of Scientific and Technical Information of China (English)

    张彦亮; 史会连; 陶臻


    药物诱导自身免疫性肝炎(drug induced autoimmune hepatitis,DIAIH) 近年来国内外已有不少相关个案报道,其兼有药物性肝损(drug induced liver injury,DILI) 以及自身免疫性肝炎(autoimmune hepatitis,IH) 两者之特征,深入了解DIAIH 的流行病学现状、病因机制、临床表现和病理特点,将有助于我们加深对其的认知,并为DIAIH 的防治提供依据.%Drug-induced autoimmune hepatitis (DIAIH) has been reported to be caused by many drugs, which possesses the characteristics of both drug induced liver injury (DILI) and autoimmune hepatitis (AIH). A better understanding of the epidemiology, pathogenesis, pathology and clinical symptoms of DIAIH can help us better diagnose and treat this disease.

  9. Autoimmune paediatric liver disease

    Institute of Scientific and Technical Information of China (English)

    Giorgina Mieli-Vergani; Diego Vergani


    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

  10. Transgenic expression of soluble human CD5 enhances experimentally-induced autoimmune and anti-tumoral immune responses.

    Directory of Open Access Journals (Sweden)

    Rafael Fenutría

    Full Text Available CD5 is a lymphoid-specific transmembrane glycoprotein constitutively expressed on thymocytes and mature T and B1a lymphocytes. Current data support the view that CD5 is a negative regulator of antigen-specific receptor-mediated signaling in these cells, and that this would likely be achieved through interaction with CD5 ligand/s (CD5L of still undefined nature expressed on immune or accessory cells. To determine the functional consequence of loss of CD5/CD5L interaction in vivo, a new transgenic mouse line was generated (shCD5EμTg, expressing a circulating soluble form of human CD5 (shCD5 as a decoy to impair membrane-bound CD5 function. These shCD5EμTg mice showed an enhanced response to autologous antigens, as deduced from the presentation of more severe forms of experimentally inducible autoimmune disease (collagen-induced arthritis, CIA; and experimental autoimmune encephalitis, EAE, as well as an increased anti-tumoral response in non-orthotopic cancer models (B16 melanoma. This enhancement of the immune response was in agreement with the finding of significantly reduced proportions of spleen and lymph node Treg cells (CD4+CD25+FoxP3+, and of peritoneal IL-10-producing and CD5+ B cells, as well as an increased proportion of spleen NKT cells in shCD5EμTg mice. Similar changes in lymphocyte subpopulations were observed in wild-type mice following repeated administration of exogenous recombinant shCD5 protein. These data reveal the relevant role played by CD5/CD5L interactions on the homeostasis of some functionally relevant lymphocyte subpopulations and the modulation of immune responses to autologous antigens.

  11. The inflammasome pyrin contributes to pertussis toxin-induced IL-1β synthesis, neutrophil intravascular crawling and autoimmune encephalomyelitis. (United States)

    Dumas, Aline; Amiable, Nathalie; de Rivero Vaccari, Juan Pablo; Chae, Jae Jin; Keane, Robert W; Lacroix, Steve; Vallières, Luc


    Microbial agents can aggravate inflammatory diseases, such as multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). An example is pertussis toxin (PTX), a bacterial virulence factor commonly used as an adjuvant to promote EAE, but whose mechanism of action is unclear. We have reported that PTX triggers an IL-6-mediated signaling cascade that increases the number of leukocytes that patrol the vasculature by crawling on its luminal surface. In the present study, we examined this response in mice lacking either TLR4 or inflammasome components and using enzymatically active and inactive forms of PTX. Our results indicate that PTX, through its ADP-ribosyltransferase activity, induces two series of events upstream of IL-6: 1) the activation of TLR4 signaling in myeloid cells, leading to pro-IL-1β synthesis; and 2) the formation of a pyrin-dependent inflammasome that cleaves pro-IL-1β into its active form. In turn, IL-1β stimulates nearby stromal cells to secrete IL-6, which is known to induce vascular changes required for leukocyte adhesion. Without pyrin, PTX does not induce neutrophil adhesion to cerebral capillaries and is less effective at inducing EAE in transgenic mice with encephalitogenic T lymphocytes. This study identifies the first microbial molecule that activates pyrin, a mechanism by which infections may influence MS and a potential therapeutic target for immune disorders.

  12. Enterocolitis induced by autoimmune targeting of enteric glial cells: A possible mechanism in Crohn's disease? (United States)

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


    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.

  13. 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


    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.

  14. Intracerebroventricular administration of TNF-like weak inducer of apoptosis induces depression-like behavior and cognitive dysfunction in non-autoimmune mice. (United States)

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


    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.

  15. 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.

  16. Reactive oxygen species induced by therapeutic CD20 antibodies inhibit natural killer cell-mediated antibody-dependent cellular cytotoxicity against primary CLL cells (United States)

    Werlenius, Olle; Aurelius, Johan; Hallner, Alexander; Akhiani, Ali A.; Simpanen, Maria; Martner, Anna; Andersson, Per-Ola; Hellstrand, Kristoffer; Thorén, Fredrik B.


    The antibody-dependent cellular cytotoxicity (ADCC) of natural killer (NK) cells is assumed to contribute to the clinical efficacy of monoclonal antibodies (mAbs) in chronic lymphocytic leukemia (CLL) and other hematopoietic malignancies of B cell origin. We sought to determine whether reactive oxygen species (ROS)-producing monocytes regulate the ADCC of NK cells against primary CLL cells using anti-CD20 as the linking antibody. The monoclonal CD20 antibodies rituximab and ofatumumab were found to trigger substantial release of ROS from monocytes. Antibody-exposed monocytes induced NK cell apoptosis and restricted NK cell-mediated ADCC against autologous CLL cells. The presence of inhibitors of ROS formation and scavengers of ROS preserved NK cell viability and restored NK cell-mediated ADCC against primary CLL cells. We propose that limiting the antibody-induced induction of immunosuppressive ROS may improve the anti-leukemic efficacy of anti-CD20 therapy in CLL. PMID:27097113

  17. Redistribution and modulation of Gross murine leukemia virus antigens induced by specific antibodies. (United States)

    Ioachim, H L; Sabbath, M


    Gross murine leukemia virus (G-MuLV)-induced rat leukemia cells in tissue culture replicate G-MuLV, express strong virus-associated membrane antigenicity, and are consistently killed by specific antibodies and complement in cytotoxicity tests. To explore the effect of specific antibodies, rat anti-G-MuLV antisera were added to the cultures of leukemia cells for variable periods of time. Redistribution of virus particles as well as of membrane virus antigens in the form of polar patches and caps was observed by electron microscopy, indirect immunofluorescence, and immunoelectron microscopy. Substantial decreases in cytotoxicity indexes accompanied these changes. The antigen modulation induced by anti-G-MuLV antibodies in vitro paralleled similar changes obtained in vivo by transplanttion of leukemia cells in rats with high anti-G-MuLV antibody titers. The importance of antigen modulation in this system resides in its direct relationship with the malignant potential of the leukemia cells.

  18. Udredning og behandling af autoimmun encefalitis

    DEFF Research Database (Denmark)

    Blaabjerg, Morten; Mærsk-Møller, Camilla C; Kondziella, Daniel;


    Autoimmune encephalitis with antibodies against neuronal surface antigens is diagnosed with increasing frequency in recent years. If treated early and aggressively, these conditions often respond favourably to immunotherapy. We describe the clinical features, diagnosis and treatment of the two mo...

  19. 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


    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).

  20. Binding induced conformational changes of proteins correlate with their intrinsic fluctuations: a case study of antibodies

    Directory of Open Access Journals (Sweden)

    Keskin Ozlem


    Full Text Available Abstract Background How antibodies recognize and bind to antigens can not be totally explained by rigid shape and electrostatic complimentarity models. Alternatively, pre-existing equilibrium hypothesis states that the native state of an antibody is not defined by a single rigid conformation but instead with an ensemble of similar conformations that co-exist at equilibrium. Antigens bind to one of the preferred conformations making this conformation more abundant shifting the equilibrium. Results Here, two antibodies, a germline antibody of 36–65 Fab and a monoclonal antibody, SPE7 are studied in detail to elucidate the mechanism of antibody-antigen recognition and to understand how a single antibody recognizes different antigens. An elastic network model, Anisotropic Network Model (ANM is used in the calculations. Pre-existing equilibrium is not restricted to apply to antibodies. Intrinsic fluctuations of eight proteins, from different classes of proteins, such as enzymes, binding and transport proteins are investigated to test the suitability of the method. The intrinsic fluctuations are compared with the experimentally observed ligand induced conformational changes of these proteins. The results show that the intrinsic fluctuations obtained by theoretical methods correlate with structural changes observed when a ligand is bound to the protein. The decomposition of the total fluctuations serves to identify the different individual modes of motion, ranging from the most cooperative ones involving the overall structure, to the most localized ones. Conclusion Results suggest that the pre-equilibrium concept holds for antibodies and the promiscuity of antibodies can also be explained this hypothesis: a limited number of conformational states driven by intrinsic motions of an antibody might be adequate to bind to different antigens.

  1. Transfusion-induced, Fc gamma-receptor-blocking antibodies: spectrum of cellular reactivity. (United States)

    Forwell, M A; Peel, M G; Froebel, K S; Belch, J J; MacSween, R N; Sandilands, G P


    In this study we have shown that transfusion-induced Fc gamma R-blocking antibodies have the capacity to react with various cell types which are known to possess this receptor i.e., lymphocytes (T and B cells), polymorphs and platelets. In contrast we were unable to demonstrate any reactivity with K (or NK) lymphocytes or with monocytes. The spectrum of cellular reactivity exhibited by these antibodies suggests that their effect on the immune system may be complex.

  2. Carrier induced epitopic suppression of antibody responses induced by virus-like particles is a dynamic phenomenon caused by carrier-specific antibodies. (United States)

    Jegerlehner, Andrea; Wiesel, Melanie; Dietmeier, Klaus; Zabel, Franziska; Gatto, Dominique; Saudan, Philippe; Bachmann, Martin F


    Pre-existing immunity against vaccine carrier proteins has been reported to inhibit the immune response against antigens conjugated to the same carrier by a process termed carrier induced epitopic suppression (CIES). Hence understanding the phenomenon of CIES is of major importance for the development of conjugate vaccines. Virus-like particles (VLPs) are a novel class of potent immunological carriers which have been successfully used to enhance the antibody response to virtually any conjugated antigen. In the present study we investigated the impact of a pre-existing VLP-specific immune response on the development of antibody responses against a conjugated model peptide after primary, secondary and tertiary immunization. Although VLP-specific immune responses led to reduced peptide-specific antibody titers, we showed that CIES against peptide-VLP conjugates could be overcome by high coupling densities, repeated injections and/or higher doses of conjugate vaccine. Furthermore we dissected VLP-specific immunity by adoptively transferring VLP-specific antibodies, B-cells or T(helper) cells separately into naïve mice and found that the observed CIES against peptide-VLP conjugates was mainly mediated by carrier-specific antibodies.

  3. Autoimmune disorders (United States)

    ... as azathioprine, cyclophosphamide, mycophenolate, sirolimus, or tacrolimus. Targeted drugs called tumor necrosis factor (TFN) blockers can be used for some diseases. Outlook (Prognosis) The outcome depends on the disease. Most autoimmune diseases are chronic , but many can be controlled ...

  4. Autoimmune hypophysitis. (United States)

    Ezzat, S; Josse, R G


    Autoimmune (lymphocytic) hypophysitis has emerged as a distinct and specific clinical and pathological disease entity. Although relatively rare compared with other autoimmune endocrine diseases, nearly a hundred cases have been described. The condition is much more common in females (9:1) and appears to have a particular predilection for the pregnant and postpartum states. The anterior pituitary, and less often the neurohypophysis, appear to be the target for inflammatory autoimmune destruction. During the evolution of the disease process, pituitary hyperfunction (usually hyperprolactinemia) has been noted. This disease should now be included in the differential diagnosis of pituitary disorders, especially in females presenting with pituitary enlargement, particularly if symptoms occur in temporal relationship to pregnancy. The disease may form part of the spectrum of the polyglandular autoimmune endocrine disorders. (Trends Endocrinol Metab 1997;8:74-80). (c) 1997, Elsevier Science Inc.

  5. Air pollution in autoimmune rheumatic diseases: a review. (United States)

    Farhat, Sylvia C L; Silva, Clovis A; Orione, Maria Angelica M; Campos, Lucia M A; Sallum, Adriana M E; Braga, Alfésio L F


    Air pollution consists of a heterogeneous mixture of gasses and particles that include carbon monoxide, nitrates, sulfur dioxide, ozone, lead, toxic by-product of tobacco smoke and particulate matter. Oxidative stress and inflammation induced by inhaled pollutants may result in acute and chronic disorders in the respiratory system, as well as contribute to a state of systemic inflammation and autoimmunity. This paper reviews the mechanisms of air contaminants influencing the immune response and autoimmunity, and it focuses on studies of inhaled pollutants triggering and/or exacerbating rheumatic diseases in cities around the world. Remarkably, environmental factors contribute to the onset of autoimmune diseases, especially smoking and occupational exposure to silica in rheumatoid arthritis and systemic lupus erythematosus. Other diseases such as scleroderma may be triggered by the inhalation of chemical solvents, herbicides and silica. Likewise, primary vasculitis associated with anti-neutrophil cytoplasmic antibody (ANCA) may be triggered by silica exposure. Only few studies showed that air pollutants could trigger or exacerbate juvenile idiopathic arthritis and systemic lupus erythematosus. In contrast, no studies of tropospheric pollution triggering inflammatory myopathies and spondyloarthropathies were carried out. In conclusion, air pollution is one of the environmental factors involved in systemic inflammation and autoimmunity. Further studies are needed in order to evaluate air pollutants and their potentially serious effects on autoimmune rheumatic diseases and the mechanisms involved in the onset and the exacerbation of these diseases.

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

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Weizao, E-mail: [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); Feng, Yang [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); Wang, Yanping [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); The Basic Research Program, Science Applications International Corporation-Frederick, Inc., National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); Zhu, Zhongyu; Dimitrov, Dimiter S. [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States)


    Highlights: Black-Right-Pointing-Pointer Some recombinant HIV-1 gp120s do not preserve their conformations on gp140s. Black-Right-Pointing-Pointer We hypothesize that CD4i antibodies could induce conformational changes in gp120. Black-Right-Pointing-Pointer CD4i antibodies enhance binding of CD4 and CD4bs antibodies to gp120. Black-Right-Pointing-Pointer 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.

  7. Anetoderma: Is It a Sign of Autoimmunity?

    Directory of Open Access Journals (Sweden)

    Hessa Al Buainain


    Full Text Available Anetoderma is a rare elastolytic disorder characterized by circumscribed areas of flaccid skin due to the loss of elastic tissue in the dermis. Primary anetoderma is frequently observed in patients with autoimmune diseases or abnormalities especially with antiphospholipid antibodies with or without antiphospholipid syndrome. In this case report we discuss a patient with primary anetoderma with positive antithyroid peroxidase antibodies, which is consistent with autoimmune thyroiditis.

  8. Autoimmune pancreatitis and cholangitis

    Institute of Scientific and Technical Information of China (English)

    Niraj; Jani; James; Buxbaum


    Autoimmune pancreatitis(AIP) is part of a systemic fibrosclerotic process characterized by lymphoplasmacytic infiltrate with immunoglobulin G subtype-4(Ig G4) positive cells. It characteristically presents with biliary obstruction due to mass-like swelling of the pancreas. Frequently AIP is accompanied by extra-pancreaticmanifestations including retroperitoneal fibrosis, thyroid disease, and salivary gland involvement. Auto-antibodies, hypergammaglobulemia, and prompt resolution of pancreatic and extrapancreatic findings with steroids signify its autoimmune nature. Refractory cases are responsive to immunomodulators and rituximab. Involvement of the biliary tree, termed IgG 4 associated cholangiopathy, mimics primary sclerosing cholangitis and is challenging to manage. High IgG 4 levels and swelling of the pancreas with a diminutive pancreatic duct are suggestive of autoimmune pancreatitis. Given similarities in presentation but radical differences in management and outcome, differentiation from pancreatic malignancy is of paramount importance. There is controversy regarding the optimal diagnostic criterion and steroid trials to make the diagnosis. Additionally, the retroperitoneal location of the pancreas and requirement for histologic sampling, makes tissue acquisition challenging. Recently, a second type of autoimmune pancreatitis has been recognized with similar clinical presentation and steroid response though different histology, serologic, and extrapancreatic findings.

  9. Autoantibodies in Autoimmune Pancreatitis

    Directory of Open Access Journals (Sweden)

    Daniel S. Smyk


    Full Text Available Autoimmune pancreatitis (AIP was first used to describe cases of pancreatitis with narrowing of the pancreatic duct, enlargement of the pancreas, hyper-γ-globulinaemia, and antinuclear antibody (ANA positivity serologically. The main differential diagnosis, is pancreatic cancer, which can be ruled out through radiological, serological, and histological investigations. The targets of ANA in patients with autoimmune pancreatitis do not appear to be similar to those found in other rheumatological diseases, as dsDNA, SS-A, and SS-B are not frequently recognized by AIP-related ANA. Other disease-specific autoantibodies, such as, antimitochondrial, antineutrophil cytoplasmic antibodies or diabetes-specific autoantibodies are virtually absent. Further studies have focused on the identification of pancreas-specific autoantigens and reported significant reactivity to lactoferrin, carbonic anhydrase, pancreas secretory trypsin inhibitor, amylase-alpha, heat-shock protein, and plasminogen-binding protein. This paper discusses the findings of these investigations and their relevance to the diagnosis, management, and pathogenesis of autoimmune pancreatitis.

  10. Mechanism of dinitrochlorobenzene-induced dermatitis in mice: role of specific antibodies in pathogenesis.

    Directory of Open Access Journals (Sweden)

    Elizabeth Yan Zhang

    Full Text Available BACKGROUND: Dinitrochlorobenzene-induced contact hypersensitivity is widely considered as a cell-mediated rather than antibody-mediated immune response. At present, very little is known about the role of antigen-specific antibodies and B cells in the development of dinitrochlorobenzene-induced hypersensitivity reactions, and this is the subject of the present investigation. METHODOLOGY/PRINCIPAL FINDINGS: Data obtained from multiple lines of experiments unequivocally showed that the formation of dinitrochlorobenzene-specific Abs played an important role in the development of dinitrochlorobenzene-induced contact hypersensitivity. The appearance of dinitrochlorobenzene-induced skin dermatitis matched in timing the appearance of the circulating dinitrochlorobenzene-specific antibodies. Adoptive transfer of sera containing dinitrochlorobenzene-specific antibodies from dinitrochlorobenzene-treated mice elicited a much stronger hypersensitivity reaction than the adoptive transfer of lymphocytes from the same donors. Moreover, dinitrochlorobenzene-induced contact hypersensitivity was strongly suppressed in B cell-deficient mice with no DNCB-specific antibodies. It was also observed that treatment of animals with dinitrochlorobenzene polarized Th cells into Th2 differentiation by increasing the production of Th2 cytokines while decreasing the production of Th1 cytokines. CONCLUSIONS/SIGNIFICANCE: In striking contrast to the long-held belief that dinitrochlorobenzene-induced contact hypersensitivity is a cell-mediated immune response, the results of our present study demonstrated that the production of dinitrochlorobenzene-specific antibodies by activated B cells played an indispensible role in the pathogenesis of dinitrochlorobenzene-induced CHS. These findings may provide new possibilities in the treatment of human contact hypersensitivity conditions.

  11. Adult autoimmune enteropathy

    Institute of Scientific and Technical Information of China (English)


    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.

  12. Autoimmunity: Experimental and clinical aspects

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, R.S.; Rose, N.R.


    This book contains five parts and a section of poster papers. Each part contains several papers. Some of the papers are: Molecular Genetics and T Cells in Autoimmunity; Gene Conversion: A Mechanism to Explain HLA-D Region and Disease Association; Genetics of the Complement System; Speculation on the Role of Somatic Mutation in the Generation of Anti-DNA Antibodies; and Monoclonal Anti-DNA Antibodies: The Targets and Origins of SLE.

  13. 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.

  14. Development of autoimmunity in lymphoma. (United States)

    Jardin, Fabrice


    Development of lymphoproliferative diseases during the course of autoimmune and chronic inflammatory conditions is well established. Conversely, development of clinical or biological signs of autoimmunity at the time of the diagnosis of lymphoma or during its course indicates that lymphoma and autoimmune manifestations may constitute two faces of the same process. The aim of this review is to describe autoimmune manifestations related to non-Hodgkin's lymphoma and Hodgkin's lymphoma, their specificity according to the lymphoma subtype and their physiopathological signification. Lymphoma-related autoimmune manifestations include mainly skin diseases, hematological manifestations, rheumatic diseases and renal lesions. Despite the lack of studies providing a systematic prospective assessment, autoimmune manifestations are observed in all lymphoma subtypes and seem particularly prevalent in marginal-zone lymphoma and T-cell lymphoma. Autoimmune manifestation's physiopathology may implicate production of autoantibodies by CD5-positive autoreactive B cells, a loss of immune tolerance, an alteration of the Fas/Fas-ligand pathway and/or a chronic antigenic stimulation. Monoclonal antibodies (including rituximab, Campath-1H or epratuzumab) constitute the most promising approach to treat lymphoma-related immune disorders.

  15. Sunitinib-associated pseudothrombocytopenia induced by IgM antibody. (United States)

    Albersen, Arjan; Porcelijn, Leendert; Schilders, Joyce; Zuetenhorst, Hanneke; Njo, Tjin; Hamberg, Paul


    Thrombocytopenia is a well-documented adverse reaction of sunitinib. Thrombocytopenia was observed in a patient with metastatic renal clear-cell carcinoma undergoing sunitinib treatment. Platelet count in an ethylenediaminetetraacetic acid (EDTA) sample was 19 × 10(9)/l. To exclude pseudothrombocytopenia (PTCP), a platelet count in citrate-anticoagulated blood was performed, showing a platelet count of 6 × 10(9)/l. Due to the apparent thrombocytopenia, the patient received platelet concentrates. Subsequent analyses revealed PTCP whereby platelet clumping was most abundant in citrate - followed by EDTA- and heparin-anticoagulated blood samples. This effect was partially reversed after placing blood samples at 37°C. The IgM antiplatelet autoantibodies responsible for in vitro agglutination are temperature and multianticoagulant dependent and did not react to amikacin pre-supplementation. Remarkably, the antibody revealed specificity to platelet antigens other than GPIIb/IIIa, GPIb/IX, GPIa/IIa, GPIV, and GPV. After 16 days of discontinuing sunitinib, no PTCP and no platelet reactive antibodies could be detected. We report a case of PTCP with clear time-relation with sunitinib, strongly suggesting the mechanism to be sunitinib dependent. Since this finding has not been described before, non-recognition of PTCP during sunitinib treatment might lead to dose reduction or unwarranted therapy.

  16. Vaccine Induced Antibody Response to Foot and Mouth Disease in Infectious Bovine Rhinotracheitis Seropositive Cattle

    Directory of Open Access Journals (Sweden)

    Murat Şevik


    Full Text Available Foot and mouth disease (FMD and infectious bovine rhinotracheitis (IBR are two important infectious diseases of cattle. Inactivated FMD vaccines are the most powerful tools to protect animals against FMD. Previous studies showed that recombinant IBR-FMD viruses protected cattle from virulent BHV-1 challenge and induced protective levels of anti-FMDV antibodies. FMD is considered to be endemic in Turkey and inactivated oil adjuvanted vaccines are used for the immunization of cattle. Previous studies showed that seroprevalence of IBR in the Turkey’s dairy herd more than 50%. In this study, antibody response in IBR seropositive cattle following vaccination against FMD was investigated. IBR seropositive (n=208 and IBR seronegative (n=212 cattle were vaccinated with oil-adjuvanted bivalent vaccine (containing O1 Manisa, A22 Iraq FMDV strains. Solid-phase competitive ELISA (SPCE was used to measure antibodies produced in cattle. Protective level of antibody against serotype O was detected in 77.4% and serotypes A in 83.6% of IBR seropositive cattle. Protective level of antibody against serotype O antibody was detected in 49% and serotypes A in 66.9% of IBR seronegative cattle. The differences between the protection rates against both serotype O (P=0.0001 and serotype A (P=0.0001 in IBR seropositive and seronegative animals were statistically important (Fisher’s exact test, P<0.01. Results showed that after FMD vaccination, IBR seropositive animals produced high titres of antibodies than seronegative animals.

  17. Protective effects of astaxanthin on ConA-induced autoimmune hepatitis by the JNK/p-JNK pathway-mediated inhibition of autophagy and apoptosis.

    Directory of Open Access Journals (Sweden)

    Jingjing Li

    Full Text Available Astaxanthin, a potent antioxidant, exhibits a wide range of biological activities, including antioxidant, atherosclerosis and antitumor activities. However, its effect on concanavalin A (ConA-induced autoimmune hepatitis remains unclear. The aim of this study was to investigate the protective effects of astaxanthin on ConA-induced hepatitis in mice, and to elucidate the mechanisms of regulation.Autoimmune hepatitis was induced in in Balb/C mice using ConA (25 mg/kg, and astaxanthin was orally administered daily at two doses (20 mg/kg and 40 mg/kg for 14 days before ConA injection. Levels of serum liver enzymes and the histopathology of inflammatory cytokines and other maker proteins were determined at three time points (2, 8 and 24 h. Primary hepatocytes were pretreated with astaxanthin (80 μM in vitro 24 h before stimulation with TNF-α (10 ng/ml. The apoptosis rate and related protein expression were determined 24 h after the administration of TNF-α.Astaxanthin attenuated serum liver enzymes and pathological damage by reducing the release of inflammatory factors. It performed anti-apoptotic effects via the descending phosphorylation of Bcl-2 through the down-regulation of the JNK/p-JNK pathway.This research firstly expounded that astaxanthin reduced immune liver injury in ConA-induced autoimmune hepatitis. The mode of action appears to be downregulation of JNK/p-JNK-mediated apoptosis and autophagy.

  18. Vaccines and autoimmunity. (United States)

    Agmon-Levin, Nancy; Paz, Ziv; Israeli, Eitan; Shoenfeld, Yehuda


    Vaccines have been used for over 200 years and are the most effective way of preventing the morbidity and mortality associated with infections. Like other drugs, vaccines can cause adverse events, but unlike conventional medicines, which are prescribed to people who are ill, vaccines are administered to healthy individuals, thus increasing the concern over adverse reactions. Most side effects attributed to vaccines are mild, acute and transient; however, rare reactions such as hypersensitivity, induction of infection, and autoimmunity do occur and can be severe and even fatal. The rarity and subacute presentation of post-vaccination autoimmune phenomena means that ascertaining causality between these events can be difficult. Moreover, the latency period between vaccination and autoimmunity ranges from days to years. In this article, on the basis of published evidence and our own experience, we discuss the various aspects of the causal and temporal interactions between vaccines and autoimmune phenomena, as well as the possible mechanisms by which different components of vaccines might induce autoimmunity.

  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. Adenovirus-mediated CTLA4-FasL gene transfer prevents autoimmune diabetes in mice induced by multiple low doses of streptozotocin

    Institute of Scientific and Technical Information of China (English)

    JIN Yongzhu; WANG Guangming; LI Ailing; HAO Jie; GAO Xiang; XIE Shusheng


    Type 1 diabetes is the result of a selective destruction of insulin-producing β cells in pancreatic islets by autoreactive T cells. Depletion of autoreactive T cell through apoptosis may be a potential strategy for the prevention of autoimmune diabetes. Simultaneous stimulation of Fas-mediated pathway and blockade of costimulation by a CTLA4-FasL fusion protein has been reported to lead to substantial inhibition of mixed lymphocyte reaction and enhanced in vitro apoptosis of peripheral lymphocytes. To test the feasibility of CTLA4-FasL-based gene therapy to prevent autoimmune diabetes, we developed recombinant adenovirus containing human CTLA4-FasL gene (AdCTLA4-FasL). A single injection of 2 × 108 plaque forming units (PFU) of AdCTLA4-FasL via tail vein dramatically reduced the incidence of autoimmune diabetes in mice induced by multiple low doses of streptozotocin. AdCTLA4-FasL administration maintained islet insulin content, significantly increased apoptosis of pancreatic lymphocytes, quantitatively reduced IFN-γand Vβ8.2 TCR chain mRNA expression in pancreatic iymphocytes. These results indicate the therapeutic potential of simultaneous stimulation of Fas-mediated pathway and blockade of costimulation by adenovirus-mediated CTLA4-FasL gene transfer in the prevention of autoimmune diabetes.

  1. 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


    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.

  2. The Role of Pathogenic Autoantibodies in Autoimmunity

    Directory of Open Access Journals (Sweden)

    Merrill J. Rowley


    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.

  3. Hepatitis A vaccine associated with autoimmune hepatitis

    Institute of Scientific and Technical Information of China (English)

    PA Berry; G Smith-Laing


    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.

  4. Diagnosis and classification of autoimmune gastritis. (United States)

    Toh, Ban-Hock


    Autoimmune gastritis is a silent and highly prevalent disease that only becomes clinically manifested with progression to corpus atrophy and development of iron deficient or B12-deficient (pernicious) anaemia. Autoimmune gastritis is associated with autoimmune thyroiditis and type 1 diabetes mellitus. Corpus atrophy may be complicated by gastric carcinoids and gastric cancer. Laboratory diagnosis of autoimmune gastritis rests on serum biomarkers of antibody to parietal cell H/K ATPase and intrinsic factor and corpus atrophy on serum biomarkers of gastrin and pepsinogen levels. Subjects with asymptomatic parietal cell antibody should be regularly assessed for serum biomarkers for progression to corpus atrophy, development of iron and B12 deficiency anaemia and for associated autoimmune thyroiditis and type 1 diabetes mellitus.

  5. RBC Antibody Screen (United States)

    ... test also may be used to help diagnose autoimmune-related hemolytic anemia in conjunction with a DAT. This condition may be caused when a person produces antibodies against his or her own RBC antigens. This can happen with some autoimmune disorders , such as lupus , with diseases such as ...

  6. Sustained systemic delivery of monoclonal antibodies by genetically modified skin fibroblasts

    DEFF Research Database (Denmark)

    Noël, D; Pelegrin, M; Brockly, F;


    In vivo production and systemic delivery of therapeutic antibodies by engineered cells might advantageously replace injection of purified antibodies for treating a variety of life-threatening diseases, including cancer, acquired immunodeficiency syndrome, and autoimmune diseases. We report here...... that skin fibroblasts retrovirally transduced to express immunoglobulin genes can be used for sustained long-term systemic delivery of cloned antibodies in immunocompetent mice. Importantly, no anti- idiotypic response against the ectopically expressed model antibody used in this study was observed....... This supports the notion that skin fibroblasts can potentially be used in antibody-based gene/cell therapy protocols without inducing any adverse immune response in treated individuals....

  7. Role of neutralizing anti-murine interleukin-17A monoclonal antibody on chronic ozone-induced airway inflammation in mice. (United States)

    Zhang, Min; Fei, Xia; Zhang, Guo-Qing; Zhang, Peng-Yu; Li, Feng; Bao, Wu-Ping; Zhang, Ying-Ying; Zhou, Xin


    Exposure to ozone has led to airway inflammation and airway hyperresponsiveness, which potential mechanisms relate to ozone-induced oxidative stress. IL-17 is a growing target for autoimmune and inflammatory diseases. The aim of the study was to examine the inhibitory effects of anti-murine interleukin-17A monoclonal antibody (IL-17mAb) on adverse effects of ozone which are noted above. After C57/BL6 mice were exposed to ozone (2.5ppm; 3h) for 12 times over 6 weeks, IL-17mAb, PBS was intraperitoneally injected into mice 1h after ozone or air exposure for 6 weeks and mice were studied 24h after final exposure, monitoring bronchial responsiveness, airway inflammatory cells, lung histology, levels of neutrophil-related chemokine and proinflammatory cytokines in bronchoalveolar lavage (BAL) fluid and serum, the expression of IL-17A mRNA and protein, glucocorticoid receptors (GR), and the phosphorylation of p38MAPK in lung tissues. The administration of IL-17mAb reduced the ozone-induced increases in total cells, especially neutrophils; decreased levels of cytokines, including IL-8 in BAL fluid, IL-8 and IL-17A in serum; mitigated the severity of airway hyperresponsiveness; attenuated lung inflammation scores and histologic analysis confirmed the suppression of lung inflammation, compared with the administration of a control PBS. Exposure to ozone results in increases in IL-17A production rate, mRNA and protein levels of IL-17A and the protein level of GR. These effects were halted and reversed by IL-17mAb treatment. Furthermore, IL-17mAb also reduced the phosphorylation of p38MAPK. Therefore, we conclude that IL-17mAb may be a useful therapy in ozone-related diseases, including COPD.

  8. Endocrine autoimmunity in Turner syndrome (United States)


    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

  9. Antibody-targeting of steady state dendritic cells induces tolerance mediated by regulatory T cells

    Directory of Open Access Journals (Sweden)

    Karsten eMahnke


    Full Text Available Dendritic cells (DCs are often defined as pivotal inducers of immunity, but these proinflammatory properties only develop after stimulation or ex vivo manipulation of DCs. Under non-inflammatory conditions in vivo, DCs are embedded into a tissue environment and encounter a plethora of self-antigens derived from apoptotic material. This material is transported to secondary lymphoid organs. As DCs maintain their non-activated phenotype in a sterile tissue environment, interaction with T cells will induce rather regulatory T cells (Treg than effector T cells. Thus, DCs are not only inducers of immunity but are also critical for maintenance of peripheral tolerance. Therapeutical intervention for the induction of long lasting tolerance in several autoimmune conditions may therefore be possible by manipulating DC activation and/or targeting of DCs in their natural tissue environment.

  10. Autoimmun hypophysitis

    DEFF Research Database (Denmark)

    Krarup, Therese; Hagen, Claus


    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...

  11. Propylthiouracil (PTU)-induced vasculitis associated with antineutrophil antibody against myeloperoxidase (MPO-ANCA). (United States)

    Nakamori, Yoshitaka; Tominaga, Takayuki; Inoue, Yasushi; Shinohara, Kenji


    A 54-year-old woman had been administered propylthiouracil (PTU) for Graves' disease for 4 years. Recently, she complained of hemoptysis due to pulmonary alveolar hemorrhage causing anemia, and also had microhematuria. Antineutrophil cytoplasmic antibody against myeloperoxidase (MPO-ANCA) was positive, and she was diagnosed with PTU-induced vasculitis. Cessation of PTU and the administration of corticosteroids ameliorated these manifestations.

  12. 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: [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)


    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.

  13. Persistence of yellow fever vaccine-induced antibodies after solid organ transplantation. (United States)

    Wyplosz, B; Burdet, C; François, H; Durrbach, A; Duclos-Vallée, J C; Mamzer-Bruneel, M-F; Poujol, P; Launay, O; Samuel, D; Vittecoq, D; Consigny, P H


    Immunization using live attenuated vaccines represents a contra-indication after solid organ transplantation (SOT): consequently, transplant candidates planning to travel in countries where yellow fever is endemic should be vaccinated prior to transplantation. The persistence of yellow fever vaccine-induced antibodies after transplantation has not been studied yet. We measured yellow-fever neutralizing antibodies in 53 SOT recipients vaccinated prior to transplantation (including 29 kidney recipients and 18 liver recipients). All but one (98%) had protective titers of antibodies after a median duration of 3 years (min.: 0.8, max.: 21) after transplantation. The median antibody level was 40 U/L (interquartile range: 40-80). For the 46 patients with a known or estimated date of vaccination, yellow-fever antibodies were still detectable after a median time of 13 years (range: 2-32 years) post-immunization. Our data suggest there is long-term persistence of antibodies to yellow fever in SOT recipients who have been vaccinated prior to transplantation.

  14. 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


    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.

  15. Autoimmune sialadenitis

    NARCIS (Netherlands)

    Guntinas-Lichius, O.; Vissink, A.; Ihrler, S.


    Using the European-American classification criteria the diagnosis of autoimmune sialadenitis in Sjogren's syndrome can generally be easily established or excluded. In addition, sonography performed by the ENT physician is helpful in diagnosing and especially in follow-up screening for MALT lymphomas

  16. Sauna as a valuable clinical tool for cardiovascular, autoimmune, toxicant- induced and other chronic health problems. (United States)

    Crinnion, Walter J


    Sauna therapy has been used for hundreds of years in the Scandinavian region as a standard health activity. Studies document the effectiveness of sauna therapy for persons with hypertension, congestive heart failure, and for post-myocardial infarction care. Some individuals with chronic obstructive pulmonary disease (COPD), chronic fatigue, chronic pain, or addictions also find benefit. Existing evidence supports the use of saunas as a component of depuration (purification or cleansing) protocols for environmentally-induced illness. While far-infrared saunas have been used in many cardiovascular studies, all studies applying sauna for depuration have utilized saunas with radiant heating units. Overall, regular sauna therapy (either radiant heat or far-infrared units) appears to be safe and offers multiple health benefits to regular users. One potential area of concern is sauna use in early pregnancy because of evidence suggesting that hyperthermia might be teratogenic.

  17. Beta-endorphin and the immune system--possible role in autoimmune diseases

    DEFF Research Database (Denmark)

    Mørch, H; Pedersen, B K


    The immune system and the neuroendocrine system are closely interconnected having such means of bidirectional communication and regulation. In this review, a hypothesis is put forward regarding the possible role of beta-endorphins in the pathogenesis of autoimmune diseases: It is suggested...... that the increased cytokine production in immunoinflammatory disorders induces production of beta-endorphins from the pituitary and the lymphocytes; the enhanced level of beta-endorphin causes inhibition of human T helper cell function, which potentially down-regulate the antibody production. Also the beta-endorphin......-induced enhancement of the natural killer cell activity may suppress the B cell function. In addition, beta-endorphin also exerts a direct inhibitory effect on the antibody production. Thus, in autoimmune disorders the enhanced cytokine level may via stimulation of the production of beta-endorphins exert a negative...

  18. A pilot study on an attenuated Chinese EIAV vaccine inducing broadly neutralizing antibodies. (United States)

    Meng, Qinglai; Lin, Yuezhi; Ma, Jian; Ma, Yan; Zhao, Liping; Li, Shenwei; Liang, Hua; Zhou, Jianhua; Shen, Rongxian; Zhang, Xiaoyan; Shao, Yiming


    The attenuated Chinese equine infectious anemia virus (EIAV) vaccine has successfully protected millions of equine animals from EIA disease in China. In this pilot study, to determine whether this attenuated vaccine can induce broadly neutralizing antibodies, we immunized four horses with the attenuated Chinese vaccine strain EIAVFDDV and then observed the evolution of neutralizing antibodies against different EIAV strains. During the vaccination phase, all vaccinees rapidly developed high levels of neutralizing antibodies against the homologous vaccine strain (pLGFD3V), and 3 out of 4 horses showed a gradual increase in serum neutralizing activity against two relatively heterologous virulent variants of the challenge strain (pLGFD3Mu12V and DLV34). After challenge, the three horses that had developed high levels of neutralizing antibodies against pLGFD3Mu12V and DLV34 did not show signs of infection, which was demonstrated by immune suppression, while the one horse producing serum that could only neutralize pLGFD3V developed a febrile episode during the 8-month observation period. To assess whether the broadly neutralizing activity is associated with immune protection, sera drawn on the day of challenge from these four vaccinees and an additional four EIAVFDDV-vaccinated horses were analyzed for neutralizing antibodies against pLGFD3V, pLGFD3Mu12V and DLV34. Although there was no significant correlation between protection from infection and serum neutralizing activity against any of these three viral strains, protection from infection was observed to correlate better with serum neutralizing activity against the two heterologous virulent strains than against the homologous vaccine strain. These data indicate that EIAVFDDV induced broadly neutralizing antibodies, which might confer enhanced protection of vaccinees from infection by the challenge virus.

  19. Prevention of herpes simplex virus induced stromal keratitis by a glycoprotein B-specific monoclonal antibody.

    Directory of Open Access Journals (Sweden)

    Adalbert Krawczyk

    Full Text Available The increasing incidence of acyclovir (ACV and multidrug-resistant strains in patients with corneal HSV-1 infections leading to Herpetic Stromal Keratitis (HSK is a major health problem in industrialized countries and often results in blindness. To overcome this obstacle, we have previously developed an HSV-gB-specific monoclonal antibody (mAb 2c that proved to be highly protective in immunodeficient NOD/SCID-mice towards genital infections. In the present study, we examined the effectivity of mAb 2c in preventing the immunopathological disease HSK in the HSK BALB/c mouse model. Therefore, mice were inoculated with HSV-1 strain KOS on the scarified cornea to induce HSK and subsequently either systemically or topically treated with mAb 2c. Systemic treatment was performed by intravenous administration of mAb 2c 24 h prior to infection (pre-exposure prophylaxis or 24, 40, and 56 hours after infection (post-exposure immunotherapy. Topical treatment was performed by periodical inoculations (5 times per day of antibody-containing eye drops as control, starting at 24 h post infection. Systemic antibody treatment markedly reduced viral loads at the site of infection and completely protected mice from developing HSK. The administration of the antiviral antibody prior or post infection was equally effective. Topical treatment had no improving effect on the severity of HSK. In conclusion, our data demonstrate that mAb 2c proved to be an excellent drug for the treatment of corneal HSV-infections and for prevention of HSK and blindness. Moreover, the humanized counterpart (mAb hu2c was equally effective in protecting mice from HSV-induced HSK when compared to the parental mouse antibody. These results warrant the future development of this antibody as a novel approach for the treatment of corneal HSV-infections in humans.

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

    NARCIS (Netherlands)

    M. Medici (Marco); E. Porcu (Eleonora); G. Pistis (Giorgio); A. Teumer (Alexander); S.J. Brown (Stephen); R.A. Jensen (Richard); R. Rawal (R.); G.L. Roef (Greet); T.S. Plantinga (Theo S.); S.H.H.M. Vermeulen (Sita); J. Lahti (Jari); M.C. Simmonds (Mark); L.L.N. Husemoen (Lise Lotte); R.M. Freathy (Rachel); B.M. Shields (Beverley); D. Pietzner (Diana); R. Nagy (Rebecca); L. Broer (Linda); L. Chaker (Layal); T.I.M. Korevaar (Tim); M.G. Plia (Maria Grazia); C. Sala (Cinzia); U. Völker (Uwe); J.B. Richards (Brent); F.C. Sweep (Fred); C. Gieger (Christian); T. Corre (Tanguy); E. Kajantie (Eero); L. Thuesen (Leif); Y.E. Taes (Youri); W.E. Visser (Wil Edward); A.T. Hattersley (Andrew); J. Kratzsch (Jürgen); A. Hamilton (Amy); W. Li (Wei); G. Homuth (Georg); M. Lobina (Monia); S. Mariotti (Stefano); N. Soranzo (Nicole); M. Cocca (Massimiliano); M. Nauck (Matthias); C. Spielhagen (Christin); H.A. Ross (Alec); A.M. Arnold (Alice); M. van de Bunt (Martijn); S. Liyanarachchi (Sandya); M. Heier (Margit); H.J. Grabe (Hans Jörgen); C. Masciullo (Corrado); T.E. Galesloot (Tessel); E.M. Lim (Ee Mun); G. Reischl (Gunilla); P.J. Leedman (Peter); S. Lai (Sandra); A. Delitala (Alessandro); A. Bremner (Alexandra); D.I.W. Philips (David I.); J.P. Beilby (John); A. Mulas (Antonella); M. Vocale (Matteo); G.R. Abecasis (Gonçalo); T. Forsen (Tom); A. James (Alan); E. Widen (Elisabeth); J. Hui (Jennie); H. Prokisch (Holger); E.E. Rietzschel (Ernst); A. Palotie (Aarno); W. Feddema (Wouter); S.J. Fletcher (Stephen); K. Schramm (Katharina); J.I. Rotter (Jerome); A. Kluttig (Alexander); D. Radke (Dörte); M. Traglia (Michela); G. Surdulescu (Gabriela); H. He (Hao); J.A. Franklyn (Jayne); D. Tiller (Daniel); B. Vaidya (Bijay); T. Meyer (Thorsten); T. Jorgensen (Torben); K. Hagen (Knut); P.C. O'Leary (Peter); E. Wichmann (Eric); A.R. Hermus (Ad); B.M. Psaty (Bruce); T. Ittermann (Till); A. Hofman (Albert); E. Bosi (Emanuele); D. Schlessinger (David); H. Wallaschofski (Henri); N. Pirastu (Nicola); Y.S. Aulchenko (Yurii); A. de la Chapelle (Albert); R.T. Netea-Maier (Romana ); J.E. Gough (Julie); H. Meyer zu Schwabedissen (Henriette); T.M. Frayling (Timothy); J.-M. Kaufman (Jean-Marc); A. Linneberg (Allan); K. Räikkönen (Katri); J.W.A. Smit (Jan); L.A.L.M. Kiemeney (Bart); F. Rivadeneira Ramirez (Fernando); A.G. Uitterlinden (André); J.P. Walsh (John); C. Meisinger (Christa); M. den Heijer (Martin); T.J. Visser (Theo); T.D. Spector (Timothy); S.G. Wilson (Scott); H. Völzke (Henry); A.R. Cappola (Anne); D. Toniolo (Daniela); S. Sanna (Serena); S. Naitza (Silvia); R.P. Peeters (Robin)


    textabstractAutoimmune 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)

  1. Identification of novel genetic Loci associated with thyroid peroxidase antibodies and clinical thyroid disease

    NARCIS (Netherlands)

    Medici, M.; Porcu, E.; Pistis, G.; Teumer, A.; Brown, S.J.; Jensen, R.A.; Rawal, R.; Roef, G.L.; Plantinga, T.S.; Vermeulen, S.; Lahti, J.; Simmonds, M.J.; Husemoen, L.L.; Freathy, R.M.; Shields, B.M.; Pietzner, D.; Nagy, R.; Broer, L.; Chaker, L.; Korevaar, T.I.; Plia, M.G.; Sala, C.; Volker, U.; Richards, J.B.; Sweep, F.C.; Gieger, C.; Corre, T.; Kajantie, E.; Thuesen, B.; Taes, Y.E.; Visser, W.E.; Hattersley, A.T.; Kratzsch, J.; Hamilton, A.; Li, W.; Homuth, G.; Lobina, M.; Mariotti, S.; Soranzo, N.; Cocca, M.; Nauck, M.; Spielhagen, C.; Ross, A.; Arnold, A.; Bunt, M. van de; Liyanarachchi, S.; Heier, M.; Grabe, H.J.; Masciullo, C.; Galesloot, T.E.; Lim, E.M.; Reischl, E.; Leedman, P.J.; Lai, S.; Delitala, A.; Bremner, A.P.; Philips, D.I.; Beilby, J.P.; Mulas, A.; Vocale, M.; Abecasis, G.; Forsen, T.; James, A.; Widen, E.; Hui, J.; Prokisch, H.; Rietzschel, E.E.; Palotie, A.; Feddema, P.; Fletcher, S.J.; Schramm, K.; Rotter, J.I.; Kluttig, A.; Radke, D.; Traglia, M.; Surdulescu, G.L.; He, H.; Franklyn, J.A.; Tiller, D.; Vaidya, B.; Meyer, T.; Jorgensen, T.; Eriksson, J.G.; O'Leary, P.C.; Wichmann, E.; Hermus, A.R.M.M.; Psaty, B.M.; Ittermann, T.; Hofman, A.; Bosi, E.; Schlessinger, D.; Wallaschofski, H.; Pirastu, N.; Aulchenko, Y.S.; Chapelle, A. dela; Netea-Maier, R.T.; Gough, S.C.; Meyer Zu Schwabedissen, H.; Frayling, T.M.; Kaufman, J.M.; Smit, J.W.; Kiemeney, B.


    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 pos

  2. Association of autoimmune hepatitis and multiple sclerosis: a coincidence?

    Directory of Open Access Journals (Sweden)

    Marta Sofia Mendes Oliveira


    Full Text Available Autoimmune hepatitis is a chronic liver inflammation resulting from deregulation of immune tolerance mechanisms. Multiple sclerosis is also an inflammatory disease in which the insulating covers of nerve cells in the brain and spinal cord are damaged. Here we present a case of an 18 year old female with multiple sclerosis was treated with glatiramer acetate and with interferon beta 1a at our hospital. Seven months after initiating treatment, liver dysfunction occurred. Clinical and laboratory findings were suggestive of drug-induced hepatitis, which led to discontinuation of treatment with interferon. Facing a new episode of acute hepatitis one year later, she was subjected to a liver biopsy, and the analysis of autoantibodies was positive for smooth muscle antibodies. Given the diagnosis of autoimmune hepatitis she started therapy with prednisolone and azathioprine, with good clinical and analytical response. Besides, the demyelinating lesions of multiple sclerosis became lower. In conclusion, there are only a few cases that describe the association of autoimmune hepatitis with multiple sclerosis, and there is a chance both diseases have the same autoimmune inflammatory origin.

  3. Autoimmun pankreatitis

    DEFF Research Database (Denmark)

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


    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....

  4. Inheritance of autoimmune neuroinflammation


    Stridh, Pernilla


    Multiple sclerosis (MS) is a chronic neuro-inflammatory disease with anticipated complex etiology. Susceptibility to MS is conferred by numerous genes, with very low odds ratios that explain minute fractions of disease. This indicates that unknown factors are responsible for the remaining genetic contribution, termed the missing heritability . Due to the similarities to MS pathogenesis, we studied myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune ...

  5. An antibody blocking activin type II receptors induces strong skeletal muscle hypertrophy and protects from atrophy. (United States)

    Lach-Trifilieff, Estelle; Minetti, Giulia C; Sheppard, KellyAnn; Ibebunjo, Chikwendu; Feige, Jerome N; Hartmann, Steffen; Brachat, Sophie; Rivet, Helene; Koelbing, Claudia; Morvan, Frederic; Hatakeyama, Shinji; Glass, David J


    The myostatin/activin type II receptor (ActRII) pathway has been identified to be critical in regulating skeletal muscle size. Several other ligands, including GDF11 and the activins, signal through this pathway, suggesting that the ActRII receptors are major regulatory nodes in the regulation of muscle mass. We have developed a novel, human anti-ActRII antibody (bimagrumab, or BYM338) to prevent binding of ligands to the receptors and thus inhibit downstream signaling. BYM338 enhances differentiation of primary human skeletal myoblasts and counteracts the inhibition of differentiation induced by myostatin or activin A. BYM338 prevents myostatin- or activin A-induced atrophy through inhibition of Smad2/3 phosphorylation, thus sparing the myosin heavy chain from degradation. BYM338 dramatically increases skeletal muscle mass in mice, beyond sole inhibition of myostatin, detected by comparing the antibody with a myostatin inhibitor. A mouse version of the antibody induces enhanced muscle hypertrophy in myostatin mutant mice, further confirming a beneficial effect on muscle growth beyond myostatin inhibition alone through blockade of ActRII ligands. BYM338 protects muscles from glucocorticoid-induced atrophy and weakness via prevention of muscle and tetanic force losses. These data highlight the compelling therapeutic potential of BYM338 for the treatment of skeletal muscle atrophy and weakness in multiple settings.

  6. Depigmented Allergoids Reveal New Epitopes with Capacity to Induce IgG Blocking Antibodies

    Directory of Open Access Journals (Sweden)

    M. Angeles López-Matas


    Full Text Available Background. The synthesis of allergen-specific blocking IgGs that interact with IgE after allergen immunotherapy (SIT has been related to clinical efficacy. The objectives were to investigate the epitope specificity of IgG-antibodies induced by depigmented-polymerized (Dpg-Pol allergoids and unmodified allergen extracts, and examine IgE-blocking activity of induced IgG-antibodies. Methods. Rabbits were immunized with native and Dpg-Pol extracts of birch pollen, and serum samples were obtained. Recognition of linear IgG-epitopes of Bet v 1 and Bet v 2 and the capacity of these IgG-antibodies to block binding of human-IgE was determined. Results. Serum from rabbits immunized with native extracts recognised 11 linear epitopes from Bet v 1, while that from Dpg-Pol-immunized animals recognised 8. For Bet v 2, 8 epitopes were recognized by IgG from native immunized animals, and 9 from Dpg-Pol immunized one. Dpg-Pol and native immunized serum did not always recognise the same epitopes, but specific-IgG from both could block human-IgE binding sites for native extract. Conclusions. Depigmented-polymerized birch extract stimulates the synthesis of specific IgG-antibodies which recognize common but also novel epitopes compared with native extracts. IgG-antibodies induced by Dpg-Pol effectively inhibit human-IgE binding to allergens which may be part of the mechanism of action of SIT.

  7. 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.

  8. Antibodies with higher bactericidal activity induced by a Neisseria gonorrhoeae Rmp deletion mutant strain. (United States)

    Li, Guocai; Xie, Rushan; Zhu, Xiaoping; Mao, Yanli; Liu, Shuangxi; Jiao, Hongmei; Yan, Hua; Xiong, Kun; Ji, Mingchun


    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.

  9. Agonist antibodies activating the Met receptor protect cardiomyoblasts from cobalt chloride-induced apoptosis and autophagy (United States)

    Gallo, S; Gatti, S; Sala, V; Albano, R; Costelli, P; Casanova, E; Comoglio, P M; Crepaldi, T


    Met, the tyrosine kinase receptor for hepatocyte growth factor (HGF), mainly activates prosurvival pathways, including protection from apoptosis. In this work, we investigated the cardioprotective mechanisms of Met activation by agonist monoclonal antibodies (mAbs). Cobalt chloride (CoCl2), a chemical mimetic of hypoxia, was used to induce cardiac damage in H9c2 cardiomyoblasts, which resulted in reduction of cell viability by (i) caspase-dependent apoptosis and (ii) – surprisingly – autophagy. Blocking either apoptosis with the caspase inhibitor benzyloxycarbonyl-VAD-fluoromethylketone or autophagosome formation with 3-methyladenine prevented loss of cell viability, which suggests that both processes contribute to cardiomyoblast injury. Concomitant treatment with Met-activating antibodies or HGF prevented apoptosis and autophagy. Pro-autophagic Redd1, Bnip3 and phospho-AMPK proteins, which are known to promote autophagy through inactivation of the mTOR pathway, were induced by CoCl2. Mechanistically, Met agonist antibodies or HGF prevented the inhibition of mTOR and reduced the flux of autophagosome formation. Accordingly, their anti-autophagic function was completely blunted by Temsirolimus, a specific mTOR inhibitor. Targeted Met activation was successful also in the setting of low oxygen conditions, in which Met agonist antibodies or HGF demonstrated anti-apoptotic and anti-autophagic effects. Activation of the Met pathway is thus a promising novel therapeutic tool for ischaemic injury. PMID:24743740

  10. Autoimmunity and type I diabetes. (United States)

    Bach, J F


    Insulin-dependent diabetes mellitus (IDDM) is a T-cell-mediated autoimmune disease. The effector mechanisms essentially involve cytokine-mediated inflammation ultimately leading to beta-cell destruction. Several candidate autoantigens have been delineated for both the pathogenic T-cell response and the nonpathogenic antibody response used for disease prediction. Because of antigen spreading, it is not yet clear which of these antigens are involved in the triggering of the autoimmune response. In any case, this TH1 autoimmune response is amplified and perpetuated by an immune dysregulation involving TH2 cells. Both effector and regulatory mechanisms are placed under the tight control of major histocompatibility complex (MHC) and non-MHC genes. (Trends Endocrinol Metab 1997; 8:71-74). (c) 1997, Elsevier Science Inc.

  11. Research advances in drug-induced autoimmune hepatitis%药物诱导的自身免疫性肝炎研究进展

    Institute of Scientific and Technical Information of China (English)

    李春敏; 张静怡; 唐颖悦; 茅益民


    Drug induced autoimmune hepatitis (DIAIH) refers to the liver injury mediated by druginduced autoimmune reaction.Since it has similar clinical features as idiopathic autoimmune hepatitis,it is often difficult to make differential diagnosis in clinical practice.A deep understanding of the development,pathogenesis,related drugs,risk factors,and clinical and histological features of DIAIH helps with the correct diagnosis and treatment of DIAIH.%药物诱导的自身免疫性肝炎是由药物诱发的自身免疫反应所介导的肝损伤,由于与特发性自身免疫性肝炎的临床特征相似,临床上鉴别诊断往往非常困难.深入了解药物诱导的自身免疫性肝炎的发生情况、发病机制、所涉及的相关药物、风险因素、临床和组织学特点等,有助于更好地正确诊断和治疗本病.

  12. CD8+ T cells prevent antigen-induced antibody-dependent enhancement of dengue disease in mice


    Zellweger, Raphaël M.; Eddy, William E.; Tang, William W.; Miller, Robyn; Shresta, Sujan


    Dengue virus (DENV) causes pathologies ranging from the febrile illness dengue fever to the potentially lethal severe dengue disease. A major risk factor for developing severe dengue disease is the presence of sub-protective DENV-reactive antibodies from a previous infection (or from an immune mother), which can induce antibody-dependent enhancement of infection (ADE). However, infection in the presence of sub-protective anti-DENV antibodies does not always result in severe disease, suggestin...

  13. Association among ANA Patterns, Anti-ENA Antibody and Anti-dsDNA Antibody in Autoimmune Disease%评价自身抗体联合检测在诊断自身免疫性疾病中的应用

    Institute of Scientific and Technical Information of China (English)

    孙善会; 郑燕; 张茂修


    目的:探讨检测抗核抗体(ANA)核型与抗可提取性核抗原(ENA)抗体及抗双链DNA(ds-DNA)抗体之间的相关性,提高对自身免疫性疾病(AID)的诊断及鉴别诊断参考价值。方法资料来源门诊及住院的AID病例血清标本进行检测,ANA检测采用间接免疫荧光法(IIF),抗ENA抗体检测采用欧蒙斑点法(抗nRNP/Sm、Sm、SSA/Ro、SSB/Lo、Scl-70和Jo-1)六项抗体及抗(ds-DNA)抗体采用ELISA法检测。结果在98例ANA阳性病例血清标本中核型分布为:细胞核均质型(36.74%),细胞核颗粒型(41.84%),细胞核仁型(11.22%),细胞核膜型(1.02%),细胞核着丝点型(1.02%);重叠核型中细胞核均质型/细胞核颗粒型(2.04%),细胞核均质型/细胞浆颗粒型(6.12%)等。98例ANA与ENA同时阳性血清标本中42例抗双链DNA抗体阳性(42.86%)。36例均质型阳性样本中抗SSA/Ro抗体(24.48%),抗SSB/Lo抗体(6.12%),抗nRNP/Sm抗体(6.12%)。41例细胞核颗粒型阳性样本抗nRNP/Sm抗体(19.39%),SSA/Ro抗体(15.31%),抗SSB/Lo抗体(6.12%)。ANA阳性可出现一种或多种自身抗体。结论 ANA常见核型有:细胞核颗粒型,细胞核均质型及细胞核仁型。ANA均质型核型检出的抗ds-DNA抗体为主,且抗ds-DNA抗体含量与荧光强度成正比。ANA核型与抗ENA抗体二者之间有一定的相对应性。ANA及核型、抗ENA抗体和抗ds-DNA抗体的联合检测可明确诊断AID,而且利于判断患者血清中各种自身抗体与临床表现的关系。%Objective To investigate the association among ANA patterns, anti-ENA antibody and anti-dsDNA antibodies in autoimmune diseases, and the reference signiifcance of detecting these antibodies on the diagnosis and differential diagnosis of autoimmune diseases. Methods Serum samples from 98 pateints with autoimmune disorder were collected. ANA, anti-ENA and anti-dsDNA antibodies were detected using IIF, immuno-dot assay and ELISA. Results

  14. In vitro induced regulatory T cells are unique from endogenous regulatory T cells and effective at suppressing late stages of ongoing autoimmunity.

    Directory of Open Access Journals (Sweden)

    Thanh-Long M Nguyen

    Full Text Available Strategies to boost the numbers and functions of regulatory T cells (Tregs are currently being tested as means to treat autoimmunity. While Tregs have been shown to be effective in this role, strategies to manipulate Tregs to effectively suppress later stages of ongoing diseases need to be established. In this study, we evaluated the ability of TGF-β-induced Tregs (iTregs specific for the major self-antigen in autoimmune gastritis to suppress established autoimmune gastritis in mice. When transferred into mice during later stages of disease, iTregs demethylated the Foxp3 promoter, maintained Foxp3 expression, and suppressed effector T cell proliferation. More importantly, these iTregs were effective at stopping disease progression. Untreated mice had high numbers of endogenous Tregs (enTregs but these were unable to stop disease progression. In contrast, iTregs, were found in relatively low numbers in treated mice, yet were effective at stopping disease progression, suggesting qualitative differences in suppressor functions. We identified several inhibitory receptors (LAG-3, PD-1, GARP, and TNFR2, cytokines (TGF-β1 and IL12p35, and transcription factors (IRF4 and Tbet expressed at higher levels by iTregs compared to enTregs isolated form mice with ongoing disease, which likely accounts for superior suppressor ability in this disease model. These data support efforts to use iTregs in therapies to treat establish autoimmunity, and show that iTregs are more effective than enTregs at suppressing inflammation in this disease model.

  15. Role of Complement in Autoimmune Hemolytic Anemia. (United States)

    Berentsen, Sigbjørn


    The classification of autoimmune hemolytic anemias and the complement system are reviewed. In autoimmune hemolytic anemia of the warm antibody type, complement-mediated cell lysis is clinically relevant in a proportion of the patients but is hardly essential for hemolysis in most patients. Cold antibody-mediated autoimmune hemolytic anemias (primary cold agglutinin disease, secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria) are entirely complement-mediated disorders. In cold agglutinin disease, efficient therapies have been developed in order to target the pathogenic B-cell clone, but complement modulation remains promising in some clinical situations. No established therapy exists for secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria, and the possibility of therapeutic complement inhibition is interesting. Currently, complement modulation is not clinically documented in any autoimmune hemolytic anemia. The most relevant candidate drugs and possible target levels of action are discussed.

  16. Exploration on value of autoimmune liver disease antibody spectrum detection in diagnosing autoimmune liver disease%自身免疫性肝病抗体谱检测在自身免疫性肝病诊断中的价值探讨

    Institute of Scientific and Technical Information of China (English)



    目的:探讨自身免疫性肝病(AILD)抗体谱检测在AILD诊断中的临床应用价值。方法采用线性免疫分析法检测不明病因肝功能异常、各种病毒性肝炎以及健康体检者(健康对照组)的血清标本,进行抗线粒体亚型-丙酮酸脱氢酶复合物(AMA/M2)、抗肝肾微粒体Ⅰ型抗体(LKM-1)、抗肝细胞胞浆Ⅰ型抗体(LC-1)、抗可溶性肝抗原/肝胰抗原抗体(SLA/LP)、糖蛋白210抗体(gp210)以及多核点抗原抗体(sp100)等6项指标的检验结果资料进行回顾分析。结果各组患者标本中的自身抗体总阳性检出率分别为自身免疫性肝炎(AIH)80.5%、原发性胆汁性肝硬化(PBC)92.3%、乙型肝炎病毒(HBV)17.2%、丙型肝炎病毒(HCV)16.7%、甲型肝炎病毒(HAV)22.2%、戊型肝炎病毒(HEV)14.3%,对照组仅为2.6%;AILD组的阳性检出率与其他各组间比较(P<0.05);AIH各亚型中AIH-Ⅰ的AMA/M2的阳性检出率与AIH-Ⅱ和AIH-Ⅲ比较(P<0.05),AIH-Ⅱ的LKM-1的阳性检出率与 AIH-Ⅰ和 AIH-Ⅲ比较(P<0.05),AIH-Ⅲ的SLA/LP的阳性检出率与 AIH-Ⅰ和 AIH-Ⅱ比较(P<0.05)。结论 AILD抗体谱检测有助于AILD的早期诊断,可为该病的分型以及治疗提供有价值的实验室依据。%Objective To investigate the clinical application value of the autoimmune liver disease antibody spectrum detection in diagnosing autoimmune liver diseases (AILD) .Methods The linear immunoassay was adopted to detect the serum specimens in the patients with unknown etiology of liver function abnormalities ,various viral hep-atitis and healthy subjects with physical examination (control group) .The detection results of 6 indexes of anti-mito-chondrial subtype-pyruvate dehydrogenase complex (AMA/M2) ,liver kidney microsomal antibody type 1 (LKM-1 type) ,anti-liver cell cytoplasmic antibody-1(LC-1) ,type I anti soluble

  17. Vaccine Induced Antibody Response to Foot and Mouth Disease in Infectious Bovine Rhinotracheitis Seropositive Cattle



    Foot and mouth disease (FMD) and infectious bovine rhinotracheitis (IBR) are two important infectious diseases of cattle. Inactivated FMD vaccines are the most powerful tools to protect animals against FMD. Previous studies showed that recombinant IBR-FMD viruses protected cattle from virulent BHV-1 challenge and induced protective levels of anti-FMDV antibodies. FMD is considered to be endemic in Turkey and inactivated oil adjuvanted vaccines are used for the immunization of cattle. Previous...

  18. Antimyeloperoxidase antibodies rapidly induce alpha-4-integrin-dependent glomerular neutrophil adhesion. (United States)

    Kuligowski, Michael P; Kwan, Rain Y Q; Lo, Cecilia; Wong, Cyndi; James, Will G; Bourges, Dorothee; Ooi, Joshua D; Abeynaike, Latasha D; Hall, Pam; Kitching, A Richard; Hickey, Michael J


    Patients with antineutrophil cytoplasmic antibodies (ANCAs) frequently develop severe vasculitis and glomerulonephritis. Although ANCAs, particularly antimyeloperoxidase (anti-MPO), have been shown to promote leukocyte adhesion in postcapillary venules, their ability to promote adhesion in the glomerular vasculature is less clear. We used intravital microscopy to examine glomerular leukocyte adhesion induced by anti-MPO. In mice pretreated with LPS, 50 microg anti-MPO induced LFA-1-dependent adhesion in glomeruli. In concert with this finding, in mice pretreated with LPS, more than 80% of circulating neutrophils bound anti-MPO within 5 minutes of intravenous administration. However, even in the absence of LPS, more than 40% of circulating neutrophils bound anti-MPO in vivo, a response not seen in MPO(-/-) mice. In addition, a higher dose of anti-MPO (200 microg) induced robust glomerular leukocyte adhesion in the absence of LPS. The latter response was beta2-integrin independent, instead requiring the alpha4-integrin, which was up-regulated on neutrophils in response to anti-MPO. These data indicate that anti-MPO antibodies bind to circulating neutrophils, and can induce glomerular leukocyte adhesion via multiple pathways. Lower doses induce adhesion only after an infection-related stimulus, whereas higher doses are capable of inducing responses in the absence of an additional inflammatory stimulus, via alternative adhesion mechanisms.

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

    NARCIS (Netherlands)

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


    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

  20. Delayed adaptive immunity is related to higher MMR vaccine-induced antibody titers in children. (United States)

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


    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.

  1. Significance of Anti-Ro-52 kDa and SSA Antibodies in Patients with Autoimmune Diseases%抗Ro-52抗体与抗SSA抗体在自身免疫病中的检测意义

    Institute of Scientific and Technical Information of China (English)

    金燕萍; 林贵高; 阎超; 鄢盛恺


    Objective To investigate the clinical correlation of anti-Ro-52 and SSA antibody and to determine the clinical diagnostic value of anti-Ro-52/SSA in Chinese patients presenting with SLE,SS and other autoimmune diseases. Methods Serum samples from 50 patients with SLE, 50 with SS and 30 other autoimmune diseases were tested for the presence of anti-Ro-52 and anti-SSA using a commercial WB kit, AN A were tested by IIF,50 health people serum as controls. Results The positive rate of anti-Ro-52 and SSA in patients with SLE were 60% and 64% respectively,patients with SS were 72% and 82% respectively,patients with other autoimmune diseases were 30% and 23. 33% respectively,higher than control group (6%),and with X2 inspection,the difference was statistically significant (P<0. 05). Conclusion High prevalence of anti-Ro-52 and SSA is of significance in diagnosis of SLE and SS,the relationship between the two needs to be further explored.%目的 探讨抗Ro-52 kDa自身抗体与抗SSA抗体的关系及其在中国人群中SLE和SS等自身免疫病的诊断价值.方法 收集自身免疫病患者血清,其中SLE 50例,SS 50例,其他自身免疫病30例,50例健康者血清作为对照,用免疫印迹法检测所有标本中抗Ro-52与抗SSA抗体,同时用间接免疫荧光法检测所有标本ANA核型.结果 抗Ro-52和抗SSA抗体阳性率在SLE患者中分别为60%和64%,在SS中分别为72%和82%,在其他自身免疫病患者中分别为30%和23.33%,均高于健康对照组(6%),经χ2检验,差异有统计学意义(P<0.05).结论 抗Ro-52和抗SSA抗体阳性对诊断SLE和SS有一定的临床价值,二者的确切关系还需进一步探讨.

  2. 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


    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.

  3. Bovine Neonatal Pancytopenia: is this alloimmune syndrome caused by vaccine-induced alloreactive antibodies? (United States)

    Bastian, Max; Holsteg, Mark; Hanke-Robinson, Heidrun; Duchow, Karin; Cussler, Klaus


    Bovine Neonatal Pancytopenia (BNP) is a new emerging disease observed since 2007 in Germany and neighbouring countries. The syndrome affects newborn calves and is characterized by pancytopenia, severe bleeding and high lethality. So far, a causative role of infectious or toxic agents has been ruled out. Instead, the syndrome is induced after ingestion of colostrum, the first milk that supplies the calf with maternal antibodies. In analogy to similar diseases in humans it has therefore been postulated that BNP is caused by alloreactive, maternal antibodies. There is a striking association between BNP and a previous vaccination of the respective dams with a particular vaccine against Bovine Virus Diarrhoea (BVD). This association has led to a suspension of the marketing authorisation for the vaccine, by the European Commission. The current study investigates the role of this vaccine in the pathogenesis of BNP. By flow cytometry we were able to demonstrate that sera of BNP dams (dams that gave birth to a BNP calf) harbour alloreactive antibodies binding to surface antigens on bovine leukocytes. A significantly weaker alloreactivity was observed with sera of non-BNP dams that have been vaccinated with the same vaccine but delivered healthy calves. No binding was seen with non-BVD-vaccinated control cows and animals that were vaccinated with other inactivated BVD vaccines so far not associated with BNP. The binding is functionally relevant, because opsonization of bovine leukocytes with alloantibodies led to an elevated cytophagocytosis by bovine macrophages. To test whether the vaccine induces alloreactive antibodies two strategies were employed: Guinea pigs were vaccinated with a panel of commercially available BVD-vaccines. Only the incriminated vaccine induced antibodies binding surface antigens on bovine leukocytes. Additionally, two calves were repeatedly vaccinated with the suspected vaccine and the development of alloreactivity was monitored. In dependence of

  4. 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.

  5. Expression of tenascin in lymphocytic autoimmune thyroiditis.


    Back, W; Heubner, C; Winter, J.; Bleyl, U


    AIMS: To study the distribution of tenascin by immunocytochemistry in autoimmune diseases of the thyroid. METHODS: Thyroids from patients with inflammatory lesions of the thyroid (lymphocytic thyroiditis Hashimoto, Grave's disease, thyroiditis DeQuervain) were studied by immunocytochemistry using antibodies against tenascin, collagen III, and collagen IV. RESULTS: In autoimmune lymphocytic thyroiditis Hashimoto there was a characteristic corona-like staining pattern of tenascin around all act...

  6. 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


    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...

  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


    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. CD44 antibodies and immune thrombocytopenia in the amelioration of murine inflammatory arthritis.

    Directory of Open Access Journals (Sweden)

    Patrick J Mott

    Full Text Available Antibodies to CD44 have been used to successfully ameliorate murine models of autoimmune disease. The most often studied disease model has been murine inflammatory arthritis, where a clear mechanism for the efficacy of CD44 antibodies has not been established. We have recently shown in a murine passive-model of the autoimmune disease immune thrombocytopenia (ITP that some CD44 antibodies themselves can induce thrombocytopenia in mice, and the CD44 antibody causing the most severe thrombocytopenia (IM7, also is known to be highly effective in ameliorating murine models of arthritis. Recent work in the K/BxN serum-induced model of arthritis demonstrated that antibody-induced thrombocytopenia reduced arthritis, causing us to question whether CD44 antibodies might primarily ameliorate arthritis through their thrombocytopenic effect. We evaluated IM7, IRAWB14.4, 5035-41.1D, KM201, KM114, and KM81, and found that while all could induce thrombocytopenia, the degree of protection against serum-induced arthritis was not closely related to the length or severity of the thrombocytopenia. CD44 antibody treatment was also able to reverse established inflammation, while thrombocytopenia induced by an anti-platelet antibody targeting the GPIIbIIIa platelet antigen, could not mediate this effect. While CD44 antibody-induced thrombocytopenia may contribute to some of its therapeutic effect against the initiation of arthritis, for established disease there are likely other mechanisms contributing to its efficacy. Humans are not known to express CD44 on platelets, and are therefore unlikely to develop thrombocytopenia after CD44 antibody treatment. An understanding of the relationship between arthritis, thrombocytopenia, and CD44 antibody treatment remains critical for continued development of CD44 antibody therapeutics.

  9. Autoimmune liver disease panel (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 ...

  10. Amplification of autoimmune disease by infection


    Posnett, David N; Yarilin, Dmitry


    Reports of infection with certain chronic persistent microbes (herpesviruses or Chlamydiae) in human autoimmune diseases are consistent with the hypothesis that these microbes are reactivated in the setting of immunodeficiency and often target the site of autoimmune inflammation. New experimental animal models demonstrate the principle. A herpesvirus or Chlamydia species can be used to infect mice with induced transient autoimmune diseases. This results in increased disease severity and even ...

  11. Antibodies induced by multi-epitope vaccine showed inhibitory activity against heterologous influenza A virus (H3N2)

    Institute of Scientific and Technical Information of China (English)

    DING Jian; WU Fan; WEI Wei; CHEN Yinghua


    In this study, recognition of 4 recombinant viral proteins (GST-NHA1) by the antibodies induced by multi-epitope vaccine was testified. Inhibitory activities of these antibodies were also investigated in vitro against four heterologous influenza A viruses (H3N2). Three epitope-specific antibodies purified by affinity chromatography could reduce the plaque formation. Interestingly, the three neutralizing antibodies in combination showed obvious enhancement of inhibitory activity, suggesting that the development of recombinant multi-epitope vaccine might be an effective way against viral mutation.

  12. Antinuclear antibody-negative, drug-induced lupus caused by lisinopril. (United States)

    Carter, J D; Valeriano-Marcet, J; Kanik, K S; Vasey, F B


    The clinical symptoms of drug-induced lupus (DIL) are similar to those of idiopathic systemic lupus erythematosus. The literature indicates that in patients with DIL, sera generally contain antinuclear antibodies (ANAs); however, ANA-negative DIL has been reported. The list of medications implicated as etiologic agents in DIL continues to grow. This list includes two different types of angiotensin-converting enzyme inhibitors--captopril and enalapril. We report the first case of DIL caused by lisinopril. Our patient had negative results on ANA testing and had histone antibodies (IgG anti-[H2A-H2B]-DNA) mirroring the disease course. Antibodies to the (H2A-H2B)-DNA complex are seen in more than 90% of patients with active DIL, excluding those with DIL due to hydralazine. Thus, it is important to recognize the clinical significance of IgG anti-(H2A-H2B)-DNA antibodies and that negative ANA test results do not preclude the diagnosis of DIL.

  13. Antithyroglobulin antibody (United States)

    Thyroglobulin antibody; Thyroiditis - thyroglobulin antibody; Hypothyroidism - thyroglobulin antibody; Thyroiditis - thyroglobulin antibody; Graves disease - thyroglobulin antibody; Underactive thyroid - thyroglobulin antibody

  14. Characterisation of antibody responses in pigs induced by recombinant oncosphere antigens from Taenia solium. (United States)

    Jayashi, César M; Gonzalez, Armando E; Castillo Neyra, Ricardo; Kyngdon, Craig T; Gauci, Charles G; Lightowlers, Marshall W


    Recombinant antigens cloned from the oncosphere life cycle stage of the cestode parasite Taenia solium (T. solium) have been proven to be effective as vaccines for protecting pigs against infections with T. solium. Previous studies have defined three different host protective oncosphere antigens, TSOL18, TSOL16 and TSOL45. In this study, we evaluated the potential for combining the antigens TSOL16 and TSOL18 as a practical vaccine. Firstly, in a laboratory trial, we compared the immunogenicity of the combined antigens (TSOL16/18) versus the immunogenicity of the antigens separately. Secondly, in a field trial, we tested the ability of the TSOL16/18 vaccine to induce detectable antibody responses in animals living under environmental stress and traditionally reared in areas where T. solium cysticercosis is endemic; and finally, we characterised the immune response of the study population. Pigs of 8-16 weeks of age were vaccinated with 200 μg each of TSOL16 and TSOL18, plus 5mg of Quil-A. Specific total IgG, IgG(1) and IgG(2) antibody responses induced by TSOL16 and TSOL18 were determined with ELISA. The immunogenicity of both antigens was retained in the combined TSOL16/18 vaccine. The combined vaccine TSOL16/18 induced detectable specific anti-TSOL18 antibody responses in 100% (113/113) and specific anti-TSOL16 in 99% (112/113) of the vaccinated animals measured at 2 weeks following the booster vaccination. From the two IgG antibody subtypes analysed we found there was stronger response to IgG(2).

  15. Cutting-edge issues in autoimmune orchitis. (United States)

    Silva, Clovis A; Cocuzza, Marcello; Borba, Eduardo F; Bonfá, Eloísa


    Autoimmune orchitis is a relevant cause of decreased fecundity in males, and it is defined as a direct aggression to the testis with the concomitant presence of anti-sperm antibodies (ASA). The presence of these specific antibodies has been observed in approximately 5-12% of infertile male partners. Primary autoimmune orchitis is defined by isolated infertility with ASA but without evidence of a systemic disease. Secondary causes of orchitis and/or testicular vasculitis are uniformly associated with autoimmune diseases, mainly in primary vasculitis such as polyarteritis nodosa, Behçet's disease, and Henoch-Schönlein purpura. The overall frequencies of acute orchitis and ASA in rheumatic diseases are 2-31% and 0-50%, respectively. The pathogenesis of primary/secondary autoimmune orchitis is not completely understood but probably involves the access of immune cells to the testicular microenvironment due to inflammation, infection or trauma, leading to apoptosis of spermatocytes and spermatids. Glucocorticoids and immunosuppressive drugs are indicated in autoimmune orchitis-associated active systemic autoimmune diseases. However, there are no standardized treatment options, and the real significance of ASA in infertile men is still controversial. Assisted reproductive technologies such as intrauterine insemination, in vitro fertilization, and intracytoplasmic sperm injection (ICSI) are therapeutic options for male infertility associated with these autoantibodies. ICSI is considered to be the best choice for patients with severe sperm autoimmunity, particularly in males with low semen counts or motility.

  16. Origin and pathogenesis of antiphospholipid antibodies

    Directory of Open Access Journals (Sweden)

    C.M. Celli


    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.

  17. Proatherogenic conditions promote autoimmune T helper 17 cell responses in vivo. (United States)

    Lim, Hoyong; Kim, Young Uk; Sun, Hua; Lee, Joyce H; Reynolds, Joseph M; Hanabuchi, Shino; Wu, Huaizhu; Teng, Ba-Bie; Chung, Yeonseok


    Patients with systemic autoimmune diseases show increased incidence of atherosclerosis. However, the contribution of proatherogenic factors to autoimmunity remains unclear. We found that atherogenic mice (herein referred to as LDb mice) exhibited increased serum interleukin-17, which was associated with increased numbers of T helper 17 (Th17) cells in secondary lymphoid organs. The environment within LDb mice was substantially favorable for Th17 cell polarization of autoreactive T cells during homeostatic proliferation, which was considerably inhibited by antibodies directed against oxidized low-density lipoprotein (oxLDL). Moreover, the uptake of oxLDL induced dendritic-cell-mediated Th17 cell polarization by triggering IL-6 production in a process dependent on TLR4, CD36, and MyD88. Furthermore, self-reactive CD4(+) T cells that expanded in the presence of oxLDL induced more profound experimental autoimmune encephalomyelitis. These findings demonstrate that proatherogenic factors promote the polarization and inflammatory function of autoimmune Th17 cells, which could be critical for the pathogenesis of atherosclerosis and other related autoimmune diseases.

  18. [Autoimmune pancreatitis]. (United States)

    Beyer, G; Menzel, J; Krüger, P-C; Ribback, S; Lerch, M M; Mayerle, J


    Autoimmune pancreatitis is a relatively rare form of chronic pancreatitis which is characterized by a lymphoplasmatic infiltrate with a storiform fibrosis and often goes along with painless jaundice and discrete discomfort of the upper abdomen. Clinically we distinguish between two subtypes, which differ in terms of their histology, clinical picture and prognosis. Type 1 autoimmune pancreatitis is the pancreatic manifestation of the IgG4-associated syndrome which also involves other organs. About one third of the patients can only be diagnosed after either histological prove or a successful steroid trail. Type 2 is IgG4-negative with the histological picture of an idiopathic duct centric pancreatitis and is to higher degree associated with inflammatory bowel disease. A definitive diagnosis can only be made using biopsy. Usually both forms show response to steroid treatment, but in type 1 up to 50 % of the patients might develop a relapse. The biggest challenge and most important differential diagnosis remains the discrimination of AIP from pancreatic cancer, because also AIP can cause mass of the pancreatic head, lymphadenopathy and ductal obstruction. This article summarizes recent advances on epidemiology, clinical presentation, diagnostic strategy, therapy and differential diagnosis in this relatively unknown disease.

  19. Autoimmune hemolytic anemia: transfusion challenges and solutions

    Directory of Open Access Journals (Sweden)

    Barros MM


    Full Text Available Melca M O Barros, Dante M Langhi Jr, José O Bordin Department of Clinical and Experimental Oncology, Universidade Federal de São Paulo, São Paulo, Brazil Abstract: Autoimmune hemolytic anemia (AIHA is defined as the increased destruction of red blood cells (RBCs in the presence of anti-RBC autoantibodies and/or complement. Classification of AIHA is based on the optimal auto-RBC antibody reactivity temperatures and includes warm, cold-reactive, mixed AIHA, and drug-induced AIHA subtypes. AIHA is a rare disease, and recommendations for transfusion are based mainly on results from retrospective data and relatively small cohort studies, including heterogeneous patient samples or single case reports. In this article, we will review the challenges and solutions to safely transfuse AIHA patients. We will reflect on the indication for transfusion in AIHA and the difficulty in the accomplishment of immunohematological procedures for the selection of the safest and most compatible RBC units. Keywords: hemolytic anemia, RBC autoantibodies, autoimmunity, hemolysis, direct ­antiglobulin test


    Directory of Open Access Journals (Sweden)



    Full Text Available The hemolytic anemia brought about by autoimmune antibodies against red cells resulting in shortening of red cell survival. And excessive erythropoiesis as a compensatory response of the marrow is autoimmune hemolytic anemia. There are two types due to wa rm antibodies and cold antibodies. Warm antibodies mediated anemia has hemolysis in spleen mediated by IgG antibody. Macrophage Fc receptor can detect IgG coated red cells in absence of C 3b. It acts in the range of 37 - 42deg c. (1 Cold antibody mediated anemia is mediated by IgM antibody, they bind avidly at 4 deg c. carry hemolysis at low temp. Liver is the major site of hemolysis. Autoimmune hemolytic anemia presents as sudden onset of pallor, jaundice, dark coloured urine, and he pato splenomegaly. In 5 cases cold antibodies were positive, 3 cases warm were positive too. 4 of the 5 cases were females and steroids were effective in management of cold auto immune hemolytic anemia.

  1. 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

  2. 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)

    Energy Technology Data Exchange (ETDEWEB)

    Giovanella, L.; Ceriani, L.; Garacini, S. [University Hospital Ospedale di Circolo e Fondazione Macchi, Dept. of Nuclear Medicine, Lab. of Endocrinology and Thyroid Unit, Varese (Italy)


    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

  3. Anti-ganglioside antibodies induced in chickens by an alum-adsorbed anti-idiotype antibody targeting NeuGcGM3.

    Directory of Open Access Journals (Sweden)

    Marcelo David Guthmann


    Full Text Available Racotumomab is a murine anti-idiotype cancer vaccine targeting NeuGcGM3 on melanoma, breast and lung cancer. In order to characterize the immunogenicity of alum-adsorbed racotumomab in a non-clinical setting, Leghorn chickens were immunized in dose levels ranging from 25 µg to 1600 µg. Racotumomab was administered subcutaneously in the birds’ neck with three identical boosters and serum samples were collected before, during and after the immunization schedule. A strong antibody response was obtained across the evaluated dose range, confirming the immunogenicity of racotumomab even at dose levels as low as 25 µg. As previously observed when using Freund´s adjuvant, alum-adsorbed racotumomab induced an idiotype-specific response in all the immunized birds and ganglioside-specific antibodies in 60-100% of the animals. In contrast to the rapid induction anti-idiotype response, detection of ganglioside-specific antibodies in responsive animals may require repeated boosting. Kinetics of anti-NeuGcGM3 antibody titers showed a slight decline two weeks after each booster, arguing in favor of repeated immunizations in order to maintain antibody titer.Interestingly, the intensity of the anti-NeuGcGM3 response paralleled that of anti-mucin antibodies and anti-tumor antibodies, suggesting that the in vitro detection of anti-ganglioside antibodies might be a surrogate for an in vivo activity of racotumomab. Taken together, these results suggest that Leghorn chicken immunization might become the means to test the biological activity of racotumomab intended for clinical use.

  4. Autoimmune-induced preferential depletion of myelin-associated glycoprotein (MAG is genetically regulated in relapsing EAE (B6 × SJL F1 mice

    Directory of Open Access Journals (Sweden)

    Dai Rujuan


    Full Text Available Abstract Background Experimental autoimmune encephalomyelitis (EAE is commonly used to investigate mechanisms of autoimmune-mediated damage to oligodendrocytes, myelin, and axons in multiple sclerosis (MS. Four distinct autoimmune mechanisms with subsequently distinct patterns of demyelination have been recognized in acute MS lesions. EAE correlates for those distinct patterns of MS lesions are unknown. An excessive loss of myelin-associated glycoprotein (MAG, as a result of distal oligodendrogliopathy, is found exclusively in the subtype III lesion. We sought to answer if types of demyelination in acute lesions during onset and relapse of EAE can replicate the specific patterns observed in MS acute lesions. Methods In parental H-2b (C57BL/6, B6 and hybrid H-2b/s [(B6 × SJL F1] EAE mice, we examined spinal cord levels of MOG, MAG, and myelin basic protein (MBP, and compared to levels of axonal neurofilament (NF160 to assess axonal function, and levels of PARPp85 as an indicator of irreversible apoptosis. Results During disease onset, levels of MOG significantly dropped in both strains, although more profoundly in H-2b/s mice. Levels of MOG recovered in relapsing mice of both strains. Regulation of MAG was dissimilar to MOG. Modest loss of MAG was found at disease onset in both strains of mice. Unexpectedly, in relapsing H-2b/s mice, a major depletion of MAG and NF160, accompanied with sharp elevation of PARPp85 levels, was measured. PARPp85 immunoreactivity was observed in cytoplasm and nuclei of some MBP containing cells. Conclusion Taken together, our results show genetically controlled distinct patterns of MOG and MAG depletion, in MOG35–55 induced EAE in H-2b and H-2b/s mice. The data also suggest distinctive immune regulation of acute lesions that develop in relapsing compared to disease onset. A profound depletion of MAG, concomitant with marked depletion of axonal NF160, and sharp elevation of PARPp85 levels, occurred exclusively in

  5. Adjuvants and immunization strategies to induce influenza virus hemagglutinin stalk antibodies.

    Directory of Open Access Journals (Sweden)

    Peter H Goff

    Full Text Available The global population remains vulnerable in the face of the next pandemic influenza virus outbreak, and reformulated vaccinations are administered annually to manage seasonal epidemics. Therefore, development of a new generation of vaccines is needed to generate broad and persistent immunity to influenza viruses. Here, we describe three adjuvants that enhance the induction of stalk-directed antibodies against heterologous and heterosubtypic influenza viruses when administered with chimeric HA proteins. Addavax, an MF59-like nanoemulsion, poly(I:C, and an RNA hairpin derived from Sendai virus (SeV Cantell were efficacious intramuscularly. The SeV RNA and poly(I:C also proved to be effective respiratory mucosal adjuvants. Although the quantity and quality of antibodies induced by the adjuvants varied, immunized mice demonstrated comparable levels of protection against challenge with influenza A viruses on the basis of HA stalk reactivity. Finally, we present that intranasally, but not intramuscularly, administered chimeric HA proteins induce mucosal IgA antibodies directed at the HA stalk.

  6. Xyloglucan antibodies inhibit auxin-induced elongation and cell wall loosening of azuki bean epicotyls but not of oat coleoptiles. (United States)

    Hoson, T; Masuda, Y; Sone, Y; Misaki, A


    Polyclonal antibodies were raised in rabbits against isoprimeverose (Xyl(1)Glc(1)), xyloglucan heptasaccharides (Xyl(3)Glc(4)), and octasaccharides (Gal(1)Xyl(3)Glc(4)). Antibodies specific for hepta- and octasaccharides suppressed auxin-induced elongation of epicotyl segments of azuki bean (Vigna angularis Ohwi and Ohashi cv Takara). These antibodies also inhibited auxin-induced cell wall loosening (decrease in the minimum stress-relaxation time and the relaxation rate of the cell walls) of azuki segments. However, none of the antibodies influenced auxin-induced elongation or cell wall loosening of coleoptile segments of oat (Avena sativa L. cv Victory). Auxin caused a decrease in molecular mass of xyloglucans in the cell walls of azuki epicotyls and oat coleoptiles. The antibodies inhibited such a change in molecular mass of xyloglucans in both species. Preimmune serum exhibited little or no inhibitory effect on auxin-induced elongation, cell wall loosening, or breakdown of xyloglucans. The results support the view that the breakdown of xyloglucans is associated with the cell wall loosening responsible for auxin-induced elongation in dicotyledons. The view does not appear to be applicable to poaceae, because the inhibition of xyloglucan breakdown by the antibodies did not influence auxin-induced elongation or cell wall loosening of oat coleoptiles.

  7. Rehabilitation or the death penalty: autoimmune B cells in the dock. (United States)

    Dahal, Lekh N; Cragg, Mark S


    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.

  8. Serum BAFF and APRIL levels in patients with autoimmune hemolytic anemia and their clinical significance. (United States)

    Xu, Zi-Zhen; Zhao, Bing-Bing; Xiong, Hong; Wei, Bei-Wen; Wang, Ye-Fei


    B cell-activating factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) play crucial roles in B cell development, survival, and antibody production. Autoimmune hemolytic anemia (AIHA) is an acquired autoimmune disease that occurs when antibodies target autologous red blood cells. Here, we analyzed the serum levels of BAFF and APRIL and their respective clinical associations in patients with AIHA. Serum BAFF and APRIL levels in patients with AIHA were significantly higher (P 480 IU/mL). Glucocorticoid treatment dramatically reduced serum levels of BAFF and APRIL. Thus, serum BAFF and APRIL levels may reflect the clinical activity of this disease. Our results indicate that analysis of serum concentrations of BAFF and APRIL potentially represents a useful tool for the assessment of AIHA disease activity and progression.

  9. 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;


    extensively studied in immune activation, roles for Arg are incompletely characterized. To investigate the role for Arg in experimental autoimmune encephalomyelitis, we studied disease development in Arg-/- mice. Methods: Arg-/- and Arg+/+ mice were generated from breeding of Arg+/- mice on the C57BL/6......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 been...... background. Mice were immunized with the myelin oligodendrocyte glycoprotein (MOG)35-55 peptide and disease development recorded. Lymphocyte phenotypes of wild type Arg+/+ and Arg-/- mice were studied by in vitro stimulation assays and flow cytometry. Results: The breeding of Arg+/+ and Arg-/- mice showed...

  10. Invasive African Salmonella Typhimurium induces bactericidal antibodies against O-antigens. (United States)

    Rondini, Simona; Lanzilao, Luisa; Necchi, Francesca; O'Shaughnessy, Colette M; Micoli, Francesca; Saul, Allan; MacLennan, Calman A


    Nontyphoidal Salmonella are a major and emerging cause of fatal invasive disease in Africa, and are genetically distinct from those found elsewhere in the world. Understanding the targets of protective immunity to these African Salmonellae is key to vaccine development. We immunized mice and rabbits with heat-inactivated wild-type African invasive Salmonella Typhimurium D23580 and rough mutants lacking O-antigen. Wild-type Salmonella, unlike rough bacteria, induced a large bactericidal antibody response mainly against O-antigen. Bactericidal ability of anti-O-antigen antibodies was confirmed following purification by affinity chromatography. The current findings support the development of an O-antigen conjugate vaccine against invasive nontyphoidal Salmonellae for Africa.

  11. A noncognate interaction with anti-receptor antibody-activated helper T cells induces small resting murine B cells to proliferate and to secrete antibody

    DEFF Research Database (Denmark)

    Owens, T


    on resting B cells (even in the presence of intact F23.1 antibody), but could induce antibody secretion by anti-Ig-preactivated B cells. Both F23.1+ clones (E9.D4 and 4.35F2) and one F23.1- clone (D2.2) could synergize with supernatants from activated E9.D4 T cells to induce B cell activation. F(ab')2......Culture of small resting allogeneic B cells (of an irrelevant haplotype) with two clones of T helper (Th) cells that were activated by the F23.1 anti-T cell receptor antibody led to the activation of B cells to proliferate and to secrete antibody. Th cell supernatants by themselves had no effect...... fragments of F23.1 induced E9.D4 to activate B cells as efficiently as intact F23.1 and B cell populations that had been incubated with F23.1 were not activated when cultured with E9.D4, although T cells recognized cell-presented F23.1 and were weakly activated. Reduction of the density of F23.1 adsorbed...

  12. Hydralazine-induced constrictive pericarditis

    NARCIS (Netherlands)

    Franssen, CFC; ElGamal, MIH; Gans, ROB; Hoorntje, SJ


    A 59-year-old man was diagnosed as having constrictive pericarditis 17 months after a typical hydralazine-induced autoimmune syndrome, This late complication of hydralazine has been reported only once. Ten years later the patient was found to have anti-neutrophil cytoplasmic antibodies directed agai

  13. Interferon-Beta-1b Induced Autoimmune Hemolytic Anemia in a Patient with MS: A Case Report


    Saeedi, M; Forughipour, M; Sasannezhad, P; Shoeibi, A


    A 26-year-old lady with the diagnosis of multiple sclerosis who had received interferon beta1-b for eleven months was visited in MS clinic of our hospital because of icter and fatigue. Laboratory tests showed anemia, indirect hyperbillirubinemia, increased LDH, positive direct and indirect coomb’s tests, and increased reticulocyte count and percentage. Other causes of autoimmune hemolytic anemia (AHA) and pre-existing AHA in the patient were ruled out. After INF discontinuation, symptoms disa...

  14. Autoimmune thyroid disease and chronic urticaria. (United States)

    Monge, Cecilia; Demarco, Paul; Burman, Kenneth D; Wartofsky, Leonard


    We report six cases of autoimmune thyroid disease associated with chronic urticaria and briefly review the literature, including the histopathological nature of such lesions, and their aetiology and pathogenesis. In view of the prevalence of thyroid disease in patients with chronic urticaria, screening measurements of thyrotropin and anti-thyroperoxidase antibodies are recommended, although negative antibodies do not exclude a relationship between urticaria and thyroid autoimmunity. After failure of conventional therapy for urticaria, patients who are apparently clinically euthyroid may be considered for a trial with levothyroxine. Improvement of urticaria was seen with levothyroxine treatment in three of four patients with only marginal abnormalities in thyroid function.

  15. Autoimmune Progesterone Anaphylaxis

    Directory of Open Access Journals (Sweden)

    Mohammad Hassan Bemanian


    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.

  16. Improvement of Anti-TNF-α Antibody-Induced Palmoplantar Pustular Psoriasis Using a 308-nm Excimer Light

    Directory of Open Access Journals (Sweden)

    Natsuko Iga


    Full Text Available Anti-tumor necrosis factor (TNF-α antibody is utilized in the treatment of a variety of chronic inflammatory conditions, including psoriasis. However, it can induce paradoxical development and/or exacerbation of psoriasis in the course of anti-TNF-α antibody treatment, which is sometimes refractory to conventional treatments. Herein, we report a case of refractory palmoplantar pustular psoriasis induced by anti-TNF-α antibody treatment, which was improved by treatment with a 308-nm excimer light. The 308-nm excimer light has less long-term risks than narrow-band UVB. The 308-nm excimer light may be a good therapeutic option for refractory psoriatic skin lesions induced by anti-TNF-α antibody therapy because of localized side effects without systemic problems, short length of treatment and low cumulative dosages of UV light.

  17. Inhibition of experimental autoimmune orchitis by fossil diatoms (United States)

    Bustuoabad, Oscar D.; Meiss, Roberto P.; Molinolo, Alfredo R.; Mayer, Alejandro M. S.


    Experimental autoimmune orchitis (EAO) induced in Swiss mice could be reduced by means of the utilization of micronized frustules of fossil diatoms (DS) containing 54% of SiO2. Experimental mice were sensitized with testicular Antigen (Ag) in Complete Freund’s Adjuvant (CFA) inoculated twice, on day 0 and day 21. 100 μg of DS suspension was inoculated into sensitized mice 10 times, once every 4 days, subcutaneously, starting on day 7 after the first Ag inoculation. Mice receiving the DS treatment showed a diminution of the delayed hypersensitivity reaction, lower antibody titer and decreased incidence of testicular injury as well as reduced grade and extension of the lesions. Possible explanation of these results would suggest alteration of monocyte and/or macrophage normal behaviour as well as alteration of antibody synthesis by different mechanisms.

  18. Historical reflections on autoimmune hepatitis

    Institute of Scientific and Technical Information of China (English)

    Ian R Mackay


    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.

  19. Discontinuation of Smoking Increases the Risk for Developing Thyroid Peroxidase Antibodies and/or Thyroglobulin Antibodies: A Prospective Study

    NARCIS (Netherlands)

    G. Effraimidis; J.G.P. Tijssen; W.M. Wiersinga


    Context: Autoimmune thyroid disease develops in genetic susceptible subjects, provoked by environmental factors. Little is known of the environment in the early stages of autoimmunity. Objective: We evaluated environmental factors contributing to de novo occurrence of thyroid antibodies. Design: We

  20. 8例自身免疫性脑炎的病例分析并文献复习%Autoimmune encephalitis associated with anti-neuronal antibodies:case analysis and literature review

    Institute of Scientific and Technical Information of China (English)

    赵伟丽; 崔其福; 任海涛; 关鸿志; 林福虹; 尹国明; 郑纪平; 李国丽; 王迎春; 乔小东; 芦军; 王洪权


    Objective To explore the characteristics of clinical presentations ,magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) and treatment outcome of autoimmune encephalitis (LE).Methods The clinical data of 8 pa-tients with AE were retrospectively analyzed .Results Among these patients ,4 of them were proved to have anti-N-methyl-D-aspartate receptor ( NMDAR) encephalitis ,while 3 of them got diagnosis of anti-leucine-rich glioma-inactivated protein 1 antibody(LGI1) encephalitis,and the other 1 had anti-γ-aminobutyric acid B receptor (GABABR) antibody encephalitis. All the patients presented cognitive and memory dysfunction and psychological symptoms .About 62%of the patients had a seizure,about 37%of the patients had involuntary movement and autonomic nerve dysfunction .About 50%of the patients showed abnormal EEG .About 50%patients had abnormal MRI signal .Lung mass was detected in 1 patient.Conclusion Testing for autoimmune disease related antibodies in blood and cerebrospinal fluid is necessary for patients with cognitive impairment ,mental and behavior disorder and new onset epilepsy .AE should be considered in order to avoid misdiagnosis .%目的:探讨自身免疫性脑炎的临床表现、磁共振( MRI)图像、脑脊液特点及治疗转归。方法回顾性分析我院8例(自2012年1月-2016年1月)自身免疫性脑炎患者的临床资料。结果8例患者平均发病年龄为44岁,其中有4例抗NMDA受体脑炎,3例LGI1蛋白抗体阳性边缘系统脑炎,1例抗GABABR脑炎,所有患者(100%)均有认知功能损害和精神症状;5例(62%)出现癫痫发作;3例(37%)出现不自主运动和自主神经功能障碍。4例(50%)患者脑电图存在异常;4例(50%)患者有磁共振检查异常信号;1例发现肺癌。结论以认知功能损害、精神行为异常、癫痫发作为主要表现的患者,要警惕自身免疫性脑炎的可能,以免误漏诊。

  1. Tissue factor in antiphospholipid antibody-induced pregnancy loss:a pro-inflammatory molecule


    Girardi, G.; MACKMAN, N.


    Fetal loss in patients with antiphospholipid antibodies (aPL) has been ascribed to thrombosis of placental vessels. However, we have shown that inflammation, specifically complement activation with generation of the anaphylotoxin C5a, is an essential mediator of fetal injury. We have analysed the role of tissue factor (TF) in a mouse model of aPL-induced pregnancy loss. TF is the major cellular activator of the coagulation cascade but also has cell signaling activity. Mice that received aPL-I...

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

    NARCIS (Netherlands)

    Roozendaal, C.; Kallenberg, Cees


    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

  3. 抗Ro-52抗体在自身免疫性肝病中的检测%Antibody to Ro-52 in patients with autoimmune liver disease

    Institute of Scientific and Technical Information of China (English)

    赵丹彤; 闫惠平; 檀玉芬; 刘妍; 赵艳; 冯霞; 向代军


    Objective To investigate the significance of antibody to Ro-52 in patients with autoim-mune liver disease(AILD). Methods One hundred and fifteen patients with abnormal liver functions, who had anti-Ro-52 detection by immunological blotting, were reviewed retrospectively. According to types of AILD, the clinical features were compared between patients with and without anti-Ro-52, respectively, κ test of concordance was used to provide a chance-corrected valve for immune-serological results. Results The rates of anti-Ro-52 in autoimmune hepatitis( AIH), primary sclerosing cholangitis(PBC) and AIH/PBC o-verlap syndrome groups were 32.43%, 24.56% and 33.33%, respectively, there were no significant differ-enees among three groups ( x2 = 0. 949, P >0. 05). The rate of anti-soluble hver antigen/liver-pancreas ( an-ti-SLA/LP) in AIH patients with anti-Ro-52 (58.33%) was higher than AIH patients without anti-Ro-52 ( 16.00% ,P 0.40, P 0.05).抗可溶性肝抗原/肝胰抗原抗体(anti-soluble liver antigen/liver-pancreas,anti-SLA/LP)在抗Ro-52阳性AIH组频率(58.33%)高于阴性组(16.00%)(x2=6.955,P<0.05),抗SLA/LP抗体在抗R0-52阳性AIH/PBC重叠综合征组频率(85.71%)高于阴性组(28.57%)(x2=6.109,P<0.05).抗Ro-52抗体和抗SLA/LP抗体结果有一致性(κ=0.466,P<0.05).AIH/PBC重叠综合征组抗Ro-52阳性患者IgG水平高于阴性患者(t=2.508,P<0.05).结论 抗Ro-52抗体在AIH、PBC和MH/PBC重叠综合征中的分布没有差别;抗Ro-52抗体与抗SLA/LP抗体检测结果有一致性;抗Ro-52抗体阳性MH/PBC重叠综合征患者IgG水平高于抗体阴性者.

  4. 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


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


    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 negati...

  5. Estrogen induces multiple regulatory B cell subtypes and promotes M2 microglia and neuroprotection during experimental autoimmune encephalomyelitis. (United States)

    Benedek, Gil; Zhang, Jun; Bodhankar, Sheetal; Nguyen, Ha; Kent, Gail; Jordan, Kelley; Manning, Dustin; Vandenbark, Arthur A; Offner, Halina


    Sex hormones promote immunoregulatory effects on multiple sclerosis. The current study evaluated estrogen effects on regulatory B cells and resident CNS microglia during experimental autoimmune encephalomyelitis (EAE). Herein, we demonstrate an estrogen-dependent induction of multiple regulatory B cell markers indicative of IL-10 dependent as well as IFN-γ dependent pathways. Moreover, although estrogen pretreatment of EAE mice inhibited the infiltration of pro-inflammatory cells into the CNS, it enhanced the frequency of regulatory B cells and M2 microglia. Our study suggests that estrogen has a broad effect on the development of regulatory B cells during EAE, which in turn could promote neuroprotection.

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

    Nechansky, Andreas


    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.

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

    Institute of Scientific and Technical Information of China (English)


    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.

  8. Autoimmune NMDA receptor encephalitis. (United States)

    Lazar-Molnar, Eszter; Tebo, Anne E


    Anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis is a treatable autoimmune disease of the central nervous system (CNS) with prominent neurologic and psychiatric features at disease onset. The disease is associated with the production of autoantibodies to NMDAR, a protein involved in memory function and synaptic plasticity. Affected patients develop a multistage progressive illness with symptoms ranging from memory deficits, seizures and psychosis, to potentially lethal catatonia, and autonomic and breathing instability. The outcome can be much improved with accurate diagnosis and early treatment using adequate immunosuppressive therapy. However, since the neurological and psychiatric symptoms as well as the clinical examination results can be non-specific, the disease is probably under-recognized. Reliable and accurate clinical testing for the identification of NMDAR autoantibodies is crucial for diagnosis, timely treatment selection, and monitoring. Recently, a cell-based indirect immunofluorescent antibody test for the detection of IgG antibodies to NMDAR has become available for diagnostic use. This review highlights the progress and challenges of laboratory testing in the evaluation and management anti-NMDAR encephalitis, and perspectives for the future.

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

    Directory of Open Access Journals (Sweden)

    Herrera-Esparza R


    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.

  10. 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


    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

  11. Antibodies to human myelin proteins and gangliosides in patients with acute neuroparalytic accidents induced by brain-derived rabies vaccine. (United States)

    Laouini, D; Kennou, M F; Khoufi, S; Dellagi, K


    Antibody responses to myelin antigens were analysed in 15 patients who developed acute neuroparalytic accidents (ANPA) during post-exposure rabies vaccination using a rabies vaccine prepared on brain tissues and in 30 individuals who were uneventfully vaccinated. High titers (> or = 100) of IgG and IgM antibodies to GM1 or GD1a gangliosides were detected by enzyme linked immunosorbent-assay (ELISA) in plasmas from ANPA patients but not in controls. These data suggest that antibodies to GM1 and GD1a gangliosides may play a pathogenic role in the demyelinating and/or inflammatory processes characteristic of rabies vaccine-induced acute neurologic complications.

  12. An antibody of TNF-alpha did not prevent thioacetamide-induced hepatotoxicity in rats. (United States)

    Demirel, Ulvi; Harputluoglu, Murat M M; Seckin, Yuksel; Ciralik, Harun; Temel, Ismail; Ozyalin, Fatma; Otlu, Baris; Yilmaz, Bilgic; Dincturk, Mehmet Sarp; Aladag, Hulya


    Tumor necrosis factor (TNF)-α antibodies have been shown to reduce liver damage in different models. We investigated the effects of infliximab (a TNF-α antibody) on liver damage in thioacetamide (TAA)-induced hepatotoxicity in rats. Group 1 (n = 8) was the control group. In group 2 (n = 8), the TAA group, the rats received 300 mg/kg intraperitoneal (ip) TAA daily for 2 days. In group 3 (n = 8), the TAA + Infliximab (INF) group, infliximab (5 mg/kg ip daily) was administered 48 hours before the first dose of TAA daily for 2 days and was maintained for 4 consecutive days. In group 4 (n = 8), the INF group, the rats received only ip infliximab (5 mg/kg) daily. Livers were excised for histopathological and biochemical tests (thiobarbituric-acid-reactive substances [TBARS], and myeloperoxidase [MPO]). Serum ammonia, aspartate transaminase (AST), alanine transaminase (ALT), TNF-α, liver TBARS and MPO levels, and liver necrosis and inflammation scores in the TAA group were significantly higher than in the control and INF groups (all p induced hepatotoxicity, and infliximab does not improve oxidative liver damage.

  13. Attenuation of Nitrogen Mustard-Induced Pulmonary Injury and Fibrosis by Anti-Tumor Necrosis Factor-α Antibody. (United States)

    Malaviya, Rama; Sunil, Vasanthi R; Venosa, Alessandro; Verissimo, Vivianne L; Cervelli, Jessica A; Vayas, Kinal N; Hall, LeRoy; Laskin, Jeffrey D; Laskin, Debra L


    Nitrogen mustard (NM) is a bifunctional alkylating agent that causes acute injury to the lung that progresses to fibrosis. This is accompanied by a prominent infiltration of macrophages into the lung and upregulation of proinflammatory/profibrotic cytokines including tumor necrosis factor (TNF)α. In these studies, we analyzed the ability of anti-TNFα antibody to mitigate NM-induced lung injury, inflammation, and fibrosis. Treatment of rats with anti-TNFα antibody (15 mg/kg, iv, every 9 days) beginning 30 min after intratracheal administration of NM (0.125 mg/kg) reduced progressive histopathologic alterations in the lung including perivascular and peribronchial edema, macrophage/monocyte infiltration, interstitial thickening, bronchiolization of alveolar walls, fibrin deposition, emphysema, and fibrosis. NM-induced damage to the alveolar-epithelial barrier, measured by bronchoalveolar lavage (BAL) protein and cell content, was also reduced by anti-TNFα antibody, along with expression of the oxidative stress marker, heme oxygenase-1. Whereas the accumulation of proinflammatory/cytotoxic M1 macrophages in the lung in response to NM was suppressed by anti-TNFα antibody, anti-inflammatory/profibrotic M2 macrophages were increased or unchanged. Treatment of rats with anti-TNFα antibody also reduced NM-induced increases in expression of the profibrotic mediator, transforming growth factor-β. This was associated with a reduction in NM-induced collagen deposition in the lung. These data suggest that inhibiting TNFα may represent an efficacious approach to mitigating lung injury induced by mustards.

  14. B Cell Autonomous TLR Signaling and Autoimmunity (United States)

    Meyer-Bahlburg, Almut; Rawlings, David J


    B cells play a central role in the pathogenesis of multiple autoimmune diseases and the recognition of importance of B cells in these disorders has grown dramatically in association with the remarkable success of B-cell depletion as a treatment for autoimmunity. The precise mechanisms that promote alterations in B cell tolerance remain incompletely defined. There is increasing evidence, however, that TLRs play a major role in these events. Stimulation of B cells via the TLR pathway not only leads to an increase in antibody production but also promotes additional changes including cytokine production and upregulation of activation markers increasing the effectiveness of B cells as APCs. Understanding the role of TLRs in systemic autoimmunity will not only provide insight into the disease pathogenesis but may also lead to the development of novel therapies. This article gives an overview of TLR signaling in B cells and the possible involvement of such signals in autoimmune diseases. PMID:18295736

  15. Autoimmune Cytopenias in Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Giovanni D'Arena


    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.

  16. Prolonged acute hepatitis A mimicking autoimmune hepatitis

    Institute of Scientific and Technical Information of China (English)

    Rintaro Mikata; Osamu Yokosuka; Fumio Imazeki; Kenichi Fukai; Tatsuo Kanda; Hiromitsu Saisho


    AIM: We report a case with a prolonged course of hepatitisA, with alanine aminotransferase (ALT) higher than 500 IU/Lfor more than 2 mo.METHODS: A middle-aged woman had an elevated IgG level of more than 2 000 mg/dL, positive arti-nudear antibodies (ANA) and anti-smooth muscle antibodies (ASMA), but no evidence of persistent hepatitis A virus (HAV) infection. Liver biopsy findings were compatible with prolonged acute hepatitis, although acute onset of autoimmune hepatitis could not be ruled out.RESULTS: It was assumed that she developed a course of hepatitis similar to autoimmune hepatitis triggered by HAV infection. Ursodeoxycholic acid (UDCA) treatment was initiated and a favorable outcome was obtained. CONCLUSION: We describe a case of a middle-aged woman who showed a prolonged course of acute hepatitis A mimicking autoimmune hepatitis. Treatment with UDCAproved to be effective.

  17. How pregnancy can affect autoimmune diseases progression? (United States)

    Piccinni, Marie-Pierre; Lombardelli, Letizia; Logiodice, Federica; Kullolli, Ornela; Parronchi, Paola; Romagnani, Sergio


    Autoimmune disorders are characterized by tissue damage, caused by self-reactivity of different effectors mechanisms of the immune system, namely antibodies and T cells. Their occurrence may be associated with genetic and/or environmental predisposition and to some extent, have implications for fertility and obstetrics. The relationship between autoimmunity and reproduction is bidirectional. This review only addresses the impact of pregnancy on autoimmune diseases and not the influence of autoimmunity on pregnancy development. Th17/Th1-type cells are aggressive and pathogenic in many autoimmune disorders and inflammatory diseases. The immunology of pregnancy underlies the role of Th2-type cytokines to maintain the tolerance of the mother towards the fetal semi-allograft. Non-specific factors, including hormonal changes, favor a switch to Th2-type cytokine profile. In pregnancy Th2, Th17/Th2 and Treg cells accumulate in the decidua but may also be present in the mother's circulation and can regulate autoimmune responses influencing the progression of autoimmune diseases.

  18. Comparison of the outer and inner epidermis : inhibition of auxin-induced elongation of maize coleoptiles by glucan antibodies. (United States)

    Hoson, T; Masuda, Y; Nevins, D J


    Polyclonal antibodies, raised against beta-d-glucans prepared from oat (Avena sativa L.) caryopses, cross-reacted specifically with (1-->3),(1-->4)-beta-d-glucans when challenged in a dot blot analysis of related polymers bound to a cellulose thin layer chromatography plate. The antibodies suppressed indoleacetic acid (IAA)-induced elongation of segments from maize (Zea mays L.) coleoptiles when the outer surface was abraded. However, IAA-induced elongation of nonabraded segments or segments with abrasion restricted to the interior of the cylinder was not influenced by the antibodies. Fab fragments prepared from the antibodies gave similar results. The capacity for IAA to overcome outward curvature of split coleoptile segments was partially reversed by treatment of the segments with the antibodies. Fluorescence microscopy revealed that antibody penetration was largely restricted to the epidermal cell wall region. These results support the view that the degradation of (1-->3),(1-->4)-beta-d-glucans in the outer epidermal cell wall serves an essential role in auxin-induced elongation of Poaceae coleoptiles.

  19. 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


    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

  20. Postural Orthostatic Tachycardia With Chronic Fatigue After HPV Vaccination as Part of the "Autoimmune/Auto-inflammatory Syndrome Induced by Adjuvants": Case Report and Literature Review. (United States)

    Tomljenovic, Lucija; Colafrancesco, Serena; Perricone, Carlo; Shoenfeld, Yehuda


    We report the case of a 14-year-old girl who developed postural orthostatic tachycardia syndrome (POTS) with chronic fatigue 2 months following Gardasil vaccination. The patient suffered from persistent headaches, dizziness, recurrent syncope, poor motor coordination, weakness, fatigue, myalgias, numbness, tachycardia, dyspnea, visual disturbances, phonophobia, cognitive impairment, insomnia, gastrointestinal disturbances, and a weight loss of 20 pounds. The psychiatric evaluation ruled out the possibility that her symptoms were psychogenic or related to anxiety disorders. Furthermore, the patient tested positive for ANA (1:1280), lupus anticoagulant, and antiphospholipid. On clinical examination she presented livedo reticularis and was diagnosed with Raynaud's syndrome. This case fulfills the criteria for the autoimmune/auto-inflammatory syndrome induced by adjuvants (ASIA). Because human papillomavirus vaccination is universally recommended to teenagers and because POTS frequently results in long-term disabilities (as was the case in our patient), a thorough follow-up of patients who present with relevant complaints after vaccination is strongly recommended.

  1. The autoimmune tautology. (United States)

    Anaya, Juan-Manuel


    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 that the pathologic mechanisms may be similar among autoimmune diseases. Lastly, genetic evidence shows that autoimmune phenotypes might represent pleiotropic outcomes of the interaction of non-specific disease genes.



    Ganesan; Josephine Latha


    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...

  3. Antibodies against potassium channel interacting protein 2 induce necrosis in isolated rat cardiomyocytes. (United States)

    Choudhury, Sangita; Schnell, Michael; Bühler, Thomas; Reinke, Yvonne; Lüdemann, Jan; Nießner, Felix; Brinkmeier, Heinrich; Herda, Lars R; Staudt, Alexander; Kroemer, Heyo K; Völker, Uwe; Felix, Stephan B; Landsberger, Martin


    Auto-antibodies against cardiac proteins have been described in patients with dilated cardiomyopathy. Antibodies against the C-terminal part of KChIP2 (anti-KChIP2 [C-12]) enhance cell death of rat cardiomyocytes. The underlying mechanisms are not fully understood. Therefore, we wanted to explore the mechanisms responsible for anti-KChIP2-mediated cell death. Rat cardiomyocytes were treated with anti-KChIP2 (C-12). KChIP2 RNA and protein expressions, nuclear NF-κB, mitochondrial membrane potential Δψm, caspase-3 and -9 activities, necrotic and apoptotic cells, total Ca(2+) and K(+) concentrations, and the effects on L-type Ca(2+) channels were quantified. Anti-KChIP2 (C-12) induced nuclear translocation of NF-κB. Anti-KChIP2 (C-12)-treatment for 2 h significantly reduced KChIP2 mRNA and protein expression. Anti-KChIP2 (C-12) induced nuclear translocation of NF-κB after 1 h. After 6 h, Δψm and caspase-3 and -9 activities were not significantly changed. After 24 h, anti-KChIP2 (C-12)-treated cells were 75 ± 3% necrotic, 2 ± 1% apoptotic, and 13 ± 2% viable. Eighty-six ± 1% of experimental buffer-treated cells were viable. Anti-KChIP2 (C-12) induced significant increases in total Ca(2+) (plus 11 ± 2%) and K(+) (plus 18 ± 2%) concentrations after 5 min. Anti-KChIP2 (C-12) resulted in an increased Ca(2+) influx through L-type Ca(2+) channels. In conclusion, our results suggest that anti-KChIP2 (C-12) enhances cell death of rat cardiomyocytes probably due to necrosis.

  4. 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 (United States)

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


    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 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 low titer ANAs (1:160 or less) may not need a further test for anti-ENA unless an ANA-associated disease is highly suspected. However a test for anti-dsDNA should be considered in positive ANA samples at any titer including low titers.

  5. [Neutralizing Monoclonal and Chimeric Antibodies to Human IFN-γ]. (United States)

    Larina, M V; Aliev, T K; Solopova, O N; Pozdnyakova, L P; Korobova, S V; Yakimov, S A; Sveshnikov, P G; Dolgikh, D A; Kirpichnikov, M P


    Autoiminune disorders are chronic diseases characterized by abnormal immune response directed against self-antigens that leads to tissue damage and violation of its normal functioning. Such diseases often result in disability or even death of patients. Nowadays a number of monoclonal antibodies to pro-inflammatory cytokines and their receptors are successfully used for the targeted treatment of autoimmune diseases. One of the perspective targets in autoimmune disease therapy is interferon gamma, a key cytokine in Th1 cells differentiation, activation of macrophages, and inflammation. In the present work, 5 monoclonal antibodies to human IFN-γ were obtained. For the development of potential therapeutic agent, we have performed neutralizing activity and affinity analysis of the antibodies. Based on the data obtained, the monoclonal antibody F1 was selected. This antibody has a dissociation constant 1.7 x 10(-9) M and IC90 = 8.9 ± 2.0 nM measured upon antibody inhibition of the IFN-γ-induced HLA-DR expression on the surface of U937 cells. We have constructed a bicistronic vector for the production of recombinant chimeric Fab fragment F1 chim in E. coli cells. The recombinant chimeric Fab fragment Fl chim neutralizes IFN-γ activity in vitro and has a dissociation constant 1.8 x 10(-9) M.

  6. The correlation study of autoimmunity antinuclear antibody and aging%抗核抗体与衰老的相关性

    Institute of Scientific and Technical Information of China (English)

    杨蓬勃; 谢志贤


    Objective To investigate the influences of age and sex on the expression of serum antinuclear antibody (ANA) and its titer level.Methods The serum ANA in 993 people aged 60 years and over were detected and titer of positive serum were analyzed. They were divided into different groups according to age and sex. Two hundred healthy cases aged less than 60 years were collected as control group. Results The serum ANA positive rate was increased with age and it was significantly higher in people aged 60 years and over than aged less than 60 years (29. 1% vs. 14.0%, x2=5. 074, P=0. 025). The serum ANA positive rates were 24.1%, 30. 5% and 33.6% in people aged 60-69 group, aged 70-79 group and aged above 80 group. Among people aged 60 years and over, the positive rate was 35.8% in female group, which was higher than in male group (22. 4%) (x2= 21. 179, P=0. 05). The titre levels of the positive samples were increased with age. In control group, the samples with 1 : 100 titre was 57.1% among the positive samples, which was higher than in the elderly group (36. 3%). And in control group, the samples with 1 : 3200 titre was 0 among the positive samples, which was lower than in the elderly people group (7.6%). The ANA preliminary screening in people aged 60 years and over showed that the titre level was less than 1 : 320-1: 1000 in female and less than 1 : 100-1: 320 in male. Its specificity could be up to about 90%. Conclusions The serum ANA positive rate in people aged 60 years and over is affected by age and sex. The positive rate is higher in female than in male and it is increased with age. It suggests that 1 : 320 to 1 : 1000 could be taken as ANA preliminary screening critical value in female and 1 : 100 to 1 : 320 in male.%目的 探讨年龄、性别对血清抗核抗体(ANA)表达的影响.方法 对993例老年人进行血清ANA检测,并依年龄及性别不同分组,同时检测200例中青年健康体检者作对照分析.结果 老年组ANA阳性率为29.1%.

  7. Effects of Early IL-17A Neutralization on Disease Induction in a Primate Model of Experimental Autoimmune Encephalomyelitis


    Kap, Yolanda S.; Jagessar, S. Anwar; Driel, Nikki; Blezer, Erwin; Bauer, Jan; van Meurs, Marjan; Smith, Paul; Laman, Jon D.; Bert A. ‘t Hart


    We report on the effect of antibody-mediated neutralization of interleukin (IL)-17A in a non-human primate experimental autoimmune encephalomyelitis (EAE) model induced with recombinant human myelin oligodendrocyte glycoprotein (rhMOG). We tested a human-anti-human IL-17A-antibody in two doses (3 and 30 mg/kg) against placebo (PBS). The treatment was started 1 day before EAE induction and continued throughout the experiment. Although all monkeys developed clinically evident EAE, the onset of ...

  8. Antibody-induced secondary treatment failure in a patient treated with botulinum toxin type A for glabellar frown lines

    Directory of Open Access Journals (Sweden)

    Stengel G


    Full Text Available Gabriele Stengel, Eva Kristina Bee Hautarztpraxis Stengel and Bee, Münster, Germany Abstract: Botulinum toxin type A (BTX-A preparations are widely used nonsurgical treatments for facial wrinkles. Higher doses of BTX-A are also used for therapeutic purposes in the treatment of conditions involving increased muscle tone, such as cervical dystonia. The phenomenon of antibody-induced treatment failure is well known in the therapeutic setting, but reports are also emerging following cosmetic use of BTX-A. We describe the case of a 41-year-old female nurse who developed secondary treatment failure during 6 years of BTX-A treatment for glabellar lines. After a good response to the first BTX-A injection, the intensity and duration of effect decreased after subsequent treatments. Antibody tests revealed a high titer of neutralizing anti-BTX-A antibodies. This case shows secondary treatment failure due to the production of neutralizing antibodies following administration of BTX-A formulations for cosmetic purposes and demonstrates that immunogenicity of BTX-A preparations is an important consideration, even in the cosmetic setting. Keywords: botulinum toxin type A, neutralizing antibodies, antibody-induced treatment failure

  9. An anti-human ICAM-1 antibody inhibits rhinovirus-induced exacerbations of lung inflammation.

    Directory of Open Access Journals (Sweden)

    Stephanie Traub

    Full Text Available Human rhinoviruses (HRV cause the majority of common colds and acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD. Effective therapies are urgently needed, but no licensed treatments or vaccines currently exist. Of the 100 identified serotypes, ∼90% bind domain 1 of human intercellular adhesion molecule-1 (ICAM-1 as their cellular receptor, making this an attractive target for development of therapies; however, ICAM-1 domain 1 is also required for host defence and regulation of cell trafficking, principally via its major ligand LFA-1. Using a mouse anti-human ICAM-1 antibody (14C11 that specifically binds domain 1 of human ICAM-1, we show that 14C11 administered topically or systemically prevented entry of two major groups of rhinoviruses, HRV16 and HRV14, and reduced cellular inflammation, pro-inflammatory cytokine induction and virus load in vivo. 14C11 also reduced cellular inflammation and Th2 cytokine/chemokine production in a model of major group HRV-induced asthma exacerbation. Interestingly, 14C11 did not prevent cell adhesion via human ICAM-1/LFA-1 interactions in vitro, suggesting the epitope targeted by 14C11 was specific for viral entry. Thus a human ICAM-1 domain-1-specific antibody can prevent major group HRV entry and induction of airway inflammation in vivo.

  10. DNA Vaccine of SARS-Cov S Gene Induces Antibody Response in Mice

    Institute of Scientific and Technical Information of China (English)

    PingZHAO; Jin-ShanKE; Zhao-LinQIN; HaoREN; Lan-JuanZHAO; Jian-GuoYU


    The spike (S) protein, a main surface antigen of SARS-coronavirus (SARS-CoV), is one of the most important antigen candidates for vaccine design. In the present study, three fragments of the truncated S protein were expressed in E.coli, and analyzed with pooled sera of convalescence phase of SARS patients.The full length S gene DNA vaccine was constructed and used to immunize BALB/c mice. The mouse serum IgG antibody against SARS-CoV was measured by ELISA with E.coli expressed truncated S protein or SARS-CoV lysate as diagnostic antigen. The results showed that all the three fragments of S protein expressed by E.coli was able to react with sera of SARS patients and the S gene DNA candidate vaccine could induce the production of specific IgG antibody against SARS-CoV efficiently in mice with seroconversion ratio of 75% after 3 times of immunization. These findings lay some foundations for further understanding the immunology of SARS-CoV and developing SARS vaccines.

  11. DNA Vaccine of SARS-Cov S Gene Induces Antibody Response in Mice

    Institute of Scientific and Technical Information of China (English)

    Ping ZHAO; Jin-Shan KE; Zhao-Lin QIN; Hao REN; Lan-Juan ZHAO; Jian-Guo YU; Jun GAO; Shi-Ying ZHU; Zhong-Tian QI


    The spike (S) protein, a main surface antigen of SARS-coronavirus (SARS-CoV), is one of the most important antigen candidates for vaccine design. In the present study, three fragments of the truncated S protein were expressed in E. Coli, and analyzed with pooled sera of convalescence phase of SARS patients.The full length S gene DNA vaccine was constructed and used to immunize BALB/c mice. The mouse serum IgG antibody against SARS-CoV was measured by ELISA with E. Coli expressed truncated S protein or SARS-CoV lysate as diagnostic antigen. The results showed that all the three fragments of S protein expressed by E. Coli was able to react with sera of SARS patients and the S gene DNA candidate vaccine could induce the production of specific IgG antibody against SARS-CoV efficiently in mice with seroconversion ratio of 75% after 3 times of immunization. These findings lay some foundations for further understanding the immunology of SARS-CoV and developing SARS vaccines.

  12. Induction of Endothelial Cell Apoptosis by Anti-alpha-enolase Antibody

    Institute of Scientific and Technical Information of China (English)

    Hong-bo Yang; Wen-jie Zheng; Xuan Zhang; Fu-lin Tang


    Objective To assess the prevalence of anti-alpha-enolase antibody in systemic autoimmune diseases in Chinese patients and its role in endothelial cell apoptosis.Methods The reactivity of anti-alpha-enolase antibody in a variety of autoimmune disorders in Chinese patients was evaluated by dot blot assay. Endothelial cell apoptosis was investigated by in vitro incubation of endothelial cells with IgG purified from anti-alpha-enolase antibody-positive sera, with or without pre-incubation with recombinant alpha-enolase.Results Anti-alpha-enolase antibody was prevalent in different systemic autoimmune diseases with relatively high reactivity in Chinese patients. In vitro incubation of endothelial cells with IgG containing anti-alpha-enolase antibody induced apoptosis in a time- and dose-dependent manner. Apoptosis was partly inhibited by pre-incubation of the endothelial cells with recombinant alpha-enolase.Conclusions Our data suggest that alpha-enolase is a common auto-antigen recognized by antiendothelial cell antibodies in connective tissue disease. Interaction between alpha-enolase and its autoantibody plays a role in endothelial cell apoptosis. Changes other than cell killing may contribute to the pathogenesis of endothelial damage and microvascular lesions.

  13. Insights into IL-37, the role in autoimmune diseases. (United States)

    Xu, Wang-Dong; Zhao, Yi; Liu, Yi


    Autoimmune diseases are characterized by the impaired function and the destruction of tissues that are caused by an immune response in which aberrant antibodies are generated and attack the body's own cells and tissues. Interleukin (IL) -37, a new member of the IL-1 family, broadly reduces innate inflammation as well as acquired immune responses. Recently, studies have shown that expression of IL-37 was abnormal in autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), ankylosing spondylitis (AS), psoriasis, Graves' disease (GD). In addition, functional analysis indicated that IL-37 is negatively involved in the development and pathogenesis of these autoimmune disorders. The strong association of this cytokine with autoimmune diseases promotes us to systematically review what had been published recently on the crucial nature of IL-37 in relation to autoimmune diseases gaining attention for its regulatory capability in these autoimmune disorders.

  14. Lethal iron deprivation induced by non-neutralizing antibodies targeting transferrin receptor 1 in malignant B cells. (United States)

    Rodríguez, José A; Luria-Pérez, Rosendo; López-Valdés, Héctor E; Casero, David; Daniels, Tracy R; Patel, Shabnum; Avila, David; Leuchter, Richard; So, Sokuntheavy; Ortiz-Sánchez, Elizabeth; Bonavida, Benjamin; Martínez-Maza, Otoniel; Charles, Andrew C; Pellegrini, Matteo; Helguera, Gustavo; Penichet, Manuel L


    A number of antibodies have been developed that induce lethal iron deprivation (LID) by targeting the transferrin receptor 1 (TfR1/CD71) and either neutralizing transferrin (Tf) binding, blocking internalization of the receptor and/or inducing its degradation. We have developed recombinant antibodies targeting human TfR1 (ch128.1 and ch128.1Av), which induce receptor degradation and are cytotoxic to certain malignant B-cells. We now show that internalization of TfR1 bound to these antibodies can lead to its sequestration and degradation, as well as reduced Tf uptake, and the induction of a transcriptional response consistent with iron deprivation, which is mediated in part by downstream targets of p53. Cells resistant to these antibodies do not sequester and degrade TfR1 after internalization of the antibody/receptor complex, and accordingly maintain their ability to internalize Tf. These findings are expected to facilitate the rational design and clinical use of therapeutic agents targeting iron import via TfR1 in hematopoietic malignancies.

  15. 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


    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

  16. [Hydroxychloroquine for autoimmune diseases]. (United States)

    Danza, Álvaro; Graña, Diego; Goñi, Mabel; Vargas, Andrea; Ruiz-Irastorza, Guillermo


    Hydroxychloroquine (HCQ) is by far the most frequently used antimalarial for the management of Systemic Autoimmune Diseases. It has immunomodulatory, hypolipidemic, hypoglycemic and antithrombotic properties and it diminishes the risk of malignancies. The most important mechanisms to explain the immunomodulatory actions are its ability to reduce inflammatory pathways and Toll-like receptors activation. The safety profile is favorable. In spite of its low frequency, retinal toxicity is potentially severe. In systemic lupus erythematous HCQ therapy reduces activity, the accrual of organ damage, risk of infections and thrombosis and improves the cardiometabolic profile. It contributes to induce lupus nephritis remission, spares steroid use and increases survival rates. In rheumatoid arthritis, it improves cardiometabolic risk and has a favorable effect in joint inflammation. In Sjögren's syndrome, an increased lacrimal quality as well as an improvement in objective and subjective inflammatory markers has been demonstrated with HCQ. In Antiphospholipid Syndrome, HCQ is effective in primary and secondary thrombosis prevention. The effectiveness of the drug in other systemic autoimmune diseases is less established. HCQ therapy may improve dermatological manifestations in Dermatomyositis and may have a positive effects in the treatment of Sarcoidosis and Still disease.

  17. Elevated levels of measles antibodies in children with autism. (United States)

    Singh, Vijendra K; Jensen, Ryan L


    Virus-induced autoimmunity may play a causal role in autism. To examine the etiologic link of viruses in this brain disorder, we conducted a serologic study of measles virus, mumps virus, and rubella virus. Viral antibodies were measured by enzyme-linked immunosorbent assay in the serum of autistic children, normal children, and siblings of autistic children. The level of measles antibody, but not mumps or rubella antibodies, was significantly higher in autistic children as compared with normal children (P = 0.003) or siblings of autistic children (P molecular weight. The antibody to this antigen was found in 83% of autistic children but not in normal children or siblings of autistic children. Thus autistic children have a hyperimmune response to measles virus, which in the absence of a wild type of measles infection might be a sign of an abnormal immune reaction to the vaccine strain or virus reactivation.

  18. Antibody-dependent-cellular-cytotoxicity-inducing antibodies significantly affect the post-exposure treatment of Ebola virus infection (United States)

    Liu, Qiang; Fan, Changfa; Li, Qianqian; Zhou, Shuya; Huang, Weijin; Wang, Lan; Sun, Chunyun; Wang, Meng; Wu, Xi; Ma, Jian; Li, Baowen; Xie, Liangzhi; Wang, Youchun


    Passive immunotherapy with monoclonal antibodies (mAbs) is an efficacious treatment for Ebola virus (EBOV) infections in animal models and humans. Understanding what constitutes a protective response is critical for the development of novel therapeutic strategies. We generated an EBOV-glycoprotein-pseudotyped Human immunodeficiency virus to develop sensitive neutralizing and antibody-dependent cellular cytotoxicity (ADCC) assays as well as a bioluminescent-imaging-based mouse infection model that does not require biosafety level 4 containment. The in vivo treatment efficiencies of three novel anti-EBOV mAbs at 12 h post-infection correlated with their in vitro anti-EBOV ADCC activities, without neutralizing activity. When they were treated with these mAbs, natural killer cell (NK)-deficient mice had lower viral clearance than WT mice, indicating that the anti-EBOV mechanism of the ADCC activity of these mAbs is predominantly mediated by NK cells. One potent anti-EBOV mAb (M318) displayed unprecedented neutralizing and ADCC activities (neutralization IC50, 0.018 μg/ml; ADCC EC50, 0.095 μg/ml). These results have important implications for the efficacy of antiviral drugs and vaccines as well as for pathogenicity studies of EBOV. PMID:28358050

  19. Autoimmune Disease

    Institute of Scientific and Technical Information of China (English)


    2007159 Acute kidney injury of systemic sclerosis: scleroderma renal crisis and crescentic glomerulonephritis. LIU Dongyan(刘冬妍), et al. Dept Nephrol, PUMC Hosp, CAMS & PUMC, Beijin 100730. Chin J Nephrol 2007;23(4):209-203. Objective To explore the clinicopathological characteristics of acute kidney injury (AKI) of systemic sclerosis (SSc). Methods A retrospective study was performed on 11 SSc patients with AKI. The clinical data were analyzed and the patients were divided into antineutrophil cytoplasmic antibodies (ANCA) negative group(n=9) and ANCA positive(n=2) group. Results In the ANCA negative group, 2 cases were without malignant hypertension, 1 was acute tubular necrosis(ATN) caused by herbs, 6 were scleroderma renal crisis(SRC), including 4 with renal biopsy, indicating hypertrophic arterial media, edema, thickened intima, onion-skin lesion in interlobular arteries and afferent arterioles, as well as ischemic lesion in glomeruli. In the MPO-ANCA positive group, 1 was crescentic glomerulonephritis. Malignant hypertension was not noticed. All patients were given steroid, 8 of them received CTX in addition. Nine patients received dialysis, and 8 cases progressed to permanent hemodialysis. Six cases with SRC were given high dose ACEI and / or ARB. Six patients resulted in early death. Conclusion Scleroderma renal crisis and ANCA associated vasculitis may cause AKI in SSc patients. Patients with positive ANCA differ from those with negative ANCA in terms of clinical manifestation, pathology and treatment. Survival and prognosis of SSc patient were bad. High dose corticosteroids increases the risk of scleroderma renal crisis, so it is thereby recommended that the dose above 15 rog/day should be avoided if possible.

  20. Peste des petits ruminants virus-like particles induce both complete virus-specific antibodies and virus neutralizing antibodies in mice. (United States)

    Liu, Fuxiao; Wu, Xiaodong; Zou, Yanli; Li, Lin; Wang, Zhiliang


    Peste des petits ruminants virus (PPRV), an etiological agent of peste des petits ruminants (PPR), is classified into the genus Morbillivirus in the family Paramyxoviridae. In a previous study, a recombinant baculovirus has been constructed to co-express the PPRV matrix (M), haemagglutinin (H) and nucleocapsid (N) proteins in insect cells, causing budding of PPR virus-like particles (VLPs) from insect cell membranes by viewing of ultrathin section with a transmission electron microscope. In this follow-up study, these PPR VLPs were purified by sucrose density gradient centrifugation for immunizing mice twice. Three weeks post-primary immunization and 2 weeks post-secondary immunization, all serum samples were obtained and subsequently subjected to indirect ELISA detection on complete virus-specific antibodies. In addition, all serum samples, which were collected 2 weeks post-secondary immunization, were used for virus neutralization test on PPRV neutralizing antibodies. The results showed that the purified PPR VLPs induced both types of antibodies mentioned above in mice, indicating a given potential of VLP-based vaccine candidate against PPR.

  1. Secondary autoimmune cytopenias in chronic lymphocytic leukemia. (United States)

    Rogers, Kerry A; Woyach, Jennifer A


    Secondary autoimmune cytopenias in chronic lymphocytic leukemia are distinct clinical entities that require specific management. These autoimmune disorders have a complex pathogenesis that involves both the leukemic cells and the immune environment in which they exist. The mechanism is not the same in all cases, and to varying degrees involves the chronic lymphocytic leukemia (CLL) cells in antibody production, antigen presentation, and stimulation of T cells and bystander polyclonal B cells. Diagnosis of autoimmune cytopenias can be challenging as it is difficult to differentiate between autoimmunity and bone marrow failure due to disease progression. There is a need to distinguish these causes, as prognosis and treatment are not the same. Evidence regarding treatment of secondary autoimmune cytopenias is limited, but many effective options exist and treatment can be selected with severity of disease and patient factors in mind. With new agents to treat CLL coming into widespread clinical use, it will be important to understand how these will change the natural history and treatment of autoimmune cytopenias.

  2. Induced refolding of a temperature denatured llama heavy-chain antibody fragment by its antigen

    NARCIS (Netherlands)

    Dolk, E.; Vliet, C. van; Perez, J.M.J.; Vriend, G.; Darbon, H.; Ferrat, G.; Cambillau, C.; Frenken, L.G.J.; Verrips, T.


    In a previous study we have shown that llama VHH antibody fragments are able to bind their antigen after a heat shock of 90°C, in contrast to the murine monoclonal antibodies. However, the molecular mechanism by which antibody:antigen interaction occurs under these extreme conditions remains unclear

  3. Combination of two anti-CD5 monoclonal antibodies synergistically induces complement-dependent cytotoxicity of chronic lymphocytic leukaemia cells

    DEFF Research Database (Denmark)

    Klitgaard, Josephine L; Koefoed, Klaus; Geisler, Christian


    secondary effector functions represent an attractive opportunity for CLL treatment. Here, a repertoire of mAbs against human CD5 was generated and tested for ability to induce complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) both as single m...

  4. Diagnosis and classification of autoimmune hemolytic anemia. (United States)

    Bass, Garrett F; Tuscano, Emily T; Tuscano, Joseph M


    Uncompensated autoantibody-mediated red blood cell (RBC) consumption is the hallmark of autoimmune hemolytic anemia (AIHA). Classification of AIHA is pathophysiologically based and divides AIHA into warm, mixed or cold-reactive subtypes. This thermal-based classification is based on the optimal autoantibody-RBC reactivity temperatures. AIHA is further subcategorized into idiopathic and secondary with the later being associated with a number of underlying infectious, neoplastic and autoimmune disorders. In most cases AIHA is confirmed by a positive direct antiglobulin test (DAT). The standard therapeutic approaches to treatment of AIHA include corticosteroids, splenectomy, immunosuppressive agents and monoclonal antibodies.

  5. Diagnostic criteria of autoimmune hepatitis. (United States)

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


    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

  6. Estriol strongly inhibits DNCB-induced contact dermatitis: role of antigen-specific antibodies in pathogenesis. (United States)

    Zhang, Elizabeth Yan; Zhu, Bao-Ting


    The endogenous estrogens are important modulators of the immune system and its functions. However, their effects are rather complex and many aspects have not been studied. In this study, we used the 1-chloro-2,4-dinitrobenzene (DNCB)-induced contact dermatitis as a disease model and investigated the effect of estriol (E3), along with two other estrogens, 17β-estradiol and estrone, on the pathogenesis of contact hypersensitivity. A series of parameters, such as ear swelling, skin inflammation, antigen-specific immunoglobulins, and lymphocyte compositions in peripheral lymphoid organs, were evaluated in mice following development of contact dermatitis. We found that administration of all three estrogens elicited strong inhibition of DNCB-induced dermatitis, while E3 exerted the strongest suppressive effect. Administration of E3 alleviated dermatitis, and this effect was accompanied by decreases in serum DNCB-specific immunoglobulins, such as IgA, IgG1, IgG2a, and IgG2b. Besides, treatment with E3 reduced B cell population, especially IgG-producing cells in the peripheral lymphoid organs following the induction of dermatitis. These observations consistently suggest that the antibody (Ab)-mediated humoral immune reactions play a critical role in the pathogenesis of DNCB-induced contact dermatitis. The results from this study demonstrate, for the first time, that estrogen administration has a strong suppressive effect on the pathogenesis of contact dermatitis. These findings offer important insights concerning the pathogenic role of antigen-specific Abs in contact dermatitis and the treatment of chemical-induced, Ab-mediated skin hypersensitivity reactions in humans.

  7. Analysis of the main components of inner ear antigens inducing autoimmune Meniere's disease in guinea pigs%豚鼠自身免疫性梅尼埃病模型的主要内耳抗原分析

    Institute of Scientific and Technical Information of China (English)

    陆玲; 谭长强; 崔毓桂; 丁贵鹏; 居晓斌; 李玉瑾; 蔡文君


    目的 探寻导致豚鼠自身免疫性梅尼埃病(autoimmune Meniere's disease,AIMD)的主要内耳组织抗原成分.方法 采用同种粗制内耳抗原免疫豚鼠,观察听觉功能、前庭功能及内耳组织形态学方面的变化,判断AIMD模型与非模型动物.采用免疫印迹法(Western blotting)对比分析模型动物与非模型动物血清内针对内耳组织抗原不同成分特异性免疫反应的差异,寻找只针对AIMD模型动物的特异性成分.结果 内耳组织所含抗原成分较多,免疫后酶联免疫吸附试验(ELISA)结果显示,AIMD模型与非AIMD模型动物均不同程度地存在针对内耳组织抗原的血清抗体水平升高.听功能检测,非AIMD模型动物听力损失不明显.Western bohting结果显示,AIMD模型动物出现针对相对分子质量为68 000、58 000、42 000及28 000蛋白质成分的反应条带,而非AIMD模型动物则未显示这些条带的特异性抗原抗体反应.结论 可能只有出现针对导致内耳自身免疫性疾病的主要抗原成分的特异性免疫反应,才会造成明显的内耳免疫病理损伤和功能障碍.相对分子质量为68 000、58 000、42 000及28 000的内耳组织抗原可能是导致豚鼠自身免疫性膜迷路积水的主要抗原成分.%Objective To investigate the main components of inner ear antigens inducing autoimmune Meniere's disease(AIMD) in guinea pigs. Methods The guinea pigs were immunized with isologous crude inner ear antigens (ICIEAg). Then, the hearing function was measured with auditory brainstem response (ABR), the vestibular function was measured with electronystagmography (including spontaneous nystagmus and caloric test), and inner ear histopatholoical changes were observed by inner eareelloidin section with haematoxylin-eosin staining and observed under light microscope. According to these results, the AIMD-model animals from non-AIMD-model ones were distinguished. The special antibodies against ICIEAg in sera were

  8. 混合抗体型自身免疫性溶血性贫血的血型定型和抗体分析%Hybrid antibody autoimmune hemolytic anemia blood grouping and antibody analysis of heat and chloroquine elu-tion

    Institute of Scientific and Technical Information of China (English)

    王洪建; 刘小慧


    Objective To analyze the blood grouping and antibody circumstances in patients with autoimmune he-molytic anemia( AIHA) , and thus to improve the clinical diagnosis and therapy. Methods From January 2009 to April 2013, 23 patients with AIHA were analyzed retrospectively. Patient’s RBC was used for ABO and rhesus typing test after it had eluted with gently heat and chloroquine. The ABO reverse typing test was performed after the autoantibodies in patient’ s plasma had been absorbed with O group blood cell. Polyethylene glycol adsorption method and auto-adsorption method were studied by comparing the total time and numbers of the adsorption. Antibodies were identified with ethylether elute. Results ABO and Rh blood group were typed correctly in 23 cases and 15 cases respectively. Two kinds of serum antibody absorption method after treatment was similar. Six cases were detected to have both allo-antibody and auo-antibody, howev-er, antibodies specificity had not been identified in 2 cases, others were simply autoantibodies, PEG absorption was signifi-cantly shorter than auto-adsorption on the time. Conclusions Gently heat elute combines chloroquine elute is a good choice to perform blood group typing test for AIHA patients with both cold and warm autoantibodies. PEG absorption meth-od is rapid, simple and effective to remove autoantibody and detect underlying alloantibody.%目的:探讨混合抗体型自身免疫性溶血性贫血( AIHA)的血型定型和抗体情况,以期提高临床诊治水平。方法回顾性分析濮阳市人民医院2009年1月至2013年4月收治的23例AIHA患者,均对患者进行分离血清和红细胞,将红细胞进行轻度热放散和氯喹放散试验,采用血型抗原分型的自身吸收实验,取适当血清,加入等量O型红细胞进行抗体吸收、吸收后的血清用于ABO反定型试验,采用PEG法和自身吸收法对自身抗体进行吸收,比较两者在吸收时间、吸收次数和吸收后抗体情况,采

  9. Sclerostin-antibody treatment of glucocorticoid-induced osteoporosis maintained bone mass and strength (United States)

    Jiang, L.; Lay, E. Y.-A.; Zhong, Z.; Ritchie, R. O.; Li, X.; Ke, H.; Lane, N. E.


    Summary This study was to determine if antibody against sclerostin (Scl-Ab) could prevent glucocorticoid (GC)-induced osteoporosis in mice. We found that Scl-Ab prevented GC-induced reduction in bone mass and bone strength and that the anabolic effects of Scl-Ab might be partially achieved through the preservation of osteoblast activity through autophagy. Introduction Glucocorticoids (GCs) inhibit bone formation by altering osteoblast and osteocyte cell activity and lifespan. A monoclonal antibody against sclerostin, Scl-Ab, increased bone mass in both preclinical animal and clinical studies in subjects with low bone mass. The objectives of this study were to determine if treatment with the Scl-Ab could prevent loss of bone mass and strength in a mouse model of GC excess and to elucidate if Scl-Ab modulated bone cell activity through autophagy. Methods We generated reporter mice that globally expressed dsRed fused to LC3, a protein marker for autophagosomes, and evaluated the dose-dependent effects of GCs (0, 0.8, 2.8, and 4 mg/kg/day) and Scl-Ab on autophagic osteoblasts, bone mass, and bone strength. Results GC treatment at 2.8 and 4 mg/kg/day of methylprednisolone significantly lowered trabecular bone volume (Tb-BV/TV) at the lumbar vertebrae and distal femurs, cortical bone mass at the mid-shaft femur (FS), and cortical bone strength compared to placebo (PL). In mice treated with GC and Scl-Ab, Tb-BV/TV increased by 60–125 %, apparent bone strength of the lumbar vertebrae by 30–70 %, FS-BV by 10–18 %, and FS-apparent strength by 13–15 %, as compared to GC vehicle-treated mice. GC treatment at 4 mg/kg/ day reduced the number of autophagic osteoblasts by 70 % on the vertebral trabecular bone surface compared to the placebo group (PL, GC 0 mg), and GC + Scl-Ab treatment. Conclusions Treatment with Scl-Ab prevented GC-induced reduction in both trabecular and cortical bone mass and strength and appeared to maintain osteoblast activity through autophagy. PMID

  10. In vitro-induced antibody production in chronic hepatitis C virus infection

    Directory of Open Access Journals (Sweden)

    Oliveira Jr. E.B.


    Full Text Available The objectives of the present study were to assess the in vitro-induced anti-hepatitis C virus (HCV antibody production (IVIAP in relation to the clinical, biochemical, virologic and histologic variables of patients with HCV infection. The study included 57 patients (60% males with HCV infection (anti-HCV and HCV-RNA positive. Alanine aminotransferase (ALT was elevated in 89% of the patients. Mean viral load was 542,241 copies/ml and histology of the liver showed chronic hepatitis in 27/52 (52% and cirrhosis in 11/52 (21% patients. IVIAP levels were determined by immunoenzymatic assay at median absorbance of 0.781 at 450 nm. IVIAP was negative in 14% of the patients. When groups with IVIAP levels above and below the median were compared, high IVIAP levels were associated with the male sex, elevated ALT levels and more advanced disease stage. After logistic regression analysis, advanced histologic damage to the liver remained as the only independent variable associated with elevated IVIAP levels. Using a receiver operator characteristic curve, the best cut-off level for IVIAP was established (= 1.540, with 71% sensitivity and 94% specificity for the detection of more advanced disease stages (grades 3 and 4. These findings are consistent with the participation of immunological mechanisms in the genesis of the hepatic lesions induced by HCV and indicate that the IVIAP test may be useful as a noninvasive marker of liver damage either alone or in combination with other markers.

  11. Antibody-mediated activation of FGFR1 induces FGF23 production and hypophosphatemia.

    Directory of Open Access Journals (Sweden)

    Ai-Luen Wu

    Full Text Available The phosphaturic hormone Fibroblast Growth Factor 23 (FGF23 controls phosphate homeostasis by regulating renal expression of sodium-dependent phosphate co-transporters and cytochrome P450 enzymes involved in vitamin D catabolism. Multiple FGF Receptors (FGFRs can act as receptors for FGF23 when bound by the co-receptor Klotho expressed in the renal tubular epithelium. FGFRs also regulate skeletal FGF23 secretion; ectopic FGFR activation is implicated in genetic conditions associated with FGF23 overproduction and hypophosphatemia. The identity of FGFRs that mediate the activity of FGF23 or that regulate skeletal FGF23 secretion remains ill defined. Here we report that pharmacological activation of FGFR1 with monoclonal anti-FGFR1 antibodies (R1MAb in adult mice is sufficient to cause an elevation in serum FGF23 and mild hypophosphatemia. In cultured rat calvariae osteoblasts, R1MAb induces FGF23 mRNA expression and FGF23 protein secretion into the culture medium. In a cultured kidney epithelial cell line, R1MAb acts as a functional FGF23 mimetic and activates the FGF23 program. siRNA-mediated Fgfr1 knockdown induced the opposite effects. Taken together, our work reveals the central role of FGFR1 in the regulation of FGF23 production and signal transduction, and has implications in the pathogenesis of FGF23-related hypophosphatemic disorders.

  12. Myelin oligodendrocyte glycoprotein (MOG35-55)-induced experimental autoimmune encephalomyelitis is ameliorated in interleukin-32 alpha transgenic mice. (United States)

    Yun, Jaesuk; Gu, Sun Mi; Yun, Hyung Mun; Son, Dong Ju; Park, Mi Hee; Lee, Moon Soon; Hong, Jin Tae


    Multiple sclerosis (MS), also known as disseminated sclerosis or encephalomyelitis disseminate, is an inflammatory disease in which myelin in the spinal cord and brain are damaged. IL-32α is known as a critical molecule in the pathophysiology of immune-mediated chronic inflammatory disease such as rheumatoid arthritis, chronic pulmonary disease, and cancers. However, the role of IL-32α on spinal cord injuries and demyelination is poorly understood. Recently, we reported that the release of proinflammatory cytokines were reduced in IL-32α-overexpressing transgenic mice. In this study, we investigated whether IL-32α plays a role on MS using experimental autoimmune encephalomyelitis (EAE), an experimental mouse model of MS, in human IL-32α Tg mice. The Tg mice were immunized with MOG35-55 suspended in CFA emulsion followed by pertussis toxin, and then EAE paralysis of mice was scored. We observed that the paralytic severity and neuropathology of EAE in IL-32α Tg mice were significantly decreased compared with that of non-Tg mice. The immune cells infiltration, astrocytes/microglials activation, and pro-inflammatory cytokines (IL-1β and IL-6) levels in spinal cord were suppressed in IL-32α Tg mice. Furthermore, NG2 and O4 were decreased in IL-32α Tg mice, indicating that spinal cord damaging was suppressed. In addition, in vitro assay also revealed that IL-32α has a preventive role against Con A stimulation which is evidenced by decrease in T cell proliferation and inflammatory cytokine levels in IL-32α overexpressed Jurkat cell. Taken together, our findings suggested that IL-32α may play a protective role in EAE by suppressing neuroinflammation in spinal cord.

  13. 药物诱发自身免疫性肝炎的研究进展%Progress of drug-induced autoimmune hepatitis

    Institute of Scientific and Technical Information of China (English)

    陈慧; 郑聘聘; 王炳元


    More and more cases of drug-induced liver injury have been reported. Drug-induced autoimmune hepatitis (DI-AIH) may occur because some drugs or its metabolites may bind to a hepatocyte surface protein, forming a neoantigen and activating autoimmune reaction, and/or due to such factors as genetic susceptibility, female and advanced age, etc. The symptoms of DIAIH are often concealed, but a few DIAIH patients can develop liver failure rapidly. Significant increase in biliary enzyme levels and disorder of bilirubin metabolism are general manifestations, while AST and ALT may elevate moderately. Unlike AIH, the autoantibodies in DIAIH patinets can change to be negative with disease improvement. In radiological findings, DIAIH usually presents with lobe liver atrophy, delayed-phase images, and few can develop cirrhosis. Diagnosis depends on the roussel uclaf causality assessment method (RUCAM) and clinical diagnostic scale (modified RUCAM). Good response to corticosteroids (CS) treatment is also an important prognostic factor. Complete remission in 1 -3 months and no relapse after withdrawal of CS mean fine prognosis. DIAIH is an a-cute auto-limit disease, and has a good outcome if diagnosis and treatment are given correctly and promptly.%随着药物(或中草药、保健品)的滥用和“被用”,药物性肝损害不断增加.某些药物本身或代谢产物可与蛋白结合形成半抗原,刺激机体发生免疫反应,和(或)由于宿主的遗传易感性、女性、高龄等因素,导致药物诱发自身免疫性肝炎( drug-induced autoimmune hepatitis,DIAIH)的发生.DIAIH的临床症状多数隐匿,但也可迅速发展致肝衰竭.一般表现为胆道酶增加和胆红素排泄障碍,AST和ALT通常为中等度升高.自身抗体的出现与AIH相似,但随着疾病的好转迅速转阴.影像学上DIAIH可见明显的肝叶萎缩、门脉期强化和造影剂排泄延迟,多数不发展至肝硬化.诊断包括因果关系评估方法(roussel uclaf

  14. Autoimmune disease and multiple autoantibodies in 42 patients with RASopathies. (United States)

    Quaio, Caio R D C; Carvalho, Jozélio F; da Silva, Clovis A; Bueno, Cleonice; Brasil, Amanda S; Pereira, Alexandre C; Jorge, Alexander A L; Malaquias, Alexsandra C; Kim, Chong A; Bertola, Débora R


    The association of RASopathies [Noonan syndrome (NS) and Noonan-related syndromes] and autoimmune disorders has been reported sporadically. However, a concomitant evaluation of autoimmune diseases and an assessment of multiple autoantibodies in a large population of patients with molecularly confirmed RASopathy have not been performed. The clinical and laboratory features were analyzed in 42 RASopathy patients, the majority of whom had NS and five individuals had Noonan-related disorders. The following autoantibodies were measured: Anti-nuclear antibodies, anti-double stranded DNA, anti-SS-A/Ro, anti-SS-B/La, anti-Sm, anti-RNP, anti-Scl-70, anti-Jo-1, anti-ribosomal P, IgG and IgM anticardiolipin (aCL), thyroid, anti-smooth muscle, anti-endomysial (AE), anti-liver cytosolic protein type 1 (LC1), anti-parietal cell (APC), anti-mitochondrial (AM) antibodies, anti-liver-kidney microsome type 1 antibodies (LKM-1), and lupus anticoagulant. Six patients (14%) fulfilled the clinical criteria for autoimmune diseases [systemic lupus erythematous, polyendocrinopathy (autoimmune thyroiditis and celiac disease), primary antiphospholipid syndrome (PAPS), autoimmune hepatitis, vitiligo, and autoimmune thyroiditis]. Autoimmune antibodies were observed in 52% of the patients. Remarkably, three (7%) of the patients had specific gastrointestinal and liver autoantibodies without clinical findings. Autoimmune diseases and autoantibodies were frequently present in patients with RASopathies. Until a final conclusion of the real incidence of autoimmunity in Rasopathy is drawn, the physicians should be alerted to the possibility of this association and the need for a fast diagnosis, proper referral to a specialist and ultimately, adequate treatment.

  15. An antibody that prevents serpin polymerisation acts by inducing a novel allosteric behaviour (United States)

    Motamedi-Shad, Neda; Jagger, Alistair M.; Liedtke, Maximilian; Faull, Sarah V.; Nanda, Arjun Scott; Salvadori, Enrico; Wort, Joshua L.; Kay, Christopher W.M.; Heyer-Chauhan, Narinder; Miranda, Elena; Perez, Juan; Ordóñez, Adriana; Haq, Imran; Irving, James A.; Lomas, David A.


    Serpins are important regulators of proteolytic pathways with an antiprotease activity that involves a conformational transition from a metastable to a hyperstable state. Certain mutations permit the transition to occur in the absence of a protease; when associated with an intermolecular interaction, this yields linear polymers of hyperstable serpin molecules, which accumulate at the site of synthesis. This is the basis of many pathologies termed the serpinopathies. We have previously identified a monoclonal antibody (mAb4B12) that, in single-chain form, blocks α1-antitrypsin (α1-AT) polymerisation in cells. Here, we describe the structural basis for this activity. The mAb4B12 epitope was found to encompass residues Glu32, Glu39 and His43 on helix A and Leu306 on helix I. This is not a region typically associated with the serpin mechanism of conformational change, and correspondingly the epitope was present in all tested structural forms of the protein. Antibody binding rendered β-sheet A — on the opposite face of the molecule — more liable to adopt an ‘open’ state, mediated by changes distal to the breach region and proximal to helix F. The allosteric propagation of induced changes through the molecule was evidenced by an increased rate of peptide incorporation and destabilisation of a preformed serpin–enzyme complex following mAb4B12 binding. These data suggest that prematurely shifting the β-sheet A equilibrium towards the ‘open’ state out of sequence with other changes suppresses polymer formation. This work identifies a region potentially exploitable for a rational design of ligands that is able to dynamically influence α1-AT polymerisation. PMID:27407165

  16. 抗核抗体荧光模型特异性抗体谱及滴度与自身免疫性疾病的关联性研究%Study on the relationship between antinuclear antibody fluorescence model, specific antibodies spectrum, ti-ter and autoimmune diseases

    Institute of Scientific and Technical Information of China (English)

    李炎梅; 莫思健; 梁太英; 莫显文; 覃平; 何玮; 莫飞; 朱金月


    Objective To investigate the relationship between antinuclear antibody ( ANA ) fluorescence model, specific antibodies spectrum, titer and autoimmune diseases(AID).Methods Four hundred and four pa-tients with AID were investigated by using indirect immunofluorescence assay to detect ANA, at the same time, using Europe and Mongolia blotting to detect 15 specific antinuclear antibodies spectrum ( ANAS), and a comparative analy-sis was performed of expression of ANA fluorescence model and the titer and ANA fluorescence model in different dis -eases.Results In AID group the positive rate of ANA was 68.81%, titers in 1∶1 000 accounted for 75.90%.ANA fluorescence model mainly showed cytoplasmic type and nuclear homogeneous type, 130 cases and 108 cases respec-tively.In ANA positive patients, the titer of ANA was higher and fluorescent hybrid model was also increased. Con-clusion The detection rate of ANA was higher in patients with AID. In fluorescent ANA positive patients with high titer the fluorescence model mainly is hybrid model. The simultaneous detection of ANA and ANAS has important clinical significance for diagnosis of autoimmune diseases.%目的:探讨抗核抗体( ANA)荧光模型、滴度及特异性抗体谱与自身免疫性疾病的关联性。方法对404例自身免疫性疾病( AID)患者,同时采用间接免疫荧光法检测ANA和欧蒙印迹法检测15项特异性抗核抗体谱( ANAS),对比分析ANA荧光模型和滴度以及ANA荧光模型在不同疾病中的表达,并与健康体检者300名进行比较。结果在AID组中的ANA检出阳性率为68.81%,滴度在1∶1000以上者占75.90%。检出的ANA荧光模型,以胞浆型和核均质型为主,分别检出130例和108例。 ANA阳性患者滴度升高,检出荧光混合模型的比例也明显增加。结论 AID患者中ANA检出率较高,高滴度的ANA阳性患者荧光模型以混合模型为主,同时检测ANA和ANAS对自身免疫性疾病诊断具有重要的临床意义。

  17. 雷公藤皂苷和白介素-10抑制树突状细胞诱导 实验性自身免疫性甲状腺炎%Tripterygium wilfordii saponins and interleukin-1O prevent induc tion of experimental autoimmune thyroiditis by dendritic cells

    Institute of Scientific and Technical Information of China (English)

    王胜军; 许化溪; 刘恭植


    目的:研究雷公藤皂苷和白介素-10(IL-10)在树突状细胞(DC)诱导实验性自身免疫性甲状腺炎(EAT)中的作用.方法:ELISA法检测甲状腺球蛋白抗体水平,TNF和NO分别采用生物学方法及Griess法测定,淋巴细胞增殖试验采用MTT掺入法.结果:DC能诱导EAT的发生,表现为甲状腺内出现淋巴细胞浸润并伴有血清中TgAb明显升高;但经雷公藤皂苷和IL-10处理后,DC不能诱导EAT的发生,表现为甲状腺无病理改变,血清中TgAb明显低下.同时,雷公藤皂苷组和IL-10组小鼠TNFβ活性、NO浓度和淋巴细胞增殖能力显著低于树突状细胞组(P<0.05).结论:雷公藤皂苷和IL-10能显著抑制DC诱导EAT的发生%AIM: To study the roles of Tripterygium wilfordii saponins (TⅡ) and interleukin-10 (IL-10) on dendritic cells (DC)-induced experimental autoimmune thyroiditis (EAT). METHODS: We used mice as autoimmune thyroiditis model animals and divided them into 4 groups,namely DC group, Ti group, IL-10 group, and control group. The level of thyroglobulin (Tg) antibody was assayed by ELISA. TNFβ production in the cultured supernatants and nitric oxide (NO) in the serum were measured by biological activation assay and Griess reaction,respectively. Tg-stimulated proliferation of lymphocytes was detected with MTT incorporation assay. The histopathological analysis of thyroid was carried out.RESULTS: Tg-pulsed DC were able to induce EAT with increase in the concentration of TgAb in serum and lymphocytes infiltration in thyroid. After treatment with TⅡ or IL-10, DC could not induce EAT with lower levels of TgAb and no lymphocyte infiltration. The concentration of NO in serum, TNFβ activation, and the proliferation of lymphocytes in response to thyroglobulin in TⅡ or IL-10 group were lower than those in DC group. CONCLUSION: TⅡ and IL-10 are able to strongly inhibit the ability of DC to induce experimental autoimmune thyroiditis.

  18. Anti-DNA antibodies in SLE

    Energy Technology Data Exchange (ETDEWEB)

    Voss, E.W.


    This book contains 8 chapters. Some of the titles are: Anti-DNA Antibodies in SLE: Historical Perspective; Specificity of Anti-DNA Antibodies in Systemic Lupus Erythematosus; Monoclonial Autoimmune Anti-DNA Antibodies; and Structure--Function Analyses of Anti-DNA Autoantibodies.

  19. Sirolimus for Autoimmune Disease of Blood Cells (United States)


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

  20. Regulatory B and T cell responses in patients with autoimmune thyroid disease and healthy controls

    DEFF Research Database (Denmark)

    Kristensen, Birte


    ). HT is primarily a T-cell mediated disease, and whether B cells play a pathogenic role in the pathogenesis is still unclear. Both GD and HT are characterized by infiltration of the thyroid gland by self-reactive T cells and B cells. In the first paper of this thesis, the role of regulatory B cells......Autoimmune diseases occur due to faulty self-tolerance. Graves' disease (GD) and Hashimoto's thyroiditis (HT) are classic examples of organ-specific autoimmune diseases. GD is an auto-antibody-mediated disease where autoantibodies are produced against the thyroid stimulating hormone receptor (TSHR...... (Bregs) and regulatory T cells (Tregs) were investigated in the context of GD and HT. First, we studied the role of the thyroid self-antigen, thyroglobulin (TG) in healthy donors. The self-antigen TG, but not the foreign recall antigen tetanus toxoid (TT), was able to induce interleukin 10 (IL-10...

  1. Aetiopathogenesis of autoimmune hepatitis

    Institute of Scientific and Technical Information of China (English)

    Diego Vergani; Giorgina Mieli-Vergani


    The histological hallmark of autoimmune hepatitis (AIH) is a dense portal mononuclear cell infiltrate that invades the surrounding parenchyma and comprises T and B lymphocytes,macrophages,and plasma cells.An unknown but powerful stimulus must be promoting the formation of this massive inflammatory cellular reaction that is likely to initiate and perpetuate liver damage.An autoimmune attack can follow different pathways to inflict damage on hepatocytes.Liver damage is likely to be orchestrated by CD4+T lymphocytes recognizing an autoantigenic liver peptide.To trigger an autoimmune response,the peptide must be embraced by an HLA class Ⅱ molecule and presented to naive CD4+T helper (Th0) cells by professional antigen presenting cells,with the co-stimulation of ligand-ligand fostering interaction between the two cells.Th0 cells become activated,differentiate into functional phenotypes according to the cytokines prevailing in the microenvironment and the nature of the antigen,and initiate a cascade of immune reactions determined by the cytokines produced by the activated T cells.Th1 cells,arising in the presence of the macrophage-derived interleukin (IL)-12,secrete mainly IL-2 and interferon-gamma (IFN-γ),which activate macrophages,enhance expression of HLA class Ⅰ (increasing liver cell vulnerability to a CD8+T cell cytotoxic attack),and induce expression of HLA class Ⅱ molecules on hepatocytes.Th2 cells,which differentiate from Th0 if the microenvironment is rich in IL-4,produce mainly IL-4,IL-10,and IL-13 which favour autoantibody production by B lymphocytes.Physiologically,Th1 and Th2 antagonize each other.Th17 cells,a recently described population,arise in the presence of transforming growth factor beta (TGF-β) and IL-6 and appear to have an important effector role in inflammation and autoimmunity.The process of autoantigen recognition is strictly controlled by regulatory mechanisms,such as those exerted by CD4+CD25+regulatory T cells,which derive from Th0

  2. The Influence and Role of Microbial Factors in Autoimmune Kidney Diseases: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Andreas Kronbichler


    Full Text Available A better understanding of the pathophysiology of autoimmune disorders is desired to allow tailored interventions. Despite increased scientific interest a direct pathogenic factor in autoimmune renal disease has been described only in a minority like membranous nephropathy or ANCA-associated vasculitis. Nonetheless the initial step leading to the formation of these antibodies is still obscure. In this review we will focus on the possible role of microbial factors in this context. Staphylococcus aureus may be a direct pathogenetic factor in granulomatosis with polyangiitis (GPA. Chronic bacterial colonization or chronic infections of the upper respiratory tract have been proposed as trigger of IgA vasculitis and IgA nephropathy. Interventions to remove major lymphoid organs, such as tonsillectomy, have shown conflicting results but may be an option in IgA vasculitis. Interestingly no clear clinical benefit despite similar local colonization with bacterial strains has been detected in patients with IgA nephropathy. In systemic lupus erythematosus injection of bacterial lipopolysaccharide induced progressive lupus nephritis in mouse models. The aim of this review is to discuss and summarize the knowledge of microbial antigens in autoimmune renal disease. Novel methods may provide insight into the involvement of microbial antigens in the onset, progression, and prognosis of autoimmune kidney disorders.

  3. Precisely Molded Nanoparticle Displaying DENV-E Proteins Induces Robust Serotype-Specific Neutralizing Antibody Responses (United States)

    Hoekstra, Gabriel; Yi, Xianwen; Stone, Michelle; Horvath, Katie; Miley, Michael J.; DeSimone, Joseph; Luft, Chris J.; de Silva, Aravinda M.


    Dengue virus (DENV) is the causative agent of dengue fever and dengue hemorrhagic fever. The virus is endemic in over 120 countries, causing over 350 million infections per year. Dengue vaccine development is challenging because of the need to induce simultaneous protection against four antigenically distinct DENV serotypes and evidence that, under some conditions, vaccination can enhance disease due to specific immunity to the virus. While several live-attenuated tetravalent dengue virus vaccines display partial efficacy, it has been challenging to induce balanced protective immunity to all 4 serotypes. Instead of using whole-virus formulations, we are exploring the potentials for a particulate subunit vaccine, based on DENV E-protein displayed on nanoparticles that have been precisely molded using Particle Replication in Non-wetting Template (PRINT) technology. Here we describe immunization studies with a DENV2-nanoparticle vaccine candidate. The ectodomain of DENV2-E protein was expressed as a secreted recombinant protein (sRecE), purified and adsorbed to poly (lactic-co-glycolic acid) (PLGA) nanoparticles of different sizes and shape. We show that PRINT nanoparticle adsorbed sRecE without any adjuvant induces higher IgG titers and a more potent DENV2-specific neutralizing antibody response compared to the soluble sRecE protein alone. Antigen trafficking indicate that PRINT nanoparticle display of sRecE prolongs the bio-availability of the antigen in the draining lymph nodes by creating an antigen depot. Our results demonstrate that PRINT nanoparticles are a promising platform for delivering subunit vaccines against flaviviruses such as dengue and Zika. PMID:27764114

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

    Directory of Open Access Journals (Sweden)

    Ivan Ćavar


    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.

  5. Modulation of IL-17 and Foxp3 expression in the prevention of autoimmune arthritis in mice.

    Directory of Open Access Journals (Sweden)

    Joana Duarte

    Full Text Available BACKGROUND: Rheumatoid Arthritis (RA is a chronic immune mediated disease associated with deregulation of many cell types. It has been reported that different T cell subsets have opposite effects in disease pathogenesis, in particular Th17 and Treg cells. METHODOLOGY AND FINDINGS: We investigated whether non-depleting anti-CD4 monoclonal antibodies, which have been reported as pro-tolerogenic, can lead to protection from chronic autoimmune arthritis in SKG mice--a recently described animal model of RA--by influencing the Th17/Treg balance. We found that non-depleting anti-CD4 prevented the onset of chronic autoimmune arthritis in SKG mice. Moreover, treated mice were protected from the induction of arthritis up to 60 days following anti-CD4 treatment, while remaining able to mount CD4-dependent immune responses to unrelated antigens. The antibody treatment also prevented disease progression in arthritic mice, although without leading to remission. Protection from arthritis was associated with an increased ratio of Foxp3, and decreased IL-17 producing T cells in the synovia. In vitro assays under Th17-polarizing conditions showed CD4-blockade prevents Th17 polarization, while favoring Foxp3 induction. CONCLUSIONS: Non-depleting anti-CD4 can therefore induce long-term protection from chronic autoimmune arthritis in SKG mice through reciprocal changes in the frequency of Treg and Th17 cells in peripheral tissues, thus shifting the balance towards immune tolerance.

  6. Diagnostic value of anti-iflamentous actin antibodies on typeⅠ autoimmune hepatitis%抗纤维肌动蛋白抗体对自身免疫性肝炎Ⅰ型的诊断价值

    Institute of Scientific and Technical Information of China (English)

    刘玲; 赵友云; 郑毅; 肖明中; 李晓东


    目的:探讨抗纤维肌动蛋白抗体(AFA)对自身免疫性肝炎(AIH)Ⅰ型的诊断价值。方法收集163例AIH-Ⅰ型、5例AIH-Ⅱ型、26例AIH-Ⅲ型、26例原发性胆汁性肝硬化(PBC)、5例原发性硬化性胆管炎(PSC)、2例重叠综合征(AIDOS)及95例其他类型肝病患者的临床资料,另外收集197例健康献血者作为对照组,采用酶联免疫吸附测定法(ELISA)分别检测上述标本的AFA和抗平滑肌抗体(ASMA),对检测结果进行统计分析。结果以浓度≥30 U/L为阳性标准判断,AFA与ASMA检测AIH-Ⅰ型患者的阳性率无统计学差异(χ2=0.37,P=0.54),但ASMA检测AIH-Ⅲ型和乙型肝炎患者的阳性率高于AFA,差异有统计学意义(χ2值分别为5.65、6.37,P值分别为0.02、0.01)。AFA对ASMA≥20 U/L的AIH患者检出率≥98.27%,检测结果与ASMA的浓度有显著相关性(r =0.88,95%CI:0.66~0.99,P =0.00)。AFA与ASMA检测AIH-Ⅰ型患者的敏感性相近(71.78%vs 68.71%),但AFA的特异性(83.87%vs 54.84%)和Youden指数(0.56vs 0.24)更高。结论与ASMA相比,AFA检测AIH-Ⅰ型患者敏感性相近,但特异性和Youden指数更高,AFA对AIH-Ⅰ型的诊断价值优于ASMA。%Objective To evaluate the diagnostic value of anti-filamentous actin antibodies (AFA) on patients with autoimmune hepatitis typeⅠ (AIH-Ⅰ).MethodsThe clinical data of 163 cases with AIH-Ⅰ, 5 cases with AIH-Ⅱ, 26 cases with AIH-Ⅲ, 26 cases with primary biliary cirrhosis (PBC), 5 cases with primary sclerosing cholangitis (PSC), 2 cases with autoimmune disease overlap syndrome (AIDOS), 95 cases with other liver diseases and 197 blood donors (controls) were collected. AFA and anti-smooth muscle antibodies (ASMA) were evaluated by ELISA and the results were analyzed.Results The positive rate of AFA and ASMA in patients with AIH-Ⅰ had no statistically signiifcant differences (χ2 = 0.37,P = 0.54). The positive

  7. In vivo expression of a single viral DNA-binding protein generates systemic lupus erythematosus-related autoimmunity to double-stranded DNA and histones. (United States)

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


    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 DNA immunogenic. We report that in vivo expression of a single DNA-binding protein, the polyoma virus T antigen, is sufficient to initiate production of anti-double-stranded DNA and anti-histone antibodies but not a panel of other autoantigens. Expression of a mutant, non-DNA-binding T antigen did result in strong production of antibodies to the T antigen, but only borderline levels of antibodies to DNA and no detectable antibodies to histones. Nonexpressing plasmid DNA containing the complete cDNA sequence for T antigen did not evoke such immune responses, indicating that DNA by itself is not immunogenic in vivo. The results represent a conceptual advance in understanding a potential molecular basis for initiation of autoimmunity in systemic lupus erythematosus. PMID:8618908

  8. 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


    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.

  9. Production of anti-double-stranded DNA antibodies in activated lymphocyte derived DNA induced lupus model was dependent on CD4+ T cells. (United States)

    Wen, Z; Xu, L; Xu, W; Xiong, S


    Our previous study demonstrated that activated lymphocyte derived DNA (ALD-DNA) could function as an autoantigen to induce production of anti-double-stranded DNA (anti-dsDNA) antibodies in syngeneic BALB/c mice. Here we carefully evaluated the potential role of T cells in the induction of anti-dsDNA antibody. We demonstrated that ALD-DNA could effectively induce production of anti-dsDNA antibodies in vivo and in vitro. In contrast, ALD-DNA could not induce the generation of anti-dsDNA antibodies in nude mice. We further showed that in vivo depletion of CD3(+) T cells blocked the induction of anti-dsDNA antibodies in BALB/c mice. Notably, we demonstrated that CD4(+) but not CD8(+) T cells conferred ALD-DNA to induce anti-dsDNA antibodies. Finally, we demonstrated that adoptive transfer of CD4(+) T cells could rescue ALD-DNA induced anti-dsDNA antibodies in nude mice. Our results suggested that T helper cells were required for ALD-DNA to induce anti-dsDNA antibodies. These findings could further our understanding about the immunogenic properties of DNA and throw new light on SLE pathogenesis.

  10. Glatiramer acetate (copaxone modulates platelet activation and inhibits thrombin-induced calcium influx: possible role of copaxone in targeting platelets during autoimmune neuroinflammation.

    Directory of Open Access Journals (Sweden)

    Sarah C Starossom

    Full Text Available BACKGROUND: Glatiramer acetate (GA, Copaxone, Copolymer-1 is an FDA approved drug for the treatment of MS and it is very effective in suppressing neuroinflammation in experimental autoimmune encephalitis (EAE, an animal model of MS. Although this drug was designed to inhibit pathogenic T cells, the exact mechanism of EAE/MS suppression by GA is still not well understood. Previously we presented evidence that platelets become activated and promote neuroinflammation in EAE, suggesting a possible pathogenic role of platelets in MS and EAE. We hypothesized that GA could inhibit neuroinflammation by affecting not only immune cells but also platelets. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the effect of GA on the activation of human platelets in vitro: calcium influx, platelet aggregation and expression of activation markers. Our results in human platelets were confirmed by in-vitro and in-vivo studies of modulation of functions of platelets in mouse model. We found that GA inhibited thrombin-induced calcium influx in human and mouse platelets. GA also decreased thrombin-induced CD31, CD62P, CD63, and active form of αIIbβ3 integrin surface expression and formation of platelet aggregates for both mouse and human platelets, and prolonged the bleeding time in mice by 2.7-fold. In addition, we found that GA decreased the extent of macrophage activation induced by co-culture of macrophages with platelets. CONCLUSIONS: GA inhibited the activation of platelets, which suggests a new mechanism of GA action in suppression of EAE/MS by targeting platelets and possibly preventing their interaction with immune cells such as macrophages. Furthermore, the reduction in platelet activation by GA may have additional cardiovascular benefits to prevent thrombosis.

  11. 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


    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.

  12. Criteria for Environmentally Associated Autoimmune Diseases (United States)

    Pollard, K. Michael; Parks, Christine G.; Germolec, Dori R.; Leung, Patrick S.C.; Selmi, Carlo; Humble, Michael C.; Rose, Noel R.


    Increasing evidence supports a role for the environment in the development of autoimmune diseases, as reviewed in the accompanying three papers from the National Institute of Environmental Health Sciences Expert Panel Workshop. An important unresolved issue, however, is the development of criteria for identifying autoimmune disease phenotypes for which the environment plays a causative role, herein referred to as environmentally associated autoimmune diseases. There are several different areas in which such criteria need to be developed, including: 1) identifying the necessary and sufficient data to define environmental risk factors for autoimmune diseases meeting current classification criteria; 2) establishing the existence of and criteria for new environmentally associated autoimmune disorders that do not meet current disease classification criteria; and 3) identifying in clinical practice specific environmental agents that induce autoimmune disease in individual patients. Here we discuss approaches that could be useful for developing criteria in these three areas, as well as factors that should be considered in evaluating the evidence for criteria that can distinguish individuals with such disorders from individuals without such disorders with high sensitivity and specificity. Current studies suggest that multiple lines of complementary evidence will be important and that in many cases there will be clinical, serologic, genetic, epigenetic, and/or other laboratory features that could be incorporated as criteria for environmentally associated autoimmune diseases to improve diagnosis and treatment and possibly allow for preventative strategies in the future. PMID:22771005

  13. TNF autovaccination induces self anti-TNF antibodies and inhibits metastasis in a murine melanoma model


    Waterston, AM; Salway, F; Andreakos, E; Butler, DM; FELDMANN M.; Coombes, RC


    TNF is a proinflammatory cytokine involved in the pathogenesis of chronic inflammatory diseases, but also in metastasis in certain types of cancer. In terms of therapy, TNF is targeted by anti-TNF neutralising monoclonal antibodies or soluble TNF receptors. Recently, a novel strategy based on the generation of self anti-TNF antibodies (TNF autovaccination) has been developed. We have previously shown that TNF autovaccination successfully generates high anti-TNF antibody titres, blocks TNF and...

  14. Digoxin-specific antibody fragments and a calcium antagonist for reversal of digoxin-induced mesenteric vasoconstriction. (United States)

    Hess, T; Scholtysik, G; Salzmann, R; Riesen, W


    The effect of digoxin-specific antibody fragments on glycoside-induced mesenteric vasoconstriction were investigated. Digoxin caused a sustained contraction of strips of isolated feline mesenteric artery lasting for several hours, while in anaesthetized cats it produced a significant decrease in blood flow and increase in resistance in the mesenteric artery. In-vitro, digoxin's contractile effect was inhibited by 'prophylactic' addition of antibody to the organ bath, but the clinical use for prophylaxis is not a practical proposition. When the antibodies were added with the contraction of the arterial strip in response to digoxin already established, the tone of the preparation decreased significantly over 3 h, but the effect of the glycoside was not fully reversible. In-vivo, control animals not treated with antibodies developed arrhythmias, mesenteric blood flow fell by more than 50% and resistance increased by more than 80% relative to the initial values. These animals died of ventricular fibrillation before the end of the experiment. Animals treated with digoxin-specific antibody fragments after receiving digoxin injections showed no further decrease in mesenteric blood flow and 90 min after the last dose of digoxin, the flow was recovering and mesenteric resistance decreasing. Furthermore, all the animals that had received antibodies remained in sinus rhythm to the end of the experiment. In view of the latent period to onset of action of the antibodies, valuable time may be lost in impaired mesenteric blood flow. To bridge the gap or, indeed, as primary treatment, calcium antagonists merit consideration; in our experiments mesenteric vasoconstriction was abolished within a few minutes by application of the dihydropyridine calcium antagonist 4-(2,1,3-benzo-oxadiazol-4-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic aid, diethyl ester (PY 108-068).

  15. Hypothalamic-Pituitary Autoimmunity and Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Federica Guaraldi


    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.

  16. Autoimmune pancreatitis: A review

    Institute of Scientific and Technical Information of China (English)


    Autoimmune pancreatitis has emerged over the last 40 years from a proposed concept to a well established and recognized entity. As an efficient mimicker of pancreatic carcinoma, its early and appropriate recognition are crucial. With mounting understanding of its pathogenesis and natural history, significant advances have been made in the diagnosis of autoimmune pancreatitis. The characteristic laboratory features and imaging seen in autoimmune pancreatitis are reviewed along with some of the proposed diagnostic criteria and treatment algorithms.

  17. Induction of Golli-MBP Expression in CNS Macrophages During Acute LPS-Induced CNS Inflammation and Experimental Autoimmune Encephalomyelitis (EAE

    Directory of Open Access Journals (Sweden)

    Tracey L. Papenfuss


    Full Text Available Microglia are the tissue macrophages of the CNS. Microglial activation coupled with macrophage infiltration is a common feature of many classic neurodegenerative disorders. The absence of cell-type specific markers has confounded and complicated the analysis of cell-type specific contributions toward the onset, progression, and remission of neurodegeneration. Molecular screens comparing gene expression in cultured microglia and macrophages identified Golli-myelin basic protein (MBP as a candidate molecule enriched in peripheral macrophages. In situ hybridization analysis of LPS/IFNg and experimental autoimmune encephalomyelitis (EAE–induced CNS inflammation revealed that only a subset of CNS macrophages express Golli-MBP. Interestingly, the location and morphology of Golli-MBP+ CNS macrophages differs between these two models of CNS inflammation. These data demonstrate the difficulties of extending in vitro observations to in vivo biology and concretely illustrate the complex heterogeneity of macrophage activation states present in region- and stage-specific phases of CNS inflammation. Taken altogether, these are consistent with the emerging picture that the phenotype of CNS macrophages is actively defined by their molecular interactions with the CNS microenvironment.

  18. Postural Orthostatic Tachycardia With Chronic Fatigue After HPV Vaccination as Part of the “Autoimmune/Auto-inflammatory Syndrome Induced by Adjuvants”

    Directory of Open Access Journals (Sweden)

    Lucija Tomljenovic PhD


    Full Text Available We report the case of a 14-year-old girl who developed postural orthostatic tachycardia syndrome (POTS with chronic fatigue 2 months following Gardasil vaccination. The patient suffered from persistent headaches, dizziness, recurrent syncope, poor motor coordination, weakness, fatigue, myalgias, numbness, tachycardia, dyspnea, visual disturbances, phonophobia, cognitive impairment, insomnia, gastrointestinal disturbances, and a weight loss of 20 pounds. The psychiatric evaluation ruled out the possibility that her symptoms were psychogenic or related to anxiety disorders. Furthermore, the patient tested positive for ANA (1:1280, lupus anticoagulant, and antiphospholipid. On clinical examination she presented livedo reticularis and was diagnosed with Raynaud’s syndrome. This case fulfills the criteria for the autoimmune/auto-inflammatory syndrome induced by adjuvants (ASIA. Because human papillomavirus vaccination is universally recommended to teenagers and because POTS frequently results in long-term disabilities (as was the case in our patient, a thorough follow-up of patients who present with relevant complaints after vaccination is strongly recommended.

  19. HSV-1-mediated IL-1 receptor antagonist gene therapy ameliorates MOG(35-55)-induced experimental autoimmune encephalomyelitis in C57BL/6 mice. (United States)

    Furlan, R; Bergami, A; Brambilla, E; Butti, E; De Simoni, M G; Campagnoli, M; Marconi, P; Comi, G; Martino, G


    Primary proinflammatory cytokines, such as IL-1beta, play a crucial pathogenic role in multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE), and may represent, therefore, a suitable therapeutic target. We have previously established the delivery of anti-inflammatory cytokine genes within the central nervous system (CNS), based on intracisternal (i.c.) injection of non-replicative HSV-1-derived vectors. Here we show the therapeutic efficacy of i.c. administration of an HSV-1-derived vector carrying the interleukin-1receptor antagonist (IL-1ra) gene, the physiological antagonist of the proinflammatory cytokine IL-1, in C57BL/6 mice affected by myelin oligodendrocyte glycoprotein-induced EAE. IL-1ra gene therapy is effective preventively, delaying EAE onset by almost 1 week (22.4+/-1.4 days post-immunization vs 15.9+/-2.1 days in control mice; P=0.0229 log-rank test), and decreasing disease severity. Amelioration of EAE course was associated with a reduced number of macrophages infiltrating the CNS and in a decreased level of proinflammatory cytokine mRNA in the CNS, suggesting an inhibitory activity of IL-1ra on effector cell recruitment, as antigen-specific peripheral T-cell activation and T-cell recruitment to the CNS is unaffected. Thus, local IL-1ra gene therapy may represent a therapeutic alternative for the inhibition of immune-mediated demyelination of the CNS.

  20. 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


    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.

  1. [VGKC-complex antibodies]. (United States)

    Watanabe, Osamu


    Various antibodies are associated with voltage-gated potassium channels (VGKCs). Representative antibodies to VGKCs were first identified by radioimmunoassays using radioisotope-labeled alpha-dendrotoxin-VGKCs solubilized from rabbit brain. These antibodies were detected only in a proportion of patients with acquired neuromyotonia (Isaacs' syndrome). VGKC antibodies were also detected in patients with Morvan's syndrome and in those with a form of autoimmune limbic encephalitis. Recent studies indicated that the "VGKC" antibodies are mainly directed toward associated proteins (for example LGI-1 and CASPR-2) that complex with the VGKCs themselves. The "VGKC" antibodies are now commonly known as VGKC-complex antibodies. In general, LGI-1 antibodies are most commonly detected in patients with limbic encephalitis with syndrome of inappropriate secretion of antidiuretic hormone. CASPR-2 antibodies are present in the majority of patients with Morvan's syndrome. These patients develop combinations of CNS symptoms, autonomic dysfunction, and peripheral nerve hyperexcitability. Furthermore, VGKC-complex antibodies are tightly associated with chronic idiopathic pain. Hyperexcitability of nociceptive pathways has also been implicated. These antibodies may be detected in sera of some patients with neurodegenerative diseases (for example, amyotrophic lateral sclerosis and Creutzfeldt-Jakob disease).

  2. Control of Her-2 tumor immunity and thyroid autoimmunity by MHC and regulatory T cells. (United States)

    Jacob, Jennifer B; Kong, Yi-chi M; Meroueh, Chady; Snower, Daniel P; David, Chella S; Ho, Ye-Shih; Wei, Wei-Zen


    Immune reactivity to self-antigens in both cancer and autoimmune diseases can be enhanced by systemic immune modulation, posing a challenge in cancer immunotherapy. To distinguish the genetic and immune regulation of tumor immunity versus autoimmunity, immune responses to human ErbB-2 (Her-2) and mouse thyroglobulin (mTg) were tested in transgenic mice expressing Her-2 that is overexpressed in several cancers, and HLA-DRB1*0301 (DR3) that is associated with susceptibility to several human autoimmune diseases, as well as experimental autoimmune thyroiditis (EAT). To induce Her-2 response, mice were electrovaccinated with pE2TM and pGM-CSF encoding the extracellular and transmembrane domains of Her-2 and the murine granulocyte macrophage colony-stimulating factor, respectively. To induce EAT, mice received mTg i.v. with or without lipopolysaccharide. Depletion of regulatory T cells (Treg) with anti-CD25 monoclonal antibody enhanced immune reactivity to Her-2 as well as mTg, showing control of both Her-2 and mTg responses by Treg. When immunized with, Her-2xDR3 and B6xDR3 mice expressing H2(b)xDR3 haplotype developed more profound mTg response and thyroid pathology than Her-2 or B6 mice that expressed the EAT-resistant H2(b) haplotype. In Her-2xDR3 mice, the response to mTg was further amplified when mice were also immunized with pE2TM and pGM-CSF. On the contrary, Her-2 reactivity was comparable whether mice expressed DR3 or not. Therefore, induction of Her-2 immunity was independent of DR3 but development of EAT was dictated by this allele, whereas Tregs control the responses to both self-antigens. These results warrant close monitoring of autoimmunity during cancer immunotherapy, particularly in patients with susceptible MHC class II alleles.

  3. Experimental autoimmune myositis model induced by pure myosin of rabbit%实验性自身免疫性肌炎动物模型的制作

    Institute of Scientific and Technical Information of China (English)



    human s in idiopathic inflammatory myopathy. The model success rate was 80%. Conclusion Experimental autoimmune myositis model induced by pure myosin, which was with low mortality and high success rate,provided better tools for the study of the pathogenesis and treatment in inflammatory myopathy. Myosin might be a probable antigen.

  4. Primary biliary cirrhosis--autoimmune hepatitis overlap syndrome associated with dermatomyositis, autoimmune thyroiditis and antiphospholipid syndrome. (United States)

    Pamfil, Cristina; Candrea, Elisabeta; Berki, Emese; Popov, Horațiu I; Radu, Pompilia I; Rednic, Simona


    Autoimmune liver diseases may be associated with extrahepatic autoimmune pathology. We report the case of a 52-year old woman who initially presented to the gastroenterology department for extreme fatigue, pale stools, dark urine and pruritus. Laboratory tests showed significant cholestasis and elevation of aminotransferase levels. Immunological tests revealed positive antinuclear (ANA=1:320) and antimitochondrial antibodies (AMA=1:40) with negative anti-smooth muscle and liver kidney microsomal type 1 antibodies. The biopsy was compatible with overlap syndrome type 1. The patient was commenced on immunosuppressive therapy according to standard of care (azathioprine 50mg, ursodeoxycholic acid and prednisone 0.5mg/kg), with moderate biochemical improvement. She subsequently developed proximal symmetrical weakness and cutaneous involvement and was diagnosed with biopsy-proven dermatomyositis. The immunosuppressive regimen was intensified to 150 mg azathioprine. At the three-month follow-up, her symptoms subsided and aminotransferases and muscle enzymes normalized. Upon further investigation the patient was diagnosed with autoimmune thyroiditis and antiphospholipid syndrome. To our knowledge, this is the first case of primary biliary cirrhosis - autoimmune hepatitis overlap syndrome associated with dermatomyositis, autoimmune thyroiditis and antiphospholipid syndrome.

  5. Cancer immunotherapy in patients with preexisting autoimmune disorders

    DEFF Research Database (Denmark)

    Donia, Marco; Pedersen, Magnus; Svane, Inge Marie


    Patients with preexisting active autoimmune disorders were excluded from clinical trials of immune checkpoint inhibitors. However, patients with autoimmune disorders are diagnosed with cancer at least as frequently as the global population, and clinicians treating patients outside clinical trials...... have generally been reluctant to offer cancer immunotherapy to this patient group. In this brief article, we review the most recent literature on the efficacy and safety of CTLA-4- and PD-1-blocking antibodies in patients with preexisting autoimmune disorders.......Patients with preexisting active autoimmune disorders were excluded from clinical trials of immune checkpoint inhibitors. However, patients with autoimmune disorders are diagnosed with cancer at least as frequently as the global population, and clinicians treating patients outside clinical trials...

  6. [Unusual presentation of juvenile idiopathic arthritis and autoimmune hepatitis]. (United States)

    Moreno Prieto, M; Carbonero Celis, M J; Cuadrado Caballero, M C


    The coexistence of autoimmune hepatitis and juvenile idiopathic arthritis is very rare. This is the case of an 18 month old female patient whose first sign of disease was torticollis due to an underlying atlanto-axial subluxation. Three months later, bilateral knee arthritis developed and she was diagnosed with Juvenile Idiopathic Arthritis. Throughout the disease a persistent elevation of liver enzymes was noted, combined with positive antinuclear antibodies and hypergammaglobulinemia, reaching the diagnosis of concomitant autoimmune hepatitis.

  7. [Antinuclear antibodies]. (United States)

    Cabiedes, Javier; Núñez-Álvarez, Carlos A


    Anti-nuclear antibodies (ANA) are immunoglobulin directed against autologous cell nuclear and cytoplasmic components. Besides the autoimmune ANA there are other ANA that can be detected in circulation, like natural and infectious ANA. Because of its high sensibility, detection of the ANA must be done by indirect immunofluorescence (IIF) as screening test and all of those positive samples are convenient to confirm its specificity by ELISA, western blot or other techniques. Positive ANA detected by IIF must be evaluated taking in to account the pattern and titer. The following recommended step is the specificity characterization (reactivity against extractable nuclear antigens [ENA], dsDNA, etc.) which is useful for the diagnosis and follow up of patients with autoimmune diseases, and by such reasoning, its detection must be performed in an orderly and reasonable way using guides or strategies focused to the good use and interpretation of the autoantibodies. The objective of this review is to present a compilation of the literature and our experience in the detection and study of the ANA.

  8. Antibodies Against Human BLyS and APRIL Attenuate EAE Development in Marmoset Monkeys


    Jagessar, Anwar; Heijmans, Nicole; Bauer, J.; Blezer, Erwin; Laman, Jon; Migone, Thi-Sau; Devalaraja, Matt; Hart, Bert


    textabstractB lymphocyte stimulator (BLyS, also indicated as BAFF (B-cell activating factor) and CD257), and A Proliferation Inducing Ligand (APRIL, CD256) are two members of the TNF superfamily with a central role in B cell survival. Antibodies against these factors have potential therapeutic relevance in autoimmune inflammatory disorders with a proven pathogenic contribution of B cells, such as multiple sclerosis (MS). In the current study we performed a multi-parameter efficacy comparison ...

  9. 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.

  10. A fusion protein encoding the second extracellular domain of CCR5 arrests chemokine-induced cosignaling and effectively suppresses ongoing experimental autoimmune encephalomyelitis. (United States)

    Sapir, Yair; Vitenshtein, Alon; Barsheshet, Yiftah; Zohar, Yaniv; Wildbaum, Gizi; Karin, Nathan


    CCR5 is a key CCR that is highly expressed on CD4(+) T cells. It binds three different ligands: CCL3 (MIP-alpha), CCL4 (MIP-beta), and CCL5 (RANTES). Recent studies suggested that the interaction between CCR5 and its ligands is essential not only for attracting these CCR5(+) T cells but also substantial for transuding cosignals for their activation. The current study explores, for the first time, the in vivo consequences of CCR5 as a costimulatory molecule. First, we show redundancy between CCR5 ligands not only in chemoattractive properties but also in their ability to induced cosignals via CCR5. This has motivated us to generate a soluble receptor-based fusion protein that would selectively bind and neutralize all three CCR5 ligands. We show in this study that a 30-aa-based CCR5-Ig fusion protein encoding the second extracellular domain of receptor selectively binds and neutralizes all three CCR5 ligands and, when administered during ongoing experimental autoimmune encephalomyelitis, rapidly suppressed the disease while arresting Ag-specific effector T cell functions. Finally, our results clearly show that although CCR5 ligands induced cosignaling for IL-2 production is directed by CCR5, other proinflammatory properties of these ligands, such as TNF-alpha, IL-17, and IFN-gamma production, are CCR5 independent and therefore likely to be mediated by the other receptors for these ligands. These findings imply that implementing a CCR5-Ig-based therapy would be advantageous over blockade of this receptor or of the use of mAbs for targeting a single CCR5 ligand.

  11. Human Monoclonal Antibodies Directed against Toxins A and B Prevent Clostridium difficile-Induced Mortality in Hamsters▿


    Babcock, Gregory J.; Broering, Teresa J.; Hernandez,Hector J; Mandell, Robert B.; Donahue, Katherine; Boatright, Naomi; Stack, Anne M.; Lowy, Israel; Graziano, Robert; Molrine, Deborah; Ambrosino, Donna M.; Thomas, William D


    Clostridium difficile is the leading cause of nosocomial antibiotic-associated diarrhea, and recent outbreaks of strains with increased virulence underscore the importance of identifying novel approaches to treat and prevent relapse of Clostridium difficile-associated diarrhea (CDAD). CDAD pathology is induced by two exotoxins, toxin A and toxin B, which have been shown to be cytotoxic and, in the case of toxin A, enterotoxic. In this report we describe fully human monoclonal antibodies (HuMA...

  12. Leucine-rich glioma inactivated-1 and voltage gated potassium channel autoimmune encephalitis associated with ischemic stroke; A Case Report

    Directory of Open Access Journals (Sweden)

    Marisa Patryce McGinley


    Full Text Available Autoimmune encephalitis is associated with a wide variety of antibodies and clinical presentations. Voltage gated potassium channel (VGKC antibodies are a cause of autoimmune non-paraneoplastic encephalitis characterized by memory impairment, psychiatric symptoms, and seizures. We present a case of VGKC encephalitis likely preceding an ischemic stroke. Reports of autoimmune encephalitis associated with ischemic stroke are rare. Several hypothesizes linking these two disease processes are proposed.

  13. [Syndrome overlap: autoimmune hepatitis and autoimmune cholangitis]. (United States)

    Guerra Montero, Luis; Ortega Alvarez, Félix; Marquez Teves, Maguin; Asato Higa, Carmen; Sumire Umeres, Julia


    Autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune cholangitis are chronic autoimmune liver disease, usually present separate, the cases where characteristics of two of the above is observed liver disease is commonly referred to as Overlap Syndromes (OS). Although there is no consensus on specific criteria for the diagnosis of OS identification of this association is important for initiating appropriate treatment and prevent its progression to cirrhosis or at least the complications of cirrhosis and death. We report the case of awoman aged 22 cirrhotic which debuted are edematous ascites, severe asthenia and jaundice compliant diagnostics SS criteria and initially present any response to treatment with ursodeoxycholic acid and oral corticosteroids, but ultimately finished performing a transplant orthotopic liver.

  14. 乳酸杆菌对自身免疫病模型小鼠免疫功能的影响%Effect of Lactobacillus rhamnosus GG on immune response: experiment with autoimmune mice induced by campylobacter jejuni

    Institute of Scientific and Technical Information of China (English)

    章琼; 陈其御


    Objective To investigate the immune effects of Lactobacillus rhamnosus GG (LGG) on immune response.Methods Fourty 1CR mice were randomly divided into 4 groups, normal control (N) group, model (M) group, LactobaciUus (LGG) group, and hydrocortisone (HC) group.The mice were induced by Campylobacter jejuni with complete Freund's adjuvant as autoimmune animal model except N group.From the fifteenth day after primary immunization, each group was given different administration through peritoneum route for 7 days.Twenty-five days after the model establishment, the mice were killed.Then the blood sample was collected the undergo ELISA to detect the level of ds-DNA antibody and interferon (IFN)-γ.The proliferation activities of the B and T cells were examined.The livers and kidneys were taken out to undergo microscopy.Results The ds-DNA antibody levels of the HC and LGG groups were not significant different from that of the M group (both P 0.05).The proliferation activities of T and B cells and IFN-γlevel of the groups LGG were all significantly lower than those of the group M[0.42 ±0.05 vs 0.60 ±0.09,0.43 ± 0.05 vs 0.60 ± 0.09, (184 ± 16) vs (195±6) pg/ml, all P < 0.01].Conclusion LGG inhibits the immune response induced by CJ to a eertain degree.%目的 探讨乳酸杆菌(LGG)对空肠弯曲菌(CJ)致敏的自身免疫病模型小鼠(CJ小鼠)免疫功能的影响.方法 ICR小鼠随机分为正常对照组、模型组、LGG组及氢化可的松(HC)组,除正常组外,其余组制备自身免疫病小鼠模型.从造模第15天起分别腹腔(或皮下)注射,连续用药7 d,造模第25大处死小鼠.用酶联免疫吸附试验(ELISA)法测定小鼠血清中ds-DNA抗体水平及脾淋巴细胞的γ干扰素(IFN-γ)分泌活性;检测脾T、B淋巴细胞的增殖活性;镜下观察肝、肾组织的病理变化.结果 LGG对ds-DNA抗体没有影响,LGG可改善脏器组织的病理性改变.LGG组GJ小鼠的T、B淋巴细胞增殖活性及脾淋巴细胞分泌IFN

  15. Several domains from VAR2CSA can induce Plasmodium falciparum adhesion-blocking antibodies

    DEFF Research Database (Denmark)

    Salanti, Ali; Resende, Mafalda; Ditlev, Sisse B


    . In this study, it is demonstrated that other domains of VAR2CSA also can induce antibodies with inhibitory activity. METHODS: All VAR2CSA domains from the 3D7 and HB3 parasites were produced in Baculovirus-transfected insect cells. Groups of three rats per protein were immunized and anti-sera were tested...... for surface reactivity against infected erythrocytes expressing FCR3 VAR2CSA and for the ability to inhibit FCR3CSA parasite adhesion to CSA. The fine specificity of the immune sera was analysed by VAR2CSA peptide arrays. RESULTS: Inhibitory antibodies were induced by immunization with DBL3-HB3 T1 and DBL1-3D......7. However, unlike the previously characterised DBL4-FCR3 response the inhibitory response against DBL1-3D7 and DBL3-HB3 T1 was poorly reproduced in the second rounds of immunizations. CONCLUSION: It is possible to induce parasite adhesion-blocking antibodies when immunizing with a number...

  16. Oral Application of T4 Phage Induces Weak Antibody Production in the Gut and in the Blood

    Directory of Open Access Journals (Sweden)

    Joanna Majewska


    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.

  17. 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


    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.


    Directory of Open Access Journals (Sweden)

    Juan-Manuel eAnaya


    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.

  19. Bistability in autoimmune diseases

    DEFF Research Database (Denmark)

    Rapin, Nicolas; Mosekilde, Erik; Lund, Ole


    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...

  20. The Autoimmune Ecology. (United States)

    Anaya, Juan-Manuel; Ramirez-Santana, Carolina; Alzate, Maria A; Molano-Gonzalez, Nicolas; Rojas-Villarraga, Adriana


    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 (SES), 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.

  1. “The NET Outcome”: Are Neutrophil Extracellular Traps of Any Relevance to the Pathophysiology of Autoimmune Disorders in Childhood? (United States)

    Giaglis, Stavros; Hahn, Sinuhe; Hasler, Paul


    Neutrophil extracellular trap (NET) formation represents a form of cell death distinct from apoptosis or necrosis, by which invading pathogens are simultaneously entangled and potentially eliminated. Increased NET formation is observed in systemic lupus erythematosus (SLE), rheumatoid arthritis, antineutrophil cytoplasmic antibody-associated small vessel vasculitis, antiphospholipid antibody syndrome (APS), and psoriasis. NETs contribute to the pathogenesis of autoimmunity by exposing cryptic autoepitopes, which may facilitate the generation of autoantibodies, induce the production of interferons, and activate the complement cascade. In SLE, augmented disease activity and renal disease are associated with increased NET formation, so that NETs could serve as a marker for the monitoring of disease activity. NETs can additionally cause endothelial cell damage and death and stimulate inflammation in atheromatous plaques, adding to the accelerated atherosclerosis witnessed in autoimmune disease. Since NETs induce production of interferons, assessing the extent of NET formation might facilitate the prediction of IFN-alpha levels and identification of SLE patients with presumably better responses to anti-IFN-alpha therapies or other novel therapeutic concepts, such as N-acetyl-cysteine and inhibitors of DNase 1 and peptidylarginine deiminase 4 (PAD4), which also target NETs. In summary, the study of NETs provides a novel approach to the understanding of autoimmune disease pathogenesis in childhood and opens new vistas in the development of sensitive disease markers and targeted therapies. PMID:27679792

  2. “The NET outcome”: are neutrophil extracellular traps of any relevance to the pathophysiology of autoimmune disorders in childhood?

    Directory of Open Access Journals (Sweden)

    Stavros Giaglis


    Full Text Available Neutrophil extracellular trap (NET formation represents a form of cell death distinct from apoptosis or necrosis, by which invading pathogens are simultaneously entangled and potentially eliminated. Increased NET formation is observed in systemic lupus erythematosus (SLE, rheumatoid arthritis (RA, antineutrophil cytoplasmic antibody (ANCA-associated and small vessel vasculitis (SVV, antiphospholipid antibody syndrome (APS and psoriasis. NETs contribute to the pathogenesis of autoimmunity by exposing cryptic autoepitopes, which may facilitate the generation of autoantibodies, induce the production of interferons and activate the complement cascade. In SLE, augmented disease activity and renal disease are associated with increased NET formation, so that NETs could serve as a marker for the monitoring of disease activity. NETs can additionally cause endothelial cell damage and death and stimulate inflammation in atheromatous plaques, adding to the accelerated atherosclerosis witnessed in autoimmune disease. Since NETs induce production of interferons, assessing the extent of NET formation might facilitate the prediction of IFN-alpha levels and identification of SLE patients with presumably better responses to anti-IFN-alpha therapies or other novel therapeutic concepts, such as N-acetyl-cysteine and inhibitors of DNase 1, and peptidylarginine deiminase 4 (PAD4, which also target NETs. In summary, the study of NETs provides a novel approach to the understanding of autoimmune disease pathogenesis and opens new vistas in the development of sensitive disease markers and therapies.

  3. Macrophage IL-12p70 Signaling Prevents HSV-1–Induced CNS Autoimmunity Triggered by Autoaggressive CD4+ Tregs (United States)

    Mott, Kevin R.; Gate, David; Zandian, Mandana; Allen, Sariah J.; Rajasagi, Naveen Kumar; van Rooijen, Nico; Chen, Shuang; Arditi, Moshe; Rouse, Barry T.; Flavell, Richard A.; Town, Terrence; Ghiasi, Homayon


    Purpose. CD4+CD25+FoxP3+ naturally occurring regulatory T cells (Tregs) maintain self-tolerance and function to suppress overly exuberant immune responses. However, it is unclear whether innate immune cells modulate Treg function. Here the authors examined the role of innate immunity in lymphomyeloid homeostasis. Methods. The involvement of B cells, dendritic cells (DCs), macrophages, natural killer (NK) cells, and T cells in central nervous system (CNS) demyelination in different strains of mice infected ocularly with herpes simplex virus type 1 (HSV-1) was investigated. Results. The authors found that depletion of macrophages, but not DCs, B cells, NK cells, CD4+ T cells, or CD8+ T cells, induced CNS demyelination irrespective of virus or mouse strain. As with macrophage depletion, mice deficient in interleukin (IL)-12p35 or IL-12p40 showed CNS demyelination after HSV-1 infection, whereas demyelination was undetectable in HSV-1–infected, IL-23p19–deficient, or Epstein-Barr virus–induced gene 3-deficient mice. Demyelination could be rescued in macrophage-depleted mice after the injection of IL-12p70 DNA and in IL-12p35−/− or IL-12p40−/− mice after injection with IL-12p35 or IL-12p40 DNA or with recombinant viruses expressing IL-12p35 or IL-12p40. Using FoxP3-, CD4-, CD8-, or CD25-depletion and gene-deficient mouse approaches, the authors demonstrated that HSV-1–induced demyelination was blocked in the absence of CD4, CD25, or FoxP3 in macrophage-depleted mice. Flow cytometry showed an elevation of CD4+CD25+FoxP3+ T cells in the spleens of infected macrophage-depleted mice, and adoptive transfer of CD4+CD25+ T cells to infected macrophage-depleted severe combined immunodeficient mice induced CNS demyelination. Conclusions. The authors demonstrated that macrophage IL-12p70 signaling plays an important role in maintaining immune homeostasis in the CNS by preventing the development of autoaggressive CD4+ Tregs. PMID:21220560

  4. Diagnostic and clinical classification of autoimmune myasthenia gravis. (United States)

    Berrih-Aknin, Sonia; Frenkian-Cuvelier, Mélinée; Eymard, Bruno


    Myasthenia gravis is characterized by muscle weakness and abnormal fatigability. It is an autoimmune disease caused by the presence of antibodies against components of the muscle membrane localized at the neuromuscular junction. In most cases, the autoantibodies are against the acetylcholine receptor (AChR). Recently, other targets have been described such as the MuSK protein (muscle-specific kinase) or the LRP4 (lipoprotein related protein 4). Myasthenia gravis can be classified according to the profile of the autoantibodies, the location of the affected muscles (ocular versus generalized), the age of onset of symptoms and thymic abnormalities. The disease generally begins with ocular symptoms (ptosis and/or diplopia) and extends to other muscles in 80% of cases. Other features that characterize MG include the following: variability, effort induced worsening, successive periods of exacerbation during the course of the disease, severity dependent on respiratory and swallowing impairment (if rapid worsening occurs, a myasthenic crisis is suspected), and an association with thymoma in 20% of patients and with other autoimmune diseases such as hyperthyroidism and Hashimoto's disease. The diagnosis is based on the clinical features, the benefit of the cholinesterase inhibitors, the detection of specific autoantibodies (anti-AChR, anti-MuSK or anti-LRP4), and significant decrement evidenced by electrophysiological tests. In this review, we briefly describe the history and epidemiology of the disease and the diagnostic and clinical classification. The neonatal form of myasthenia is explained, and finally we discuss the main difficulties of diagnosis.

  5. Granulocyte antigen systems and antibodies and their clinical significance

    Energy Technology Data Exchange (ETDEWEB)

    McCullough, J.


    Granulocyte alloantibodies and autoantibodies have a key role in the pathophysiology of several clinical problems. These include febrile transfusion reactions, severe pulmonary reactions to transfusion, isoimmune neonatal neutropenia, failure of effective granulocyte transfusion, autoimmune neutropenia, drug-induced neutropenia, and neutropenias secondary to many other diseases. Although many techniques are available for detecting granulocyte antibodies, the optimal in-vitro tests for predicting the antibodies' clinical effects are not established. Use of indium-111-labeled granulocytes may provide valuable information regarding the in-vivo effects of different granulocyte antibodies. Granulocyte transfusions continue to be used for a limited number of severely infected neutropenic patients who do not respond to antibiotic therapy.

  6. Variability in detection and quantification of interferon β-1b–induced neutralizing antibodies

    Directory of Open Access Journals (Sweden)

    Hartung Hans-Peter


    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.

  7. 抗核抗体与抗核抗体谱联合检测在自身免疫性疾病诊断上的应用%Amplification of the combinational detection of antinuclear antibody and antinuclear antibodies spectrum in the diagnosis of autoimmune diseases

    Institute of Scientific and Technical Information of China (English)

    林益强; 曾燕丽; 周建锋; 陈美珺


    目的 探讨抗核抗体(antinuclear antibody,ANA)和抗核抗体谱(antinuclear antibodies spectrum,ANAs)联合检测在自身免疫性疾病(autoimmune diseases,AID)诊断上的应用方案及价值,从而降低现症及潜在AID患者的漏检率.方法 对1231份本院门诊和住院疑似AID患者的血清标本分别采用间接免疫荧光法(indirect immunofluorescence,IIF)和免疫印迹法(immumoblot test,IBT)检测ANA和ANAs,对其中IIF-ANA1∶100(-)/IBT-ANAs(+)标本分别进行1∶10及1∶32稀释后采用IIF检测ANA,最后对上述检测结果 进行统计分析.结果 1231份血清标本中ANA阳性414份,占33.63%,ANAs阳性429份,占34.85%.按不同检测方案进行分组,发现同时检测IIF-ANA与IBT-ANAs的方案对确诊/疑似AID病人检出率最高(43.05%),分别与应用IIF-ANA进行AID的初筛的方案、仅检测IBT-ANAs的方案相比均有统计学意义(x2=23.12,P< 0.05,x2=17.42,P< 0.05).对116份(9.42%)IIF-ANA 1∶100(-)/IBT-ANAs(+)的标本分别进行1∶32及1∶10稀释后再采用IIF检测ANA,发现其中103份标本ANA荧光结果 ≥1∶32,10份标本ANA荧光结果 <1∶32而≥1∶10,3份标本ANA荧光结果 <1∶10;将标本增加1∶32和1∶10稀释度可将AID确诊/疑似病例检出率分别提高8.37%(x2=20.84,P< 0.05)与9.18%(X2=24.70,P<0.05),但二者之间相比则无统计学意义(X2=0.17,P>0.5).结论 IIF-ANA可应用于大范围AID病人初筛以减轻病人经济负担及实验室工作量压力.但是仅检测IIF-ANA或IBT-ANAs均可导致临床上患有AID或潜在的AID病人的漏检.联合检测IIF-ANA和IBT-ANAs,尤其是对临床高度怀疑AID、且ANA荧光结果 ≥1∶32的标本进行IBT-ANAs的检测可显著提高检出率,从而降低现症及潜在AID患者的漏检率.%Autoantibody is an important diagnostic index of autoimmune diseases (AID). In order to investigate the diagnostic value of antinuclear antibody (ANA) and antinuclear antibodies spectrum (ANAs

  8. Heat-shock proteins can promote as well as regulate autoimmunity. (United States)

    Rajaiah, Rajesh; Moudgil, Kamal D


    Heat-shock proteins (Hsps) are among the most highly conserved and immunogenic proteins shared by microbial agents and mammals. Under physiological conditions, the ubiquitously distributed Hsps maintain the integrity and function of other cellular proteins when cells are exposed to stressful stimuli. However, owing to their conserved nature and stress inducibility, Hsps may become targets of immune response. The T cells and/or antibodies induced by a microbial Hsp may crossreact with the corresponding mammalian Hsp (molecular mimicry) and trigger an autoimmune response, which if unchecked can lead to immune pathology and clinical manifestations. Furthermore, enhanced expression of Hsp under stress can unveil previously hidden antigenic determinants that can initiate and perpetuate autoimmune reactivity. Also, the innate immune mechanisms activated by an Hsp can reinforce and even direct the type of adaptive immune response to that protein. Hsps have been implicated in the induction and propagation of autoimmunity in several diseases, including rheumatoid arthritis, atherosclerosis and type 1 diabetes. However, Hsps possess immunoregulatory attributes as well and therefore, are being exploited for immunomodulation of various immune-mediated disorders.

  9. All eyes on the next generation of HIV vaccines: strategies for inducing a broadly neutralizing antibody response. (United States)

    Ahlers, Jeffrey D


    HIV-1 broadly neutralizing antibodies (BNAbs) develop after several years of infection through a recursive process of memory B cell adaptation and maturation against co-evolving virus quasispecies. Advances in single-cell sorting and memory B cell antibody cloning methods have identified many new HIV BNAbs targeting conserved epitopes on the HIV envelope (env) protein. 3D crystal structures and biophysical analyses of BNAbs bound to invariant virus structures expressed on monomeric gp120, epitope scaffolds, core structures, and native trimers have helped us to visualize unique binding interactions and paratope orientations that have been instrumental in guiding vaccine design. A paradigm shift in the approach to structure-based design of HIV-1 envelope immunogens came recently after several laboratories discovered that native viral envelopes or "env-structures" reverse-engineered to bind with high affinity to a handful of broadly neutralizing antibodies did not in fact bind the predicted germline precursors of these broadly neutralizing antibodies. A major challenge for HIV-1 B cell vaccine development moving forward is the design of new envelope immunogens that can trigger the selection and expansion of germline precursor and intermediate memory B cells to recapitulate B cell ontogenies associated with the maturation of a broadly neutralizing antibody response. Equally important for vaccine development is the identification of delivery systems, prime-boost strategies, and synergistic adjuvant combinations that can induce the magnitude and quality of antigen-specific T follicular helper (TFH) cell responses needed to drive somatic hypermutation (SHM) and B cell maturation against heterologous primary virus envelopes. Finding the combination of multi-protein envelope immunogens and immunization strategies that can evolve a potent broadly neutralizing antibody response portends to require a complex vaccine regimen that might be difficult to implement on any scale

  10. A novel bispecific antibody, S-Fab, induces potent cancer cell killing. (United States)

    Li, Li; He, Ping; Zhou, Changhua; Jing, Li; Dong, Bin; Chen, Siqi; Zhang, Ning; Liu, Yawei; Miao, Ji; Wang, Zhong; Li, Qing


    Bispecific antibodies that engage immune cells to kill cancer cells have been actively studied in cancer immunotherapy. In this study, we present a novel bispecific format, S-Fab, fabricated by linking a single-domain anti-carcinoembryonic antigen VHH to a conventional anti-CD3 Fab. In contrast to most bispecific antibodies, the S-Fab bispecific antibody can be efficiently expressed and purified from bacteria. The purified S-Fab is stable in serum and is able to recruit T cells to drive potent cancer cell killing. In xenograft models, the S-Fab antibody suppresses tumor growth in the presence of human immune cells. Our study suggested that the bispecific S-Fab format can be applied to a wide range of immunotherapies.

  11. 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


    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

  12. 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.

  13. Dengue E Protein Domain III-Based DNA Immunisation Induces Strong Antibody Responses to All Four Viral Serotypes. (United States)

    Poggianella, Monica; Slon Campos, José L; Chan, Kuan Rong; Tan, Hwee Cheng; Bestagno, Marco; Ooi, Eng Eong; Burrone, Oscar R


    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.

  14. 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 (Frans); P.A. van Doorn (Pieter); C.W. Ang (Wim)


    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

  15. 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.

  16. Autoimmune Cholangitis: A Variant Syndrome of Autoimmune Hepatitis


    Brij Sharma; Sujeet Raina; Rajesh Sharma


    Autoimmune cholangitis (AIC) or autoimmune cholangiopathy is a chronic inflammation of liver and a variant syndrome of autoimmune hepatitis (AIH). We present a case of an adult female who had biochemical features of cholestasis and transaminasemia but aminotransferases were not in the hepatitis range and had histological evidence of bile duct injury which was subsequently diagnosed as autoimmune cholangitis.

  17. [Autoimmune connective tissue diseases and vaccination]. (United States)

    Więsik-Szewczyk, Ewa; Jahnz-Różyk, Karina


    The idea that infectious agents can induce autoimmune diseases in genetically susceptible subjects has been a matter of discussion for years. Moreover, increased incidence of autoimmune diseases and introduction of prophylactic vaccinations from early childhood suggest that these two trends are linked. In the medical literature and even non-professional media, case reports or events temporally related to vaccination are reported. It raises the issue of vaccination safety. In everyday practice medical professionals, physicians, rheumatologists and other specialists will be asked their opinion of vaccination safety. The decision should be made according to evidence-based medicine and the current state of knowledge. The purpose of this paper is to discuss a potential mechanism which links infections, vaccinations and autoimmunity. We present an overview of published case reports, especially of systemic connective tissue diseases temporally related to vaccination and results from case-nested studies. As yet, no conclusive evidence supports a causal relationship between vaccination and autoimmune diseases. It has to be determined whether the performed studies are sufficiently sensitive to detect the link. The debate is ongoing, and new data may be required to explain the pathogenesis of autoimmunity. We would like to underscore the need for prophylactic vaccination in patients with autoimmune rheumatic diseases and to break down the myth that the vaccines are contraindicated in this target group.

  18. Ameliorating Role Exerted by Al-Hijamah in Autoimmune Diseases: Effect on Serum Autoantibodies and Inflammatory Mediators. (United States)

    Baghdadi, Hussam; Abdel-Aziz, Nada; Ahmed, Nagwa Sayed; Mahmoud, Hany Salah; Barghash, Ayman; Nasrat, Abdullah; Nabo, Manal Mohamed Helmy; El Sayed, Salah Mohamed


    Autoimmune diseases have common properties characterized by abnormal blood chemistry with high serum autoimmune antibodies, and inflammatory mediators. Those causative pathological substances (CPS) cannot be excreted by physiological mechanisms. Current treatments for autoimmune diseases involve steroids, cytotoxic drugs, plasmapheresis and monoclonal antibodies. Wet cupping therapy (WCT) of prophetic medicine is called Al-hijamah that treats numerous diseases having different etiology and pathogenesis via a pressure-dependent and size-dependent non-specific filtration then excretion of CPS causing clearance of blood and interstitial fluids. Al-hijamah clears blood passing through the fenestrated skin capillaries. Medical bases of Al-hijamah were reported in the evidence-based Taibah mechanism (Taibah theory). Al-hijamah was reported to be an excellent treatment for rheumatoid arthritis that improved patients' blood chemistry and induced significant clinical improvement and pharmacological potentiation. Al-hijamah improved the natural immunity and suppressed the pathological immunity through decreasing the serum level of autoantibodies, inflammatory mediators, and serum ferritin (a key player in autoimmunity). Al-hijamah reduced significantly pain severity, number of swollen joints and disease activity with no significant side effects. Main steps of Al-hijamah are skin suction (cupping), scarification (sharatmihjam in Arabic) and second suction (triple S technique) that is better therapeutically than the traditional WCT (double S technique). Whenever an excess noxious substance is to be removed from patients' blood and interstitial fluids, Al-hijamah is indicated. Shartatmihjam is a curative treatment in prophetic teachings according to the prophetic hadeeth: "Cure is in three: in shartatmihjam, oral honey and cauterization. I do not recommend my nation to cauterize". Al-hijamah may have better therapeutic benefits than plasmapheresis. Al-hijamah may be promising

  19. Interferon gamma-inducible protein 16 (IFI16 and anti-IFI16 antibodies in primary Sjögren’s syndrome: findings in serum and minor salivary glands

    Directory of Open Access Journals (Sweden)

    A. Alunno


    Full Text Available The interferon (IFN signature, namely the overexpression of IFN-inducible genes is a crucial aspect in the pathogenesis of primary Sjögren’s syndrome (pSS. The IFN-inducible IFI16 protein, normally expressed in cell nuclei, may be overexpressed, mislocalized in the cytoplasm and secreted in the extracellular milieu in several autoimmune disorders including pSS. This leads to tolerance breaking to this self-protein and development of anti-IFI16 antibodies. The aim of this study was to identify pathogenic and clinical significance of IFI16 and anti-IFI16 autoantibodies in pSS. IFI16 and anti-IFI16 were assessed in the serum of 30 pSS patients and one-hundred healthy donors (HD by ELISA. IFI16 was also evaluated in 5 minor salivary glands (MSGs of pSS patients and 5 MSGs of non-pSS patients with sicca symptoms by immunohistochemistry. Normal MSGs do not constitutively express IFI16. Conversely, in pSS-MSGs a marked expression and cytoplasmic mislocalization of IFI16 by epithelial cells was observed with infiltrations in lymphocytes and peri/ intra-lesional endothelium. pSS patients display higher serum levels of both IFI16 and anti-IFI16 autoantibodies compared to HD. Our data suggest that IFI16 protein may be involved in the initiation and perpetuation of glandular inflammation occurring in pSS.

  20. Psoriasis and autoimmunity. (United States)

    Sticherling, Michael


    Psoriasis is one of the most common chronic inflammatory human skin diseases. Though clinically well characterized, the exact etiological and pathogenic mechanisms are still not known in detail. Current knowledge indicates distinct overlap to other inflammatory as well as autoimmune disorders. However, the one or more relevant autoantigens could not be characterized so-far. On the other side, several autoimmune diseases were shown to be associated with psoriasis. In addition, serological autoimmune phenomena, namely diverse circulating specific autoantibodies could be demonstrated in the past. A matter of current debate is if psoriasis is a primary autoimmune disease or secondarily evolving into autoimmunity as seen in other chronic inflammatory diseases. Related to this aspect is the concept of autoinflammation versus autoimmunity where psoriasis shares mechanisms of both entities. Though T-cells remain among the most important cellular players in the pathogenesis of psoriasis and current therapeutic strategies successfully target these cells or their products irrespective of these concepts, autoimmunity if relevant will add to the treatment armamentarium by using protective and prophylactic antigen-specific modalities.

  1. Immunometabolism and autoimmunity. (United States)

    Freitag, Jenny; Berod, Luciana; Kamradt, Thomas; Sparwasser, Tim


    A continuous increase in the prevalence of autoimmune diseases is to be expected in the aging societies worldwide. Autoimmune disorders not only cause severe disability and chronic pain, but also lead to considerable socio-economic costs. Given that the current treatment options are not curative, have substantial side effects and a high percentage of non-responders, innovative options to the existing therapeutic armament against autoimmune diseases are urgently required. Accumulating evidence suggests that changes in the metabolism of immune cells are associated with, and contribute to the pathogenesis of autoimmunity. Additionally, some autoimmune diseases share alterations in metabolic pathways, key metabolites or metabolic byproducts such as reactive oxygen species. Other examples for metabolic changes in autoimmune settings include modifications in amino acid and cholesterol levels or glucose catabolism. Thus, the emerging field of immunometabolism may hold the potential to discover new therapeutic targets. Here, we discuss recent findings describing metabolic changes in autoimmune arthritis, multiple sclerosis as well as type 1 diabetes, focusing on pathophysiological aspects.

  2. Hepatitis C Virus E1 and E2 Proteins Used as Separate Immunogens Induce Neutralizing Antibodies with Additive Properties (United States)

    Beaumont, Elodie; Roch, Emmanuelle; Chopin, Lucie; Roingeard, Philippe


    Various strategies involving the use of hepatitis C virus (HCV) E1 and E2 envelope glycoproteins as immunogens have been developed for prophylactic vaccination against HCV. However, the ideal mode of processing and presenting these immunogens for effective vaccination has yet to be determined. We used our recently described vaccine candidate based on full-length HCV E1 or E2 glycoproteins fused to the heterologous hepatitis B virus S envelope protein to compare the use of the E1 and E2 proteins as separate immunogens with their use as the E1E2 heterodimer, in terms of immunogenetic potential and the capacity to induce neutralizing antibodies. The specific anti-E1 and anti-E2 antibody responses induced in animals immunized with vaccine particles harboring the heterodimer were profoundly impaired with respect to those in animals immunized with particles harboring E1 and E2 separately. Moreover, the anti-E1 and anti-E2 antibodies had additive neutralizing properties that increase the cross-neutralization of heterologous strains of various HCV genotypes, highlighting the importance of including both E1 and E2 in the vaccine for an effective vaccination strategy. Our study has important implications for the optimization of HCV vaccination strategies based on HCV envelope proteins, regardless of the platform used to present these proteins to the immune system. PMID:26966906

  3. Hepatitis C Virus E1 and E2 Proteins Used as Separate Immunogens Induce Neutralizing Antibodies with Additive Properties. (United States)

    Beaumont, Elodie; Roch, Emmanuelle; Chopin, Lucie; Roingeard, Philippe


    Various strategies involving the use of hepatitis C virus (HCV) E1 and E2 envelope glycoproteins as immunogens have been developed for prophylactic vaccination against HCV. However, the ideal mode of processing and presenting these immunogens for effective vaccination has yet to be determined. We used our recently described vaccine candidate based on full-length HCV E1 or E2 glycoproteins fused to the heterologous hepatitis B virus S envelope protein to compare the use of the E1 and E2 proteins as separate immunogens with their use as the E1E2 heterodimer, in terms of immunogenetic potential and the capacity to induce neutralizing antibodies. The specific anti-E1 and anti-E2 antibody responses induced in animals immunized with vaccine particles harboring the heterodimer were profoundly impaired with respect to those in animals immunized with particles harboring E1 and E2 separately. Moreover, the anti-E1 and anti-E2 antibodies had additive neutralizing properties that increase the cross-neutralization of heterologous strains of various HCV genotypes, highlighting the importance of including both E1 and E2 in the vaccine for an effective vaccination strategy. Our study has important implications for the optimization of HCV vaccination strategies based on HCV envelope proteins, regardless of the platform used to present these proteins to the immune system.

  4. Hepatitis C Virus E1 and E2 Proteins Used as Separate Immunogens Induce Neutralizing Antibodies with Additive Properties.

    Directory of Open Access Journals (Sweden)

    Elodie Beaumont

    Full Text Available Various strategies involving the use of hepatitis C virus (HCV E1 and E2 envelope glycoproteins as immunogens have been developed for prophylactic vaccination against HCV. However, the ideal mode of processing and presenting these immunogens for effective vaccination has yet to be determined. We used our recently described vaccine candidate based on full-length HCV E1 or E2 glycoproteins fused to the heterologous hepatitis B virus S envelope protein to compare the use of the E1 and E2 proteins as separate immunogens with their use as the E1E2 heterodimer, in terms of immunogenetic potential and the capacity to induce neutralizing antibodies. The specific anti-E1 and anti-E2 antibody responses induced in animals immunized with vaccine particles harboring the heterodimer were profoundly impaired with respect to those in animals immunized with particles harboring E1 and E2 separately. Moreover, the anti-E1 and anti-E2 antibodies had additive neutralizing properties that increase the cross-neutralization of heterologous strains of various HCV genotypes, highlighting the importance of including both E1 and E2 in the vaccine for an effective vaccination strategy. Our study has important implications for the optimization of HCV vaccination strategies based on HCV envelope proteins, regardless of the platform used to present these proteins to the immune system.

  5. Xyloglucan Antibodies Inhibit Auxin-Induced Elongation and Cell Wall Loosening of Azuki Bean Epicotyls but Not of Oat Coleoptiles 1 (United States)

    Hoson, Takayuki; Masuda, Yoshio; Sone, Yoshiaki; Misaki, Akira


    Polyclonal antibodies were raised in rabbits against isoprimeverose (Xyl1Glc1), xyloglucan heptasaccharides (Xyl3Glc4), and octasaccharides (Gal1Xyl3Glc4). Antibodies specific for hepta- and octasaccharides suppressed auxin-induced elongation of epicotyl segments of azuki bean (Vigna angularis Ohwi and Ohashi cv Takara). These antibodies also inhibited auxin-induced cell wall loosening (decrease in the minimum stress-relaxation time and the relaxation rate of the cell walls) of azuki segments. However, none of the antibodies influenced auxin-induced elongation or cell wall loosening of coleoptile segments of oat (Avena sativa L. cv Victory). Auxin caused a decrease in molecular mass of xyloglucans in the cell walls of azuki epicotyls and oat coleoptiles. The antibodies inhibited such a change in molecular mass of xyloglucans in both species. Preimmune serum exhibited little or no inhibitory effect on auxin-induced elongation, cell wall loosening, or breakdown of xyloglucans. The results support the view that the breakdown of xyloglucans is associated with the cell wall loosening responsible for auxin-induced elongation in dicotyledons. The view does not appear to be applicable to poaceae, because the inhibition of xyloglucan breakdown by the antibodies did not influence auxin-induced elongation or cell wall loosening of oat coleoptiles. ImagesFigure 1Figure 2 PMID:16668221

  6. Target Proteins in Human Autoimmunity: Cytochromes P450 and Udp-Glycoronosyltransferases

    Directory of Open Access Journals (Sweden)

    Petra Obermayer-Straub


    Full Text Available Cytochromes P450 (CYPs and UDP-glucuronosyltransferases (UGTs are targets of autoantibodies in several hepatic and extrahepatic autoimmune diseases. Autoantibodies directed against hepatic CYPs and UGTs were first detected by indirect immunofluorescence as antiliver and/or kidney microsomal antibodies. In autoimmune hepatitis (AIH type 2, liver and/or kidney microsomal (LKM type 1 autoantibodies are detected and are directed against CYP2D6. About 10% of AIH-2 sera further contain LKM-3 autoantibodies directed against family 1 UGTs. Chronic infections by hepatitis C virus and hepatitis delta virus may induce several autoimmune phenomena, and multiple autoantibodies are detected. Anti-CYP2D6 autoantibodies are detected in up to 4% of patients with chronic hepatitis C, and anti-CYP2A6 autoantibodies are detected in about 2% of these patients. In contrast, 14% of patients with chronic hepatitis delta virus infections generate anti-UGT autoantibodies. In a small minority of patients, certain drugs are known to induce immune-mediated, idiosyncratic drug reactions, also known as ’drug-induced hepatitis’. Drug-induced hepatitis is often associated with autoantibodies directed against hepatic CYPs or other hepatic proteins. Typical examples are tienilic acid-induced hepatitis with anti-CYP2C9, dihydralazine hepatitis with anti-CYP1A2, halothane hepatitis with anti-CYP2E1 and anticonvulsant hepatitis with anti-CYP3A. Recent data suggest that alcoholic liver disease may be induced by mechanisms similar to those that are active in drug-induced hepatitis. Autoantibodies directed against several CYPs are further detected in sera from patients with the autoimmune polyglandular syndrome type 1. Patients with autoimmune polyglandular syndrome type 1 with hepatitis often develop anti-CYP1A2; patients with adrenal failure develop anti-CYP21, anti- CYP11A1 or CYP17; and patients with gonadal failure develop anti-CYP11A1 or CYP17. In idiopathic Addison disease

  7. Autoimmune-mediated peripheral neuropathies and autoimmune pain. (United States)

    Klein, Christopher J


    Peripheral neuropathies have diverse acquired and inherited causes. The autoimmune neuropathies represent an important category where treatment is often available. There are overlapping signs and symptoms between autoimmune neuropathies and other forms. Making a diagnosis can be challenging and first assisted by electrophysiologic and sometimes pathologic sampling, with autoimmune biomarkers providing increased assistance. Here we provide a review of the autoimmune and inflammatory neuropathies, their available biomarkers, and approaches to treatment. Also discussed is new evidence to support a mechanism of autoimmune pain.

  8. Broadly Neutralizing Hemagglutinin Stalk-Specific Antibodies Induce Potent Phagocytosis of Immune Complexes by Neutrophils in an Fc-Dependent Manner

    Directory of Open Access Journals (Sweden)

    Caitlin E. Mullarkey


    Full Text Available Broadly neutralizing antibodies that recognize the conserved hemagglutinin (HA stalk have emerged as exciting new biotherapeutic tools to combat seasonal and pandemic influenza viruses. Our general understanding of the mechanisms by which stalk-specific antibodies achieve protection is rapidly evolving. It has recently been demonstrated that broadly neutralizing HA stalk-specific IgG antibodies require Fc-Fcγ receptor (FcγR interactions for optimal protection in vivo. Here we examine the neutrophil effector functions induced by stalk-specific antibodies. As the most abundant subset of blood leukocytes, neutrophils represent a critical innate effector cell population and serve an instrumental role in orchestrating downstream adaptive responses to influenza virus infection. Yet, the interplay of HA stalk-specific IgG, Fc-FcγR engagement, and neutrophils has remained largely uncharacterized. Using an in vitro assay to detect the production of reactive oxygen species (ROS, we show that human and mouse monoclonal HA stalk-specific IgG antibodies are able to induce the production of ROS by neutrophils, while HA head-specific antibodies do not. Furthermore, our results indicate that the production of ROS is dependent on Fc receptor (FcR engagement and phagocytosis. We went on to assess the ability of monoclonal HA stalk-specific IgA antibodies to induce ROS. Consistent with our findings for monoclonal IgGs, only HA stalk-specific IgA antibodies elicited ROS production by neutrophils. This induction is dependent on the engagement of FcαR1. Taken together, our findings describe a novel FcR-dependent effector function induced by HA stalk-specific IgG and IgA antibodies, and importantly, our studies shed light on the mechanisms by which HA stalk-specific antibodies achieve protection.

  9. Broadly Neutralizing Hemagglutinin Stalk-Specific Antibodies Induce Potent Phagocytosis of Immune Complexes by Neutrophils in an Fc-Dependent Manner. (United States)

    Mullarkey, Caitlin E; Bailey, Mark J; Golubeva, Diana A; Tan, Gene S; Nachbagauer, Raffael; He, Wenqian; Novakowski, Kyle E; Bowdish, Dawn M; Miller, Matthew S; Palese, Peter


    Broadly neutralizing antibodies that recognize the conserved hemagglutinin (HA) stalk have emerged as exciting new biotherapeutic tools to combat seasonal and pandemic influenza viruses. Our general understanding of the mechanisms by which stalk-specific antibodies achieve protection is rapidly evolving. It has recently been demonstrated that broadly neutralizing HA stalk-specific IgG antibodies require Fc-Fcγ receptor (FcγR) interactions for optimal protection in vivo Here we examine the neutrophil effector functions induced by stalk-specific antibodies. As the most abundant subset of blood leukocytes, neutrophils represent a critical innate effector cell population and serve an instrumental role in orchestrating downstream adaptive responses to influenza virus infection. Yet, the interplay of HA stalk-specific IgG, Fc-FcγR engagement, and neutrophils has remained largely uncharacterized. Using an in vitro assay to detect the production of reactive oxygen species (ROS), we show that human and mouse monoclonal HA stalk-specific IgG antibodies are able to induce the production of ROS by neutrophils, while HA head-specific antibodies do not. Furthermore, our results indicate that the production of ROS is dependent on Fc receptor (FcR) engagement and phagocytosis. We went on to assess the ability of monoclonal HA stalk-specific IgA antibodies to induce ROS. Consistent with our findings for monoclonal IgGs, only HA stalk-specific IgA antibodies elicited ROS production by neutrophils. This induction is dependent on the engagement of FcαR1. Taken together, our findings describe a novel FcR-dependent effector function induced by HA stalk-specific IgG and IgA antibodies, and importantly, our studies shed light on the mechanisms by which HA stalk-specific antibodies achieve protection.

  10. Autoimmunity in Immunodeficiency (United States)

    Todoric, Krista; Koontz, Jessica B.; Mattox, Daniel; Tarrant, Teresa K.


    Primary immunodeficiencies (PID) comprise a diverse group of clinical disorders with varied genetic defects. Paradoxically, a substantial proportion of PID patients develop autoimmune phenomena in addition to having increased susceptibility to infections from their impaired immunity. Although much of our understanding comes from data gathered through experimental models, there are several well-characterized PID that have improved our knowledge of the pathways that drive autoimmunity. The goals of this review will be to discuss these immunodeficiencies and to review the literature with respect to the proposed mechanisms for autoimmunity within each put forth to date. PMID:23591608

  11. 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


    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.

  12. Gamma ray-induced mutants as a tool for the production and characterisation of monoclonal antibodies against HLA-alloantigens

    Energy Technology Data Exchange (ETDEWEB)

    Spring, B.; Pawelec, G.; Ziegler, A.


    To simplify the screening procedure for murine monoclonal antibodies specific for polymorphic HLA determinants, spleen cells from a mouse immunized with the human cell line BJAB-B95.8.6 were fused with NS1 mouse myeloma cells, and hybridoma supernatants were screened for their reactivity on BJAB-B95.8.6 and two gamma ray-induced HLA-loss mutants of this line. The use of these HLA-loss mutants allowed the rapid identification of two new allospecific MOABs designated TU160 and TU161. Serological as well as biochemical studies revealed TU160 to be specific for HLA=A2, and TU161 for HLA-B13 molecules, respectively. Both MOABs were determined to be antibodies of the IgG class and were able to precipitate their antigens from lysates of radioactively labeled cells.

  13. Vaccination of dogs with Trypanosoma rangeli induces antibodies against Trypanosoma cruzi in a rural area of Córdoba, Argentina. (United States)

    Basso, Beatriz; Marini, Vanina; Gauna, Diego; Frias, Maria


    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. cruzi infection, received three immunisations with fixed T. rangeli epimastigotes. Dogs were not challenged with T. cruzi, but they were left in their environment. This immunisation induced antibodies against T. cruzi for more than three years in dogs in their natural habitat, while control dogs remained serologically negative.

  14. Murine pattern recognition receptor dectin-1 is essential in the development of experimental autoimmune uveoretinitis. (United States)

    Stoppelkamp, Sandra; Reid, Delyth M; Yeoh, Joyce; Taylor, Julie; McKenzie, Emma J; Brown, Gordon D; Gordon, Siamon; Forrester, John V; Wong, Simon Y C


    Mycobacteria in complete Freund's adjuvant (CFA) are an essential component of immunization protocols in a number of autoimmune disease animal models including experimental autoimmune encephalomyelitis and uveoretinitis (EAE and EAU, respectively). We determined the role in EAU of two C-type lectin receptors on myeloid cells that recognize and respond to mycobacteria. Using receptor-specific antibodies and knockout mice, we demonstrated for the first time that the macrophage mannose receptor delays disease development but does not affect severity. In contrast, dectin-1 is critically involved in the development of CFA-mediated EAU. Disease severity is reduced in dectin-1 knockout mice and antibody blockade of dectin-1 during the induction, but not the effector phase, prevents EAU development. Significantly, similar blockade of dectin-1 in vivo has no effect in non-CFA-mediated, spontaneously induced or adoptive transfer models of EAU. Thus dectin-1 plays a critical role in the ability of complete Freund's adjuvant to induce EAU in mice.

  15. Anti-tumor immunological response induced by cryoablation and anti-CTLA-4 antibody in an in vivo RM-1 cell prostate cancer murine model. (United States)

    Li, F; Guo, Z; Yu, H; Zhang, X; Si, T; Liu, C; Yang, X; Qi, L


    Cryoablation combination therapy with blockade of the T-cell inhibitory receptor CTL-associated antigen-4 (CTLA-4) may augment the anti-tumor immune response (ATIR). It is crucial to determine the duration of ATIR after cryoablation and anti-CTLA-4 antibody therapy to determine the most appropriate treatment interval of therapy. To investigate the characteristics of ATIR induced by cryoablation and anti-CTLA-4 antibody therapy, we developed a prostate cancer model system to test the capacity of cryoablation and anti -CTLA-4 antibody to generate ATIR. Mice were randomly assigned to receive no treatment (group A), cryoablation only (group B), cryoablation plus anti-CTLA-4 antibody (group C), or anti-CTLA-4 antibody only (group D). We collected specimens on days 0, 7, 14 and 21 to study the ATIR through different techniques. Our results indicated that cryoablation induced ATIR and further enhanced this effect and reduced the number of distant metastases through combination with anti-CTLA-4 antibody. ATIR induced by cryoablation was achieved through decreasing regulatory T cell (Treg) number. The number of Tregs induced by cryoablation was lowest on day 14 but then returned to preoperative levels on day 21, indicating that ATIR induced by cryoablation was time-dependent. However, ATIR induced by anti-CTLA-4 antibody might be mainly achieved through influencing Treg function, which was exactly not by decreasing Treg number and still maintain its ATIR effect on day 21 after therapy. In conclusion, ATIR induced by cryoablation was achieved through decreasing Treg number and is time-dependent, whereas ATIR caused by anti-CTLA-4 antibody was achieved exactly not by decreasing Treg number and not time-dependent in the first 21 days after therapy.

  16. Alterations in nuclear structure promote lupus autoimmunity in a mouse model

    Directory of Open Access Journals (Sweden)

    Namrata Singh


    Full Text Available 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.LbricF1 offspring were evaluated for induction of lupus autoimmunity. Only female (NZW×B6.LbricF1 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.LbricF1 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

  17. Alterations in nuclear structure promote lupus autoimmunity in a mouse model (United States)

    Singh, Namrata; Johnstone, Duncan B.; Martin, Kayla A.; Tempera, Italo; Kaplan, Mariana J.


    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