Islet-Cell Antibodies and Insulin Autoantibodies in Association With Common Viral Infections

Bodansky, H. J.; Dean, B M; Bottazzo, Gian Franco; Grant, Peter J.; McNally, J. M.; Hambling, M.H.; Wales, J. K.

doi:10.1016/s0140-6736(86)92003-9

Cited by 72 publications

(33 citation statements)

References 18 publications

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“…The frequent finding of IAA not associated with ICA in sera from patients with common viral infections has been reported previously (18). It has been postulated that viruses may trigger the production of IAA through polyclonal immunocyte activation (18). In another study, an increase in IAA levels not associated with ICA was observed after IFN-␣ therapy, but none of the positive patients developed type 1 diabetes (19).…”

Section: Clinical Studymentioning

confidence: 73%

“…IAA levels did not change during the IFN-␣ therapy and none of the IAA + patients developed type 1 diabetes. The frequent finding of IAA not associated with ICA in sera from patients with common viral infections has been reported previously (18). It has been postulated that viruses may trigger the production of IAA through polyclonal immunocyte activation (18).…”

Section: Clinical Studymentioning

confidence: 84%

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Autoimmunity against pancreatic islets and other tissues before and after interferon-alpha therapy in patients with hepatitis C virus chronic infection.

et al. 2000

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OBJECTIVE -The aim of the study was to investigate the prevalence of clinical and latent autoimmune diseases in Italian patients with hepatitis C virus (HCV) chronic infection before and after treatment with interferon-␣ (IFN-␣).RESEARCH DESIGN AND METHODS -The evidence of clinical autoimmune disease and the presence of autoantibodies were assessed in 70 patients with HCV chronic infection. Autoantibodies to islet cell (ICA), glucagon-producing cells (GCA), parietal cell (PCA), adrenal cortex (ACA), adrenal medulla (AdMA), nuclei (ANA), liver-kidney microsomal (LKM-Ab), mitochondrial, and smooth muscle (SMA) were tested using the classic indirect immunofluorescence technique. Autoantibodies to GAD (GADAb), second islet cell autoantigen (IA2-Ab), and insulin (IAA) were tested by radioimmunoassay, and thyroid microsomal autoantibodies (TMHA) and thyroglobulin autoantibodies (TGHA) were assessed by hemoagglutination test.RESULTS -None of the 70 patients studied showed evidence of clinical disease before treatment with IFN-␣. However, 1 (1.4%) patient was positive for ICA, 2 (2.8%) were positive for GCA, 2 (2.8%) for GADAb, 5 (7.1%) for PCA, 2 (2.8%) for ANA, 3 (3.7%) for SMA, 4 (5.7%) for TMHA, and 2 (2.8%) for TGHA. These frequencies were not significantly different when compared with healthy control subjects. There were 29 (41%) patients who were positive for IAA at low titers compared with 2% of the control subjects (significantly different P Ͻ 0.0001). ICA titers of one patient positive for ICA/GADAb increased during the IFN-␣ therapy, and the patient developed type 1 diabetes 5 months after the beginning of treatment. IAA levels did not change during the course of treatment, and none of the IAA + patients developed diabetes. Thyroid autoantibody titers increased in 3 of the 4 initially positive patients, with 1 patient becoming positive and 2 thyroid antibody-positive patients developing overt hypothyroidism during IFN-␣ treatment. PCA titers increased in 1 of 5 positive patients. Antibodies to other autoantigens did not change during the course of treatment.CONCLUSIONS -We have not found an increased frequency of clinical or latent autoimmune diseases in patients with chronic HCV infection. However, this study suggests that screening patients for autoantibodies (in particular, thyroid and pancreas) before and during IFN-␣ ther-

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Section: Clinical Studymentioning

confidence: 73%

Section: Clinical Studymentioning

confidence: 84%

Autoimmunity against pancreatic islets and other tissues before and after interferon-alpha therapy in patients with hepatitis C virus chronic infection.

et al. 2000

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“…There are also a few studies on the isotype profile of autoantibodies to GAD65 in prediabetic individuals who manifest type 1 diabetes during prospective follow-up and in children who remain unaffected, and one of these suggested a more immature isotype distribution in the nonprogressors who had higher levels of IgE and IgM antibodies than the progressors (9), but conflicting results have also been reported (21). Little is known about the immunoglobulin isotype profile of IAA, but they have been reported to be of either IgG or IgM class (23,24). In patients with type 1 diabetes, insulin antibodies comprise mainly IgG1 antibodies, whereas IgG3 antibodies are more prevalent before the initiation of exogenous insulin (25).…”

mentioning

confidence: 99%

Insulin Autoantibody Isotypes during the Prediabetic Process in Young Children with Increased Genetic Risk of Type 1 Diabetes

et al. 2004

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“…The small molecule (5800 Da) is produced by the pancreatic ␤ cells of all mammals, and it circulates postprandially in low concentrations as part of the physiological response to glucose. Abs that bind autologous hormone are routinely produced after administration of the hormone in the treatment of diabetes mellitus, and spontaneous Abs are detected following viral infections, hypersensitivity states, and in the prodrome of autoimmune endocrine disease (17)(18)(19)(20)(21). To directly investigate the nature of tolerance in the B cell repertoire for insulin, we introduced the V region genes from mAb125 into the germline of C57BL/6 mice as an IgMa transgene (125Tg).…”

mentioning

confidence: 99%

Anergy and not Clonal Ignorance Determines the Fate of B Cells that Recognize a Physiological Autoantigen

Rojas

Hulbert

Thomas

2001

The Journal of Immunology

107

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Autoantibodies to insulin arise spontaneously in the insulin autoimmune syndrome and in type I diabetes. In addition, administration of insulin to individuals without autoimmune disease routinely results in Abs that bind autologous hormone. These observations and findings in transgenic models of tolerance led to an inference that physiological levels of hormones and growth factors, such as insulin, are not sufficient to induce tolerance in B cells, a state termed clonal ignorance. In contrast, we have discovered that virtually all conventional B cells expressing a low affinity anti-insulin transgene interact with endogenous insulin and are effectively silenced for Ig production and for T cell-dependent immune responses. A fraction of transgenic B cells escapes silencing and functions autonomously to produce insulin Abs that may lower fasting blood sugars similar to an insulin autoimmune syndrome. These B cells have characteristics of a B1-like subset and are depleted by hypotonic peritoneal lysis. These findings question the concept of clonal ignorance and show that physiological concentrations of Ag may effectively silence conventional B cells even when the affinity for autoantigen is low. Self-reactivity may arise in the repertoire because of compartmental differences that govern the fate of B cells and not as a result of true clonal ignorance.

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Islet-Cell Antibodies and Insulin Autoantibodies in Association With Common Viral Infections

Cited by 72 publications

References 18 publications

Autoimmunity against pancreatic islets and other tissues before and after interferon-alpha therapy in patients with hepatitis C virus chronic infection.

Autoimmunity against pancreatic islets and other tissues before and after interferon-alpha therapy in patients with hepatitis C virus chronic infection.

Insulin Autoantibody Isotypes during the Prediabetic Process in Young Children with Increased Genetic Risk of Type 1 Diabetes

Anergy and not Clonal Ignorance Determines the Fate of B Cells that Recognize a Physiological Autoantigen

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