Selective IgG Subclass Antibody Response to Insulin in Diabetic Patients Receiving Animal Insulin Replacement Therapy

Siddiqi, Mushtaq A.; Wangnoo, Subash K.

doi:10.1159/000234922

Cited by 3 publications

(2 citation statements)

References 12 publications

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“…Blocking experiments with anti IgGl-4 mAh strongly sug gested that the anti-insulin antibodies in plasma and on basophil membranes were of the IgG4 class. A high level of anti-insulin IgG4 in diabetics receiving exogenous in sulin was correlated to a relative insulin resistance [24). But to our knowledge auto-insulin IgG4 antibodies have not yet been reported in insulin-dependent diabetic pa tients before insulin therapy.…”

Section: Discussionmentioning

confidence: 72%

“…The autoimmune etiology of type I diabetes has been well documented after the discovery of anti-islet and anti insulin antibodies before exogenous insulin administra tion [1,2,[4][5][6][7][8], Increased anti-insulin IgG4 concentrations have been reported during insulin treatment [24], Autoan tibodies restricted to the IgG4 subclass have been found in bullous pemphigoid [25]. Moreover, this subclass is in volved in immune complex deposists in tissues [26] and in rheumatoid arthritis, IgG4 was found to be an important fraction of the IgG rheumatoid factor [27].…”

Section: Discussionmentioning

confidence: 99%

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Presence of Anti-Insulin Reaginic Auto-Antibodies of the lgG4 Class in Insulin-Dependent (Type I) Diabetic Patients before Insulin Therapy

Bidet

Beauvais²,

Timsit³

et al. 1993

Int Arch Allergy Immunol

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The autoimmune aetiology of type I diabetes has been well documented. We studied whether anti-insulin anaphylactic antibodies were present on the membrane of basophils from type I diabetics by the toluidine blue method (detecting basophil activation after stimulation by insulin). We observed that basophils of recently diagnosed insulin-dependent diabetic patients (n = 13) were statistically more frequently activated by insulin than basophils from nonin-sulin-dependent diabetics (p < 0.002, n = 8) or non-diabetic subjects (p < 0.05, n = 9). Basophils from normal donors were passively sensitized with plasma from insulin-dependent diabetics and could then be activated by insulin. This sensitization still occurred when using plasma previously heated to 56°C, indicating that the sensitizing antibodies were not of the IgE class. When basophils from type I diabetics were preincubated with anti-IgG subclasses, only anti-IgG4 monoclonal antibodies inhibited the insulin-induced basophil activation. By contrast, preincubation with blocking concentrations of anti-IgG1-3 antibodies or desensitization of the IgE pathway did not modify basophil activation. These experiments strongly suggest the presence of anti-insulin antibodies of the IgG4 subclass in insulin-dependent diabetics before any insulin administration and provide a simple tool to complement the usual method of detecting auto-antibodies in diabetes.

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Presence of Anti-Insulin Reaginic Auto-Antibodies of the lgG4 Class in Insulin-Dependent (Type I) Diabetic Patients before Insulin Therapy

Bidet

Beauvais²,

Timsit³

et al. 1993

Int Arch Allergy Immunol

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Complications of Insulin Therapy

Fineberg

Anderson

2003

International Textbook of Diabetes Mellitus

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Insulin allergic reactions were seen in the first insulin preparations used for therapy of diabetes mellitus. The use of highly purified animal insulins, semisynthetic, and recombinant DNA human insulins has resulted in a dramatic reduction in the immunological complications of insulin therapy. However, subcutaneous human insulin administration with biosynthetic insulins has been shown to incite antibody responses in nondiabetic individuals as well as in diabetic individuals via subcutaneous, respiratory, and peritoneal routes. Further, anti‐insulin antibodies commonly precede the appearance of type 1 diabetes, especially in children. Hypertrophy of subcutaneous fat at sites of repeated insulin injections continues to be a common nonimmunological complication of therapy. In addition, hypertrophy of omental fat has been reported to be a cause of catheter occlusion during the course of intraperitoneal delivery of concentrated insulin by implantable insulin pumps. Edema associated with insulin therapy is an unusual and usually self‐limited disorder. Hypoglycemia secondary to insulin therapy is the expected outcome of a mismatch between nutrients, insulin levels, insulin action, and glucose counterregulatory mechanisms. This chapter reviews insulin immunology and the immunological and nonimmunological complications of insulin therapy.

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Immunoglobulin Subclasses in Patients with Neutralizing and Nonneutralizing Antibodies Against IFN-β1b

Deisenhammer

Reindl

Berger

2001

Journal of Interferon & Cytokine Research

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Treatment of multiple sclerosis (MS) with interferon-beta1b (IFN-beta1b) induces the production of antibodies in some patients. A proportion of these antibodies can reduce the biologic activity of IFN-beta, and they are, therefore, referred to as neutralizing antibodies (NAB). The remaining antibodies do not interfere with the biologic activity of IFN-beta and are referred to as nonneutralizing antibodies (NNAB) in this paper. Immunoglobulin (Ig) subtyping of these antibodies was carried out, and Ig subclass patterns in 20 patients with NAB were compared with those of NNAB in 39 patients. In patients with NAB, IgG2 and IgG4 were found to occur more frequently than in patients with NNAB (30% vs. 3%, p = 0.05, and 55% vs. 18%, p = 0.003, respectively) The NAB titer correlated strongly with the IgG4 titer (r = 0.53, p = 0.02). Median total IgG, IgG1, and IgG4 titers were significantly higher in NAB than in NNAB patients (respectively, 8000 vs. 3200, p = 0.01; 1600 vs. 400, p = 0.0004; 200 vs. 0, p = 0.004). It is concluded that the development of NAB is related to both the quantity and the quality of the antibodies against IFN-beta1b.

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Selective IgG Subclass Antibody Response to Insulin in Diabetic Patients Receiving Animal Insulin Replacement Therapy

Cited by 3 publications

References 12 publications

Presence of Anti-Insulin Reaginic Auto-Antibodies of the lgG4 Class in Insulin-Dependent (Type I) Diabetic Patients before Insulin Therapy

Presence of Anti-Insulin Reaginic Auto-Antibodies of the lgG4 Class in Insulin-Dependent (Type I) Diabetic Patients before Insulin Therapy

Complications of Insulin Therapy

Immunoglobulin Subclasses in Patients with Neutralizing and Nonneutralizing Antibodies Against IFN-β1b

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