Autoantibodies against human insulin.

Wilkin, Terence J.; Nicholson, Sarah

doi:10.1136/bmj.288.6414.349

Cited by 56 publications

(12 citation statements)

References 14 publications

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“…Thus, both of these studies reported a frequency of elevated insulin binding that is below that presented here (at least 50%). Wilkin and Nicholson 35 have previously reported a small percentage of individuals with insulin autoantibodies that bind human, but not porcine, insulin. Because these antibodies would not be detected in our assay, one would have predicted a slightly lower percentage of positive sera at diagnosis in our study.…”

Section: Discussionmentioning

confidence: 99%

Anti-Insulin Antibodies in Children With Type I Diabetes Mellitus: Genetic Regulation of Production and Presence at Diagnosis Before Insulin Replacement

McEvoy

Witt²,

Ginsberg‐Fellner³

et al. 1986

Diabetes

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We evaluated the production of antibodies against insulin in a genetically well-defined population. In the first study, 124 young patients with type I diabetes for longer than 6 mo were included. Anti-insulin antibodies were detected by polyethyleneglycol (PEG) precipitation after incubation of acidified, charcoal-stripped sera with 125I-labeled pork insulin and were expressed as microunits insulin bound per milliliter whole serum. For comparison, the patients were divided into six groups based on HLA DR antigens: 3/3, 3/-, 4/4, 4/-, 3/4, and -/-(-is non-DR3 or -DR4). The mean age of the patients was 14.7 +/- 0.5 yr; the duration of diabetes was 5.8 +/- 0.4 yr; and the glucose control, as measured by hemoglobin A1c was average (7.6 +/- 0.2%). There were no significant differences in any of these parameters among the patients in any of the HLA DR groups. Patients expressing DR3/3 had significantly lower insulin binding than the rest of the groups (2.5 +/- 0.4 vs. 13.6 +/- 1.4 microU/ml, P less than 0.0001). Patients with DR3/ - did not differ in insulin-binding capacity from the other groups. The type of insulin used for replacement was not correlated with the serum insulin-binding capacity. In a second study, sera from 48 children, newly diagnosed with type I diabetes, were examined for the presence of insulin binding before treatment with exogenous insulin and compared with sera from 80 children without diabetes or a family history of diabetes and from 103 unaffected HLA-identical or haploidentical siblings of a child with type I diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 99%

Anti-Insulin Antibodies in Children With Type I Diabetes Mellitus: Genetic Regulation of Production and Presence at Diagnosis Before Insulin Replacement

McEvoy

Witt²,

Ginsberg‐Fellner³

et al. 1986

Diabetes

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“…Insulin autoantibodies detectable by ELISA in nondiabetic individuals are frequently monoclonal and directed to human insulin, whereas antibodies in insulin-treated individuals are usually polyclonal and do not discriminate among species (1,27,28). Noncompetitive-binding ELISAs have been used to analyze binding kinetics; however, the validity of this approach has been disputed (29)(30)(31).…”

Section: Discussionmentioning

confidence: 99%

“…I nsulin-dependent (type I) diabetes mellitus has been reported to be associated with insulin autoantibodies detectable by radiobinding assays up to 40% of the time in individuals who are <20 yr of age (1)(2)(3)(4). The incidence of such autoantibodies in older individuals with diabetes, in individuals who are family members of patients with diabetes, and those who are islet cell antibody (ICA) positive appears to be more common than in the general population (5).…”

mentioning

confidence: 99%

Presence of Insulin Autoantibodies as Regular Feature of Nondiabetic Repertoire of Immunity

Fineberg

Biegel²,

Dürr³

et al. 1991

Diabetes

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With an ultrasensitive noncompetitive enzyme-linked immunosorbent assay (ELISA), we tested the hypothesis that the presence of insulin autoantibodies in nondiabetic individuals is a normal event. Plasma and peripheral blood mononuclear cells were obtained from 50 nondiabetic whites for determination of insulin autoantibodies by ELISA and radioimmunoassay (anti-insulin IgG [AI-IgG] and 125I-labeled insulin bound [%]), islet cell antibodies, anti-nuclear antibodies and rheumatoid factor, and HLA class II-type antigens (DR, DRw, and DQ). The range of 125I-insulin binding was significantly less than was seen in pretreatment sera from individuals with diabetes (from -0.4 to 0.4% vs. -0.8 to 7.7%, respectively, P = 0.001). Eighty-eight percent of these nondiabetic individuals had significant levels of AI-IgG with preferential binding to human insulin. The geometric mean of AI-IgG concentrations in individuals with significant levels was 180 pM. Binding to human insulin was seen in 88%, to pork insulin in 42%, and to beef insulin in 24% of individuals (P less than 0.001 overall; P less than 0.05 where more bound to pork than beef insulin). Binding of AI-IgG to human insulin-coated plates was substantially inhibited by preincubation with human insulin (median inhibition 57.6%) with little if any inhibition by glucagon, C-peptide, albumin, or IgG. Four individuals had highly specific human AI-IgG as shown by immunoaffinity studies. AI-IgGs were significantly higher in individuals with the HLA haplotype DR4,DRw53,DQ3 and lower in individuals with DR5,DRw52,DQ1 (P = 0.03 for both).(ABSTRACT TRUNCATED AT 250 WORDS)

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“…In the latter case the level of TSH bioactivity was normal. Other examples in which circulating antibodies to the hormone could give rise to misleading immunoassays are autoantibodies to insulin (Wilkin & Nicholson, 1984).…”

Section: ) Circulating Antibodies To Hormonementioning

confidence: 99%