Insulin autoantibodies at diagnosis of insulin-dependent diabetes: Effect on the antibody response to insulin treatment

Sutton, M. St. John; Klaff, Leslie J.; Asplin, Chris M.; Clemons, Peter; Tatpati, Olga; Lyen, Kenneth; Raghu, Prema; Baker, Lester; Guthrie, Rufus K.; Sperling, Mark A.; Palmer, Jerry P.

doi:10.1016/0026-0495(88)90058-3

Cited by 9 publications

(8 citation statements)

References 11 publications

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“…2b). IA frequently develop in patients treated with exogenous insulin and reach higher levels in individuals who were IAA‐positive before the diagnosis of T1D 30. Eight out of 12 T1D patients in our study were positive for IA, and only 2 of these 8 had high IL‐4 responses.…”

Section: Resultsmentioning

confidence: 56%

Relationship between T and B Cell Responses to Proinsulin in Human Type 1 Diabetes

Durinovic‐Belló

Maisel

Schlosser

et al. 2003

Annals of the New York Academy of Sciences

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In type 1 diabetes, humoral and cell-mediated responses to insulin and proinsulin are detectable. Autoantibodies to insulin are associated with impending disease in young individuals and are used as predictive markers to determine disease risk. The aim of this study was to investigate whether different cytokine patterns of cellular reactivity to insulin might serve as additional specific markers of disease maturation and might improve disease prediction in individuals at risk. We correlated T and B cell responses to insulin in subjects with increased genetic risk (HLA-DRB1*04, DQB1*0302) for diabetes with or without islet autoantibodies (Ab+ subjects and controls, respectively) and HLA-matched patients. Peripheral blood mononuclear cells were stimulated with 15 overlapping proinsulin peptides (16-mer), and proinflammatory Th1 (IFNgamma) and anti-inflammatory Th2 (IL-4) cytokines were analyzed. We observed a simultaneous increase in IL-4 and IFNgamma secretion in early islet autoimmunity of Ab+ subjects, but not in insulin-treated T1D patients. Furthermore, the increase in IL-4 secretion in Ab+ subjects was associated with insulin autoantibody responses. There was no correlation of either IFNgamma or IL-4 secretion with insulin antibody responses in patients already treated with exogenous insulin. In conclusion, our findings reveal that quantification of cytokine responses to proinsulin in peripheral blood may prove to be a promising specific marker of diabetes progression and could, in addition to insulin autoantibodies, be used in the prediction of type 1 diabetes.

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Section: Resultsmentioning

confidence: 56%

Relationship between T and B Cell Responses to Proinsulin in Human Type 1 Diabetes

Durinovic‐Belló

Maisel

Schlosser

et al. 2003

Annals of the New York Academy of Sciences

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“…The sensitive and specific antiinsulin assay used in our study allowed us to clearly show that jet-injected insulin produces little to no antibody response in the short duration of insulin treatment needed in GDM, compared with needle therapy. Because maximum antibody response to injected insulin occurs after 4 -6 mo of treatment (17), longer treatment of the two groups might show more of an antibody response, especially in the jet-injected patients.…”

Section: Results-mentioning

confidence: 95%

“…Studies of nonpregnant, type I diabetic patients show that a significant antibody response develops within weeks of starting therapy in patients naive to insulin therapy (17). Although the exact mechanism whereby human insulin causes an antibody response in humans is not known, the answer probably is that the threedimensional structure of conventional insulin is different from endogenous insulin, and hence it is immunogenic.…”

Section: Results-mentioning

confidence: 97%

“…Randomization divided the women into two comparable groups that were not significantly different from each other ( Table 1). All women underwent the following laboratory determinations: HbA lc by ion-exchange high-pressure liquid chromatography (normal value for this gestational week of 4.0 ± 0.5%), C-peptide (15), and insulin antibodies (16,17). Blood was drawn every 2 wk for HbA lc and every week for antibodies.…”

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confidence: 99%

“…Insulin antibodies were measured by a fluid-phase RIA using an acid charcoal methyl cellulose extraction step developed by Dixon (16) and modified by Sutton et al (17), monoiodinated human insulin tracer, and displacement with an excess of unlabeled insulin for quantitation of specific binding. The results are expressed as the percentage of binding displaced by cold insulin with values >mean + 3 SD of normal control subjects (0.8%) being considered positive (18).…”

mentioning

confidence: 99%

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