دورية أكاديمية

Hybrid Insulin Peptides Are Autoantigens in Type 1 Diabetes.

التفاصيل البيبلوغرافية
العنوان: Hybrid Insulin Peptides Are Autoantigens in Type 1 Diabetes.
المؤلفون: Baker, Rocky L., Rihanek, Marynette, Hohenstein, Anita C., Nakayama, Maki, Michels, Aaron, Gottlieb, Peter A., Haskins, Kathryn, Delong, Thomas
المصدر: Diabetes; Sep2019, Vol. 68 Issue 9, p1830-1840, 11p
مصطلحات موضوعية: TYPE 1 diabetes, AUTOANTIGENS, PEPTIDES, CLONE cells, T cells
مستخلص: We recently established that hybrid insulin peptides (HIPs) are present in human islets and that T cells reactive to HIPs are found in the residual islets of organ donors with type 1 diabetes (T1D). Here, we investigate whether HIP-reactive T cells are indicative of ongoing autoimmunity in patients with T1D. We used interferon-γ enzyme-linked immune absorbent spot analyses on peripheral blood mononuclear cells (PBMCs) to determine whether patients with new-onset T1D or control subjects displayed T-cell reactivity to a panel of 16 HIPs. We observed that nearly one-half of the patients responded to one or more HIPs. Responses to four HIPs were significantly elevated in patients with T1D but not in control subjects. To characterize the T cells reactive to HIPs, we used a carboxyfluorescein succinimidyl ester-based assay to clone T cells from PBMCs. We isolated six nonredundant, antigen-specific T-cell clones, most of which reacting to their target HIPs in the low nanomolar range. One T-cell clone was isolated from the same patient on two different blood draws, indicating persistence of this T-cell clone in the peripheral blood. This work suggests that HIPs are important target antigens in human subjects with T1D and may play a critical role in disease. [ABSTRACT FROM AUTHOR]
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قاعدة البيانات: Complementary Index
الوصف
تدمد:00121797
DOI:10.2337/db19-0128