Details

Autor(en) / Beteiligte

• Demeester, Simke
• Keymeulen, Bart
• Kaufman, Leonard
• Van Dalem, Annelien
• Balti, Eric V
• Van de Velde, Ursule
• Goubert, Patrick
• Verhaeghen, Katrijn
• Davidson, Howard W
• Wenzlau, Janet M
• Weets, Ilse
• Pipeleers, Daniel G
• Gorus, Frans K

Titel

Preexisting Insulin Autoantibodies Predict Efficacy of Otelixizumab in Preserving Residual [Beta]-Cell Function in Recent-Onset Type 1 Diabetes

Ist Teil von

• Diabetes care, 2015-04, Vol.38 (4), p.644

Ort / Verlag

Alexandria: American Diabetes Association

Erscheinungsjahr

2015

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Immune intervention trials in recent-onset type 1 diabetes would benefit from biomarkers associated with good therapeutic response. In the previously reported randomized placebo-controlled anti-CD3 study (otelixizumab; GlaxoSmithKline), we tested the hypothesis that specific diabetes autoantibodies might serve this purpose. In the included patients (n = 40 otelixizumab, n = 40 placebo), ...-cell function was assessed as area under the curve (AUC) C-peptide release during a hyperglycemic glucose clamp at baseline (median duration of insulin treatment: 6 days) and every 6 months until 18 months after randomization. (Auto)antibodies against insulin (I[A]A), GAD (GADA), IA-2 (IA-2A), and ZnT8 (ZnT8A) were determined on stored sera by liquid-phase radiobinding assay. At baseline, only better preserved AUC C-peptide release and higher levels of IAA were associated with better preservation of ...-cell function and lower insulin needs under anti-CD3 treatment. In multivariate analysis, IAA (P = 0.022) or the interaction of IAA and C-peptide (P = 0.013) independently predicted outcome together with treatment. During follow-up, good responders to anti-CD3 treatment (i.e., IAA+ participants with relatively preserved ...-cell function [≥25% of healthy control subjects]) experienced a less pronounced insulin-induced rise in I(A)A and lower insulin needs. GADA, IA-2A, and ZnT8A levels were not influenced by anti-CD3 treatment, and their changes showed no relation to functional outcome. There is important specificity of IAA among other diabetes autoantibodies to predict good therapeutic response of recent-onset type 1 diabetic patients to anti-CD3 treatment. If confirmed, future immune intervention trials in type 1 diabetes should consider both relatively preserved functional ...-cell mass and presence of IAA as inclusion criteria. (ProQuest: ... denotes formulae/symbols omitted.)