{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:56:05Z","timestamp":1790283365575,"version":"4.1.0"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T00:00:00Z","timestamp":1675296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>GAD-alum given into lymph nodes to Type 1 diabetes (T1D) patients participating in a multicenter, randomized, placebo-controlled double-blind study seemed to have a positive effect for patients with DR3DQ2 haplotype, who showed better preservation of C-peptide than the placebo group. Here we compared the immunomodulatory effect of GAD-alum administered into lymph nodes of patients with T1D versus placebo with focus on patients with DR3DQ2 haplotype.<\/jats:p><jats:sec><jats:title>Methods<\/jats:title><jats:p>GAD autoantibodies, GADA subclasses, GAD<jats:sub>65<\/jats:sub>-induced cytokine secretion (Luminex panel) and proliferation of peripheral mononuclear cells were analyzed in T1D patients (n=109) who received either three intra-lymphatic injections (one month apart) with 4 \u00b5g GAD-alum and oral vitamin D supplementation (2000 IE daily for 120 days), or placebo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Higher GADA, GADA subclasses, GAD<jats:sub>65<\/jats:sub>-induced proliferation and cytokine secretion was observed in actively treated patients after the second injection of GAD-alum compared to the placebo group. Following the second injection of GAD-alum, actively treated subjects with DR3DQ2 haplotype had higher GAD<jats:sub>65<\/jats:sub>-induced secretion of several cytokine (IL4, IL5, IL7, IL10, IL13, IFN\u03b3, GM-CSF and MIP1\u03b2) and proliferation compared to treated individuals without DR3DQ2. Stratification of samples from GAD-alum treated patients according to C-peptide preservation at 15 months revealed that \u201cgood responder\u201d individuals with better preservation of C-peptide secretion, independently of the HLA haplotype, had increased GAD<jats:sub>65<\/jats:sub>-induced proliferation and IL13 secretion at 3 months, and a 2,5-fold increase of IL5 and IL10 as compared to \u201cpoor responders\u201d. The second dose of GAD-alum also induced a more pronounced cytokine secretion in \u201cgood responders\u201d with DR3DQ2, compared to few \u201cgood responders\u201d without DR3DQ2 haplotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Patients with DR3DQ2 haplotype had a distinct early cellular immune response to GAD-alum injections into the lymph node, and predominant GAD<jats:sub>65<\/jats:sub>-induced IL13 secretion and proliferation that seems to be associated with a better clinical outcome. If confirmed in the ongoing larger randomized double-blind placebo-controlled clinical trial (DIAGNODE-3), including only patients carrying DR3DQ2 haplotype, these results might be used as early surrogate markers for clinical efficacy.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1112570","type":"journal-article","created":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T17:25:39Z","timestamp":1675358739000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Intralymphatic glutamic acid decarboxylase administration in type 1 diabetes patients induced a distinctive early immune response in patients with DR3DQ2 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