Long-Lasting Immune Responses 4 Years after GAD-Alum Treatment in Children with Type 1 Diabetes

Axelsson, Stina (författare): Linköpings universitet,Pediatrik,Hälsouniversitetet

Chéramy, Mikael (författare): Linköpings universitet,Pediatrik,Hälsouniversitetet

Hjorth, Maria (författare): Linköpings universitet,Pediatrik,Hälsouniversitetet

Pihl, Mikael (författare): Linköpings universitet,Pediatrik,Hälsouniversitetet

Åkerman, Linda (författare): Linköpings universitet,Pediatrik,Hälsouniversitetet

Ludvigsson, Johnny (författare): Östergötlands Läns Landsting,Linköpings universitet,Pediatrik,Hälsouniversitetet,Barn- och ungdomskliniken i Linköping

Casas, Rosaura (författare): Linköpings universitet,Pediatrik,Hälsouniversitetet

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Abstract Ämnesord

Stäng

A phase II clinical trial with glutamic acid decarboxylase (GAD) 65 formulated with aluminium hydroxide (GAD-alum) has shown efficacy in preserving residual insulin secretion in children and adolescents with recent-onset type 1 diabetes (T1D). We have performed a 4-year follow-up study of 59 of the original 70 patients to investigate long-term cellular and humoral immune responses after GAD-alum-treatment. Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with GAD(65). Frequencies of naive, central and effector memory CD4+ and CD8+ T cells were measured, together with cytokine secretion, proliferation, gene expression and serum GAD(65) autoantibody (GADA) levels. We here show that GAD-alum-treated patients display increased memory T-cell frequencies and prompt T-cell activation upon in vitro stimulation with GAD(65), but not with control antigens, compared with placebo subjects. GAD(65)-induced T-cell activation was accompanied by secretion of T helper (Th) 1, Th2 and T regulatory cytokines and by induction of T-cell inhibitory pathways. Moreover, post-treatment serum GADA titres remained persistently increased in the GAD-alum arm, but did not inhibit GAD(65) enzymatic activity. In conclusion, memory T- and B-cell responses persist 4 years after GAD-alum-treatment. In parallel to a GAD(65)-induced T-cell activation, our results show induction of T-cell inhibitory pathways important for regulating the GAD(65) immunity.

Av författaren/redakt...: Axelsson, Stina; Chéramy, Mikael; Hjorth, Maria; Pihl, Mikael; Åkerman, Linda; Martinuzzi, Eman ...; visa fler...; Mallone, Roberto; Ludvigsson, John ...; Casas, Rosaura; visa färre...

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