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. 2020 Oct;63(10):2177-2181.
doi: 10.1007/s00125-020-05227-z. Epub 2020 Aug 5.

Efficacy of GAD-alum immunotherapy associated with HLA-DR3-DQ2 in recently diagnosed type 1 diabetes

Ulf Hannelius  1 , Craig A Beam  2 , Johnny Ludvigsson  3   4
Affiliations

Efficacy of GAD-alum immunotherapy associated with HLA-DR3-DQ2 in recently diagnosed type 1 diabetes

Ulf Hannelius et al. Diabetologia. 2020 Oct.

Abstract

Aims/hypothesis: The aim of this study was to determine if retention of C-peptide following immunotherapy using recombinant GAD65 conjugated to aluminium hydroxide (GAD-alum) is influenced by HLA risk haplotypes DR3-DQ2 and DR4-DQ8.

Methods: HLA-dependent treatment effect of GAD-alum therapy on C-peptide retention in individuals with recent-onset type 1 diabetes was evaluated using individual-level patient data from three placebo-controlled, randomised clinical trials using a mixed repeated measures model.

Results: A significant and dose-dependent effect was observed in individuals positive for the genotypes that include HLA-DR3-DQ2 but not HLA-DR4-DQ8 and in the broader subgroup of individuals positive for all genotypes that include HLA-DR3-DQ2 (i.e. including those also positive for HLA-DR4-DQ8). Higher doses (three or four injections) showed a treatment effect ratio of 1.596 (95% CI 1.132, 2.249; adjusted p = 0.0035) and 1.441 (95% CI 1.188, 1.749; adjusted p = 0.0007) vs placebo for the two respective HLA subgroups.

Conclusions/interpretation: GAD65-specific immunotherapy has a significant effect on C-peptide retention in individuals with recent-onset type 1 diabetes who have the DR3-DQ2 haplotype. Graphical abstract.

Keywords: Antigen-specific; Autoimmune diabetes; C-peptide; GAD; Glutamic acid decarboxylase; HLA; Immunotherapy; Type 1 diabetes; Vaccine.

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Figures

None
Graphical abstract
Fig. 1
Fig. 1
Estimated treatment effect ratio (C-peptide retention; active vs placebo) at 15 months post baseline in patients with or without genotypes that include HLA-DR3-DQ2 (n = 266 and 255), or HLA-DR3-DQ2 but not HLA-DR4-DQ8 (n = 127 and n = 394). Adjusted p values using the Bonferroni- Šidák correction are reported along with two-sided 95% CIs
See this image and copyright information in PMC

References

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