Autoimmunity to CD38 and GAD in type I and type II diabetes: CD38 and HLA genotypes and clinical phenotypes

A. Antonelli, T. Tuomi, M. Nannipieri, P. Fallahi, C. Nesti, H. Okamoto, L. Groop, E. Ferrannini

Research output: Contribution to journalArticlepeer-review

84 Citations (Scopus)

Abstract

Aims/hypothesis. Autoantibodies against CD38 have been found in some patients with Type II (non-insulin-dependent) diabetes mellitus and have been shown to stimulate insulin secretion by cultured human islets. We tested whether this new form of autoimmunity, (i) overlaps with anti-GAD autoimmunity, (ii) identifies an insulin-deficient phenotype, (iii) is under the influence of genetic factors. Methods. We screened 496 adults by immuno-blot analysis in the Botnia Study (298 with Type II and 98 with Type I (insulin-dependent) diabetes mellitus, 100 non-diabetic control subjects). Results. CD38-autoantibodies were found in 8.4% of Type II diabetic patients (p<0.003 vs 0% of control subjects), particularly in anti-GAD positive (14% vs 6% of anti-GAD negative, p=0.0004). CD38ab were also found in 4% of Type I diabetic patients; in the whole study group, 59% of anti-CD38 positive had DQB1*02 compared with 38% of anti-CD38 negative (p=0.04). On the OGTT, beta-cell function (as the ratio of insulin-to-glucose areas) was impaired (p=0.02) only in association with anti-GAD positivity (3.2±3.1 U/mol, mean ± SD) but not in anti-CD38 positive patients (5.6±2.9) as compared with patients free of autoimmunity (4.5±4.6,p=NS). In 44 Type II diabetic patients (22 negative and 22 positive for anti-CD38), no mutations were detected in any of the 8 exons, 5′ end of intron 1 or the 5′ and 3′ untranslated regions of the CD38 gene. The previously described missense mutation (Arg140Trp) in exon 3 was not found in this cohort. There was no association between the PvUII polymorphism and clinical phenotype. Conclusion. Anti-CD38 autoimmunity identifies a clinical phenotype similar to non-autoimmune Type II diabetes, with relative preserved beta-cell function and weak genetic influence.

Original languageEnglish
Pages (from-to)1298-1306
Number of pages9
JournalDiabetologia
Volume45
Issue number9
DOIs
Publication statusPublished - 2002

Keywords

  • CD38 antibodies
  • CD38 gene
  • CD38 polymorphisms
  • GAD antibodies
  • HLA
  • Insulin secretion
  • LADA
  • Missense mutation
  • Type I diabetes mellitus
  • Type II diabetes mellitus

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Fingerprint Dive into the research topics of 'Autoimmunity to CD38 and GAD in type I and type II diabetes: CD38 and HLA genotypes and clinical phenotypes'. Together they form a unique fingerprint.

Cite this