Article

Journal of Clinical Immunology

, Volume 32, Issue 4, pp 778-785

First online:

Autoantibodies and High-Risk HLA Susceptibility Markers in First-Degree Relatives of Brazilian Patients with Type 1 Diabetes Mellitus: A Progression to Disease Based Study

  • L. I. AlvesAffiliated withLaboratory of Medical Investigation LIM-18, Ambulatory of Endocrinology of Hospital das Clinicas of University São Paulo Medical School
  • , E. DaviniAffiliated withLaboratory of Medical Investigation LIM-18, Ambulatory of Endocrinology of Hospital das Clinicas of University São Paulo Medical School
  • , M. R. CorreiaAffiliated withLaboratory of Medical Investigation LIM-18, Ambulatory of Endocrinology of Hospital das Clinicas of University São Paulo Medical School
  • , R. T. FukuiAffiliated withLaboratory of Medical Investigation LIM-18, Ambulatory of Endocrinology of Hospital das Clinicas of University São Paulo Medical School
  • , R. F. SantosAffiliated withLaboratory of Medical Investigation LIM-18, Ambulatory of Endocrinology of Hospital das Clinicas of University São Paulo Medical School
  • , M. R. CunhaAffiliated withLaboratory of Medical Investigation LIM-18, Ambulatory of Endocrinology of Hospital das Clinicas of University São Paulo Medical School
  • , D. M. RochaAffiliated withLaboratory of Medical Investigation LIM-18, Ambulatory of Endocrinology of Hospital das Clinicas of University São Paulo Medical School
  • , W. M. G. VolpiniAffiliated withLaboratory of Immunology, University of Campinas
  • , M. E. R. SilvaAffiliated withLaboratory of Medical Investigation LIM-18, Ambulatory of Endocrinology of Hospital das Clinicas of University São Paulo Medical SchoolLaboratory of Medical Investigation—LIM-18, University of São Paulo Medical School Email author 

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Abstract

Purpose

The objective of this study was to determine the frequencies of autoantibodies to heterogeneous islet-cell cytoplasmic antigens (ICA), glutamic acid decarboxylase65 (GAD65A), insulinoma-associated antigen-2 (IA-2A) and insulin (IAA)–and human leukocyte antigen (HLA) class II markers (HLA-DR and -DQ) in first degree relatives of heterogeneous Brazilian patients with type I diabetes(T1DM). A major focus of this study was to determine the influence of age, gender, proband characteristics and ancestry on the prevalence of autoantibodies and HLA-DR and -DQ alleles on disease progression and genetic predisposition to T1DM among the first-degree relatives.

Methods

IAA, ICA, GAD65A, IA-2A and HLA- class II alleles were determined in 546 first-degree-relatives, 244 siblings, 55 offspring and 233 parents of 178 Brazilian patients with T1DM.

Results

Overall, 8.9% of the relatives were positive for one or more autoantibodies. IAA was the only antibody detected in parents. GAD65 was the most prevalent antibody in offspring and siblings as compared to parents and it was the sole antibody detected in offspring. Five siblings were positive for the IA-2 antibody. A significant number (62.1%) of siblings had 1 or 2 high risk HLA haplotypes. During a 4-year follow-up study, 5 siblings (expressing HLA-DR3 or –DR4 alleles) and 1 offspring positive for GAD65A progressed to diabetes.

Conclusions

The data indicated that the GAD65 and IA-2 antibodies were the strongest predictors of T1DM in our study population. The high risk HLA haplotypes alone were not predictive of progression to overt diabetes.

Keywords

Type I diabetes autoantibodies HLA-DR/DQ GAD65A IAA IA2-A