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

• Published in: Journal of clinical immunology 2012-08, Vol.32 (4), p.778-785
• Main Authors: Alves, L. I., Davini, E., Correia, M. R., Fukui, R. T., Santos, R. F., Cunha, M. R., Rocha, D. M., Volpini, W. M. G., Silva, M. E. R.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age; Age Factors; Aged; Autoantibodies; Autoantibodies - blood; Autoantibodies - immunology; Biomarkers - blood; Biomedical and Life Sciences; Biomedicine; Brazil; Child; Child, Preschool; Data processing; Diabetes mellitus; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; Disease Progression; Family; Female; Genetic Predisposition to Disease; Genotype; Glutamate Decarboxylase - immunology; Glutamic acid; Haplotypes; Histocompatibility antigen HLA; HLA-DQ Antigens - immunology; HLA-DR Antigens - immunology; Humans; Immunology; Infant; Infectious Diseases; Insulin; Insulin - immunology; Internal Medicine; Male; Medical Microbiology; Middle Aged; Population studies; Progeny; Receptor-Like Protein Tyrosine Phosphatases, Class 8 - immunology; Risk factors; Risk groups; Sex Factors; Siblings; Young Adult
• ISSN: 0271-9142; 1573-2592
• DOI: 10.1007/s10875-012-9673-4

Purpose The objective of this study was to determine the frequencies of autoantibodies to heterogeneous islet-cell cytoplasmic antigens (ICA), glutamic acid decarboxylase 65 (GAD 65 A), 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, GAD 65 A, 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. GAD 65 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 GAD 65 A progressed to diabetes. Conclusions The data indicated that the GAD 65 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.