title: 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.
abstract: OBJECTIVE
  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.
authors.affiliation: Laboratory of Medical Investigation LIM-18, Ambulatory of Endocrinology of Hospital das Clinicas of University São Paulo Medical School, São Paulo, Brazil.
authors.forename: L I
authors.initials: LI
authors.lastname: Alves
authors.forename: E
authors.initials: E
authors.lastname: Davini
authors.forename: M R
authors.initials: MR
authors.lastname: Correia
authors.forename: R T
authors.initials: RT
authors.lastname: Fukui
authors.forename: R F
authors.initials: RF
authors.lastname: Santos
authors.forename: M R
authors.initials: MR
authors.lastname: Cunha
authors.forename: D M
authors.initials: DM
authors.lastname: Rocha
authors.forename: W M G
authors.initials: WM
authors.lastname: Volpini
authors.forename: M E R
authors.initials: ME
authors.lastname: Silva
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D001938:Brazil; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D018450:Disease Progression; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005968:Glutamate Decarboxylase / Q000276:immunology; D006683:HLA-DQ Antigens / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007223:Infant; D007328:Insulin / Q000276:immunology; D008297:Male; D008875:Middle Aged; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8 / Q000276:immunology; D012737:Sex Factors; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D007328:Insulin; C024211:islet cell antibody; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D005968:Glutamate Decarboxylase