PMID- 22402866
OWN - NLM
STAT- MEDLINE
DCOM- 20130122
LR  - 20211021
IS  - 1573-2592 (Electronic)
IS  - 0271-9142 (Linking)
VI  - 32
IP  - 4
DP  - 2012 Aug
TI  - 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.
PG  - 778-85
LID - 10.1007/s10875-012-9673-4 [doi]
AB  - 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.
FAU - Alves, L I
AU  - Alves LI
AD  - Laboratory of Medical Investigation LIM-18, Ambulatory of Endocrinology of 
      Hospital das Clinicas of University Sao Paulo Medical School, Sao Paulo, Brazil.
FAU - Davini, E
AU  - Davini E
FAU - Correia, M R
AU  - Correia MR
FAU - Fukui, R T
AU  - Fukui RT
FAU - Santos, R F
AU  - Santos RF
FAU - Cunha, M R
AU  - Cunha MR
FAU - Rocha, D M
AU  - Rocha DM
FAU - Volpini, W M G
AU  - Volpini WM
FAU - Silva, M E R
AU  - Silva ME
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120309
PL  - Netherlands
TA  - J Clin Immunol
JT  - Journal of clinical immunology
JID - 8102137
RN  - 0 (Autoantibodies)
RN  - 0 (Biomarkers)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Insulin)
RN  - 0 (islet cell antibody)
RN  - EC 3.1.3.48 (Receptor-Like Protein Tyrosine Phosphatases, Class 8)
RN  - EC 4.1.1.15 (Glutamate Decarboxylase)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Age Factors
MH  - Aged
MH  - Autoantibodies/*blood/immunology
MH  - Biomarkers/blood
MH  - Brazil
MH  - Child
MH  - Child, Preschool
MH  - Diabetes Mellitus, Type 1/*genetics/*immunology
MH  - Disease Progression
MH  - Family
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Genotype
MH  - Glutamate Decarboxylase/immunology
MH  - HLA-DQ Antigens/immunology
MH  - HLA-DR Antigens/immunology
MH  - Humans
MH  - Infant
MH  - Insulin/immunology
MH  - Male
MH  - Middle Aged
MH  - Receptor-Like Protein Tyrosine Phosphatases, Class 8/immunology
MH  - Sex Factors
MH  - Young Adult
EDAT- 2012/03/10 06:00
MHDA- 2013/01/23 06:00
CRDT- 2012/03/10 06:00
PHST- 2012/01/15 00:00 [received]
PHST- 2012/02/15 00:00 [accepted]
PHST- 2012/03/10 06:00 [entrez]
PHST- 2012/03/10 06:00 [pubmed]
PHST- 2013/01/23 06:00 [medline]
AID - 10.1007/s10875-012-9673-4 [doi]
PST - ppublish
SO  - J Clin Immunol. 2012 Aug;32(4):778-85. doi: 10.1007/s10875-012-9673-4. Epub 2012 
      Mar 9.