PMID- 18331414
OWN - NLM
STAT- MEDLINE
DCOM- 20080807
LR  - 20140730
IS  - 1399-5448 (Electronic)
IS  - 1399-543X (Linking)
VI  - 9
IP  - 3 Pt 1
DP  - 2008 Jun
TI  - Progression to type 1 diabetes and autoantibody positivity in relation to 
      HLA-risk genotypes in children participating in the ABIS study.
PG  - 182-90
LID - 10.1111/j.1399-5448.2008.00369.x [doi]
AB  - BACKGROUND: Autoantibodies against beta-cell antigens together with human 
      leukocyte antigen (HLA)-risk genotypes are used as predictive markers for type 1 
      diabetes (T1D). In this study, we have investigated the role of HLA-risk and 
      -protective genotypes for development of beta-cell autoantibodies and progression 
      to T1D in healthy children. METHODS: T1D-related HLA genotypes and autoantibodies 
      against glutamic acid decarboxylase [glutamic acid decarboxylase antibodies 
      (GADA)] and islet antigen-2 (IA-2A) were studied at 1, 2.5 and 5 yr of age in 
      unselected healthy children and children with T1D participating in the All Babies 
      In Southeast Sweden (ABIS) study. RESULTS: GADA or IA-2A positivity at 5 yr of 
      age was associated with DR4-DQ8 haplotype and DR3-DQ2/DR4-DQ8 genotype. By the 
      age of 6-7 yr, we identified 32 children with T1D among the 17 055 participants 
      in the ABIS study. Eight of 2329 (0.3%) non-diabetic children had permanent 
      autoantibodies, and 143 of 2329 (6%) children had transient autoantibodies. 
      HLA-risk genotypes associated with T1D, whereas protective genotypes were seldom 
      found in children with T1D. Children with permanent autoantibodies had more often 
      risk-associated DR4-DQ8 haplotype than autoantibody-negative children. No 
      associations with HLA-risk or -protective genotypes were found for transient 
      autoantibodies. CONCLUSIONS: The strong relation between HLA-risk alleles and T1D 
      once again confirmed that HLA-risk genotypes play an important role for 
      development of T1D. However, HLA genotypes seem not to explain induction of 
      autoantibodies, especially transient autoantibodies, in the general population, 
      emphasizing the role of environmental factors in the initiation of autoimmunity. 
      It seems that HLA-risk genotypes are responsible for maturation of the permanent 
      autoantibody response.
FAU - Gullstrand, Camilla
AU  - Gullstrand C
AD  - Division of Pediatrics and Diabetes Research Centre, Department of Molecular and 
      Clinical Medicine, Faculty of Health Sciences, Linkoping University, Linkoping, 
      Sweden. camgu@imk.liu.se
FAU - Wahlberg, Jeanette
AU  - Wahlberg J
FAU - Ilonen, Jorma
AU  - Ilonen J
FAU - Vaarala, Outi
AU  - Vaarala O
FAU - Ludvigsson, Johnny
AU  - Ludvigsson J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080305
PL  - Denmark
TA  - Pediatr Diabetes
JT  - Pediatric diabetes
JID - 100939345
RN  - 0 (Autoantibodies)
RN  - 0 (HLA Antigens)
RN  - 0 (HLA-D Antigens)
RN  - EC 4.1.1.15 (Glutamate Decarboxylase)
SB  - IM
MH  - Autoantibodies/*blood
MH  - Child
MH  - Diabetes Mellitus, Type 1/epidemiology/genetics/*immunology
MH  - Disease Progression
MH  - Genotype
MH  - Glutamate Decarboxylase/immunology
MH  - HLA Antigens/*genetics
MH  - HLA-D Antigens/genetics
MH  - Humans
MH  - Incidence
MH  - Risk Assessment
MH  - Sweden/epidemiology
EDAT- 2008/03/12 09:00
MHDA- 2008/08/08 09:00
CRDT- 2008/03/12 09:00
PHST- 2008/03/12 09:00 [pubmed]
PHST- 2008/08/08 09:00 [medline]
PHST- 2008/03/12 09:00 [entrez]
AID - PDI369 [pii]
AID - 10.1111/j.1399-5448.2008.00369.x [doi]
PST - ppublish
SO  - Pediatr Diabetes. 2008 Jun;9(3 Pt 1):182-90. doi: 
      10.1111/j.1399-5448.2008.00369.x. Epub 2008 Mar 5.