PMID- 17406641
OWN - NLM
STAT- MEDLINE
DCOM- 20070926
LR  - 20220321
IS  - 1018-4813 (Print)
IS  - 1018-4813 (Linking)
VI  - 15
IP  - 8
DP  - 2007 Aug
TI  - Specific combinations of HLA-DR2 and DR3 class II haplotypes contribute graded 
      risk for disease susceptibility and autoantibodies in human SLE.
PG  - 823-30
AB  - The human leukocyte antigen (HLA) Class II antigen presentation alleles DR and DQ 
      are associated with susceptibility to systemic lupus erythematosus (SLE) and the 
      production of lupus-related autoantibodies. Here, we explore the effect of 
      different combinations of Class II risk haplotypes in a large, multi-center 
      collection of 780 SLE families. Haplotypes bearing the DRB1*1501/DQB1*0602 (DR2) 
      and DRB1*0301/DQB1*0201 (DR3) alleles were present in nearly two-thirds of SLE 
      cases and were significantly associated with disease susceptibility in both 
      family-based and case-control study designs. DR3-containing haplotypes conferred 
      higher risk for disease than DR2, and individual homozygous for DR3 or compound 
      heterozygous for DR3 and DR2 showed the highest risk profile. DR2 haplotypes were 
      also found to be associated with antibodies to the nuclear antigen Sm, and, as 
      previously observed, DR3 genotypes were associated with Ro and La autoantibodies. 
      Interestingly, SLE cases and unaffected family members who were DR2/DR3 compound 
      heterozygotes showed particularly strong risk of developing antibodies to Ro, and 
      were enriched for La and Sm. These data provide convincing evidence that 
      particular combinations of HLA Class II DR2 and DR3 haplotypes are key 
      determinants of autoantibody production and disease susceptibility in human SLE.
FAU - Graham, Robert R
AU  - Graham RR
AD  - Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical 
      School, Boston, MA, USA.
FAU - Ortmann, Ward
AU  - Ortmann W
FAU - Rodine, Peter
AU  - Rodine P
FAU - Espe, Karl
AU  - Espe K
FAU - Langefeld, Carl
AU  - Langefeld C
FAU - Lange, Ethan
AU  - Lange E
FAU - Williams, Adrienne
AU  - Williams A
FAU - Beck, Stephanie
AU  - Beck S
FAU - Kyogoku, Chieko
AU  - Kyogoku C
FAU - Moser, Kathy
AU  - Moser K
FAU - Gaffney, Patrick
AU  - Gaffney P
FAU - Gregersen, Peter K
AU  - Gregersen PK
FAU - Criswell, Lindsey A
AU  - Criswell LA
FAU - Harley, John B
AU  - Harley JB
FAU - Behrens, Timothy W
AU  - Behrens TW
LA  - eng
GR  - 5 M01 RR00079/RR/NCRR NIH HHS/United States
GR  - P60 AR053308/AR/NIAMS NIH HHS/United States
GR  - AR42460/AR/NIAMS NIH HHS/United States
GR  - AI32584/AI/NIAID NIH HHS/United States
GR  - AI24717/AI/NIAID NIH HHS/United States
GR  - AR12253/AR/NIAMS NIH HHS/United States
GR  - RR024013/RR/NCRR NIH HHS/United States
GR  - AR048940/AR/NIAMS NIH HHS/United States
GR  - AR048094/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070404
PL  - England
TA  - Eur J Hum Genet
JT  - European journal of human genetics : EJHG
JID - 9302235
RN  - 0 (Autoantibodies)
RN  - 0 (HLA-DR2 Antigen)
RN  - 0 (HLA-DR3 Antigen)
SB  - IM
MH  - Autoantibodies/*biosynthesis
MH  - Case-Control Studies
MH  - Cohort Studies
MH  - Female
MH  - *Genetic Predisposition to Disease
MH  - HLA-DR2 Antigen/*genetics
MH  - HLA-DR3 Antigen/*genetics
MH  - Haplotypes/*genetics
MH  - Humans
MH  - Lupus Erythematosus, Systemic/*genetics/*immunology
MH  - Male
MH  - Risk Assessment
EDAT- 2007/04/05 09:00
MHDA- 2007/09/27 09:00
CRDT- 2007/04/05 09:00
PHST- 2007/04/05 09:00 [pubmed]
PHST- 2007/09/27 09:00 [medline]
PHST- 2007/04/05 09:00 [entrez]
AID - 5201827 [pii]
AID - 10.1038/sj.ejhg.5201827 [doi]
PST - ppublish
SO  - Eur J Hum Genet. 2007 Aug;15(8):823-30. doi: 10.1038/sj.ejhg.5201827. Epub 2007 
      Apr 4.