PMID- 24598797
OWN - NLM
STAT- MEDLINE
DCOM- 20150212
LR  - 20220321
IS  - 1476-5470 (Electronic)
IS  - 1466-4879 (Print)
IS  - 1466-4879 (Linking)
VI  - 15
IP  - 4
DP  - 2014 Apr
TI  - MHC associations with clinical and autoantibody manifestations in European SLE.
PG  - 210-7
LID - 10.1038/gene.2014.6 [doi]
AB  - Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease 
      affecting multiple organ systems and characterized by autoantibody formation to 
      nuclear components. Although genetic variation within the major 
      histocompatibility complex (MHC) is associated with SLE, its role in the 
      development of clinical manifestations and autoantibody production is not well 
      defined. We conducted a meta-analysis of four independent European SLE case 
      collections for associations between SLE sub-phenotypes and MHC single-nucleotide 
      polymorphism genotypes, human leukocyte antigen (HLA) alleles and variant HLA 
      amino acids. Of the 11 American College of Rheumatology criteria and 7 
      autoantibody sub-phenotypes examined, anti-Ro/SSA and anti-La/SSB antibody 
      subsets exhibited the highest number and most statistically significant 
      associations. HLA-DRB1*03:01 was significantly associated with both 
      sub-phenotypes. We found evidence of associations independent of MHC class II 
      variants in the anti-Ro subset alone. Conditional analyses showed that anti-Ro 
      and anti-La subsets are independently associated with HLA-DRB1*0301, and that the 
      HLA-DRB1*03:01 association with SLE is largely but not completely driven by the 
      association of this allele with these sub-phenotypes. Our results provide strong 
      evidence for a multilevel risk model for HLA-DRB1*03:01 in SLE, where the 
      association with anti-Ro and anti-La antibody-positive SLE is much stronger than 
      SLE without these autoantibodies.
FAU - Morris, D L
AU  - Morris DL
AD  - Department of Medical & Molecular Genetics, King's College London School of 
      Medicine, Guy's Hospital, London, UK.
FAU - Fernando, M M A
AU  - Fernando MM
AD  - Department of Medical & Molecular Genetics, King's College London School of 
      Medicine, Guy's Hospital, London, UK.
FAU - Taylor, K E
AU  - Taylor KE
AD  - Rosalind Russell Medical Research Center for Arthritis, Department of Medicine, 
      University of California San Francisco, San Francisco, CA, USA.
FAU - Chung, S A
AU  - Chung SA
AD  - Rosalind Russell Medical Research Center for Arthritis, Department of Medicine, 
      University of California San Francisco, San Francisco, CA, USA.
FAU - Nititham, J
AU  - Nititham J
AD  - Rosalind Russell Medical Research Center for Arthritis, Department of Medicine, 
      University of California San Francisco, San Francisco, CA, USA.
FAU - Alarcon-Riquelme, M E
AU  - Alarcon-Riquelme ME
AD  - 1] Department of Human DNA Variability, GENYO, Centro de Genomica e Investigacion 
      Oncologica Pfizer-Universidad de Granada-Junta de Andalucia, Granada, Spain [2] 
      Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, 
      Oklahoma, OK, USA.
FAU - Barcellos, L F
AU  - Barcellos LF
AD  - Genetic Epidemiology and Genomics Laboratory, Division of Epidemiology, School of 
      Public Health, University of California, Berkeley, CA, USA.
FAU - Behrens, T W
AU  - Behrens TW
AD  - Immunology Biomarkers Group, Genentech, South San Francisco, CA, USA.
FAU - Cotsapas, C
AU  - Cotsapas C
AD  - Department of Neurology, Yale School of Medicine, Connecticut, CT, USA.
FAU - Gaffney, P M
AU  - Gaffney PM
AD  - Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, 
      Oklahoma, OK, USA.
FAU - Graham, R R
AU  - Graham RR
AD  - Immunology Biomarkers Group, Genentech, South San Francisco, CA, USA.
FAU - Pons-Estel, B A
AU  - Pons-Estel BA
AD  - Rheumatology Service, Hospital Provincial de Rosario, Sanatorio Parque, Rosario, 
      Argentina.
FAU - Gregersen, P K
AU  - Gregersen PK
AD  - The Robert S. Boas Center for Genomics and Human Genetics, Feinstein Institute 
      for Medical Research, North Shore LIJ Health System, Manhasset, NY, USA.
FAU - Harley, J B
AU  - Harley JB
AD  - Cincinnati Children's Hospital Medical Center and US Department of Veterans 
      Affairs Medical Center, Cincinnati, OH, USA.
FAU - Hauser, S L
AU  - Hauser SL
AD  - Department of Neurology, University of California San Francisco, San Francisco, 
      CA, USA.
FAU - Hom, G
AU  - Hom G
AD  - Immunology Biomarkers Group, Genentech, South San Francisco, CA, USA.
FAU - Langefeld, C D
AU  - Langefeld CD
AD  - Department of Biostatistical Sciences, Wake Forest University Health Sciences, 
      Wake Forest, NC, USA.
FAU - Noble, J A
AU  - Noble JA
AD  - Children's Hospital Oakland Research Institute, Oakland, CA, USA.
FAU - Rioux, J D
AU  - Rioux JD
AD  - Department of Medicine, Universite de Montreal and Research Center, Montreal 
      Heart Institute, Montreal, QC, Canada.
FAU - Seldin, M F
AU  - Seldin MF
AD  - University of California Davis, Davis, CA, USA.
CN  - Systemic Lupus Erythematosus Genetics Consortium
FAU - Vyse, T J
AU  - Vyse TJ
AD  - Department of Medical & Molecular Genetics, King's College London School of 
      Medicine, Guy's Hospital, London, UK.
FAU - Criswell, L A
AU  - Criswell LA
AD  - Rosalind Russell Medical Research Center for Arthritis, Department of Medicine, 
      University of California San Francisco, San Francisco, CA, USA.
LA  - eng
GR  - AI62629/AI/NIAID NIH HHS/United States
GR  - AI067152/AI/NIAID NIH HHS/United States
GR  - AR052300/AR/NIAMS NIH HHS/United States
GR  - P01 AR048929/AR/NIAMS NIH HHS/United States
GR  - KL2TR000143/TR/NCATS NIH HHS/United States
GR  - AR22804/AR/NIAMS NIH HHS/United States
GR  - P01 AR049084/AR/NIAMS NIH HHS/United States
GR  - R01 AR043274/AR/NIAMS NIH HHS/United States
GR  - U19 AI067152/AI/NIAID NIH HHS/United States
GR  - AR049084/AR/NIAMS NIH HHS/United States
GR  - DE15223/DE/NIDCR NIH HHS/United States
GR  - R01 DE015223/DE/NIDCR NIH HHS/United States
GR  - P60 AR053308/AR/NIAMS NIH HHS/United States
GR  - N01AR62277/AR/NIAMS NIH HHS/United States
GR  - R01 AI063274/AI/NIAID NIH HHS/United States
GR  - M01 RR000079/RR/NCRR NIH HHS/United States
GR  - AI31584/AI/NIAID NIH HHS/United States
GR  - P20 RR020143/RR/NCRR NIH HHS/United States
GR  - U19 AI082714/AI/NIAID NIH HHS/United States
GR  - AR048929/AR/NIAMS NIH HHS/United States
GR  - AR42460/AR/NIAMS NIH HHS/United States
GR  - 5 M01 RR-00079/RR/NCRR NIH HHS/United States
GR  - KL2 TR000143/TR/NCATS NIH HHS/United States
GR  - 17761/ARC_/Arthritis Research UK/United Kingdom
GR  - R56 AI063274/AI/NIAID NIH HHS/United States
GR  - AI083194/AI/NIAID NIH HHS/United States
GR  - AR19084/AR/NIAMS NIH HHS/United States
GR  - 18239/ARC_/Arthritis Research UK/United Kingdom
GR  - RR20143/RR/NCRR NIH HHS/United States
GR  - R01 AI031584/AI/NIAID NIH HHS/United States
GR  - R01 AI065841/AI/NIAID NIH HHS/United States
GR  - 076113/WT_/Wellcome Trust/United Kingdom
GR  - AR052125/AR/NIAMS NIH HHS/United States
GR  - N01 AR062277/AR/NIAMS NIH HHS/United States
GR  - R01 AR052125/AR/NIAMS NIH HHS/United States
GR  - AI063274/AI/NIAID NIH HHS/United States
GR  - P30 GM110766/GM/NIGMS NIH HHS/United States
GR  - M01 RR001271/RR/NCRR NIH HHS/United States
GR  - HG006828/HG/NHGRI NIH HHS/United States
GR  - AI082714/AI/NIAID NIH HHS/United States
GR  - U19 AI062629/AI/NIAID NIH HHS/United States
GR  - U01 HG006828/HG/NHGRI NIH HHS/United States
GR  - R37 AI024717/AI/NIAID NIH HHS/United States
GR  - R01 AR042460/AR/NIAMS NIH HHS/United States
GR  - R01 AI024717/AI/NIAID NIH HHS/United States
GR  - N01AI40076/AI/NIAID NIH HHS/United States
GR  - P50 AR048940/AR/NIAMS NIH HHS/United States
GR  - I01 BX001834/BX/BLRD VA/United States
GR  - 085475/WT_/Wellcome Trust/United Kingdom
GR  - R01 AR052300/AR/NIAMS NIH HHS/United States
GR  - AI53747/AI/NIAID NIH HHS/United States
GR  - R01 MH063420/MH/NIMH NIH HHS/United States
GR  - AI024717/AI/NIAID NIH HHS/United States
GR  - AR043274/AR/NIAMS NIH HHS/United States
GR  - P01 AI083194/AI/NIAID NIH HHS/United States
GR  - K24 AR002175/AR/NIAMS NIH HHS/United States
GR  - AR02175/AR/NIAMS NIH HHS/United States
GR  - R21 AI053747/AI/NIAID NIH HHS/United States
GR  - AR48940/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20140306
PL  - England
TA  - Genes Immun
JT  - Genes and immunity
JID - 100953417
RN  - 0 (Autoantibodies)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (HLA-DRB1*03:01 antigen)
SB  - IM
MH  - *Autoantibodies/genetics/immunology
MH  - Europe
MH  - Female
MH  - *HLA-DRB1 Chains/genetics/immunology
MH  - Humans
MH  - Lupus Erythematosus, Systemic/*genetics/immunology
MH  - Male
MH  - *Models, Genetic
PMC - PMC4102853
MID - NIHMS595460
COIS- CONFLICT OF INTEREST The authors declare no conflict of interest.
FIR - Harley, John B
IR  - Harley JB
FIR - Alarcon-Riquelme, Marta E
IR  - Alarcon-Riquelme ME
FIR - Criswell, Lindsey A
IR  - Criswell LA
FIR - Gaffney, Patrick M
IR  - Gaffney PM
FIR - Jacob, Chaim O
IR  - Jacob CO
FIR - Kimberly, Robert P
IR  - Kimberly RP
FIR - Sivils, Kathy L M
IR  - Sivils KL
FIR - Tsao, Betty P
IR  - Tsao BP
FIR - Vyse, Timothy J
IR  - Vyse TJ
FIR - Langefeld, Carl D
IR  - Langefeld CD
EDAT- 2014/03/07 06:00
MHDA- 2015/02/13 06:00
PMCR- 2014/07/18
CRDT- 2014/03/07 06:00
PHST- 2013/10/15 00:00 [received]
PHST- 2014/01/07 00:00 [revised]
PHST- 2014/01/10 00:00 [accepted]
PHST- 2014/03/07 06:00 [entrez]
PHST- 2014/03/07 06:00 [pubmed]
PHST- 2015/02/13 06:00 [medline]
PHST- 2014/07/18 00:00 [pmc-release]
AID - gene20146 [pii]
AID - 10.1038/gene.2014.6 [doi]
PST - ppublish
SO  - Genes Immun. 2014 Apr;15(4):210-7. doi: 10.1038/gene.2014.6. Epub 2014 Mar 6.