Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.

Identification of Major Histocompatibility Complex Class II Alleles Associated with Systemic Sclerosis Through Imputation Strategy.

Martin1,  Jose Ezequiel, International Scleroderma Group,  , Radstake3,  Timothy RD, Tan4,  Filemon K., Arnett4,  Frank C., Mayes4,  Maureen D., de Bakker5,  Paul

Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, Armilla (Granada), Spain
Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
University of Texas Health Science Center at Houston, Houston, TX
Brigham and Women's Hospital, Boston, MA
University Medical Center Utrecht, Utrecht, Netherlands
Instituto de Parasitologia y Biomedicina Lopez-Neyra (CSIC), Granada, Spain


Different alleles of MHC class II molecules (namely, HLA-DRB1, DPB1 and DQB1) have been described to be associated either with risk to systemic sclerosis (SSc) or its subphenotypes. Due to the high cost of HLA typing, studies have been limited to small sample sizes, preventing definitive statements as to which HLA alleles are likely causal.


We have imputed the MHC class I and II alleles of 2,296 cases and 5,356 controls from the US, Spain, Germany and The Netherlands with a method previously developed, which uses genotype data from ~2000 SNPs in the MHC region and an independent reference panel of dense SNP and classical HLA typing data in >2700 unrelated Europeans. We obtained actual HLA typing data for both class I and II molecules for the Spanish and US cohorts, and compared the accuracy of the imputation. Besides classical HLA alleles, we also imputed amino acid changes encoded by genetic variants within the different MHC molecules. We compared the frequencies of the different alleles between cases and controls for SNPs, amino acids and classical HLA alleles.


The accuracy of the imputations ranged from 90% to 98% depending on the alleles being imputed with an average of 93% for all alleles in both populations. We confirmed previous associations of HLA alleles with SSc or its auto-antibody positive subgroups (HLA-DRB1*0701, HLA-DPB1*1301, HLA-DRB1*1104, HLA-DQB1*0501). We define in deeper detail some of these associations down to the level of aminoacidic positions which affect epitope binding. Furthermore, we describe new associations of HLA alleles with auto-antibody positive subgroups, HLA-DRB1*0801, with the presence of anti-centromere auto-antibodies and HLA-DQB1*0301 with the presence of anti-topoisomerase I auto-antibodies. No associations in the MHC class I molecules was found.


Our data indicate that most associations of HLA alleles (and more precisely aminoacidic positions within them) are specific to the presence of auto-antibodies. Also, only MHC class II alleles are associated and not MHC class I.

To cite this abstract, please use the following information:
Martin, Jose Ezequiel, International Scleroderma Group, , Radstake, Timothy RD, Tan, Filemon K., Arnett, Frank C., Mayes, Maureen D., et al; Identification of Major Histocompatibility Complex Class II Alleles Associated with Systemic Sclerosis Through Imputation Strategy. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :2313

Abstract Supplement

Meeting Menu