Journal article
Molecular basis for increased susceptibility of Indigenous North Americans to seropositive rheumatoid arthritis
SW Scally, SC Law, YT Ting, JV Heemst, J Sokolove, AJ Deutsch, E Bridie Clemens, AK Moustakas, GK Papadopoulos, DVD Woude, I Smolik, CA Hitchon, DB Robinson, ED Ferucci, CN Bernstein, X Meng, V Anaparti, T Huizinga, K Kedzierska, HH Reid Show all
Annals of the Rheumatic Diseases | BMJ PUBLISHING GROUP | Published : 2017
Abstract
Objective The pathogenetic mechanisms by which HLA-DRB1 alleles are associated with anticitrullinated peptide antibody (ACPA)-positive rheumatoid arthritis (RA) are incompletely understood. RA high-risk HLA-DRB1 alleles are known to share a common motif, the â € shared susceptibility epitope (SE)'. Here, the electropositive P4 pocket of HLA-DRB1 accommodates self-peptide residues containing citrulline but not arginine. HLA-DRB1 His/Phe13β stratifies with ACPA-positive RA, while His13βSer polymorphisms stratify with ACPA-negative RA and RA protection. Indigenous North American (INA) populations have high risk of early-onset ACPA-positive RA, whereby HLA-DRB1∗04:04 and HLA-DRB1∗14:02 are impli..
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Awarded by Australian Research Council
Funding Acknowledgements
This work was supported by the Australian National Health and Medical Research Council (NHMRC), Australian Research Council (ARC) and Canadian Institutes of Health Research (CIHR: MOP77700) funding. JR is an ARC Australian Laureate Fellow and RT an NHMRC Fellow.