Muhammad Haroon1, Robert Winchester2, Jon T Giles2, Eric Heffernan3, Oliver FitzGerald1. 1. Department of Rheumatology, St Vincent's University Hospital, Dublin, Ireland. 2. Division of Rheumatology, Columbia University, College of Physicians and Surgeons, New York, New York, USA. 3. Department of Diagnostic Imaging, St Vincent's University Hospital, Dublin, Ireland.
Abstract
OBJECTIVES: Psoriatic arthritis (PsA) susceptibility is associated with several different class I alleles, suggesting separate patterns of MHC effect. This exploratory study was based on the hypothesis that heterogeneity of the clinical phenotype of PsA might be explained by differing associations of clinical features with these susceptibility genes. METHODS: The clinical phenotype of 282 PsA patients in a cohort previously studied for associations with human leukocyte antigen (HLA)-B and HLA-C genotypes was first preliminarily assessed by univariate associations of susceptibility genes with specific clinical characteristics. To explore the potential genotypic effects of pairwise combinations of different HLA-B and C alleles/haplotypes, we created a series of allele/haplotype risk scores combining single alleles/haplotypes separately associated with being in the highest PsA severity propensity tertile based on the features studied by univariate analysis. RESULTS: In exploratory univariate analyses, B*27:05:02 was positively associated with enthesitis, dactylitis and symmetric sacroiliitis, whereas B*08:01:01-C*07:01:01and its component alleles were positively associated with joint fusion and deformities, asymmetrical sacroiliitis, and dactylitis. HLA-C*06:02:01 was negatively associated with asymmetrical sacroiliitis. The highest propensity score for severe PsA was with B*27:05:02-C*02:02:02, B*08:01:01-C*07:01:01 and B*37:01:01-C*06:02:01, but not the B*27:05:02-C*01:01:01 or B*57:01:01-C*06:02:01 haplotypes. In contrast, B*44 haplotypes were associated with presence of milder disease, and in univariate analysis with a decreased frequency of enthesitis, joint fusion, deformities and dactylitis. CONCLUSIONS: Different HLA susceptibility genes were associated with particular features that defined the PsA phenotype of a given patient. Additive interactions between different susceptibility HLA alleles defined the propensity for a more severe or milder musculoskeletal phenotype. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
OBJECTIVES:Psoriatic arthritis (PsA) susceptibility is associated with several different class I alleles, suggesting separate patterns of MHC effect. This exploratory study was based on the hypothesis that heterogeneity of the clinical phenotype of PsA might be explained by differing associations of clinical features with these susceptibility genes. METHODS: The clinical phenotype of 282 PsA patients in a cohort previously studied for associations with humanleukocyte antigen (HLA)-B and HLA-C genotypes was first preliminarily assessed by univariate associations of susceptibility genes with specific clinical characteristics. To explore the potential genotypic effects of pairwise combinations of different HLA-B and C alleles/haplotypes, we created a series of allele/haplotype risk scores combining single alleles/haplotypes separately associated with being in the highest PsA severity propensity tertile based on the features studied by univariate analysis. RESULTS: In exploratory univariate analyses, B*27:05:02 was positively associated with enthesitis, dactylitis and symmetric sacroiliitis, whereas B*08:01:01-C*07:01:01and its component alleles were positively associated with joint fusion and deformities, asymmetrical sacroiliitis, and dactylitis. HLA-C*06:02:01 was negatively associated with asymmetrical sacroiliitis. The highest propensity score for severe PsA was with B*27:05:02-C*02:02:02, B*08:01:01-C*07:01:01 and B*37:01:01-C*06:02:01, but not the B*27:05:02-C*01:01:01 or B*57:01:01-C*06:02:01 haplotypes. In contrast, B*44 haplotypes were associated with presence of milder disease, and in univariate analysis with a decreased frequency of enthesitis, joint fusion, deformities and dactylitis. CONCLUSIONS: Different HLA susceptibility genes were associated with particular features that defined the PsA phenotype of a given patient. Additive interactions between different susceptibility HLA alleles defined the propensity for a more severe or milder musculoskeletal phenotype. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Authors: Georg Schett; Proton Rahman; Christopher Ritchlin; Iain B McInnes; Dirk Elewaut; Jose U Scher Journal: Nat Rev Rheumatol Date: 2022-05-05 Impact factor: 20.543
Authors: Robert Winchester; Jon Giles; Deepak Jadon; Muhammed Haroon; Neil McHugh; Oliver FitzGerald Journal: Clin Immunol Date: 2016-07-25 Impact factor: 3.969