Major histocompatibility complex class i and class II alleles may confer susceptibility to or protection against morphea: Findings from the morphea in adults and children cohort

Heidi Jacobe, Chul Ahn, Frank C. Arnett, John D. Reveille

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Objective To determine the HLA class I and class II alleles of the human major histocompatibility complex showing an association with morphea (localized scleroderma) in the Morphea in Adults and Children (MAC) cohort, using a nested case-control association study. Methods Patients with morphea were identified from the MAC cohort, and matched controls were obtained from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases Scleroderma Family Registry and DNA Repository and from the Division of Rheumatology at the University of Texas Health Science Center at Houston. HLA class II genotyping and single-strand conformational polymorphism typing were performed to identify HLA-A, B, and C alleles. Associations between HLA class I and class II alleles and morphea, as well as its subphenotypes, were determined. Results Two hundred eleven patients with morphea and 726 matched controls were available for HLA class I typing, and 158 patients with morphea and 1,008 matched controls were available for HLA class II typing. The strongest associations were found with DRB1∗04:04 (odds ratio [OR] 2.3, 95% confidence interval [95% CI] 1.4-4.0, P = 0.002), and HLA-B∗37 conferred the highest OR among the class I alleles (OR 3.2, 95% CI 1.5-6.5, P = 0.001). Comparison of the risk allele profile in this cohort with the risk alleles previously identified in patients with systemic sclerosis, determined using the same methods and same control population, revealed one allele in common, DRB∗04:04. Conclusion These results demonstrate that specific HLA class I and class II alleles are associated with morphea and are also likely to be associated with generalized and linear subtypes of morphea. The morphea-associated alleles are different from those found in scleroderma, suggesting that morphea is immunogenetically distinct. Risk alleles in morphea are also associated with conditions such as rheumatoid arthritis (RA) and other autoimmune conditions. Population-based studies have indicated that patients with RA have an increased risk of morphea, and therefore a common susceptibility allele may be implicated.

Original languageEnglish (US)
Pages (from-to)3170-3177
Number of pages8
JournalArthritis and Rheumatology
Volume66
Issue number11
DOIs
StatePublished - Nov 1 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

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