The Role of HLA-B Typing in Behçet’s Disease and Spondyloarthritis: Genetic and Clinical Insights

TL;DR

This study explores how specific HLA-B genes are linked to Behçet’s disease and spondyloarthritis, showing genetic differences and clinical traits that help distinguish these inflammatory conditions.

Contribution

The study provides extended HLA-B allele profiling in Behçet’s disease and spondyloarthritis, revealing new genetic associations and clinical distinctions.

Findings

HLA-B*51 is strongly associated with Behçet’s disease, while HLA-B*27 and its combinations are prevalent in spondyloarthritis.

Behçet’s disease patients show higher inflammatory markers and specific clinical features compared to non-BD patients.

Spondyloarthritis patients exhibit longer disease duration, more NSAID use, and higher prevalence of enthesitis and psoriasis.

Abstract

Background: Behçet’s disease (BD) is a systemic inflammatory disorder marked by recurrent mucocutaneous and ocular manifestations, predominantly affecting populations along the historic Silk Road. Genetic susceptibility, especially involving HLA-B*51, is well established. Spondyloarthritis (SpA) shares immunogenetic and clinical overlaps with BD, notably through associations with HLA class I alleles, particularly HLA-B*27. However, extended HLA-B allele profiling in these conditions remains limited. This study aimed to investigate the extended distribution of HLA-B alleles in patients presenting with clinical features suggestive of BD or SpA and to compare their clinical and laboratory profiles. Methods: In a prospective observational study at a Bulgarian rheumatology center, 120 patients with suspected BD or SpA were enrolled between January 2023 and June 2025. Diagnoses were confirmed using International Criteria for Behçet’s Disease (ICBD) and ASAS criteria for SpA. Comprehensive clinical evaluations, laboratory assessments including HLA-B typing by Sanger sequencing, and inflammatory markers were collected and analyzed. Results: Of the cohort, 15 patients (12.5%) were diagnosed with BD and 30 (25%) with SpA. HLA-B*51 was predominantly associated with BD, while HLA-B*27 and its heterozygous combinations were prevalent in SpA patients. Suspected BD patients exhibited significantly higher levels of inflammatory markers (CRP, ESR) and characteristic clinical features such as oral/genital ulcers and uveitis compared to non-BD patients. Suspected SpA patients showed longer disease duration, increased NSAID use and higher prevalence of enthesitis, psoriasis and peripheral arthritis compared to non-SpA patients. Conclusions: This study confirms the strong associations of HLA-B*51 with Behçet’s disease and HLA-B*27 with spondyloarthritis while revealing additional heterozygous and less common alleles that suggest a broader genetic influence. These findings highlight the genetic diversity and clinical heterogeneity of BD and SpA, supporting the use of extended HLA typing to improve the diagnosis and understanding of these diseases.

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