Nagit Ruxandra-Elena, Pavel-Tanasa Mariana, Cianga Corina, Rezus Elena, Cianga Petru
Immunology Department, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iași, Romania.
Immunology Laboratory, "St. Spiridon" Clinical Hospital, 700106 Iași, Romania.
Int J Mol Sci. 2025 Aug 6;26(15):7617. doi: 10.3390/ijms26157617.
This study examined the distribution and disease associations of non-HLA-B27 HLA-B alleles in Romanian spondyloarthritis (SpA) patients, aiming to address the underrepresentation of Eastern European populations in immunogenetic research. Methods: We analyzed 263 HLA-B27-negative patients from Northeastern Romania fulfilling ASAS criteria. HLA-B genotyping was performed at two-digit resolution, and allele distributions were compared with two Romanian HLA-B27-negative control groups ( = 335 and = 1705 cases), using chi-square testing and logistic regression. Compared to controls, HLA-B47 ( = 0.0007) and HLA-B54 ( = 0.0013) were significantly enriched, while HLA-B40 was underrepresented ( = 0.0287). Notably, HLA-B54 was observed exclusively in axial SpA. Within the cohort, both HLA-B13 and HLA-B57 alleles were associated with psoriasis, while HLA-B37 and HLA-B41 alleles were clustered within the reactive arthritis group. The HLA-B35 and HLA-B18 alleles were the most frequently observed alleles across most clinical phenotypes. When comparing the frequency of HLA-B associations, the most common genotypes among SpA patients were B08-B18, B13-B35, and B35-B51. Notably, B08-B18 was more frequent in patients with radiographic sacroiliitis grade ≥ 2, while B35-B51 was more frequent in those with confirmed systemic inflammation, as indicated by elevated CRP or ESR levels. Analysis of peptide-binding patterns revealed a cluster of risk alleles, HLA-B08, B18, B35, B40, and B54, sharing similar features, distinct from the canonical profile of B27. These findings highlight the contribution of non-B27 HLA-B alleles to SpA susceptibility in an Eastern European population and support the notion that HLA-B27-negative SpA may represent a distinct clinical and immunological entity, driven by alternative pathogenic mechanisms. They also emphasize the importance of population-specific immunogenetic profiling and support expanding genetic characterization in HLA-B27-negative patients.
本研究调查了罗马尼亚脊柱关节炎（SpA）患者中非HLA - B27的HLA - B等位基因的分布及其与疾病的关联，旨在解决东欧人群在免疫遗传学研究中代表性不足的问题。方法：我们分析了罗马尼亚东北部符合ASAS标准的263例HLA - B27阴性患者。HLA - B基因分型以两位数分辨率进行，并使用卡方检验和逻辑回归将等位基因分布与两个罗马尼亚HLA - B27阴性对照组（分别为335例和1705例）进行比较。与对照组相比，HLA - B47（P = 0.0007）和HLA - B54（P = 0.0013）显著富集，而HLA - B40的比例较低（P = 0.0287）。值得注意的是，HLA - B54仅在轴向SpA中观察到。在该队列中，HLA - B13和HLA - B57等位基因均与银屑病相关，而HLA - B37和HLA - B41等位基因聚集在反应性关节炎组中。HLA - B35和HLA - B18等位基因是大多数临床表型中最常观察到的等位基因。比较HLA - B关联的频率时，SpA患者中最常见的基因型是B08 - B18、B13 - B35和B35 - B51。值得注意的是，B08 - B18在放射学骶髂关节炎≥2级的患者中更常见，而B35 - B51在CRP或ESR水平升高所表明的确诊系统性炎症患者中更常见。肽结合模式分析揭示了一组风险等位基因，HLA - B08、B18、B35、B40和B54，它们具有相似的特征，与B27的典型特征不同。这些发现突出了非B27的HLA - B等位基因对东欧人群SpA易感性的贡献，并支持HLA - B27阴性SpA可能代表由替代致病机制驱动的独特临床和免疫实体的观点。它们还强调了人群特异性免疫遗传分析的重要性，并支持扩大对HLA - B27阴性患者的基因特征描述。
