Background/Purpose: Takayasu arteritis (TAK) is a granulomatous large-vessel vasculitis affecting the aorta and its main branches. There are multiple HLA and non-HLA susceptibility loci for TAK and the HLA-B*52 subtype is the leading genetic susceptibility factor identified to date. However, the magnitude of this association varies substantially across ethnic groups. Given the high genetic diversity of the Brazilian population, this study aims to assess the frequency of HLA-B*52 in Brazilian TAK patients and the association between this allele and the risk of developing TAK compared to population controls. In addition, the study sought to investigate the role of other HLA-B locus alleles in disease susceptibility.

Methods: This monocenter cross-sectional study included 76 patients with TAK. Inclusion criteria were: age ≥18 years, fulfillment of the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria for TAK and written informed consent. Patients presenting another systemic autoimmune or inflammatory disease and Indigenous individuals were excluded. The control group comprised 1,273,311 adult donors from a Brazilian bone marrow donor registry (REDOME), who met the same ethnic exclusion criterion. HLA-B locus genotyping was performed by PCR-SSO (polymerase chain reaction-sequence-specific oligonucleotide) at a two-digit resolution. Allele frequencies were compared between patients and controls by logistic regression; alleles significant in univariate analysis entered a multivariate model adjusted for age, sex, and self-reported race/ethnicity. The associations were expressed as odds ratios (OR) with 95% confidence intervals (95% CI), and significance was set at p-value < 0.05.

Results: The most frequent HLA-B subtypes in TAK patients were HLA-B*44 (32.9%), HLA-B*35 (21.1%), HLA-B*15 (15.8%) and HLA-B*7 (13.2%), while HLA-B*35 (12.1%), HLA-B*44 (10.5%), HLA-B*15 (8.8%) and HLA-B*51 (8.6%) were the most frequent HLA-B subtypes among controls. The HLA-B*52 subtype was present in 10.5% of TAK patients compared to 1.95% of controls (OR = 2.93; 95%CI: 1.217-6.111; p = 0.009). The subtypes HLA-B*44 and HLA-B*41 were also associated with increased susceptibility to TAK (OR = 1.854; 95% CI: 1.093-3.063; p = 0.014 and OR = 3.065; 95% CI: 1.088-7.013; p = 0.018, respectively). After adjusting for age, sex, and self-reported race/ethnicity in a multivariate analysis, three HLA-B locus alleles remained independently associated with TAK (Table 1).

Conclusion: HLA-B*52 is a susceptibility factor for TAK in the Brazilian population, extending an association that was previously described in other population groups, particularly in Asian cohorts. The independent identification of HLA-B*41 and HLA-B*44 also indicates that the HLA-B locus contributes more broadly to the genetic susceptibility of the disease. These findings require confirmation in larger cohorts using higher-resolution genotyping.

This study was supported by the FAPE of the Brazilian Society of Rheumatology and by FAPESP grant nr. 2025/04048-5.

Table 1. Adjusted associations between HLA-B locus alleles and TAK diagnosis.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/is-the-hla-b52-allele-associated-with-an-increased-risk-of-developing-takayasu-arteritis-in-brazil-a-monocenter-cross-sectional-study/