Background: Takayasu arteritis (TA) is a chronic systemic vasculitis of large vessels, usually affecting the aorta and its major branches. Chronic granulomatous inflammation of the arterial walls can cause structural changes in the affected arteries, ultimately leading to stenosis, occlusion, and aneurysm formation. The pathogenesis of the disease is not fully understood; however, an association with certain genetic factors has been identified, in particular, the HLA-B5(52)/*B52:01:01 antigen/allele and other HLA antigens/alleles.

Objectives: To study the distribution of HLA-A, -B, -C, -DRB1, -DPB1, -DQB1 , and - DQA1 gene alleles in patients with Takayasu arteritis in the Kyrgyz and Russian populations.

Methods: The case-control study included 102 patients with AT and 100 controls of Kyrgyz ethnicity, as well as 36 patients with AT and 160 controls of the Russian population. All patients met the 2022 ACR/EULAR classification criteria. Sequencing of the exons of the HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DPB1, HLA-DQB1 , and HLA-DQA1 genes was performed on the Illumina MiSeq platform using the MiSeq Reagent Kit v3. Statistical data processing, including a comparison of HLA allele frequencies in the AT patient groups with the corresponding control groups, was performed in the Python software environment using the NumPy, Pandas, and Scikit-learn libraries.

Results: In the Kyrgyz population of patients with AT, the HLA-A*24:02:01, B*51:01:01 and C*15:02:01 alleles were detected statistically significantly less frequently compared to the control group (p<0.02). At the same time, the B*52:01:01 allele was found almost 2 times more often in the group of patients than in the control group (21.6% and 12.0%, respectively), but the difference did not reach the level of statistical significance (p>0.05). Haplotype A*02:01:01-B*52:01:01-C*12:02:02 was identified as a risk marker of AT in the Kyrgyz population (OR=5.3; 95% CI 1.1–24.9], p<0.03). No statistically significant differences were found in any clinical and instrumental parameters in AT patients carrying the B*51:01:01 allele. In the group of Russian AT patients, an association with the haplotype A*02:01:01-B*13:02:01-C*06:02:01-DPB1*17:01:01-DQB1*02:02:01-DRB1*07:01:01 was found (OR=19.9 [3.5 - 112.7], p=0.000). It should be noted that all alleles included in this haplotype also had a statistically significant increase in frequencies in AT patients compared to the control (p=0.000). The frequency of the B*52:01:01 allele was increased in patients with AT compared to controls (11.1% and 4.4%, respectively), but the difference did not reach the level of statistical significance (p>0.05).

Conclusions: We conducted a pilot study of seven major genes and their alleles in the HLA system in patients with Takayasu arteritis in Kyrgyz and Russian populations under an international agreement. We compared the distribution of allele frequencies with a control group and identified HLA markers for AT. Currently, we have a small sample of Russian patients with AT, which will be expanded, as will the sample of Kyrgyz patients. The difference in the frequency of the B*52:01:01 allele in the Kyrgyz and Russian healthy control populations (12,0% and 4,4% respectively) is noteworthy, which may have some impact on the different prevalence and incidence of AT in Kyrgyz Republic and Russia.

REFERENCES: NIL.

Acknowledgments: NIL.

Disclosure of Interests: None declared.