Decoding human leukocyte antigen Beta-27; its active alleles in Ankylosing Spondylitis and computational insights of potential inhibitors: HLA-B27 in AS; its variants and inhibitors.

OBJECTIVES: This study aimed to determine the diverse inborn and adventitious variables that contribute to the rise of Ankylosing Spondylitis (AS) and to elucidate the genotypic study of HLA-B*27 alleles along with sub-alleles and in-silico inhibition of their respective abnormal receptor proteins by natural compounds.

METHODS: Case-control study was piloted. Allele-specific DNA-based HLA typing was performed after DNA extraction. Patient questionnaires and Molecular docking was applied to identify AS prognosis and potential HLA-B*27 inhibitors respectively.

RESULTS: Results revealed a 72.72% prevalence of HLA-B*27 alleles in patients versus 9.09% in controls. Sub-alleles HLA-B*27:02, 04, and 05 were identified in 87.5% of patients but were absent in controls. The chi-square (χ2) values for HLA-B*27 alleles and sub-alleles were significant, with p-values of 0.0024 and 0.0220, respectively. The study found no significant association of AS with gender, age, marital status, or environmental factors, but a strong association with family history of back pain, elevated CRP, ESR, body inflammation, and uveitis. In silico analysis identified Rutin, curcumin, and coumaroylquinic acid as natural compounds with the highest binding affinity to HLA-B27 chains A and F, suggesting their probability to modulate the structure and function of HLA-B27 proteins.

CONCLUSIONS: AS is more prevalent in individuals with family history of backache, uveitis and elevated inflammatory markers, Sub-alleles of HLA-B*27 should be used as diagnostic tools alongside alleles, as they were found only in patients, not in healthy individuals. Furthermore, Rutin, curcumin, and coumaroylquinic acid may temper the function of HLA associated with AS.