Genetic variability of three common NK and γδ T cell receptor genes (FCγ3R, NCR3, and DNAM-1) and their role in Polish patients with rheumatoid arthritis and ankylosing spondylitis

• Published in: Immunologic research 2024-08, Vol.72 (4), p.614-625
• Main Authors: Biały, Sylwia, Iwaszko, Milena, Świerkot, Jerzy, Kolossa, Katarzyna, Wielińska, Joanna, Jeka, Sławomir, Bogunia-Kubik, Katarzyna
• Format: Article
• Language: English
• Subjects: Adult; Aged; Alleles; Allergology; Ankylosing spondylitis; Antigens, Differentiation, T-Lymphocyte - genetics; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - immunology; Biomedical and Life Sciences; Biomedicine; Blood donors; CD226 antigen; Female; Gene Frequency; Gene polymorphism; Genetic Predisposition to Disease; Genetic variability; Genotype; Genotype & phenotype; Humans; Immunology; Internal Medicine; Killer Cells, Natural - immunology; Lymphocytes T; Male; Medicine/Public Health; Middle Aged; Natural killer cells; Original; Original Article; Poland; Polymorphism, Single Nucleotide; Receptors, Antigen, T-Cell, gamma-delta - genetics; Receptors, IgG - genetics; Rheumatoid arthritis; Rheumatoid factor; Spondylitis, Ankylosing - genetics; Spondylitis, Ankylosing - immunology; T cell receptors; Tumor necrosis factor
• ISSN: 0257-277X; 1559-0755; 1559-0755
• DOI: 10.1007/s12026-024-09488-3

Various lymphocyte subpopulations, including NK cells as well as γδ T cells, have been considered an important element in the pathogenesis of autoimmune, inflammatory, rheumatic diseases, such as rheumatoid arthritis (RA) and ankylosing spondylitis (AS). The aim of this study was to assess the potential role of polymorphic variations in the genes coding for three NK and γδ T cell receptors: NCR3, FCγR3A, and DNAM-1 (rs1052248, rs396991, and rs763361, respectively) in the disease susceptibility and the efficacy of treatment with TNF inhibitors. The study included 461 patients with RA, 168 patients with AS, and 235 voluntary blood donors as controls. The NCR3 rs1052248 AA homozygosity prevailed in RA in patients lacking rheumatoid factor ( p  = 0.044) as well as in those who manifested the disease at a younger age ( p  = 0.005) and had higher CRP levels after 12 weeks of anti-TNF therapy ( p  = 0.021). The FCγR3A rs396991 polymorphism was associated with pain visual analogue scale (VAS) values before the initiation of anti-TNF treatment. Lower VAS values were observed in the GG homozygous RA patients ( p  = 0.024) and in AS patients with the TT genotype ( p  = 0.012). Moreover, AS heterozygous patients with the TG genotype presented higher CRP levels in the 12th week of anti-TNF treatment ( p  = 0.021). The findings suggest that the NCR3 rs1052248 AA homozygosity may have an adverse effect on RA, while the T allele potentially plays a protective role in the development of AS. Moreover, the rs1052248 T allele and TT genotype appear to have a favorable impact on the response to anti-TNF therapy in RA patients.