The subset composition of follicular T helpers and B lymphocytes in patients with ankylosing spondylitis depending on HLA-B27 status
https://doi.org/10.18699/SSMJ20240319
Abstract
Immune relationships involved in a wide range of immunopathological conditions, including ankylosing spondylitis (AS), are formed due to the characteristics of the subset composition of follicular T helper cells (Tfh) and B lymphocytes. Expression of the HLA-B27 antigen can change the reactivity of cells of the immune system and, accordingly, their interaction and participation in the immunopathogenesis of AS. The aim of this study was to investigate the characteristics of the subset composition of Tfh and B cells in HLA-B27-positive and negative patients with AS. Material and methods. 66 patients (17 women and 49 men) aged 20–58 years with a diagnosis of AS were examined. Molecular genetic research on HLA-B27 expression was carried out using the quantitative PCR method with real-time detection. The subset composition of Tfh and B cells was studied using flow cytometry. Results. An increase in the amount of Tfh2 in the blood is observed in all patients with AS. The number of Tfh1 was reduced in HLA-B27-positive AS patients, but Tfh17 cell content was increased. Changes in the subset composition of B lymphocytes, which were found only in patients with an HLA-B27-positive form of the disease, manifest themselves primarily as an imbalance in the distribution of B cell memory. Only negative correlations of Tfh1 and Tfh17 content with “double-negative” B cell and plasmablast precursors percentage are detected in HLA-B27-negative AS patients. Tfh1 cell number correlate negatively with naïve and activated naïve B cell content in HLA-B27-positive disease, Tfh2 cell percentage – with memory B cell fraction number. CCR6+ Tfh and Tfh17 have positive regulatory effects on plasmablast precursors. Conclusions. The subset composition of Tfh characterizes the dominance in the immunopathogenesis of AS of the direction of the regulatory influence of follicular T helper cells on B lymphocytes regardless of the carriage of the HLA-B27 gene in AS patients. High levels of Tfh type 17 are also detected in HLA-B27-positive patients. The relationships between the subsets of Tfh and B cells in HLA-B27-negative AS patients characterize the presence of processes aimed at inhibiting B cells. The influence of Tfh1 is aimed at suppression of B-cell immunity in HLA-B27-positive AS while Tfh2 and Tfh17 stimulate B-cell mechanisms.
About the Authors
P. A. ShesternyaRussian Federation
Pavel A. Shesternya, doctor of medical sciences, professor
660022, Krasnoyarsk, Partizan Zheleznyaka st., 1а
A. A. Savchenko
Russian Federation
Andrey A. Savchenko, doctor of medical sciences, professor
660022, Krasnoyarsk, Partizan Zheleznyaka st., 1а;
660022, Krasnoyarsk, Partizana Zheleznyaka st., 3g
I. V. Kudryavtsev
Russian Federation
Igor V. Kudryavtsev, candidate of biological sciences
197022, St. Petersburg, Academician Pavlova st., 12;
690922, Vladivostok, Russky Island, 10 Ajax Bay
A. A. Masterova
Russian Federation
Alena A. Masterova
660022, Krasnoyarsk, Partizana Zheleznyaka st., 3g
A. G. Borisov
Russian Federation
Alexandr G. Borisov, candidate of medical sciences
660022, Krasnoyarsk, Partizan Zheleznyaka st., 1а;
660022, Krasnoyarsk, Partizana Zheleznyaka st., 3g
References
1. Russian clinical guidelines. Rheumatology. Ed. E.L.Nasonov. Moscow: GEOTAR-MED, 2019. 448 p. [In Russian].
2. Erdes Sh.F., Sakharova K.V. Clinical picture of ankylosing spondylitis in HLA-B27 positive and negative patients. Sovremennaya revmatologiya = Modern Rheumatology Journal. 2023;17(5):61–66. [In Russian]. doi: 10.14412/1996-7012-2023-5-61-66
3. Xiong Y., Cai M., Xu Y., Dong P., Chen H., He W., Zhang J. Joint together: The etiology and pathogenesis of ankylosing spondylitis. Front. Immunol. 2022;13:996103. doi: 10.3389/fimmu.2022.996103
4. Bai Y., Zhao N., Sun H., Yin L., Chen J., Hu N. Associations between ERAP1 polymorphisms and ankylosing spondylitis susceptibility in HLA-B27 positive population: a Meta-analysis and bioinformatics analysis. Nucleosides Nucleotides Nucleic Acids. 2022;41(4):407–418. doi: 10.1080/15257770.2022.2036344
5. Kenyon M., Maguire S., Rueda Pujol A., O’Shea F., McManus R. The genetic backbone of ankylosing spondylitis: how knowledge of genetic susceptibility informs our understanding and management of disease. Rheumatol. Int. 2022;42(12):2085–2095. doi: 10.1007/s00296-022-05174-5
6. Lorente E., Fontela M.G., Barnea E., Martín-Galiano A.J., Mir C., Galocha B., Admon A., Lauzurica P., López D. Modulation of natural HLA-B*27:05 ligandome by ankylosing spondylitis-associated endoplasmic reticulum aminopeptidase 2 (ERAP2). Mol. Cell. Proteomics. 2020;19(6):994–1004. doi: 10.1074/mcp.RA120.002014
7. Smith J.A. The role of the unfolded protein response in axial spondyloarthritis. Clin. Rheumatol. 2016;35(6):1425–1431. doi: 10.1007/s10067-015-3117-5
8. Lejon K., Hellman U., Do L., Kumar A., Forsblad-d’Elia H. Increased proportions of inflammatory T cells and their correlations with cytokines and clinical parameters in patients with ankylosing spondylitis from northern Sweden. Scand. J. Immunol. 2022;96(3):e13190. doi: 10.1111/sji.13190
9. Shesternya P.A., Savchenko A.A., Gritsenko O.D., Vasileva A.O., Kudryavtsev I.V., Masterova A.A., Isakov D.V., Borisov A.G. Features of peripheral blood th-cell subset composition and serum cytokine level in patients with activity-driven ankylosing spondylitis. Pharmaceuticals (Basel). 2022;15(11):1370.
10. Peng J., Gong Y., Zhang Y., Wang D., Xiao Z. Immunohistological analysis of active sacroiliitis in patients with axial spondyloarthritis. Medicine (Baltimore). 2017;96(16):e6605. doi: 10.1097/MD.0000000000006605
11. Wilbrink R., Spoorenberg A., Verstappen G.M.P.J., Kroese F.G.M. B cell involvement in the pathogenesis of ankylosing spondylitis. Int. J. Mol. Sci. 2021;22(24):13325. doi: 10.3390/ijms222413325
12. Gong F., Zheng T., Zhou P. T Follicular helper cell subsets and the associated cytokine IL-21 in the pathogenesis and therapy of asthma. Front. Immunol. 2019;10:2918. doi: 10.3389/fimmu.2019.02918
13. Kurata I., Matsumoto I., Sumida T. T-follicular helper cell subsets: a potential key player in autoimmunity. Immunol. Med. 2021;44(1):1–9. doi: 10.1080/25785826.2020.1776079
14. van der Linden S., Valkenburg H.A., Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum. 1984;27(4):361–368. doi: 10.1002/art.1780270401
15. Machado P.M., Landewé R., Heijde D.V., Assessment of SpondyloArthritis international Society (ASAS). Ankylosing Spondylitis Disease Activity Score (ASDAS): 2018 update of the nomenclature for disease activity states. Ann. Rheum. Dis. 2018;77(10):1539–1540. doi: 10.1136/annrheumdis-2018-213184
16. Golovkin A., Kalinina O., Bezrukikh V., Aquino A., Zaikova E., Karonova T., Melnik O., Vasilieva E., Kudryavtsev I. Imbalanced immune response of T-cell and B-cell subsets in patients with moderate and severe COVID-19. Viruses. 2021;13(10):1966. doi: 10.3390/v13101966
17. Kudryavtsev I.V., Arsentieva N.A., Batsunov O.K., Korobova Z.R., Khamitova I.V., Isakov D.V., Kuznetsova R.N., Rubinstein A.A., Stanevich O.V., Lebedeva A.A., … Totolian A.A. Alterations in B cell and follicular T-helper cell subsets in patients with acute COVID-19 and COVID-19 convalescents. Curr. Issues Mol. Biol. 2022;44(1):194–205. doi: 10.3390/cimb44010014
18. Bohnhorst J.O., Thoen J.E., Natvig J.B., Thompson K.M. Significantly depressed percentage of CD27+ (memory) B cells among peripheral blood B cells in patients with primary Sjögren’s syndrome. Scand. J. Immunol. 2001;54(4):421–427. doi: 10.1046/j.1365-3083.2001.00989.x
19. Sanz I., Wei C., Lee F.E., Anolik J. Phenotypic and functional heterogeneity of human memory B cells. Semin. Immunol. 2008;20(1):67–82. doi: 10.1016/j.smim.2007.12.006
20. Shen F., Shen Y., Xu Y., Zhao J., Zhao Z., Liu J., Ge Y. Dysregulation of circulating T follicular helper cell subsets and their potential role in the pathogenesis of syphilis. Front. Immunol. 2023;14:1264508. doi: 10.3389/fimmu.2023.1264508
21. Wang Y., Liu J., Burrows P.D., Wang J.Y. B cell development and maturation. Adv. Exp. Med. Biol. 2020;1254:1–22. doi: 10.1007/978-981-15-3532-1_1
22. Beckers L., Somers V., Fraussen J. IgD-CD27-double negative (DN) B cells: Origins and functions in health and disease. Immunol. Lett. 2023;255:67–76. doi: 10.1016/j.imlet.2023.03.003
23. Savchenko A.A., Gritsenko O.D., Borisov A.G., Kudryavtsev I.V., Serebriakova M.K., Masterova A.A., Shesternya P.A. Features of T lymphocyte subpopulation profile in patients with ankylosing spondylitis undergoing genetically engineered biological therapy. Meditsinskaya immunologiya = Medical Immunology. 2021;23(6):1319–1332. [In Russian]. doi: 10.15789/1563-0625-FOT-2349