Clinical and immunological features of PD-1 and Tim-3 expression on monocytes in axial spondyloarthritis
https://doi.org/10.15789/1563-0625-CAI-3260
Abstract
Regulation of inflammation in inflammatory/autoimmune rheumatic diseases, particularly axial spondyloarthritis, is critically important for alleviating disease symptoms. Recent studies have demonstrated the key role of inhibitory receptors PD-1 and Tim-3 in regulating the functional phenotype of monocytes in inflammatory/autoimmune diseases. The aim of this study was to investigate the expression of inhibitory receptors PD-1 and Tim-3 in monocyte subsets in patients with axial spondyloarthritis (axSpA) and to assess their association with clinical parameters and the tolerogenic marker Mer tyrosine kinase (MerTK). The expression of PD-1 and Tim-3 in classical, intermediate, and non-classical monocytes was evaluated using multicolor flow cytometry in peripheral blood mononuclear cells of 60 patients with axial spondyloarthritis and 40 healthy donors. Analysis of circulating monocyte subpopulations revealed an increased proportion of classical monocytes, which positively correlated with systemic inflammation markers ESR and CRP. As in donors, the highest expression of PD-1 and Tim-3 in axSpA patients was observed in intermediate and non-classical monocytes. However, the relative proportions of PD-1+ and PD-1+Tim-3+ cells in intermediate and non-classical monocyts were significantly decreased in axSpA patients, while Tim-3 expression levels did not differ from donor values. Notably, the proportion of PD-1+ cells directly correlated with MerTK expression (a molecule mediating the anti-inflammatory activity of monocytes/macrophages) in all monocyte subsets. A statistically significant decrease in PD-1 expression and co-expression of PD-1 and Tim-3 was detected in HLA-B27 antigen carriers, patients with advanced and late-stage disease, and those with peripheral axSpA, including hip joint involvement. In contrast, in HLA-B27-negative patients and those with early/non-radiographic stage disease, PD-1 expression was comparable to donor levels, while Tim-3+ cell content was increased in the classical monocytes. It should be noted that in patients receiving first-line therapy, decreased PD-1 expression and PD-1+Tim-3+ co-expression directly correlated with disease activity. The obtained data on reduced PD-1 expression and PD-1+Tim-3+ co-expression in intermediate and non-classical monocytes in patients with genetic predisposition, advanced disease stages, and peripheral joint involvement, as well as the association between PD-1+ cell number and MerTK expression in all monocyte subsets, indicate dysregulation of inhibitory checkpoint receptor expression under inflammatory conditions. These findings could suggest diminished anti-inflammatory capacity of monocytes.
About the Authors
Ekaterina Ya. ShevelaRussian Federation
Ludmila Sakhno
Russian Federation
Marina Tikhonova
Tamara Tyrinova
Anastasiia Morenkova
Oksana Chumasova
Nadezhda Ilina
Nadezhda Shkaruba
Yuliya Kurochkina
Anastasia Fedorova
Vitaly Omelchenko
Elena Letyagina
Maxim Korolev
Aleksey Sizikov
Elena Chernykh
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Shevela E.Ya., Sakhno L., Tikhonova M., Tyrinova T., Morenkova A., Chumasova O., Ilina N., Shkaruba N., Kurochkina Yu., Fedorova A., Omelchenko V., Letyagina E., Korolev M., Sizikov A., Chernykh E. Clinical and immunological features of PD-1 and Tim-3 expression on monocytes in axial spondyloarthritis. Medical Immunology (Russia). (In Russ.) https://doi.org/10.15789/1563-0625-CAI-3260