Altered CD39 and CD73 Expression in Rheumatoid Arthritis: Implications for Disease Activity and Treatment Response
2023
María Angels Ortiz | Cesar Diaz-Torné | Juan Jose De Agustin | Paula Estrada | Delia Reina | María Victoria Hernandez | Hye Sang | Carlos Zamora | Elisabet Cantó | Hector Corominas | Silvia Vidal
In rheumatoid arthritis (RA) synovium, ATP, and ADP are released, sparking inflammation. Ectoenzymes CD39 and CD73 metabolize these purine nucleotides, generating anti-inflammatory adenosine. Therefore, dysregulated CD39 and CD73 expression may impact RA development. We assessed CD39 and CD73 expression in peripheral blood from 15 healthy controls (Cs) and 35 RA patients at baseline and after 3 and 6 months of tocilizumab treatment using flow cytometry. Additionally, ectoenzyme expression was examined on cultured T cells to understand activation and IL-6 effects. At baseline, RA patients exhibited a lower CD8<sup>+</sup>CD39<sup>−</sup>CD73<sup>+</sup> cell percentage, which inversely correlated with DAS28. Additionally, they had lower percentages of Treg CD39<sup>+</sup>CD73<sup>+</sup> and CD39<sup>−</sup>CD73<sup>−</sup> cells. Good responders tended to have lower B CD39<sup>+</sup>CD73<sup>+</sup> cell percentages at baseline and 3 months. Additionally, Treg, CD8<sup>+</sup> T and B cells inversely correlated with DAS28. T-cell activation increased CD39 and decreased CD73 expression, regardless of IL-6. IL-6 reduced IFNγ-secreting CD4<sup>+</sup> T-cell percentage in Cs, but increased the percentage of IFNγ-secreting CD4<sup>+</sup> and CD8<sup>+</sup> T cells in RA patients. These findings indicate differing CD39 and CD73 expression in RA and Cs, influenced by T-cell activation and IL-6. Correlations between these molecules and RA activity suggest their role in dysregulated inflammation in RA.
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