Altered CD39 and CD73 Expression in Rheumatoid Arthritis: Implications for Disease Activity and Treatment Response
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
Affiliations
María Angels Ortiz
Inflammatory Diseases, Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), 08041 Barcelona, Spain
Cesar Diaz-Torné
Rheumatology Department, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain
Rheumatology Department, Hospital Moisès Broggi, Sant Joan Despí, 08970 Barcelona, Spain
Delia Reina
Rheumatology Department, Hospital Moisès Broggi, Sant Joan Despí, 08970 Barcelona, Spain
María Victoria Hernandez
Rheumatology Department, Hospital Clínic de Barcelona, 08036 Barcelona, Spain
Hye Sang
Rheumatology Department, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain
Carlos Zamora
Inflammatory Diseases, Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), 08041 Barcelona, Spain
Elisabet Cantó
Inflammatory Diseases, Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), 08041 Barcelona, Spain
Hector Corominas
Rheumatology Department, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain
Silvia Vidal
Inflammatory Diseases, Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), 08041 Barcelona, Spain
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+CD39−CD73+ cell percentage, which inversely correlated with DAS28. Additionally, they had lower percentages of Treg CD39+CD73+ and CD39−CD73− cells. Good responders tended to have lower B CD39+CD73+ cell percentages at baseline and 3 months. Additionally, Treg, CD8+ 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+ T-cell percentage in Cs, but increased the percentage of IFNγ-secreting CD4+ and CD8+ 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.
