Co-stimulation modulation improves Rheumatoid Arthritis despite reducing the proportion of CD4+CD25high T regulatory cells

• Main Authors: Charalampos Papagoras, Theodora E. Markatseli, Assimina Petsiou, Achilleas Karamoutsios, Alexandros A. Drosos
• Format: Article
• Language: English
• Published: PCO Convin S.A. 2016-01-01
• Series: Mediterranean Journal of Rheumatology
• Subjects: rheumatoid arthritis; regulatory t cells; abatacept; ctla-4
• Online Access: https://www.mjrheum.org/assets/files/792/file32_567.pdf

Objective/Aims: Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) is constitutively expressed on the surface of regulatory T cells (Treg), although its function in this context remains unclear. Abatacept, a soluble CTLA-4·Ig construct is a co-stimulation modulator that is used for the treatment of rheumatoid arthritis (RA). We studied the effects of abatacept on peripheral blood Treg cell population in RA patients starting abatacept therapy. Material and Methods: Peripheral blood was collected from 8 RA patients before the first and fifth abatacept infusion and from 8 healthy volunteers. The percentage of Treg cells (CD4+CD25high− CD127−/low) was measured by flow cytometry. Results: Initially, patients had a mean percentage of Treg cells 2.7%, which was similar to that of controls (3.25%, p=0.495). The baseline mean DAS28 was 4.87, whereas by the fifth infusion it had decreased to 3.3 (p=0.017). By the fifth infusion the mean percentage of Treg cells had also decreased to 1.15%, which was lower compared to baseline (p=0.012). The difference of Treg percentage between both time points positively correlated with the difference in the swollen joint count (r=0.856, p=0.007). Conclusion: Abatacept significantly improved disease activity, but also decreased the percentage of Treg cells among the peripheral CD4+ T cells.