Background Abatacept (CTLA4-Ig) prevents T-cell activation through inhibition of B7-CD28 interaction. However, abatacept may also modulate B cells, which express B7 molecules.
Objectives The objectives of this study were to evaluate if pre-treatment lymphocyte subtype levels may be associated with the response in patients with rheumatoid arthritis (RA), and to assess the effects of abatacept therapy on lymphocyte phenotype.
Methods We included in this study 22 RA patients treated by abatacept in our center with available data on lymphocyte phenotype at the moment of abatacept initiation. Among them, 16 patients had another lymphocyte phenotyping 6 months later. Patients who previously received rituximab were excluded. Response was defined at 6 months using EULAR definition. Patients were compared to 22 age and sex-matched healthy controls. Peripheral blood lymphocyte phenotyping was performed by flow cytometry using the following surface markers: CD3, CD4, CD8, CD56, CD19, IgD, CD27, CD38, and CD24. Absolute numbers (expressed as cells/μL) of each lymphocyte subset were computed.
Results Median age of the patients was 60 years (IQR 54-73.5), median disease duration 17 years (6-26.3), and sex ratio 16 females/6 males. We did not find significant differences in lymphocyte subset levels between RA patients and matched controls. 14 patients were responders at 6 months and 8 did not respond to abatacept. Responders and non-responders did not differ in terms of age, disease duration, sex ratio, ACPA positivity, previous therapies, concomitant steroids and methotrexate use, and total lymphocyte, T-cell and NK-cell counts. Conversely, responders had a higher CD19+ B cell count at baseline than non-responders: 290 (140-370) vs 121 (76-154), p=0.037. Using ROC curve analysis, 250 B cells/μL was the best cut-off to predict the response at 6 months, with a sensitivity of 57% and a specificity of 100%. Switched memory B cells (IgD-CD27+) but not pre-swithed memory B cells (IgD+CD27+) were lower in non-responders than in responders. In the 16 patients with baseline and 6-month lymphocyte phenotyping, we did not observe any variation in the levels of total lymphocytes, T cells or NK cells after abatacept; conversely, there was a significant decrease of CD19+ B cells in responders but not in non-responders.
Conclusions The mechanism of action of abatacept in RA seems to rely largely on the presence of B cells. Further studies are needed to understand how abatacept may modulate B-cell physiology.
Disclosure of Interest None declared