Abstract
Rituximab (Rtx) is a monoclonal antibody against CD20, inducing rapid depletion of B lymphocytes and registered for treatment of rheumatoid arthritis (RA). Its effect is based on the antibody-dependent cell-mediated cytotoxicity (ADCC) and the main effectors are NK cells.
Their initial consumption is followed by increased production and prolonged life span. NKT cells and gamma/delta T lymphocytes (gamma/delta T, CD3bright) have immunoregulatory function by rapid secretion of cytokines and also cytotoxic abilities.
Decreased numbers of both NK and NKT cells in circulation and their expansion in the inflammatory tissue of patients with RA were found. Elevation of percentage and absolute numbers of NK and NKT cells in circulation of patients with SLE or RA treated with Rtx was described.
We evaluated relation of NK and NKT changes in peripheral blood to clinical response of RA patients treated with Rtx. Using 7-coulour flow cytometry; we have found significant increase of NK, NKT and CD3bright T lymphocyte percentage in peripheral blood (p=0.004; 0.007 and 0.002) in 25 RA patients 8 weeks after treatment with Rtx.
Also absolute numbers of NK and gamma/delta T cells (p=0.02) increased significantly. NK, NKT and gamma/delta T cells significantly increased in patients with RA after depletion of B cells with rituximab.
The lesser increase of NK cell percentage preceding better clinical response to the Rtx treatment points to their possible continuing consumption during ongoing ADCC. We suggest that similar mechanism could be true also for the dynamics of NKT cells.
The positive correlation of NK or NKT cell absolute number elevation with the clinical disease activity improvement is related to the course of absolute lymphocyte count. This also points to their role in the regulatory effect of anti-CD20 treatment and their possible redistribution from the sites of inflammatory activity to the circulation.