Circulating CD4+ T-cell number decreases in rheumatoid patients with clinical response to rituximab.

Abstract

patients were identified (female: 85 %; age: 51 (41–66); disease duration: 10 (1–20) years; RF+: 85 %; ACPA+: 82 %; previous therapy with anti-TNFα agents: 70 %, with other biologic therapies: 21 %; concomitant therapy with methotrexate: 79 % (dosage: 15 (10–15) mg/week) and with prednisone: 94 % (dosage: 6.7 (3.6–10) mg/day)). Patients received a 1.000-mg infusion of rituximab preceded by a 100-mg intravenous pulse of methylprednisolone, at baseline (T = 0) and week 2. Tand B-cell counts were determined by four-color flow cytometry (Cytomics FC-500, Beckman Coulter Inc., USA) at T = 0 and 6 months after infusion (T = 6). Absolute cell count was determined by single-platform analysis using Flow-Count beads. At T = 6, according the EULAR Criteria of Response to the treatment, twenty-six patients obtained a moderate or good response, whereas seven patients did not respond. Patients of two groups had similar clinical disease activity at baseline (CRP-DAS28 = 5.32 (4.1–6.5) vs. 5.68 (5.1– 7.3), p = 0.12), as well as positivity for RF (85 vs. 86 %; p = 1) or ACPA (88 vs. 57 %; p = 0.09). Dividing patients by the positivity for autoantibodies or not, there was no significant difference with respect to the T-cell subpopulations at baseline and after 6 months. Comparing responders and non-responders, there was no difference in the percentage or absolute number of CD4+ T cells between the two groups at T0 (p = 0.88 and p = 0.5, respectively), but it should be acknowledged that the small number of non-responders may limit the possibility to detect differences. At T = 6, B-cell number was below 5 μl in 30/33 patients. The variations of CD3+CD4+ cells tended to be different in responders as compared with non-responders [median: −126 μl (−609.3 to +33) vs. +181 μl (+112 to +530.4); p:0.06]. The reduction in responders was Rituximab is a chimeric anti-CD20 monoclonal antibody that induces the depletion of mature B and pre-B cells and has been proven to be effective in the treatment of rheumatoid arthritis (RA) [1]. In the pathophysiology of RA, B cells play a central role, which is not limited to the production of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (ACPA), but includes secretion of cytokines and the capability to activate T cells [2, 3]. The roles of B and T cells should therefore be considered tightly linked. However, studies of lymphocyte subpopulation counts during rituximab treatment in patients with RA have been focused mainly on the B-cell compartment only. In a recent report, Melet et al. [4] described that rituximab induced a decrease in circulating T-cell number, mainly of CD4+ cells, in RA. The depletion of CD4+ T cells was substantial in some patient, with a decrease below 200 μl, a threshold carrying a risk for opportunistic infections in HIV+ individuals; [5] in 5.8 % of the cases. Of note, the decrease in CD4+ T cells was associated with clinical response. We have retrospectively evaluated our experience in RA patients who received their first course of rituximab at our institution between 2006 and 2013. Data are presented as percentage or median (10th–90th percentile). Nonparametric tests were used for the comparisons. Thirty-three