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Our objective was to evaluate the contribution of monitoring B cell subset depletion after rituximab in patients with rheumatoid arthritis (RA) in order to guide reintroduction to forestall relapse. This prospective, monocentre study included all RA patients receiving two 1-g rituximab infusions at a 15-day interval. The patients were followed clinically and biologically every 2 months until rituximab reintroduction. The physician was blinded to lymphocyte-typing results to diagnose relapse and, hence, retreatment. Among the 39 patients included between March 2010 and December 2011 and followed until April 2013, seven received two rituximab cycles, yielding a total of 46 cycles for analysis. After the two rituximab cycles, the total number of CD19(+) B cells decreased significantly (0·155 versus 0·0002 G/l, P < 0·0001), with complete depletions in all patients of CD19(+) CD38(++) CD24(++) (transitional) (P < 0·0001) and CD19(+) CD27(+) (memory) B lymphocytes. A significant majority of patients relapsed within the 4 months following repopulation of total B (P = 0·036), B transitional (P = 0·007) and B memory (P = 0·01) lymphocytes. CD19(+) B lymphocyte repopulation preceded clinical RA relapse and enabled its prediction 4 months in advance. Hence, monitoring of CD19(+) B lymphocytes could serve as a tool to predict those relapses., (© 2014 British Society for Immunology.)

Objective: To analyse the therapeutic effects of etanercept (ETA) or adalimumab (ADA) on the numbers and phenotypes of CD4+CD25hi Tregs in RA patients., Methods: RA patients received ADA (n = 28) or ETA (n = 20) and stable-dose MTX or LEF. Therapeutic responses were assessed with the 28-joint DAS (DAS-28) criteria after 12 weeks of treatment. Treg numbers and phenotypes, determined by flow cytometry using different gating strategies, were compared between responders and non-responders before and after 6 and 12 weeks of treatment., Results: The percentages of good, moderate and non-responders among patients given ADA or ETA, respectively, were 46.5, 35.7 and 17.8% or 30, 20 and 50%, with respective mean (s.d.) pre-treatment CD4+CD25hi Treg percentages of 5.5 (0.04)% or 4.95 (0.02)%. Overall, for patients with active RA given ADA or ETA, neither TNF-α-blocking agent had an effect on Tregs percentage and absolute number. Moreover, CD4+CD25hi Treg counts remained unaffected in RA responders to ADA or ETA, compared with RA non-responders. Furthermore, the CD4+CD25hiCD45RA+, CD4+CD25hiCD45RO+ and CD4+CD25hiCD62L+ cell populations were unchanged by TNF-α-blocking agents., Conclusion: Neither ADA nor ETA modified the percentages or absolute numbers of circulating CD4+CD25hi Tregs and their phenotypes after being administered for 6 and 12 weeks to RA patients., Trial Registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00234234.

Peripheral blood stem cell transplantation (PBSCT) is an alternative to bone marrow transplantation (BMT). Although CD4(+)CD25(+)CD127(lo) regulatory T cells (Tregs) have been shown to play important roles in the control of T cell reactivity, the Treg contents of both graft types have not been analyzed comparatively to date. We report herein that Treg frequencies are significantly reduced in PBSC compared to BM transplants. Furthermore, most Tregs from PBSC transplants are CD62L(lo), a phenotype reported to have poor suppressor activity. Both granulocyte-colony stimulating factor (G-CSF) administration and leukapheresis were found to contribute to the loss of CD62L(+) Tregs. Although higher T cell numbers are infused in PBSCT than in BMT, it is possible that the reduced Treg content of PBSC transplants may represent 1 factor contributing to the higher risk of GVHD reported after PBSCT., (Copyright (c) 2010 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)