Memory B Cells and Response to Abatacept in Rheumatoid Arthritis

作者：Gazeau Pierre; Alegria Guillermo Carvajal; Devauchelle Pensec Valerie; Jamin Christophe; Lemerle Julie; Bendaoud Boutahar; Brooks Wesley H; Saraux Alain; Cornec Divi; Renaudineau Yves^*

来源：Clinical Reviews in Allergy and Immunology, 2017, 53(2): 166-176.

DOI：10.1007/s12016-017-8603-x

• Rheumatoid arthritis
• Abatacept
• Therapeutic response
• Memory B cells

Abatacept is a fusion protein (CTLA4-Ig) and therapeutic molecule labeled for the treatment of rheumatoid arthritis (RA). Abatacept acts both by disrupting the CD28-mediated activation of T cells and by interacting with CD80/CD86 molecules present on antigen presenting cells such as monocytes and memory B cells. Accordingly and to evaluate clinical and biological parameters associated with response to abatacept, a retrospective monocentric study was conducted in 43 patients with RA, and the clinical response was evaluated at 6 months according to EULAR response criteria. Median age of the patients was 59.8 +/- 15.1 years including 35 females and 8 males. At baseline, no difference was observed between non-responders (NR, n = 11), moderate responders (MR, n = 21), and good responders (GR, n = 11) to abatacept with regards to demographic, biological, and clinical characteristics of the patients (age, sex, anti-CCP, RF, Fc gamma R3AV158F polymorphism, and C3/C4 complement reduction). Moreover, peripheral blood lymphocyte phenotyping was performed by flow cytometry revealing in 30 RA patients compared to controls (n = 45; median age 56.7 +/- 13.5 years) that the initial CD19(+) B cell count was reduced in NR and MR but not in GR. No differences were observed with regards to total lymphocyte, T cell, and NK cell counts. Next, we further explored the effects of abatacept on B cell subsets (IgD/CD38 in panel 1 and IgD/CD27 in panel 2) and observed that the basal level of CD38(+) and/or CD27(+) memory B cell count was important for an abatacept response and that a selective effect of abatacept was observed on memory B cells after 6 months. In conclusion, and although these data need to be confirmed in an independent cohort, our data support a role for memory B cells in the mechanism of action of abatacept in RA.

• 出版日期2017-10