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Memory B Cells and Response to Abatacept in Rheumatoid Arthritis

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Abstract

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, FcγR3A V158F 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.

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Acknowledgements

The author expresses gratitude to Simone Forest and Geneviève Michel for their help in typing the paper.

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Author notes

  1. Yves Renaudineau and Divi Cornec have contributed equally as senior authors

Authors and Affiliations

  1. Laboratory of Immunology and Immunotherapy, CHU Morvan, Brest, France

    Pierre Gazeau, Guillermo Carvajal Alegria, Christophe Jamin, Julie Lemerle, Boutahar Bendaoud & Yves Renaudineau

  2. Unit of Rheumatology, CHRU Brest-Carhaix, Hôpital Cavale Blanche, Brest, France

    Pierre Gazeau, Guillermo Carvajal Alegria, Valérie Devauchelle-Pensec, Alain Saraux & Divi Cornec

  3. INSERM U1227, LabEx IGO “Immunotherapy Graft Oncolog”, Réseau épigénétique et réseau canaux ioniques du Cancéropole Grand Ouest, European University of Brittany, Brest, France

    Valérie Devauchelle-Pensec, Christophe Jamin, Boutahar Bendaoud, Alain Saraux, Divi Cornec & Yves Renaudineau

  4. Department of Chemistry, University of South Florida, Tampa, FL, USA

    Wesley H Brooks

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Correspondence to Yves Renaudineau.

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Gazeau, P., Alegria, G.C., Devauchelle-Pensec, V. et al. Memory B Cells and Response to Abatacept in Rheumatoid Arthritis. Clinic Rev Allerg Immunol 53, 166–176 (2017). https://doi.org/10.1007/s12016-017-8603-x

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