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Rheumatology Advance Access originally published online on November 28, 2006
Rheumatology 2007 46(4):612-616; doi:10.1093/rheumatology/kel395
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

CD95-Mediated control of anti-citrullinated protein/peptides antibodies (ACPA)-producing plasma cells occurring in rheumatoid arthritis inflamed joints

Beatriz Rodríguez-Bayona, José J. Pérez-Venegas1, Carmen Rodríguez* and José A. Brieva*

Servicio de Inmunología and 1Reumatología, Hospital Universitario Puerta del Mar, Cádiz, Spain.

Correspondence to: José A. Brieva, Servicio de Inmunología, Hospital Universitario Puerta del Mar, Avenida Ana de Viya 21, 11009 Cádiz, Spain. E-mail: josea.brieva.sspa{at}juntadeandalucia.es


  Abstract

Objective. Serum anti-citrullinated protein/peptides antibodies (ACPA) are a valuable diagnostic parameter that might be involved in rheumatoid arthritis (RA) pathogenesis. CD95-dependent apoptosis is defective in RA synovium. The present study explores the occurrence of ACPA IgG, and the CD95-mediated control of ACPA IgG-secreting plasma cells (PC) in RA patients.

Methods. Mononuclear cells (MC) were purified from synovial fluid (SF) and peripheral blood (PB) of 15 RA patients. PC capable of secreting ACPA IgG were detected in MC cultures. ACPA IgG present in serum and SF, and PB and SF MC culture supernatant was measured by ELISA. CD95, CD27 and CD138 expression was examined on RA PC identified as CD19low CD38high cells by flow cytometry. CD95-ligation was obtained by treatment of cultured MC with the anti-CD95 Ab CH11. Apoptotic PC were identified as Annexin-V+.

Results. ACPA IgG level was found higher in patients’ SF than in their serum. PC were detectable in SF and PB, and exhibited high CD95 and CD27 expression. In contrast, SF, but not PB, PC expressed elevated levels of CD138. SF, but not PB, PC actively secreted ACPA IgG in cultures, in a linear fashion for at least 14 days, and CD95-ligation markedly reduced this activity and provoked PC apoptosis.

Conclusions. The results suggest that RA synovium is a prominent site for ACPA IgG formation and for the accumulation of ACPA IgG-secreting PC exhibiting prolonged survival, probably due to RA defective CD95-mediated control.

KEY WORDS: Human, RA, SF, Anti-citrullinated protein/peptides antibodies (ACPA) IgG, plasma cell, CD95-mediated apoptosis

*Both authors contributed equally to this work.

Submitted 17 May 2006; revised version accepted 25 October 2006.
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