Could Rheumatoid Synovium Be a Nursery for ACPA Producing Plasma Cells ? Save

One of the hallmarks of aggressive rheumatoid arthritis (RA) is presence of antibodies against citrullinated protein antigens (ACPA). ACPA often predates the onset of clinic symptoms and in majority of cases signifies more aggressive disease course with more erosive joint destruction and extra-articular disease manifestations in comparison with ACPA-negative patients.

Little is known about the mechanism of progressive erosive joint damage in ACPA positive RA patients.  As plasma cells (PCs) can produce excessive amounts of antibodies and survive in respective niches for years, they may be involved in driving and maintaining disease-specific pathogenic processes.  ACPA-secreting PCs have been shown to reside in synovial tissue and ACPA were successfully cloned from synovial fluid (SF) B cells.

Kerkman et al. has hypothesized that spontaneously ACPA-secreting PBs/PCs could be frequent in SF, and that the synovial compartment and its cellular composition could provide a microenvironment supporting the long-term survival of (auto)antibody-secreting cells.

What they found is, while cells spontaneously secreting ACPA-IgG were detectable in peripheral blood of ACPA–positive RA patients in a much higher concentrations than in synovial fluid, synovial fluid mononuclear cells (SFMC), showed up to 200-fold increase in ex vivo ACPA –IgG secretion.

ACPA –IgG secretion was maintained after depletion of the CD20+ B cell compartment and  were detectable fore several month. Peculiarly, PCs rapidly died in in vitro cultures unless they are seeded on a layer of tissue-derived stromal cells, assuming that SFMC can create an environment that promotes survival of ACPA-IgG-secreting PCs and, consequently, secretion of ACPA-IgG.

This study concluded that SFMC can create an environment that promotes survival of ACPA-IgG-secreting PCs and, consequently, secretion of ACPA-IgG for months.  

Further studies using these spontaneously generated niches could provide more detailed knowledge on how ACPA-secreting PCs survive in vivo and identify potential targets that could shorten the lifespan of ACPA-secreting PCs.