Session Title: B-cell Biology and Targets in Autoimmune Disease
Session Type: Abstract Submissions (ACR)
Anti citrullinated protein antibodies (ACPA) are highly specific for rheumatoid arthritis (RA) and predict disease onset and severity. Accumulating evidence indicates that ACPA could play an important role in RA pathogenesis by contributing to inflammation and joint destruction. So far, however, little is known on the characteristics of ACPA producing B cells. In this study, we set out to define ACPA producing B cells in more detail in order to allow for specific targeting of these cells.
Peripheral blood CD19 positive B cells from patients with ACPA positive RA (n=30) were isolated using magnetic beads. In addition, B cell subsets were purified by FACS-sorting based on the expression of surface markers CD19, CD20 and CD27. Isolated B cell populations were either cultured in vitro in the presence of anti-IgM, IL-21 and BAFF on a layer of irradiated CD40L transfected fibroblasts, or left in medium without additional stimulation. Following culture for 6 and/or 13 days, supernatants were assessed for the presence of ACPA-IgG and non-specific total IgG by ELISA.
Following stimulation, ACPA could be detected in up to 100% of culture wells. Both the average ACPA titer in the wells as well as the percentage of positive wells correlated with measures of disease activity. No reactivity was observed against the arginine containing control antigen. No ACPA production was detectable by B cells isolated from ACPA negative RA patients or healthy controls. Of interest, ACPA were also produced spontaneously ex-vivo without stimulation. Active ACPA production was detectable for extended periods of time (up to 4 weeks). FACS-sorting experiments comparing isolated B cell subsets indicated that spontaneous ACPA production resides, for a large part, in the circulating plasmablast population. Spontaneous ACPA production was still observed after depletion of the CD20 positive B cell population.
We show that ACPA producing plasmablasts circulate in the peripheral blood of ACPA positive RA patients in a disease activity dependent manner. Ex vivo, these plasmablasts were not short-lived and were not targeted by an anti-CD20 antibody. These observations enhance our understanding of ACPA producing B cells and could be relevant for future targeted therapies.
E. I. H. van der Voort,
L. A. Trouw,
T. W. J. Huizinga,
R. E. M. Toes,
H. U. Scherer,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/circulating-plasmablasts-as-a-source-of-anti-citrullinated-protein-antibodies-in-patients-with-rheumatoid-arthritis/