Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.

TNF-a and Chemerin Cross-Talk in Rheumatoid Arthritis.

Lebre2,  M. C., Ramos2,  M. I., Hofstra3,  C., van Eenennaam3,  H., Aarrass2,  S., Tak1,  Paul P.

Academic Med Ctr/Univ of Amsterdam, Amsterdam, The Netherlands
Division of Clinical Immunology & Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
Merck Research Laboratories, Oss, The Netherlands


Rheumatoid arthritis (RA) synovium is characterized by a dense infiltrate, consisting of macrophages, T and B cells, plasma cells and dendritic cells (DC). Inflammatory chemokines present in RA synovium may contribute to the accumulation of these immune cells. We have recently shown that plasmacytoid DC (pDC) are enriched in RA synovial tissue (ST) compared to CD1c+ myeloid DC. In line with these observations, we have shown that chemerin (and its receptor chemR23) expression is upregulated in RA ST compared to non-RA arthritis patients. Moreover, in RA ST ChemR23 was specifically expressed by CD68+ macrophages and pDC, while chemerin expression was confined to endothelial cells (CD31 and vWF positive).


To investigate the regulation of chemerin expression in an ex-vivo model of human RA.


Arthroscopic synovial tissue biopsies were obtained from patients with active RA and cultured in medium or in the presence of recombinant (r)-TNF-a or r-chemerin. After 6 days, cell-free supernatants were harvested and the levels of TNF-a or chemerin were analyzed by Luminex or ELISA, respectively. When indicated, anti-chemerin or anti-ChemR23 neutralizing antibodies were added to TNF-a-stimulated cultures.

Summary of the Results:

RA synovial biopsies released chemerin spontaneously. Interestingly, TNF-a stimulation induced significantly higher levels of chemerin compared to medium control. In addition, RA synovial biopsies released TNF-a spontaneously and addition of chemerin to the cultures strongly induced TNF-a release, suggesting a vicious cycle. Of importance, spontaneous and TNF-a-induced chemerin could be blocked by the addition of neutralizing antibodies against chemerin or against ChemR23. Moreover, spontaneous TNF-a could also be blocked by the addition of neutralizing antibodies against chemerin.


These findings suggest that elevated levels of chemerin in RA synovial tissue might regulate local TNF-a release and vice-versa in a positive feedback loop. The reciprocal interplay between chemerin and TNF-a is novel and might represent an attractive candidate for future drug development by blocking the chemerin/ChemR23 system to disrupt disease perpetuation.

To cite this abstract, please use the following information:
Lebre, M. C., Ramos, M. I., Hofstra, C., van Eenennaam, H., Aarrass, S., Tak, Paul P.; TNF-a and Chemerin Cross-Talk in Rheumatoid Arthritis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1534
DOI: 10.1002/art.29300

Abstract Supplement

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