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AB0154 Pathogenic Role of Irhom2 in Seropositive Rheumatoid Arthritis
  1. Y.J. Kim1,
  2. E.-J. Lee1,
  3. S. Hong1,
  4. B.S. Koo1,
  5. W.J. Seo2,
  6. J. Oh3,
  7. Y.-G. Kim1,
  8. C.-K. Lee1,
  9. B. Yoo1
  1. 1Division of Rheumatology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine
  2. 2Division of Rheumatology, Department of Internal Medicine, Seoul Veterans Hospital, Seoul
  3. 3Division of Rheumatology, Department of Internal Medicine, Ulsan University Hospital, Ulsan, Korea, Republic Of


Background Tumor necrosis factor (TNF)-α is a major pathologic cytokine in rheumatoid arthritis (RA) and the current target of RA treatment has been on blocking the TNF-α. iRHOM2 is a regulator of TNF-α convertase that mediate the release of TNF-α from immune cells. Moreover, immune complexes (ICs) are known to induce expression of iRHOM2 via Fc receptors (FcλRIIIa/CD16) in monocytes, regulating the production of TNF-α.

Objectives We hypothesized that the expression of iRHOM2 and Fc receptors are up regulated in seropositive RA patients, that is mediated by immune complex.

Methods The level of TNF-α was measured in the serum of seropositive (+) and seronegative (−) RA patients by ELISA. Messenger RNA expression of iRHOM2 and CD16 was evaluated on peripheral blood mononuclear cells of (+) RA, (−) RA patients, and healthy controls. ICs were extracted from serum of RA patients by adding polyethylene glycol. Isolated ICs were added to THP1-cell cultures to examine the induction of iRHOM2 and CD16.

Results Serum level of TNF-α was similar between (+) RA patients and (−) RA patients (3.23±(5.97) pg/ml vs. 1.99±(1.93) pg/ml). Increased iRHOM2 and CD16 mRNA expression was found on PBMC in (+) RA patients compared to those in (−) RA patients (figure). IC isolated from (+) RA patient could enhance the expression of iRHOM2 as well as CD16 from THP-1 cells.

Conclusions iRHOM2, highly expressed in (+) RA monocytes, might be regulated by immune complex containing anti-cyclic citrullinated peptides antibody, although serum TNF-α level was not different in (+) and (−) RA patient.


  1. Lichtenthaler SF. iRHOM2 takes control of rheumatoid arthritis. J Clin Invest 2013;123:560-2.

  2. Issuree PD, Maretzky T, McIlwain DR et al. iRHOM2 is a critical pathogenic mediator of inflammatory arthritis. J Clin Invest 2013;123:928-32.

  3. Cooper DL, Martin SG, Robinson JI et al. FcgammaRIIIa expression on monocytes in rheumatoid arthritis: role in immune-complex stimulated TNF production and non-response to methotrexate therapy. PLoS One 2012;7:e28918.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.3199

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