Functional characterization of a soluble gp130 isoform and its therapeutic capacity in an experimental model of inflammatory arthritis

Arthritis Rheum. 2006 May;54(5):1662-72. doi: 10.1002/art.21818.


Objective: Soluble gp130 is the naturally occurring antagonist of the interleukin-6 (IL-6)/soluble IL-6 receptor (sIL-6R) complex and selectively inhibits IL-6 trans-signaling. Several isoforms of soluble gp130 have been identified, including an autoantigenic form termed gp130-RAPS (for gp130 of the rheumatoid arthritis antigenic peptide-bearing soluble form) that is present in the serum and synovial fluid of patients with rheumatoid arthritis. The aim of this study was to evaluate the functional properties of gp130-RAPS.

Methods: To define a role for gp130-RAPS in arthritis, a recombinant version was generated using a baculovirus expression system, and its activities were tested in vitro and in vivo.

Results: Gp130-RAPS was shown to bind with high affinity to the stable IL-6/sIL-6R complex, hyper-IL-6, and to effectively modulate leukocyte migration in murine acute peritonitis. A single intraarticular injection of gp130-RAPS suppressed chronic antigen-induced arthritis in association with a reduction in local activation of signal transducer and activator of transcription 3. Although gp130-RAPS contains the previously identified autoantigenic sequence Asn-Ile-Ala-Ser-Phe (NIASF), no increase in the prevalence of anti- gp130-RAPS antibodies was observed in serum or synovial fluid obtained from patients with rheumatoid arthritis.

Conclusion: The use of inhibitory antibodies to block IL-6 responses has shown considerable clinical promise. However, the results presented herein suggest that selective targeting of IL-6 trans-signaling may represent a viable alternative to this strategy. In this respect, our present results suggest that the soluble gp130 isoform gp130-RAPS may be useful in the treatment of chronic inflammatory arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis / drug therapy*
  • Arthritis / immunology
  • Cytokine Receptor gp130 / isolation & purification*
  • Cytokine Receptor gp130 / therapeutic use*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Protein Isoforms
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / therapeutic use


  • Protein Isoforms
  • Recombinant Proteins
  • Cytokine Receptor gp130