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Negative association between autoantibodies against IL-17, IL-17/anti-IL-17 antibody immune complexes and destruction in rheumatoid arthritis
  1. Ndieme Ndongo-Thiam1,
  2. Alice Clement1,
  3. Jean-Jacques Pin2,
  4. Diane Razanajaona-Doll2,
  5. Pierre Miossec1
  1. 1 Immunogenomics and Inflammation Research Unit EA 4130 and the Department of Clinical Immunology and Rheumatology, University of Lyon, Lyon, France
  2. 2 Dendritics, Bioparc Laennec, Lyon, France
  1. Correspondence to Professor P Miossec, Clinical Immunology Unit, Departments of Immunology and Rheumatology, Hôpital Edouard Herriot, Lyon Cedex 03 69437, France; miossec{at}univ-lyon1.fr

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Autoantibodies against proinflammatory cytokines1 such as interleukin (IL)-1α are protective and a marker of good prognosis in rheumatoid arthritis (RA).2 ,3 They bind their antigen, that is, the cytokine, forming immune complexes (ICs). IL-17 is a new therapeutic target for a growing number of disorders,4 and levels of circulating bioactive IL-17 are associated with RA severity.5 Our objective was to define the contribution of anti-IL-17 autoantibodies and IL-17-anti-IL-17 ICs.

A competitive ELISA was developed to measure anti-IL-17 autoantibodies. A positive control with added anti-IL-17 antibodies showed an inverse dose–response curve reflecting the competition, with no variation with irrelevant antibodies (figure 1A). Plasma of 30 healthy donors were first tested to determine the threshold (absorbance=0.9±0.1 at 1/2 dilution) with no variation between 1/4 and 1/8 dilutions, indicating an absence of anti-IL-17 autoantibodies. In contrast, they were detected in 36.6% of the 60 patients with RA (p<0.05 vs controls, figure 1B). To study the relationship with severity, 30 destructive RA (wrist Larsen score: 2 and over) versus 30 non-destructive RA (Larsen score: 0 or 1) were tested. The two groups had similar mean age (71.3±9.3 vs 66.1±10.8 years), disease duration (23.0±9.8 vs 18.6±9.6 years), DAS28 (4.0±1.4 vs 3.9±1.2) but a different level of bone destruction (Larsen score: 0.5±0.5 vs 3.3±1.0, p<0.0001). Anti-IL-17 autoantibodies were detected in 46.6% of …

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Footnotes

  • Contributors NN-T: experiments and writing; AC, J-JP and DR-D: development of assays and PM: concept and writing.

  • Funding NN-T is supported by the IHU prometteur OPERA. PM is a senior member of and supported by the Institut Universitaire de France.

  • Competing interests NN-T and PM hold a patent on the determination of bioactive IL-17 and have filed a patent for these results.

  • Patient consent Obtained.

  • Ethics approval Ethics committee of the hospitals of Lyon.

  • Provenance and peer review Not commissioned; externally peer reviewed.