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Decrease in immunoglobulin free light chains in patients with rheumatoid arthritis upon rituximab (anti-CD20) treatment correlates with decrease in disease activity
  1. T Groot Kormelink1,
  2. J Tekstra2,
  3. R M Thurlings3,
  4. M H J Boumans3,
  5. K Vos3,
  6. P P Tak3,
  7. J W J Bijlsma2,
  8. F P J G Lafeber2,
  9. F A Redegeld1,
  10. J A G van Roon2
  1. 1Division of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
  2. 2Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands
  3. 3Department of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
  1. Correspondence to Frank A Redegeld, Division of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Sorbonnelaan 16, 3584CA Utrecht, The Netherlands; f.a.m.redegeld{at}uu.nl

Abstract

Objectives Immunoglobulin (Ig) free light chains (FLCs) are short-lived B cell products that contribute to inflammation in several experimental disease models. In this study, FLC concentrations in inflamed joints of patients with rheumatoid arthritis (RA) as compared to patients with osteoarthritis were investigated. In addition, the relationship of FLCs and disease activity upon B cell depletion (rituximab) in patients with RA was studied.

Methods Synovial fluid (SF) and tissue from patients with RA were analysed for local presence of FLCs using ELISA and immunohistochemistry. In addition, FLC concentrations were measured (at baseline, 3 and 6 months after treatment) in 50 patients with RA with active disease who were treated with rituximab. Changes in FLCs were correlated to changes in disease activity and compared to alterations in IgM, IgG, IgA, IgM-rheumatoid factor (RF) and IgG-anti-citrullinated protein antibody (ACPA) concentrations.

Results FLCs were detected in synovial tissue from patients with RA, and high FLC concentrations were found in SF from inflamed joints, which positively correlate with serum FLC concentrations. Serum FLC concentrations significantly correlated with disease activity score using 28 joint counts, erythrocyte sedimentation rate (ESR) and C reactive protein, and changes in FLC correlated with clinical improvement after rituximab treatment. Moreover, effect of treatment on FLC concentrations discriminated clinical responders from non-responders, whereas IgM-RF and IgG-ACPA significantly decreased in both patient groups.

Conclusions FLCs are abundantly present in inflamed joints and FLC levels correlate with disease activity. The correlation of FLC concentrations and disease activity indicates that FLCs may be relevant biomarkers for treatment response to rituximab in patients with RA and suggests that targeting FLC may be of importance in the therapy of RA.

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Footnotes

  • FAR and JAGvR contributed equally to this work.

  • Ethics approval This study was conducted with the approval of the Ethics Committee Utrecht and Amsterdam.

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

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