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.
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.
Authors: Carsten P Bramlage; Britta Froelich; Manuel Wallbach; Joan Minguet; Clemens Grupp; Cornelia Deutsch; Peter Bramlage; Gerhard A Müller; Michael Koziolek Journal: Rheumatol Int Date: 2017-02-18 Impact factor: 2.631
Authors: L Chiche; J M Cournac; J Mancini; N Bardin; G Thomas; R Jean; N Schleinitz; G Kaplanski; J M Durand; J Boucraut; J R Harlé Journal: Clin Rheumatol Date: 2011-01-11 Impact factor: 2.980
Authors: Carsten Paul Bramlage; Britta Froelich; Manuel Wallbach; Joan Minguet; Clemens Grupp; Cornelia Deutsch; Peter Bramlage; Michael Koziolek; Gerhard Anton Müller Journal: Clin Rheumatol Date: 2016-10-12 Impact factor: 2.980
Authors: Xiaoli Deng; Cynthia S Crowson; S Vincent Rajkumar; Angela Dispenzieri; Dirk R Larson; Terry M Therneau; Eric L Matteson; Robert A Kyle; Jerry A Katzmann; Sherine E Gabriel; John M Davis Journal: J Rheumatol Date: 2015-01-15 Impact factor: 4.666
Authors: Krzysztof Bryniarski; Wlodzimierz Ptak; Asha Jayakumar; Kerstin Püllmann; Michael J Caplan; Arthit Chairoungdua; Jun Lu; Brian D Adams; Emilia Sikora; Katarzyna Nazimek; Susanna Marquez; Steven H Kleinstein; Panjamaporn Sangwung; Yasuko Iwakiri; Eric Delgato; Frank Redegeld; Bart R Blokhuis; Jacek Wojcikowski; Anna Wladyslawa Daniel; Tom Groot Kormelink; Philip W Askenase Journal: J Allergy Clin Immunol Date: 2013-05-31 Impact factor: 10.793