Decrease in immunoglobulin free light chains in patients with rheumatoid arthritis upon rituximab (anti-CD20) treatment correlates with decrease in disease activity.
OBJECTIVE
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.
Kormelink
T Groot
TG
Division of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands.
Tekstra
J
J
Thurlings
R M
RM
Boumans
M H J
MH
Vos
K
K
Tak
P P
PP
Bijlsma
J W J
JW
Lafeber
F P J G
FP
Redegeld
F A
FA
van Roon
J A G
JA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D018951:Antigens, CD20 / Q000276:immunology; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D001323:Autoantibodies / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000097:blood / Q000378:metabolism*; D007136:Immunoglobulins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000276:immunology; D010456:Peptides, Cyclic / Q000276:immunology; D012217:Rheumatoid Factor / Q000378:metabolism; D000069283:Rituximab; D013583:Synovial Membrane / Q000276:immunology; D016896:Treatment Outcome; D055815:Young Adult
D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D018501:Antirheumatic Agents; D001323:Autoantibodies; D015415:Biomarkers; D007147:Immunoglobulin Light Chains; D007136:Immunoglobulins; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D000069283:Rituximab; D012217:Rheumatoid Factor