Depletion of B lymphocytes in rheumatoid arthritis patients modifies IL-8-anti-IL-8 autoantibody network.
Cytokines and chemokines are key regulatory molecules involved in rheumatoid arthritis (RA). B-cell depletion therapy improves RA clinically but its mechanism is not completely understood. One possible mechanism for this therapy is the modification of the proinflammatory cytokine homeostasis of RA. We show here that the levels of the proinflammatory chemokine IL-8 in serum samples from RA patients unexpectedly increased by up to 100-fold 8 weeks after the administration of rituximab, despite clinical improvement. We also show that RA patients produced anti-IL-8 autoantibodies and that their levels dropped after RTX treatment. Moreover, we identified antibody-IL-8 immune complexes in the synovial fluid and serum of RA patients, and found that the amount of these complexes decreased after the administration of RTX. Our results indicate that B-cell depletion therapy modifies the cytokine-autoantibody network by reducing the levels of anti-cytokine autoantibodies and, consequentially, the formation of antibody-cytokine immune complexes.
Keren
Zohar
Z
Technion, Bruce Rappaport Faculty of Medicine, Haifa 31096, Israel.
Braun-Moscovici
Yolanda
Y
Markovits
Doron
D
Rozin
Alexander
A
Nahir
Menahem
M
Balbir-Gurman
Alexandra
A
Melamed
Doron
D
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D000936:Antigen-Antibody Complex / Q000097:blood / Q000276:immunology; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000628:therapy*; D001323:Autoantibodies / Q000097:blood*; D001402:B-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D000069285:Infliximab; D016209:Interleukin-8 / Q000097:blood / Q000276:immunology*; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D013582:Synovial Fluid / Q000276:immunology
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000936:Antigen-Antibody Complex; D018501:Antirheumatic Agents; D001323:Autoantibodies; D016207:Cytokines; D016209:Interleukin-8; D000069283:Rituximab; D000069285:Infliximab