title: Depletion of B lymphocytes in rheumatoid arthritis patients modifies IL-8-anti-IL-8 autoantibody network.
abstract: 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.
authors.affiliation: Technion, Bruce Rappaport Faculty of Medicine, Haifa 31096, Israel.
authors.forename: Zohar
authors.initials: Z
authors.lastname: Keren
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Braun-Moscovici
authors.forename: Doron
authors.initials: D
authors.lastname: Markovits
authors.forename: Alexander
authors.initials: A
authors.lastname: Rozin
authors.forename: Menahem
authors.initials: M
authors.lastname: Nahir
authors.forename: Alexandra
authors.initials: A
authors.lastname: Balbir-Gurman
authors.forename: Doron
authors.initials: D
authors.lastname: Melamed
mesh_terms: 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
chemical_list: 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