Cutting edge: anti-tumor necrosis factor therapy in rheumatoid arthritis inhibits memory B lymphocytes via effects on lymphoid germinal centers and follicular dendritic cell networks.
Rheumatoid arthritis (RA) is mediated by a proinflammatory cytokine network with TNF at its apex. Accordingly, drugs that block TNF have demonstrated significant efficacy in the treatment of RA. A great deal of experimental evidence also strongly implicates B cells in the pathogenesis of RA. Yet, it remains unclear whether these two important players and the therapies that target them are mechanistically linked. In this study we demonstrate that RA patients on anti-TNF (etanercept) display a paucity of follicular dendritic cell networks and germinal center (GC) structures accompanied by a reduction in CD38+ GC B cells and peripheral blood memory B cell lymphopenia compared with healthy controls and RA patients on methotrexate. This study provides initial evidence in humans to support the notion that anti-TNF treatment disrupts GC reactions at least in part via effects on follicular dendritic cells.
Anolik
Jennifer H
JH
Department of Medicine, Division of Allergy, Immunology, and Rheumatology, University of Rochester, NY 14642, USA. jennifer_anolik@urmc.rochester.edu
Ravikumar
Rajan
R
Barnard
Jennifer
J
Owen
Teresa
T
Almudevar
Anthony
A
Milner
Eric C B
EC
Miller
Chase H
CH
Dutcher
Paul O
PO
Hadley
James A
JA
Sanz
Iñaki
I
D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects*; D020566:Dendritic Cells, Follicular / Q000187:drug effects / Q000276:immunology; D000068800:Etanercept; D005260:Female; D018858:Germinal Center / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology / Q000627:therapeutic use*; D007156:Immunologic Memory / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D014066:Palatine Tonsil / Q000276:immunology / Q000473:pathology; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept