Immune effects of therapy with Adalimumab in patients with rheumatoid arthritis.
The aim of this study was to assess the effect of Adalimumab on different immune parameters in patients with RA. Adalimumab was administered (40 mg every other week for 26 weeks) to eight patients with RA that were refractory to conventional drug therapy. Peripheral blood samples were obtained at days 0, 15 and 180 of Adalimumab therapy, and the following immune parameters were assessed: Number, phenotype, and function of regulatory T lymphocytes. The induction of apoptosis of immune cells and the in vitro and in vivo reactivity towards M. tuberculosis were also analysed. All patients responded to Adalimumab (ACR response 50-70), and a modest but significant increase in the number and function of regulatory T cells was observed at day 15 of anti-TNF-alpha therapy. In addition, an increased percent of apoptotic cells was detected in the peripheral blood at day 15 of Adalimumab therapy. Unexpectedly, most of these effects were not further observed at day 180. However, two patients showed a persistent and marked reduction in the reactivity to M. tuberculosis. Although we have found that Adalimumab affects the number and function of regulatory T lymphocytes, and the apoptosis of immune cells, these effects are transient and its possible causal relationship with the therapeutic activity of this biological agent remains to be determined. Nevertheless, the down-regulatory effect of Adalimumab on the reactivity to M. tuberculosis could be related to an enhanced risk of tuberculosis reactivation.
Departamento de Inmunología, Facultad de Medicina, UASLP, 78210 San Luis Potosí, México.
M
M
Vigna-Pérez
C
C
Abud-Mendoza
H
H
Portillo-Salazar
B
B
Alvarado-Sánchez
E
E
Cuevas-Orta
R
R
Moreno-Valdés
L
L
Baranda
O
O
Paredes-Saharopulos
R
R
González-Amaro
D000068879:Adalimumab; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000942:Antigens, Bacterial / Q000276:immunology; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D018655:Lymphocyte Count; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology; D010865:Pilot Projects; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D014374:Tuberculin Test; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000942:Antigens, Bacterial; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab