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Capsoni, Franco and Sarzi-Puttini, Piercarlo and Atzeni, Fabiola and Minonzio, Francesca and Bonara, Paola and Doria, Andrea and Carrabba, Mario (2004) Effect of adalimumab on neutrophil function in patients with rheumatoid arthritis. [Online journal papers]

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Per gentile concessione di: http://arthritis-research.com/content/7/2/R250

Abstract (english)

Neutrophils are known to be targets for the biological activity of tumour necrosis factor (TNF)-? in the pathogenensis of rheumatoid arthritis (RA). Therefore, these cells may be among the targets of anti-TNF-? therapy. In this study we evaluated the effect of therapy with adalimumab (a fully human anti-TNF-? mAb; dosage: 40 mg subcutaneously every other week) on certain phenotypic and functional aspects of neutrophils obtained from 10 selected patients with RA and 20 healthy control individuals. Peripheral blood neutrophils were obtained at baseline and during anti-TNF-? therapy (2, 6 and 12 weeks after the first administration of adalimumab). All patients had been receiving a stable regimen of hydroxychloroquine, methotrexate and prednisone for at least 3 months before and during the study. Baseline neutrophil chemotaxis was significantly decreased in RA patients when compared with control individuals (P < 0.001). Two weeks after the first administration of adalimumab, chemotactic activity was completely restored, with no differences noted between patients and control individuals; these normal values were confirmed 6 and 12 weeks after the start of anti-TNF-? therapy. Phagocytic activity and CD11b membrane expression on neutrophils were similar between RA patients and control individuals; no modifications were observed during TNF-? neutralization. The production of reactive oxygen species, both in resting and PMA (phorbol 12-myristate 13-acetate)-stimulated cells, was significantly higher in RA patients at baseline (P < 0.05) and was unmodified by anti-TNF-? mAb. Finally, we showed that the activation antigen CD69, which was absent on control neutrophils, was significantly expressed on neutrophils from RA patients at baseline (P < 0.001, versus control individuals); however, the molecule was barely detectable on cells obtained from RA patients during adalimumab therapy. Because CD69 potentially plays a role in the pathogenesis of arthritis, our findings suggest that neutrophils are among the targets of anti-TNF-? activity in RA and may provide an insight into a new and interesting mechanism of action of anti-TNF-? mAbs in the control of inflammatory arthritis.

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EPrint type:Online journal papers
Anno di Pubblicazione:2004
Key Words:rheumatoid arthritis, neutrophils
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/16 Reumatologia
Struttura di riferimento:Dipartimenti > pre 2012 - Dipartimento di Medicina Clinica e Sperimentale
Codice ID:1247
Depositato il:09 Dec 2008
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