Activation status of peripheral blood neutrophils and the complement system in adult rheumatoid arthritis patients undergoing combined therapy with infliximab and methotrexate

Autor(es)

Marchi, Larissa F. ^[1] ; Paoliello-Paschoalato, Adriana B. ^{[1, 2]} ; Oliveira, Rene D. R. ^[3] ; Azzolini, Ana Elisa C. S. ^[1] ; Kabeya, Luciana M. ^[1] ; Donadi, Eduardo A. ^[2] ; Lucisano-Valim, Yara Maria ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Phys & Chem, Ave Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Internal Med, Ave Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Div Rheumatol, Ave Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: RHEUMATOLOGY INTERNATIONAL; v. 38, n. 6, p. 1043-1052, JUN 2018.
• Citações Web of Science: 2

Resumo

We examined the functional activity of peripheral blood neutrophils and the complement system activation status in patients with rheumatoid arthritis (RA) undergoing infliximab/methotrexate combined therapy. We studied female RA patients under treatment with infliximab (3-5 mg/kg) and methotrexate (15-25 mg/week) who presented inactive (i-RA; n = 34, DAS-28 <= 2.6) or at least moderately active disease (a-RA; n = 29, DAS-28 > 3.2), and age-matched healthy women (n = 38). We measured the levels of reactive oxygen species (ROS) generation (chemiluminescence assay) and membrane expression of Fc gamma RIIa/CD32, Fc gamma RIIIb/CD16, CR1/CD35, and CR3/CD11b receptors (ELISA assay) in neutrophils. We also determined the hemolytic activity of the alternative and classical pathways of the complement system (spectrophotometry), serum levels of C5a and Bb (ELISA assay), and serum chemotactic activity (Boyden chamber). Compared with the control group, i-RA and a-RA patients exhibited: (1) increased neutrophil ROS production and membrane expression of Fc gamma RIIa/CD32, Fc gamma RIIIb/CD16, and CR1/CD35, indicating neutrophil activation; and (2) increased serum chemotactic activity and decreased activity of the alternative complement pathway, indicating systemic complement system activation. The levels of C-reactive protein in a-RA patients were augmented, compared with i-RA patients. Although infliximab/methotrexate combined therapy induced disease remission according to the DAS-28 criteria, both i-RA and a-RA patients still exhibited significant levels of systemic activation of neutrophils and the complement system. (AU)

• Processo FAPESP: 13/20810-7 - Estudo sistemático dos mecanismos moleculares envolvidos na inibição do metabolismo oxidativo de neutrófilos exercida pela Baccharis dracunculifolia, derivado 3-fenilcumarinicos e 3,5,7-triidroxiflavona: implicação em uma nova abordagem terapêutica da AR
• Beneficiário: Yara Maria Lucisano Valim
• Modalidade de apoio: Auxílio à Pesquisa - Regular