Activation of Complement Alternative Pathway in Rheumatoid Arthritis: Implications in Peripheral Neutrophils Functions

ABSTRACT

Evaluation of the respiratory burst induced by receptors FcγR and CR was carried out in peripheral blood neutrophils (PBN) in rheumatoid arthritis (RA) patients with active and inactive disease. Simultaneously, cooperation between these receptors and their expression, PBN chemotaxis, and complement system systemic activity were also investigated. Neutrophils were stimulated with IC-IgG opsonized with normal human serum (NHS) or not, or with IC-IgG opsonized with RA human serum (RAHS). ROS production was increased in neutrophils of patients with active or inactive RA stimulated of IC-IgG opsonized with NHS compared to the response of the cells mediated by ICIgG. However, there was poor FcγR/CR cooperation in these RA neutrophils, as indicated by decreased ROS production upon stimulation with IC-IgG opsonized with RAHS. In the case of active RA patients, neutrophils presented significantly higher CR1 and CR3 expression, as well as slight elevation in CD32 and CD16 expression. Positive correlations between FcγR and CR, complement alternative pathway activation, and increased RA serum chemotaxic activity were only detected in active RA patients. Taken together, these results indicate that several abnormalities of the complement system exist at the systemic level, namely impaired membrane receptor cooperation, alternative pathway activation, and presence of pre-existing chemoattractant factors in the serum, as reflected by the neutrophil function in the particular case of active RA patients. All, these abnormalities may synergistically contribute to RA pathogenesis.

Keywords:

Neutrophils, rheumatoid arthritis, oxidative stress, Fc-gamma and CR receptors, complement system.