Background Innate immune response in rheumatoid arthritis seems to be over responsive and to contribute directly to articular lesion1. The autoantibodies rheumatoid factor (RF) and anti-cyclic citrullinated peptides (anti-CCP) have not only diagnostic values but also correlate with the severity of the disease2.
Objectives To evaluate phagocytosis and reactive oxygen species production of neutrophils and monocytes in early rheumatoid arthritis (ERA) individuals (less than one year of symptoms at diagnosis)and to verify if the presence of autoantibodies RF and anti-CCP influences phagocyte functions.
Methods Neutrophils and monocytes of 30 ERA individuals and 20 healthy controls were incubated with opsonized or non-opsonized S. cerevisiae with the individual’s own serum and phagocytosis was assessed. Superoxide anion production was assessed with the nitroblue tetrazolium test after yeast cell challenge. The phagocytic index (PI) was evaluated by the product of the percentage of phagocytes engaged in phagocytosis by the mean of yeast cell intake. Serum from each subject was tested for RF and CCP2 isotypes by enzyme-linked immunosorbent assay.
Results The median PI of monocytes through opsonin receptors was 1.79 times higher on ERA individuals (176.5) in contrast to the control group (98.8) (p=0.0001, t test with Welch’s correction). Phagocytosis through pattern recognition receptors (PRRs) was 2.28 times higher on ERA individuals (p=0.0009, t test with Welch’s correction). Neutrophils of ERA individuals showed the median PI of 231.5 in contrast to 174.7 for the control group (p=0.03, Mann Whitney) through opsonin receptors, and a median PI of 8.5 in contrast to 2 for the control group (p<0.0001, Mann Whitney) through PRRs. Neutrophils from individuals anti-CCP2 positive (12.25) achieved a higher PI through PRRs than anti-CCP2 negative (3.71) (p=0.01, Mann Whitney). RF positive individuals achieved a higher PI (14) than RF negative individuals (4.5) (p=0.01, Mann Whitney). Superoxide anion production was 1.13 times higher on ERA individuals (p<0.0001, t test). Anti-CCP2 and RF positivity did not influence superoxide anion production.
Conclusions Phagocytes from ERA individuals have higher phagocytosis and superoxide anion production, showing hyperactivation of the innate immune response. This may occur secondary to the production of inflammatory cytokines, such as TNF-α. A higher PI by neutrophils of individuals positive to anti-CCP2 and RF suggests that these antibodies may act as opsonins providing further activation for the innate immune response and thus corresponding to worse prognosis. Assessment of phagocytosis is a direct indicator of innate immune response activation and may be a sensitive predictor of the disease activity.
Gierut et al. Innate immunity and rheumatoid arthritis. Rheum Dis Clin North Am 36: 271–296, 2010.
Mota LMH et al. Consensus of the Brazilian Society of Rheumatology for diagnosis and early assessment of rheumatoid arthritis. Rev Bras Reum 51: 207-219, 2011.
Disclosure of Interest None Declared
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