Autoantibody levels influences the number and phenotype of infiltrating neutrophils in inflamed joints of patients with rheumatoid arthritis

GORLINO CV; DÍAZ-GABUTTI MS; DAVE MN; BLAS R; MUNARRIZ A; TAMASHIRO H; PARDO-HIDALGO RA; PISTORESI-PALENCIA MC; DI GENARO MS

Buenos Aires

Congreso; II French-Argentine Immunology Congress y LXIII Reunión Anual de la Sociedad Argentina de Inmunología; 2015

SAI

Abstract: Background: Neutrophils are abundant cells in synovial fluid (SF) of rheumatoid arthritis (RA) patients. Anti-cyclic citrullinated peptide antibodies (ACPA) are RA-specific biomarker. However, the pathogenic role of ACPA is unclear. The aim was to investigate the association between synovial neutrophil infiltration and ACPA presence in RA. Methods: Synovial fluid (SF) were obtained from 65 patients who full-filled the American College of Rheumatology RA classification criteria. Disease activity was evaluated by 28-joint count Disease Activity Score (DAS-28). Immunoglobulin G (IgG) ACPA (CCP3) and interleukin (IL)-8 levels were tested by ELISA, and total IgG by radial immunodiffusion assay. Expression of CD16, CD62L, CXCR1 and CD54 on in vitro-stimulated neutrophils from peripheral blood of healthy individuals and on SF-neutrophils from RA patients was assessed by flow cytometry. Correlations analysis was performed by Spearman test. Results: In ACPA-positive patients, synovial neutrophils correlated with DAS-28 (p=0.014). Additionally, neutrophil counts correlated positively with IL-8 levels (p=0.04) and higher levels of this cytokine were related with worse clinical manifestations (r=0.3; p=0.04). The ratio of ACPA/total IgG in SF correlated positively with DAS-28 (p=0.03). In vitro-stimulation of peripheral blood-neutrophils with SF induced the CD16highCD62Llow subset, which was higher after stimulation with SF with higher ACPA/total IgG ratio. This subset was also found in SF of RA patients, and related with ACPA/total IgG ratio. These cells showed decreased CXCR1 and increased CD54 expressions. Conclusions: Our results suggest that ACPA levels may modulate neutrophil activity and contribute with joint inflammation in RA.