Differential Neutrophil and Eosinophil Infiltrations in the Sub-Lining Compartment of Rheumatoid Versus Osteoarthritic Synovium.

Background: The role of innate immunity in the perpetuation of synovial inflammation may have been overlooked in rheumatoid arthritis (RA). Herein, we compared and quantified neutrophil and eosinophil infiltrations in lining and sub-lining compartments of RA versus osteoarthritis (OA) synovium. Methods: Synovia were obtained from consecutive RA and OA patients (n=8, each) with destructive knee arthritis who underwent arthroplasty. Histological stainings and fluorescence immune-stainings were performed on paraffin tissue sections. Neutrophils and eosinophils were imaged with a confocal microscopy using the pan-leukocyte marker anti-CD45 combined with anti-CD14 and anti-CD294 specific antibodies, respectively. Antibodies against CD90 were used for neutrophil-fibroblast and/or eosinophil- sub-lining fibroblast tissue co-localisation analysis. Results: In both RA and OA patients, higher numbers of leukocytes were quantified in the sub-lining vs lining synovial compartment. In RA, the numbers of neutrophils were higher in the sub-lining vs lining compartment, being increased by 5-fold, which was not the case in OA. On the other hand, eosinophils could be exclusively found in the sub-lining compartment of either RA or OA-derived synovium, being increased in RA. Concerning their possible function we found that both neutrophils and eosinophils could be found in proximity with sub-lining fibroblasts in RA-derived synovia, but not in OA, indicating a crosstalk between these leukocytes and RA synovial fibroblasts. Conclusion: Increased neutrophilic infiltrations and the presence of eosinophils in synovial sub-lining compartment discriminate RA from OA. Studies to elucidate the contribution of innate immunity cells to the pathophysiology of joint destruction in RA through interactions with fibroblasts are warranted.