Difference between phenotypes of bone marrow and peripheral blood leukocytes indicate rheumatoid arthritis bone marrow as an important site for cell activation and proliferation

Abstract

Objectives Although the pathogenesis of RA is still unknown, recent data suggest bone marrow compartment is an important site contributing to the initiation and perpetuation of chronic inflammation that may spread to the joint. The aim of the present study was to compare phenotypes of bone marrow and peripheral blood leukocytes isolated from rheumatoid arthritis (RA) and osteoarthritis (OA) patients that may indicate whether bone marrow is implicated in the activation and propagation of mature leukocytes. Methods Mononuclear cells were isolated from peripheral blood and bone marrow of patients with RA and OA undergoing hip replacement. Sodium citrate was used as an anticoagulant. To assess cell phenotypes, specific monoclonal antibodies against: CD3, CD19, CD20, CD4, CD8, CD16, CD56, CD38, CD27, CD25, CD69, CD14, CD123, CD11c, HLA-DR, BDCA-1 and BDCA-2 were used for staining, followed by flow cytometric analysis. Results Preliminary results indicate that RA bone marrow compartment contained different proportions of activated CD4+ and CD8+ T cell, B-cells, NK-cells and macrophages than paired peripheral blood. Unlike in peripheral blood from RA and OA, where relatively small differences in cell phenotypes were detected, composition of bone marrow mononuclear cells differed substantially between these two diseases. Conclusions Phenotypic differences between leukocytes from bone marrow and peripheral blood indicate that in RA bone marrow microenvironment provides stronger signals leading to activation and maturation of leukocytes than in OA. Thus, these data support notion that bone marrow actively participates in the pathogenesis of RA. Acknowledgements This work was partially supported by funds from the European Community's FP6 Project 018661 Autocure.