Abnormalities in Bone Marrow of Patients with Rheumatoid Arthritis

In a previous study we showed the presence of abnormal myeloid lineage cells in epiphyseal bone marrow (BM) adjacent to joints affected with severe rheumatoid arthritis (RA). In this study, we have investigated the abnormalities of the cellular population related to RA in the iliac BM, in vitro production and modulation of abnormal myeloid lineage cells, and the microenvironment in BM which may support these unique cellular changes specific to RA patients. Mononuclear cells (MNCs) were prepared from iliac BM aspirates from RA patients. Two-color flow cytometry was carried out to analyze the phenotypes of MNCs freshly isolated from BM aspirates, and the presence of abnormal myeloid cells under various cultured conditions. The absolute number of MNCs in the iliac BM was increased 3-fold in the RA patients compared with the non-RA controls. In CD8+ cell and myeloid cell fractions, significant differences were recognized between RA patients and non-RA controls. The production of abnormal myeloid cells was enhanced by granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-1β, but inhibited by T lymphocytes. Stromal cell lines from RA BM with nursing activity were established. Characteristic changes of the iliac BM suggest an important role of systemic BM in the pathogenesis of RA.