Gene expression in systemic lupus erythematosus: Bone marrow analysis differentiates active from inactive disease and reveals apoptosis and granulopoiesis signatures

Objective—The cells of the immune system originate from the bone marrow (BM), where many of them also mature. To better understand the aberrant immune response in systemic lupus erythematosus (SLE), we examined the BM in lupus patients using DNA microarrays and compared it to the peripheral blood (PB). Patients and Methods—Bone marrow mononuclear cells (BMMCs) from 20 SLE patients (11 with active disease and 9 with inactive disease) and peripheral blood mononuclear cells (PBMCs) from 27 patients (16 active/ 11 inactive); BMMCs and PBMCs from 7 healthy individuals and 3 osteoarthritis patients served as controls. Samples were analyzed on genome-scale microarrays with 21,329 genes represented. Results—We found 102 differentially expressed genes between patients’ and controls’ BMMCs (unpaired student t-test), involved in various biologic processes; 53 of them are involved in major networks including cell death, growth, signaling and proliferation. Comparative analysis between BM and PB of patients identified 88 genes differentially expressed; 61 out of 88 participate in cell growth and differentiation, cellular movement and morphology, immune response and other hematopoietic cell functions. Unsupervised clustering of highly expressed genes revealed two major SLE patient clusters (active and inactive) in BM, but not in PB. The upregulated genes in the bone marrow of active patients included genes involved in cell death and granulopoiesis. Conclusion—Microarray analysis of the bone marrow differentiates active from inactive lupus patients and provides further evidence for the role of apoptosis and granulocytes in the pathogenesis of the disease. Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease characterized by the production of autoantibodies to components of the cell nucleus in association with diverse clinical manifestations encompassing almost all organ systems. Although its etiology is not established, much is known about the pathogenic pathways that lead to tissue injury (1,2)