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, where many of them also mature. This study was undertaken to examine gene expression in the bone marrow of patients with systemic lupus erythematosus (SLE), in order to better understand the aberrant immune response in this disease.


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 with active disease and 11 with inactive disease) were studied; BMMCs and PBMCs from 7 healthy individuals and 3 osteoarthritis patients were studied as controls. Samples were analyzed on genome-scale DNA microarrays, with 21,329 genes represented.


RESULTS
We identified 102 genes involved in various biologic processes that were differentially expressed between patient and control BMMCs; 53 of them are genes that are involved in major networks, including cell death, growth, signaling, and proliferation. Comparative analysis revealed 88 genes that were differentially expressed between bone marrow and blood, the majority of which are involved in cell growth and differentiation, cellular movement and morphology, immune response, and other hematopoietic cell functions. Unsupervised clustering of highly expressed genes revealed 2 major SLE patient clusters (active disease and inactive disease) based on gene expression in bone marrow, but not in peripheral blood. The up-regulated genes in the bone marrow of patients with active disease included genes involved in cell death and granulopoiesis.


CONCLUSIONS
Microarray analysis of the bone marrow differentiated active from inactive SLE and provided further evidence of the role of apoptosis and granulocytes in the pathogenesis of the disease.
Nakou
Magdalene
M
University of Crete Medical School, Heraklion, Greece.
Knowlton
Nicholas
N
Frank
Mark B
MB
Bertsias
George
G
Osban
Jeanette
J
Sandel
Clayton E
CE
Papadaki
Helen
H
Raptopoulou
Amalia
A
Sidiropoulos
Prodromos
P
Kritikos
Iraklis
I
Tassiulas
Ioannis
I
Centola
Michael
M
Boumpas
Dimitrios T
DT
D017209:Apoptosis / Q000502:physiology*; D001853:Bone Marrow / Q000276:immunology; D005260:Female; D015870:Gene Expression; D006098:Granulocytes / Q000166:cytology*; D006410:Hematopoiesis / Q000502:physiology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010003:Osteoarthritis / Q000276:immunology