Dysregulated expression of CXCR4/CXCL12 in subsets of patients with systemic lupus erythematosus.
OBJECTIVE
CXCR4 is a chemokine with multiple effects on the immune system. In murine lupus models, we demonstrated that monocytes, neutrophils, and B cells overexpressed CXCR4 and that its ligand, CXCL12, was up-regulated in diseased kidneys. We undertook this study to determine whether CXCR4 expression was increased in peripheral blood leukocytes from patients with systemic lupus erythematosus (SLE) and whether CXCL12 expression was increased in kidneys from patients with SLE.


METHODS
Peripheral blood leukocytes from 31 SLE patients, 8 normal controls, and 9 patients with rheumatoid arthritis were prospectively analyzed by flow cytometry for CXCR4 expression. Biopsy samples (n = 14) from patients with lupus nephritis (LN) were immunostained with anti-CXCL12 antibody.


RESULTS
CD19+ B cells and CD4+ T cells from SLE patients displayed a >2-fold increase (P = 0.0001) and >3-fold increase (P < 0.0001), respectively, in median CXCR4 expression compared with that in controls (n = 7-8). Moreover, CXCR4 expression on B cells was 1.61-fold higher in patients with SLE Disease Activity Index (SLEDAI) scores >10 (n = 8) than in patients with SLEDAI scores ≤10 (n = 16) (P = 0.0008), 1.71-fold higher in patients with class IV LN (n = 5) than in patients with other classes of LN (n = 7) (P = 0.02), and 1.40-fold higher in patients with active neuropsychiatric SLE (NPSLE) (n = 6) than in patients with inactive NPSLE (n = 18) (P = 0.01). CXCL12 was significantly up-regulated in the tubules and glomeruli of kidneys in patients with LN (n = 14), with the percentage of positive cells correlating positively with the severity of LN.


CONCLUSIONS
CXCR4 appears to be up-regulated in multiple leukocyte subsets in SLE patients. The heightened expression of CXCR4 on B cells in active NPSLE and of CXCL12 in nephritic kidneys suggests that the CXCR4/CXCL12 axis might be a potential therapeutic target for SLE patients with kidney and/or central nervous system involvement.
Wang
Andrew
A
University of Texas Southwestern Medical Center, Dallas, TX 75390-8884, USA.
Guilpain
Philippe
P
Chong
Benjamin F
BF
Chouzenoux
Sandrine
S
Guillevin
Loïc
L
Du
Yong
Y
Zhou
Xin J
XJ
Lin
Fangming
F
Fairhurst
Anna-Marie
AM
Boudreaux
Christopher
C
Roux
Christian
C
Wakeland
Edward K
EK
Davis
Laurie S
LS
Batteux
Frederic
F
Mohan
Chandra
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D054377:Chemokine CXCL12 / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000378:metabolism*; D008181:Lupus Nephritis / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019718:Receptors, CXCR4 / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation / Q000276:immunology
C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4