Document Detail


Dysregulated expression of CXCR4/CXCL12 in subsets of patients with systemic lupus erythematosus.
MedLine Citation:
PMID:  20722038     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
CONCLUSION: 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.
Authors:
Andrew Wang; Philippe Guilpain; Benjamin F Chong; Sandrine Chouzenoux; Loïc Guillevin; Yong Du; Xin J Zhou; Fangming Lin; Anna-Marie Fairhurst; Christopher Boudreaux; Christian Roux; Edward K Wakeland; Laurie S Davis; Frederic Batteux; Chandra Mohan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  62     ISSN:  1529-0131     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-02     Completed Date:  2010-11-30     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3436-46     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2010 by the American College of Rheumatology.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Chemokine CXCL12 / immunology,  metabolism*
Female
Flow Cytometry
Humans
Immunohistochemistry
Leukocytes / immunology,  metabolism
Lupus Erythematosus, Systemic / immunology,  metabolism*
Lupus Nephritis / immunology,  metabolism
Male
Middle Aged
Receptors, CXCR4 / immunology,  metabolism*
Up-Regulation / immunology
Grant Support
ID/Acronym/Agency:
P01 AI039824/AI/NIAID NIH HHS; P01-AI-039824/AI/NIAID NIH HHS; P50 CORT-AR-055503/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/CXCL12 protein, human; 0/CXCR4 protein, human; 0/Chemokine CXCL12; 0/Receptors, CXCR4

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