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.
Expression of CD44 variant isoforms CD44v3 and CD44v6 is increased on T cells from patients with systemic lupus erythematosus and is correlated with disease activity. (Arthritis Rheum. 2010; 62:1431-1437.)
Abstract
Objective: To quantify the expression of CD44 and variant isoforms CD44v3 and CD44v6 on T cells from patients with systemic lupus erythematosus (SLE), and to assess correlations of the level of expression of these molecules with disease manifestations.
Methods: Information on clinical and demographic characteristics was collected, and blood samples were obtained from 72 patients with SLE and 32 healthy control subjects matched to the patients by sex, race, and age. Expression of CD44 and variants CD44v3 and v6 on T cell subsets was determined by flow cytometry, and Pearson’s correlations of their expression levels with clinical variables, SLE Disease Activity Index (SLEDAI) scores, and presence of lupus nephritis were determined. Wilcoxon’s rank sum tests and conditional multivariable regression analyses were applied to identify differences in the expression of CD44 between patients with SLE and healthy controls.
Results: Expression of CD44 was higher on CD4+ and CD8+ T cells from SLE patients compared with controls (P<0.03). Expression of CD44v3 and CD44v6 was also higher on total T cells and CD4+ and CD8+ T cells from SLE patients compared with controls (P<0.03). Cell surface levels of CD44v3 on total T cells, CD4+ T cells, and CD8+ T cells as well as cell surface expression of CD44v6 on total T cells and CD4+ T cells were correlated with the SLEDAI score (P<0.05). The presence of lupus nephritis was associated with the expression of CD44v6 on total T cells, CD4+ T cells, and CD4-CD8- T cells (P<0.05). Positivity for anti-double-stranded DNA antibodies was associated with the expression levels of CD44v6 on T cells (P<0.05).