SAT0180 B7-H4 expression of renal tubular epithelial cells in patients with lupus nephritis

Abstract

Background B7-H4 is a newly identified B7 family negative co-stimulate molecule, the expression and function of B7-H4, in the pathogenesis of lupus nephritis (LN) is still unclear. Objectives To investigate the expression of B7-H4 in patients with LN and the function of renal tubular epithelial cells (TECs)-associated B7-H4 in the regulation of T cell activation in vitro. Methods 90 LN patients, 3 acute kidney injury patients and 20 healthy donors were referred. Disease activity was assessed by SLEDAI scores. The expression of B7-H4 on kidney biopsies from patients with LN and acute kidney injury was measured using immunohistochemistry. In vitro, B7-H4 antigen on cultured HK-2 cells with or without stimulation by inflammatory factors was detected by flow cytometry. After co-cultured with HK-2 and purified CD4+T cells labeled with CFSE for 72 hours, T cell proliferation was detected by flow cytometry. The soluble B7-H4 in sera of LN patients and healthy donors were analyzed using ELISA. Results B7-H4 antigen expressed on tubular epithelium, the percentage of B7-H4 positive expression renal tubules from LN patients (45±16) % was lower than acute kidney injury patients (86±11) % (P<0.05). In vitro, the expression of B7-H4 on HK-2 cells was elevated upon stimulation by inflammatory factors, mixed lymphocyte reactions revealed that HK-2-related B7-H4 inhibits proliferation of co-cultured T cells. The soluble B7-H4 in serum of LN patients (61.45±29.38ng/ml) was not significantly lower than healthy controls (70.57±27.24ng/ml), but stronger association of serum soluble B7-H4 with serum creatinine levels was observed in LN patients (r=0.353, p=0.005). In addition, the mean concentration of soluble B7-H4 level in high activity group (74.40±31.95 ng/ml) was significantly higher than those in moderate group (51.89±21.79 ng/ml) (p=0.017) Conclusions B7-H4 molecules may play a role in the progress of LN, a clear understanding of its functional roles may further elucidate the pathogenesis of this disease. Disclosure of Interest None Declared

Immunosuppressive Effect of B7-H4 Pathway in a Murine Systemic Lupus Erythematosus Model

“…B7-H4-deficient mice in a BALB/c background mounted slightly enhanced T-helper type 1T cell responses and displayed mildly lowered parasite burdens upon Leishmania infection compared to wild-type mice, suggesting a B7-H4 has an inhibitory, albeit mild, effect on Th1 responses ( 54 ). Others have also reported that the soluble B7-H4 in serum of lupus nephritis patients was strongly associated with serum creatinine levels ( 55 ), suggesting a possible correction between SLE and B7-H4 signal pathway.…”

“…Upregulation of B7-H4 on APCs by IL-10 secreted by Tregs has been proposed as a potential inhibitory mechanism of regulatory T cells ( 44 ). B7-H4 Ig also can alleviate the disease of CIA ( 53 ) and moderate MOG ( 35 – 55 )/CFA-induced EAE in C57BL/6 mice ( 57 ). However, the role of B7-H4 in SLE has not been thoroughly investigated.…”