Expression of endothelial protein C receptor in cortical peritubular capillaries associates with a poor clinical response in lupus nephritis

Abstract

Increased mEPCR expression in PTCs may represent a novel marker of poor response to therapy for LN.

Biomarkers for Lupus Nephritis

“…Unexpectedly, mEPCR was found to be upregulated in the renal peritubular capillaries of patients with lupus nephritis compared with peritubular capillaries from normal kidneys (54). Those patients whose biopsies showed that more than 25% of the cortical peritubular capillaries expressed mEPCR responded poorly to therapy at 6 and 12 mo and tended to develop CKD (54). Interestingly, mEPCR as a biomarker of response to treatment was independent of biopsy class, activity and chronicity indices, GFR, and tubulointerstitial damage (54).…”

“…The receptor may be shed in patients with active lupus (53). Unexpectedly, mEPCR was found to be upregulated in the renal peritubular capillaries of patients with lupus nephritis compared with peritubular capillaries from normal kidneys (54). Those patients whose biopsies showed that more than 25% of the cortical peritubular capillaries expressed mEPCR responded poorly to therapy at 6 and 12 mo and tended to develop CKD (54).…”

“…Those patients whose biopsies showed that more than 25% of the cortical peritubular capillaries expressed mEPCR responded poorly to therapy at 6 and 12 mo and tended to develop CKD (54). Interestingly, mEPCR as a biomarker of response to treatment was independent of biopsy class, activity and chronicity indices, GFR, and tubulointerstitial damage (54). The functional role of mEPCR in the pathogenesis of lupus nephritis remains to be determined, but these data suggest that intrarenal endothelial activation may select for treatment-resistance.…”

Single cell RNA sequencing to dissect the molecular heterogeneity in lupus nephritis

“…Although there have been intense efforts to identify biomarkers in serum and urine from LN patients, these have not yet yielded sufficiently robust markers to replace the renal biopsy. Previous studies have shown that endothelial changes such as increased protein levels of membrane protein C receptor (encoded by PROCR) in patients with LN predicts poor responses to therapy (9). Furthermore, increased levels were noted in biopsies of nonlesional, non-sun-exposed skin of LN patients, suggesting that alterations in the microvasculature are widespread and extend to the dermal vasculature (9).…”

“…Previous studies have shown that endothelial changes such as increased protein levels of membrane protein C receptor (encoded by PROCR) in patients with LN predicts poor responses to therapy (9). Furthermore, increased levels were noted in biopsies of nonlesional, non-sun-exposed skin of LN patients, suggesting that alterations in the microvasculature are widespread and extend to the dermal vasculature (9). Thus, analysis of this more readily accessible tissue, even distant from the primary affected organ, may provide an opportunity to explore surrogates for renal tissue analyses (10).…”