NLRC5: potential novel non-invasive biomarker for predicting and refecting the progression of IgA nephritis

Background: The nucleotide oligomerization domain-like receptor subfamily C5 (NLRC5) is primarily expressed in the adaptive and innate immune systems. NLRC5 was recently discovered to regulate immunity and infammatory responses. Abnormal immune and infammatory responses are considered critical pathogenesis in IgA nephritis (IgAN). However, the role of NLRC5 in IgAN is unknown. We previously showed that NLRC5 can be detected in patients with IgAN; herein, we further examined the pathophysiological signifcance of NLRC5 in the serum and renal deposits of patients with IgAN. This study is the frst to fnd that NLRC5 is closely correlated with IgAN.

Methods: IgAN patients (n=50) who were diagnosed by renal biopsy provided blood and renal biopsy tissue, and agematched healthy control subjects (blood donators n=22; tissue donators n=5) were included. Renal biopsies were diagnosed, and blood biochemical parameters were tested. Serum creatinine, urea, proteinuria, haematuria, albumin, and immunoglobulin A levels were recorded. Serum NLRC5 concentrations were detected by enzymelinked immunosorbent assay, and tissue NLRC5 expression in kidney tissue was detected by immunohistochemical analysis. ROC curve analysis was used to evaluate the diagnostic value of the serum NLRC5 concentration in IgAN.

Results: Serum NLRC5 concentration was signifcantly decreased in the IgAN group compared to that in the healthy control group (P<0.0001), especially in S1 (Oxford classifcation) patients (P<0.0001). Furthermore, serum NLRC5 concentration had a negative correlation with Lee’s grade (r=0.3526, P=0.0060) and proteinuria levels (r=0.4571, P=0.0004). Tissue NLRC5 expression was signifcantly increased in the IgAN group compared to that in the healthy control group (P<0.0001); a more signifcant increase was identifed in the S1 group (P<0.05) and had a positive correlation with Lee’s grade (r=0.497, P<0.0001). We proposed a cut-of value of 1415 pg/ml for serum NLRC5 concentration, which was able to predict IgAN with 77.27% sensitivity and 87.5% specifcity.

Conclusions: Serum NLRC5 concentrations in IgAN are signifcantly decreased, and tissue NLRC5 expression is signifcantly increased in IgAN renal tissue, which is consistent with pathological severity. This fnding suggests that NLRC5 could potentially be a diagnostic index and represents a prognostic factor in IgAN patients.