Clinicopathological Phenotype and Outcomes of NCAM-1+membranous Lupus Nephritis

Background No studies have explored the long-term outcomes of neural cell adhesion molecule 1 (NCAM1)-associated membranous lupus nephritis (MLN) patients.Method We performed immunohistochemical studies on kidney biopsy specimens against NCAM1 in consecutive MLN patients. The clinical and histopathological characteristics and outcomes of cases of NCAM1-associated MLN patients are described and compared with NCAM1-negative patients. In addition, we detected serum circulating anti-NCAM1 antibodies through western blotting and indirect immunofluorescence assays.Results Among 361 MLN cases, 18 (5.0%) were glomerular NCAM1-positive. NCAM1-positive MLN patients were older [35 years (interquartile range, IQR 27-43) versus 28 (22-37); P = .050] and had lower systemic lupus erythematosus disease activity index [11 (IQR 8-12) versus 14 (10-18); P = .007], serum creatinine [60 mu mol/L (IQR 50-70) versus 70 (54-114); P = .029] and activity index [3 (IQR 2-6) versus 6 (3-9); P = .045] at kidney biopsy compared with NCAM1-negative patients. The percentage of positive anti-Sj & ouml;gren's syndrome-related antigen A antibodies in NCAM1-positive patients was significantly greater (83.3% versus 58.2%; P = .035) than in the NCAM1-negative patients. However, no evidence of neuropsychiatric disorders was found in these 18 patients. There were no significant differences in the treatment response and the risk of end-stage renal diseases between NCAM1-positive and -negative groups (P = .668 and P = .318, respectively). However, the risk of death was much higher in the NCAM1-positive group than the NCAM1-negative group (27.8% vs 8.1%; P = .007). Moreover, the risk of death was also much higher in the NCAM1-positive group than the matched NCAM1-negative group (Log-rank P = .013). Additionally, circulating anti-NCAM1 antibodies can be detected in 1/5 (20%) patients who had serum available.Conclusion The prevalence of NCAM1 positivity was 5.0% in our cohort of MLN and the high mortality in these subgroup patients are needed to validate in future studies. Graphical Abstract