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 μmol/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-Sjögren'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.