Evaluation of the significance of complement-related genes mutations in atypical postinfectious glomerulonephritis: a
Feng Xu1, Changming Zhang1, Mingchao Zhang1
1National Clinical Research Center for Kidney Disease, Jinling Hospital, Nanjing Medical University, 305 East Zhongshan Road, Nanjing, 210018, Jiangsu, China.
Background:
Postinfectious glomerulonephritis with C3-dominant glomerular deposition (C3-PIGN) involves C3-dominant glomerular deposition without immunoglobulin. Atypical C3-PIGN involves persistent hypocomplementemia. We investigated the clinical features and explored complement-related gene mutations in atypical PIGN patients.
Methods:
We enrolled atypical C3-PIGN patients and collected data regarding the clinical presentation and pathological characteristics and follow-up data. We measured the levels of complement associated antibodies and performed whole-exome sequencing (WES) to detect mutations in complement-related genes.
Results:
The analysis included six atypical C3-PIGN patients. All patients were antistreptolysin-O (ASO) positive. All patients had varying degrees of hematuria, and four patients had proteinuria. None of the patients were positive for complement-related antibodies. All patients possessed mutations of genes related to the complement pathway, including alternative complement pathway genes-CFI, CFH, CFHR3, CFHR5; the lectin pathway gene-MASP2; and the common complement pathway gene-C8A. The rare variant of CFHR3 has been reported in C3 glomerulonephritis. During 56-73 months of follow-up, the levels of urine markers in three patients recovered within 6 months, and the remaining patients had abnormal urine test results over 12 months. Patients who received glucocorticoid therapy recovered faster.
Conclusions:
Our study suggested that complement-related gene mutations may be an important cause of persistent hypocomplementemia in atypical C3-PIGN patients. In addition to variations in alternate pathway-related genes, we also found variations in lectin pathway-related genes, especially MASP2 genes. Although the overall prognosis was good, atypical C3-PIGN patients exhibited a longer period for recovery. Our results suggested that atypical C3-PIGN patients should receive more medical attention and need testing for mutations in complement-related genes.
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