Evaluation of the significance of complement-related genes mutations in atypical postinfectious glomerulonephritis: a pilot study

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.