Role of fluid-phase complement system regulation in the development of hepatitis C virus-associated glomerulonephritis

PLoS One. 2022 Oct 13;17(10):e0276017. doi: 10.1371/journal.pone.0276017. eCollection 2022.

Abstract

Objectives: It is not known why only some hepatitis C virus (HCV) infected patients develop glomerulonephritis (GN). Therefore, we investigated the role of soluble complement regulators in the development of HCV associated GN.

Methods: Patients with HCV associated GN who were admitted to our nephrology unit between July 2016 and July 2018 were recruited to the study (group 1). Two other age and sex matched groups were studied as control groups: patients with HCV without GN (group 2) and healthy HCV negative volunteers (group 3). There were 26 participants in each of the three groups at the end of the recruitment period. An assay of serum fluid-phase complement regulators was performed using enzyme linked immunosorbent assay technique. Three complement single nucleotide polymorphisms (SNPs) were analyzed using real time polymerase chain reaction (Taqman; thermo fisher scientific): rs2230199 and rs1047286 for complement 3 (C3) and rs800292 for complement factor H (CFH).

Results: Serum levels of complement 4 binding protein (C4BP) were significantly lower in group 1 (median 70 ng/ml) than in groups 2 (median 88.8 ng/ml) and 3 (median 82.8 ng/ml) with p value of 0.007. The minor allele (allele A) of rs800292 for CFH was significantly higher in group 2 and group 3 (G 54% and A 46%) than in group 1 (G 73% and A 27%), p = 0.04.

Conclusions: Low C4BP levels are associated with GN in HCV infected patients. In addition, rs800292 SNP in CFH protects against GN in patients with HCV.

MeSH terms

  • Complement C2 / genetics
  • Complement C3 / genetics
  • Complement C4
  • Complement Factor H / genetics
  • Glomerulonephritis*
  • Hepacivirus
  • Hepatitis C* / complications
  • Hepatitis C* / genetics
  • Humans
  • Polymorphism, Single Nucleotide

Substances

  • Complement C2
  • Complement C3
  • Complement C4
  • Complement Factor H

Grants and funding

The authors received no specific funding for this work.