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

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.

[1]  Chengliang Zhu,et al.  Hepatitis B virus inhibits the expression of complement C3 and C4, in vitro and in vivo. , 2018, Oncology letters.

[2]  Chengliang Zhu,et al.  Hepatitis B virus inhibits the expression of complement C 3 and C 4 , in vitro and in vivo , 2018 .

[3]  A. D. den Hollander,et al.  A Novel Complotype Combination Associates with Age-Related Macular Degeneration and High Complement Activation Levels in vivo , 2016, Scientific Reports.

[4]  C. Schreck,et al.  Comparison Between CKD-EPI Creatinine and MDRD Equations to Estimate Glomerular Filtration Rate in Kidney Transplant Patients. , 2016, Transplantation proceedings.

[5]  R. Gish,et al.  Hepatitis C virus as a systemic disease: reaching beyond the liver , 2015, Hepatology International.

[6]  P. Messa,et al.  Novel evidence on hepatitis C virus-associated glomerular disease. , 2014, Kidney international.

[7]  K. Meyer,et al.  Inhibition of C3 Convertase Activity by Hepatitis C Virus as an Additional Lesion in the Regulation of Complement Components , 2014, PloS one.

[8]  K. Meyer,et al.  Hepatitis C Virus Suppresses C9 Complement Synthesis and Impairs Membrane Attack Complex Function , 2013, Journal of Virology.

[9]  F. Fervenza,et al.  Membranoproliferative glomerulonephritis--a new look at an old entity. , 2012, The New England journal of medicine.

[10]  K. Meyer,et al.  Hepatitis C Virus Proteins Inhibit C3 Complement Production , 2011, Journal of Virology.

[11]  L. Katz,et al.  Allelic Variants of Complement Genes Associated with Dense Deposit Disease , 2011, Journal of the American Society of Nephrology : JASN.

[12]  D. Fearon,et al.  Common polymorphisms in C3, factor B, and factor H collaborate to determine systemic complement activity and disease risk , 2011, Proceedings of the National Academy of Sciences.

[13]  L. Fried,et al.  HCV infection and the incidence of CKD. , 2011, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[14]  K. Meyer,et al.  Transcriptional Repression of C4 Complement by Hepatitis C Virus Proteins , 2011, Journal of Virology.

[15]  B. Morgan,et al.  The disease-protective complement factor H allotypic variant Ile62 shows increased binding affinity for C3b and enhanced cofactor activity. , 2009, Human molecular genetics.

[16]  P. Zipfel,et al.  Complement regulators and inhibitory proteins , 2009, Nature Reviews Immunology.

[17]  E. Vittinghoff,et al.  Association of hepatitis C seropositivity with increased risk for developing end-stage renal disease. , 2007, Archives of internal medicine.

[18]  M. Walport,et al.  Spontaneous hemolytic uremic syndrome triggered by complement factor H lacking surface recognition domains , 2007, The Journal of experimental medicine.

[19]  M. Matsushita,et al.  Cryoprecipitate of patients with cryoglobulinemic glomerulonephritis contains molecules of the lectin complement pathway. , 2001, Clinical immunology.

[20]  M. Szklo,et al.  Prevalence of Type 2 Diabetes Mellitus among Persons with Hepatitis C Virus Infection in the United States , 2000, Annals of Internal Medicine.

[21]  E. Morales,et al.  Glomerulonephritis associated with hepatitis C virus infection , 1999 .

[22]  C. Alpers,et al.  Focal Segmental Glomerular Sclerosis among Patients Infected with Hepatitis C Virus , 1999, Nephron.

[23]  Stephen M. Johnson,et al.  Renal thrombotic microangiopathy associated with anticardiolipin antibodies in hepatitis C-positive renal allograft recipients. , 1999, Journal of the American Society of Nephrology : JASN.

[24]  V. D’Agati,et al.  Hepatitis C viral infection is associated with fibrillary glomerulonephritis and immunotactoid glomerulopathy. , 1998, Journal of the American Society of Nephrology : JASN.

[25]  K. Chayama,et al.  Glomerulonephritis in autopsy cases with hepatitis C virus infection. , 1998, Internal medicine.

[26]  P. Whelton,et al.  Risk of End-stage Renal Disease in Diabetes Mellitus: A Prospective Cohort Study of Men Screened for MRFIT , 1997 .

[27]  J. Reichen,et al.  Prescribing in liver disease. , 1997, Journal of hepatology.

[28]  C. Alpers,et al.  Hepatitis C virus-associated glomerulonephritis. Effect of α-interferon therapy , 1994 .

[29]  K. Whaley,et al.  Interferon-induced transcriptional and post-transcriptional modulation of factor H and C4 binding-protein synthesis in human monocytes. , 1990, The Biochemical journal.

[30]  K. Whaley,et al.  Regulation of C1-inhibitor synthesis by interferons and other agents. , 1989, Behring Institute Mitteilungen.

[31]  J. Weiler,et al.  Steroids inhibit activation of the alternative-amplification pathway of complement , 1983, Infection and immunity.