C3 glomerulonephritis: clinicopathological findings, complement abnormalities, glomerular proteomic profile, treatment, and follow-up.
C3 glomerulonephritis (C3GN) is a recently described disorder that typically results from abnormalities in the alternative pathway (AP) of complement. Here, we describe the clinical features, kidney biopsy findings, AP abnormalities, glomerular proteomic profile, and follow-up in 12 cases of C3GN. This disorder equally affected all ages, both genders, and typically presented with hematuria and proteinuria. In both the short and long term, renal function remained stable in the majority of patients with native kidney disease. In two patients, C3GN recurred within 1 year of transplantation and resulted in a decline in allograft function. Kidney biopsy mainly showed a membranoproliferative pattern, although both mesangial proliferative and diffuse endocapillary proliferative glomerulonephritis were noted. AP abnormalities were heterogeneous, both acquired and genetic. The most common acquired abnormality was the presence of C3 nephritic factors, while the most common genetic finding was the presence of H402 and V62 alleles of Factor H. In addition to these risk factors, other abnormalities included Factor H autoantibodies and mutations in CFH, CFI, and CFHR genes. Laser dissection and mass spectrometry of glomeruli from patients with C3GN showed accumulation of AP and terminal complement complex proteins. Thus, C3GN results from diverse abnormalities of the alternative complement pathway leading to subsequent glomerular injury.
Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA. Sethi.sanjeev@mayo.edu
Sanjeev
S
Sethi
Fernando C
FC
Fervenza
Yuzhou
Y
Zhang
Ladan
L
Zand
Julie A
JA
Vrana
Samih H
SH
Nasr
Jason D
JD
Theis
Ahmet
A
Dogan
Richard J H
RJ
Smith
D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000032:analysis; D001706:Biopsy; D002648:Child; D003176:Complement C3 / Q000032:analysis*; D003178:Complement C3 Nephritic Factor / Q000032:analysis; D017242:Complement Factor H / Q000235:genetics; D003170:Complement Pathway, Alternative / Q000235:genetics; D003165:Complement System Proteins / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D015432:Glomerulonephritis, Membranoproliferative / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D006417:Hematuria / Q000276:immunology; D006801:Humans; D007678:Kidney Glomerulus / Q000276:immunology* / Q000473:pathology; D016030:Kidney Transplantation; D061346:Laser Capture Microdissection; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D008910:Minnesota; D008969:Molecular Sequence Data; D009154:Mutation; D011237:Predictive Value of Tests; D011507:Proteinuria / Q000276:immunology; D040901:Proteomics / Q000379:methods; D012008:Recurrence; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D001323:Autoantibodies; C493495:CFH protein, human; D003176:Complement C3; D003178:Complement C3 Nephritic Factor; D017242:Complement Factor H; D003165:Complement System Proteins