title: C3 glomerulonephritis and autoimmune disease: more than a fortuitous association?
abstract: C3 glomerulonephritis (C3GN) results from genetic or acquired dysregulation of the alternative complement pathway. A subset of patients may have clinical and biochemical characteristics compatible with an autoimmune disorder. We studied a cohort of 85 patients with confirmed C3GN (2007-2014), of which ten patients (3 male, 7 female; mean age 38.5 years) had an associated autoimmune disorder. All patients had abnormal ANA titers, 6 also had positive ds-DNA titers. At the time of presentation with C3GN, all 7 female patients had autoimmune-related presentations. Of the 3 male patients, only 1 patient had autoimmune-related presentations. Kidney biopsy showed predominantly mesangial proliferative or membranoproliferative glomerulonephritis. In 5 patients, the alternative pathway was evaluated. All had allele variants/polymorphisms associated with C3GN. One patient was also positive for C3Nefs. Treatment varied form conservative management to the use of prednisone alone or with cytotoxic therapy. Mean serum creatinine decreased from 2.0 to 1.4 mg/dL while proteinuria decreased from 2300 to 994 mg/24 h in 8 patients with follow-up. The study highlights the association between C3GN and autoimmune disorders, particularly in female patients. The study suggests that an autoimmune milieu may act as a trigger for the development of C3GN in genetically susceptible patients. Short-term prognosis of C3GN associated with autoimmune disorders appears excellent.
authors.affiliation: Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street, SW, Rochester, MN, 55905, USA.
authors.forename: Mariam P
authors.initials: MP
authors.lastname: Alexander
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: Fernando C
authors.initials: FC
authors.lastname: Fervenza
authors.affiliation: Division of Nephrology, AZ Sint-Jan Brugge, Brugge, Belgium.
authors.forename: An S
authors.initials: AS
authors.lastname: De Vriese
authors.affiliation: Otolaryngology and Renal Research Laboratories, Division of Nephrology, Departments of Internal Medicine and Pediatrics, Carver College of Medicine, Iowa, IA, USA.
authors.forename: Richard J H
authors.initials: RJH
authors.lastname: Smith
authors.affiliation: Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street, SW, Rochester, MN, 55905, USA.
authors.forename: Samih H
authors.initials: SH
authors.lastname: Nasr
authors.affiliation: Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street, SW, Rochester, MN, 55905, USA.
authors.forename: Lynn D
authors.initials: LD
authors.lastname: Cornell
authors.affiliation: Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street, SW, Rochester, MN, 55905, USA.
authors.forename: Loren P
authors.initials: LP
authors.lastname: Herrera Hernandez
authors.affiliation: Otolaryngology and Renal Research Laboratories, Division of Nephrology, Departments of Internal Medicine and Pediatrics, Carver College of Medicine, Iowa, IA, USA.
authors.forename: Yuzhou
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street, SW, Rochester, MN, 55905, USA. sethi.sanjeev@mayo.edu.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Sethi
mesh_terms: D000328:Adult; D001327:Autoimmune Diseases / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D015551:Autoimmunity / Q000187:drug effects / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D003167:Complement Activation / Q000187:drug effects / Q000235:genetics; D003176:Complement C3 / Q000235:genetics / Q000276:immunology*; D003178:Complement C3 Nephritic Factor / Q000032:analysis; D004359:Drug Therapy, Combination; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015432:Glomerulonephritis, Membranoproliferative / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007678:Kidney Glomerulus / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011241:Prednisone / Q000627:therapeutic use; D012307:Risk Factors; D012737:Sex Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; C038245:C3 protein, human; D003176:Complement C3; D003178:Complement C3 Nephritic Factor; D005819:Genetic Markers; D005938:Glucocorticoids; D011241:Prednisone
keywords: ANA; Autoimmune disease; C3 glomerulonephritis; C3 glomerulopathy; ds-DNA