title: Serum properdin consumption as a biomarker of C5 convertase dysregulation in C3 glomerulopathy.
abstract: Properdin (P) stabilizes the alternative pathway (AP) convertases, being the only known positive regulator of the complement system. In addition, P is a pattern recognition molecule able to initiate directly the AP on non-self surfaces. Although P deficiencies have long been known to be associated with Neisseria infections and P is often found deposited at sites of AP activation and tissue injury, the potential role of P in the pathogenesis of complement dysregulation-associated disorders has not been studied extensively. Serum P levels were measured in 49 patients with histological and clinical evidence of C3 glomerulopathy (C3G). Patients were divided into two groups according to the presence or absence of C3 nephritic factor (C3NeF), an autoantibody that stabilizes the AP C3 convertase. The presence of this autoantibody results in a significant reduction in circulating C3 (P < 0·001) and C5 levels (P < 0·05), but does not alter factor B, P and sC5b-9 levels. Interestingly, in our cohort, serum P levels were low in 17 of the 32 C3NeF-negative patients. This group exhibited significant reduction of C3 (P < 0·001) and C5 (P < 0·001) and increase of sC5b-9 (P < 0·001) plasma levels compared to the control group. Also, P consumption was correlated significantly with C3 (r = 0·798, P = 0·0001), C5 (r = 0·806, P < 0·0001), sC5b-9 (r = -0·683, P = 0·043) and a higher degree of proteinuria (r = -0·862, P = 0·013). These results illustrate further the heterogeneity among C3G patients and suggest that P serum levels could be a reliable clinical biomarker to identify patients with underlying surface AP C5 convertase dysregulation.
authors.affiliation: Unidad de Inmunología, IdiPAZ, Hospital Universitario La Paz, Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER U754), Madrid, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Corvillo
authors.affiliation: Unidad de Inmunología, IdiPAZ, Hospital Universitario La Paz, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Bravo García-Morato
authors.affiliation: Unidad de Inmunología, IdiPAZ, Hospital Universitario La Paz, Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER U754), Madrid, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Nozal
authors.affiliation: Unidad de Inmunología, IdiPAZ, Hospital Universitario La Paz, Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER U754), Madrid, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Garrido
authors.affiliation: Centro De Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain (CIB-CSIC), Centro de Investigación Biomédica en Red de Enfermedades Raras (CBERER U738), Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Tortajada
authors.affiliation: Centro De Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain (CIB-CSIC), Centro de Investigación Biomédica en Red de Enfermedades Raras (CBERER U738), Madrid, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Rodríguez de Córdoba
authors.affiliation: Unidad de Inmunología, IdiPAZ, Hospital Universitario La Paz, Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER U754), Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: López-Trascasa
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D002648:Child; D003176:Complement C3 / Q000235:genetics / Q000276:immunology; D003178:Complement C3 Nephritic Factor / Q000235:genetics / Q000276:immunology; D050577:Complement C3-C5 Convertases / Q000235:genetics / Q000276:immunology*; D003182:Complement C5 / Q000235:genetics / Q000276:immunology; D011415:Complement Factor B / Q000235:genetics / Q000276:immunology; D051056:Complement Inactivating Agents / Q000097:blood; D015938:Complement Membrane Attack Complex / Q000235:genetics / Q000276:immunology; D003170:Complement Pathway, Alternative; D005260:Female; D005786:Gene Expression Regulation; D005921:Glomerulonephritis / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011414:Properdin / Q000235:genetics / Q000276:immunology*; D011507:Proteinuria / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D012189:Retrospective Studies; D012720:Severity of Illness Index; D015398:Signal Transduction
chemical_list: D015415:Biomarkers; D003176:Complement C3; D003178:Complement C3 Nephritic Factor; D003182:Complement C5; D051056:Complement Inactivating Agents; D015938:Complement Membrane Attack Complex; C047610:SC5b-9 protein complex; D011414:Properdin; D050577:Complement C3-C5 Convertases; D011415:Complement Factor B
keywords: C3 glomerulonephritis; C3 glomerulopathy; C3 nephritic factor; complement; properdin