title: Recurrent IgA nephropathy is predicted by altered glycosylated IgA, autoantibodies and soluble CD89 complexes.
abstract: IgA nephropathy (IgAN), the most common primary glomerulonephritis worldwide, frequently leads to end-stage renal disease and kidney transplantation. However, disease recurrence often occurs after transplantation. Here we evaluated the predictive value of three markers for IgAN recurrence: the presence of galactose-deficient IgA1, IgG anti-IgA autoantibodies, and IgA-soluble (s) CD89 complexes. This was analyzed in 38 kidney transplant recipients with IgAN recurrence and compared with 22 patients transplanted for IgAN but without recurrence and with 17 healthy controls. Pre-transplantation galactose-deficient IgA1 serum levels were significantly higher in the recurrence compared with the no recurrence or control groups. IgA-IgG complexes were significantly elevated in the recurrence group. Both the recurrence and no recurrence groups had increased values of IgA-sCD89 complexes compared with healthy controls, but values were significantly lower in patients with recurrence compared with no recurrence. Areas under the receiver operating curve of the markers in pre-transplantation sera were 0.86 for galactose-deficient-IgA, 0.82 for IgA-IgG, and 0.78 for sCD89-IgA; all significant. Disease recurrence was associated with decreased serum galactose-deficient IgA1 and appearance of mesangial-galactose-deficient IgA1 deposits, whereas increased serum IgA-sCD89 complexes were associated with mesangial sCD89 deposits. Thus, galactose-deficient-IgA1, IgG autoantibodies, and IgA-sCD89 complexes are valuable biomarkers to predict disease recurrence, highlighting major pathogenic mechanisms in IgAN.
authors.affiliation: INSERM U1149, Faculté Bichat Medical School, ELR8252 CNRS, Center for Research on Inflammation, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, DHU Fire, France.|Inflamex Laboratory of Excellence, Site Xavier Bichat, France.
authors.forename: Laureline
authors.initials: L
authors.lastname: Berthelot
authors.affiliation: Department of Nephrology, Hôpital Maison Blanche-CHU Reims, Reims, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Robert
authors.affiliation: Department of Nephrology, Hôpital Maison Blanche-CHU Reims, Reims, France.|CNRS URCA UMR 7369, Reims, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Vuiblet
authors.affiliation: Laboratory of Immunology, EA3798 CHU Reims, IFR53 URCA, Reims, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Tabary
authors.affiliation: Department of Nephrology, Hôpital Maison Blanche-CHU Reims, Reims, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Braconnier
authors.affiliation: Department of Research and Innovation, CHU Reims, Reims, France.
authors.forename: Moustapha
authors.initials: M
authors.lastname: Dramé
authors.affiliation: Department of Nephrology, Hôpital Maison Blanche-CHU Reims, Reims, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Toupance
authors.affiliation: Department of Nephrology, Hôpital Maison Blanche-CHU Reims, Reims, France.|CNRS URCA UMR 7369, Reims, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Rieu
authors.affiliation: INSERM U1149, Faculté Bichat Medical School, ELR8252 CNRS, Center for Research on Inflammation, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, DHU Fire, France.|Inflamex Laboratory of Excellence, Site Xavier Bichat, France.|Service d'Immunologie, Assistance Publique de Paris, Hôpital Bichat-Claude Bernard, DHU Fire, Paris, France.
authors.forename: Renato C
authors.initials: RC
authors.lastname: Monteiro
authors.affiliation: Department of Nephrology, Hôpital Maison Blanche-CHU Reims, Reims, France.|CNRS URCA UMR 7369, Reims, France.
authors.forename: Fatouma
authors.initials: F
authors.lastname: Touré
mesh_terms: D000328:Adult; D000368:Aged; D000936:Antigen-Antibody Complex / Q000097:blood*; D015703:Antigens, CD / Q000097:blood*; D019540:Area Under Curve; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005922:Glomerulonephritis, IGA / Q000097:blood* / Q000175:diagnosis / Q000276:immunology / Q000601:surgery; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood*; D007668:Kidney / Q000276:immunology / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000175:diagnosis / Q000276:immunology / Q000601:surgery; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012372:ROC Curve; D011961:Receptors, Fc / Q000097:blood*; D012008:Recurrence; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D001323:Autoantibodies; D015415:Biomarkers; C036832:Fc(alpha) receptor; D007070:Immunoglobulin A; D011961:Receptors, Fc; C042441:glycosylated IgA