title: Anti-alpha-actinin antibodies are part of the anti-cell membrane antibody spectrum that characterize patients with lupus nephritis.
abstract: Anti-membrane autoantibodies (MbA) have been reported in sera from patients with lupus nephritis (LN) but the targets of the MbA remain to be explored, which is the aim of the current study. Sera were collected from 40 patients with LN determined by renal biopsy, and from 30 systemic lupus erythematosus (SLE) patients without clinical evidence of LN. Thirty autoimmune disease control patients (rheumatoid arthritis, Sjögren's syndrome and systemic sclerosis), and 30 healthy controls were also included. Using flow cytometry, the presence of anti-MbA was explored revealing that IgG anti-MbA positivity was associated with LN (62.5% vs 13.3%) when compared to non-LN SLE patients, autoimmune disease patients (6.7%) and healthy controls (0%). Next, using purified plasma membrane fractions from human embryonic kidney (HEK) cells, the more prominent targets and their occurrence rates were located at 50 kDa, 60/65 kDa, 90 kDa, 110 kDa, 180 kDa and 220 kDa. Alpha-actinin (110 kDa) autoAb was characterized as a major target in LN patients positive for anti-MbA, and anti-MbA binding activity was reduced (36.9 ± 13.7%) in the presence of α-actinin. Laminin (200 kDa) was also characterized as a minor target, which was not the case for annexin A2 (36 kDa). Finally, anti-MbA IgG subclass analysis indicated a predominance of IgG2. In conclusion, IgG anti-MbA were detected at high levels in LN patients supporting a primary pathogenic role for anti-MbA and anti-MbA/α-actinin+ in LN that needs further research.
authors.affiliation: Research Unit INSERM ESPRI, ERI29/EA2216 Laboratory of Immunotherapy and B Cell Diseases, SFR ScinBios, Réseau épigénétique et Réseau canaux ioniques du Cancéropôle Grand Ouest, Labex IGO, European University of Brittany, Brest, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Seret
authors.affiliation: Research Unit INSERM ESPRI, ERI29/EA2216 Laboratory of Immunotherapy and B Cell Diseases, SFR ScinBios, Réseau épigénétique et Réseau canaux ioniques du Cancéropôle Grand Ouest, Labex IGO, European University of Brittany, Brest, France.
authors.forename: Felipe
authors.initials: F
authors.lastname: Cañas
authors.affiliation: Research Unit INSERM ESPRI, ERI29/EA2216 Laboratory of Immunotherapy and B Cell Diseases, SFR ScinBios, Réseau épigénétique et Réseau canaux ioniques du Cancéropôle Grand Ouest, Labex IGO, European University of Brittany, Brest, France; Laboratory of Immunology and Immunotherapy, Brest University Medical School, Morvan, Brest, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Pougnet-Di Costanzo
authors.affiliation: Unit of Nephrology, Brest University Medical School, La Cavale Blanche, Brest, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Hanrotel-Saliou
authors.affiliation: Research Unit INSERM ESPRI, ERI29/EA2216 Laboratory of Immunotherapy and B Cell Diseases, SFR ScinBios, Réseau épigénétique et Réseau canaux ioniques du Cancéropôle Grand Ouest, Labex IGO, European University of Brittany, Brest, France; Unit of Rheumatology, Brest University Medical School, La Cavale Blanche, Brest, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Jousse-Joulin
authors.affiliation: Research Unit INSERM ESPRI, ERI29/EA2216 Laboratory of Immunotherapy and B Cell Diseases, SFR ScinBios, Réseau épigénétique et Réseau canaux ioniques du Cancéropôle Grand Ouest, Labex IGO, European University of Brittany, Brest, France; Unit of Nephrology, Brest University Medical School, La Cavale Blanche, Brest, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Le Meur
authors.affiliation: Research Unit INSERM ESPRI, ERI29/EA2216 Laboratory of Immunotherapy and B Cell Diseases, SFR ScinBios, Réseau épigénétique et Réseau canaux ioniques du Cancéropôle Grand Ouest, Labex IGO, European University of Brittany, Brest, France; Unit of Rheumatology, Brest University Medical School, La Cavale Blanche, Brest, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Saraux
authors.affiliation: Unit of Urology, Brest University Medical School, La Cavale Blanche, Brest, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Valeri
authors.affiliation: Division of Rheumatology, Montefiore Medical Center, Bronx, NY 10467, USA.
authors.forename: Chaim
authors.initials: C
authors.lastname: Putterman
authors.affiliation: Research Unit INSERM ESPRI, ERI29/EA2216 Laboratory of Immunotherapy and B Cell Diseases, SFR ScinBios, Réseau épigénétique et Réseau canaux ioniques du Cancéropôle Grand Ouest, Labex IGO, European University of Brittany, Brest, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Youinou
authors.affiliation: Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences Universidad del Rosario, Bogotá, Colombia.
authors.forename: Adriana
authors.initials: A
authors.lastname: Rojas-Villarraga
authors.affiliation: Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences Universidad del Rosario, Bogotá, Colombia.
authors.forename: Juan-Manuel
authors.initials: JM
authors.lastname: Anaya
authors.affiliation: Research Unit INSERM ESPRI, ERI29/EA2216 Laboratory of Immunotherapy and B Cell Diseases, SFR ScinBios, Réseau épigénétique et Réseau canaux ioniques du Cancéropôle Grand Ouest, Labex IGO, European University of Brittany, Brest, France; Unit of Nephrology, Brest University Medical School, La Cavale Blanche, Brest, France. Electronic address: yves.renaudineau@univ-brest.fr.
authors.forename: Yves
authors.initials: Y
authors.lastname: Renaudineau
mesh_terms: D000185:Actinin / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D057809:HEK293 Cells; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008181:Lupus Nephritis / Q000276:immunology*; D008297:Male; D050527:Mesangial Cells / Q000276:immunology; D008875:Middle Aged; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D000185:Actinin
keywords: Anti-actinin; Auto-antibody; Cell membrane; Lupus nephritis