title: Anti-alpha-actinin antibodies: a new marker of lupus nephritis.
abstract: The exact role of anti-ds (double stranded) DNA antibodies in the pathogenesis of kidney injury in lupus nephritis remains a focus of continuing investigation. One theory explaining the pathogenicity of anti-dsDNA antibodies in lupus nephritis is direct cross-reactivity with renal antigens. Several years ago, alpha-actinin was identified as a major cross-reactive target for pathogenic anti-dsDNA antibodies in murine SLE. Indeed, binding of a nephritogenic murine anti-dsDNA antibody was stronger to the alpha-actinin derived from a lupus prone mouse mesangial cell line as compared to alpha-actinin in a non-autoimmune mouse mesangial cell line. Furthermore, we recently showed that immunization of non-autoimmune mice with alpha-actinin induces anti-chromatin antibodies, glomerular IgG deposition and proteinuria. In humans, anti-alpha-actinin autoantibodies (Ab) were associated with anti-dsDNA Ab in SLE. In those patients, anti-alpha-actinin rather than anti-dsDNA Ab were significantly associated with glomerulonephritis and disease activity. The anti-alpha-actinin reactivity was associated with high avidity anti-dsDNA Ab. Moreover, the anti-alpha-actinin response was related to the actin-binding site of alpha-actinin. Taken together, these studies indicate that detection of anti-alpha-actinin Ab, in association with anti-dsDNA Ab, may constitute a new marker in lupus nephritis.
authors.affiliation: Brest University Medical School, Brest, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Renaudineau
authors.forename: Bisram
authors.initials: B
authors.lastname: Deocharan
authors.forename: Sandrine
authors.initials: S
authors.lastname: Jousse
authors.forename: Eric
authors.initials: E
authors.lastname: Renaudineau
authors.forename: Chaim
authors.initials: C
authors.lastname: Putterman
authors.forename: Pierre
authors.initials: P
authors.lastname: Youinou
mesh_terms: D000185:Actinin / Q000276:immunology*; D000818:Animals; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D006801:Humans; D008181:Lupus Nephritis / Q000175:diagnosis / Q000276:immunology*; D051379:Mice
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D000185:Actinin