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, α-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 α-actinin derived from a lupus prone mouse mesangial cell line as compared to α-actinin in a non-autoimmune mouse mesangial cell line. Furthermore, we recently showed that immunization of non-autoimmune mice with α-actinin induces anti-chromatin antibodies, glomerular IgG deposition and proteinuria. In humans, anti-α-actinin autoantibodies (Ab) were associated with anti-dsDNA Ab in SLE. In those patients, anti-α-actinin rather than anti-dsDNA Ab were significantly associated with glomerulonephritis and disease activity. The anti-α-actinin reactivity was associated with high avidity anti-dsDNA Ab. Moreover, the anti-α-actinin response was related to the actin-binding site of α-actinin. Taken together, these studies indicate that detection of anti-α-actinin Ab, in association with anti-dsDNA Ab, may constitute a new marker in lupus nephritis.