The role of anti-α-actinin antibodies in the pathogenesis and monitoring of lupus nephritis

Antibodies to double-stranded DNA are important in the pathogenesis of nephritis, a major clinical manifestation in lupus patients. Since earlier diagnosis of renal involvement may lead to better outcomes, identification of the nephritogenic specificity of lupus-associated autoantibodies is important in understanding the disease, while monitoring their titer clinically may serve as an improved biomarker. Based upon work in animal models and cross-sectional human studies, kidney alpha-actinin was thought to be a plausible cross-reactive target for pathogenic lupus antibodies. Manson and colleagues longitudinally evaluated anti-nucleosome, anti-DNA, and anti-alpha-actinin antibodies in 16 lupus patients with new-onset nephritis. While anti-nucleosome and anti-DNA antibody levels were significantly associated and correlated with measures of kidney disease, these were not found to be significant with anti-alpha-actinin antibodies. While in lupus patients the diagnostic use of serum anti-alpha-actinin antibodies, alone or with other novel biomarkers, is still under investigation, such studies are vital in improving our monitoring of systemic lupus erythematosus patients and in developing new treatment paradigms that meet the continuing clinical challenge of lupus nephritis.