Alpha-actinin-binding antibodies in relation to systemic lupus erythematosus and lupus nephritis

Abstract

This study investigated the overall clinical impact of anti-α-actinin antibodies in patients with pre-selected autoimmune diseases and in a random group of anti-nuclear antibody (ANA)-positive individuals. The relation of anti-α-actinin antibodies with lupus nephritis and anti-double-stranded DNA (anti-dsDNA) antibodies represented a particular focus for the study. Using a cross-sectional design, the presence of antibodies to α-actinin was studied in selected groups, classified according to the relevant American College of Rheumatology classification criteria for systemic lupus erythematosus (SLE) (n = 99), rheumatoid arthritis (RA) (n = 68), Wegener's granulomatosis (WG) (n = 85), and fibromyalgia (FM) (n = 29), and in a random group of ANA-positive individuals (n = 142). Renal disease was defined as (increased) proteinuria with haematuria or presence of cellular casts. Sera from SLE, RA, and Sjøgren's syndrome (SS) patients had significantly higher levels of anti-α-actinin antibodies than the other patient groups. Using the geometric mean (± 2 standard deviations) in FM patients as the upper cutoff, 20% of SLE patients, 12% of RA patients, 4% of SS patients, and none of the WG patients were positive for anti-α-actinin antibodies. Within the SLE cohort, anti-α-actinin antibody levels were higher in patients with renal flares (p = 0.02) and correlated independently with anti-dsDNA antibody levels by enzyme-linked immunosorbent assay (p < 0.007) but not with other disease features. In the random ANA group, 14 individuals had anti-α-actinin antibodies. Of these, 36% had SLE, while 64% suffered from other, mostly autoimmune, disorders. Antibodies binding to α-actinin were detected in 20% of SLE patients but were not specific for SLE. They correlate with anti-dsDNA antibody levels, implying in vitro crossreactivity of anti-dsDNA antibodies, which may explain the observed association with renal disease in SLE.

Relationship between anti-dsDNA, anti-nucleosome and anti-alpha-actinin antibodies and markers of renal disease in patients with lupus nephritis: a prospective longitudinal study

“…However, the electron-dense deposits that are the sites of autoantibody deposition in lupus-prone NZB/W F1 mice do not co-localise with α-actinin. Three previous clinical studies have looked at anti-α-actinin levels in patients with SLE [ 17 - 19 ]. One study showed that purified anti-dsDNA antibodies from patients with SLE were more likely to cross-react with α-actinin if the patients had nephritis [ 17 ].…”

“…Although cross-reactivity with a number of proteins (including laminin and type IV collagen) has been postulated (reviewed in [ 13 ]), the importance of anti-α-actinin antibodies has been particularly stressed in recent years. This emphasis on the possible pathogenic role of anti-α-actinin antibodies has arisen as a result of studies in murine models [ 6 , 16 ] and clinical studies [ 17 - 19 ], although anti-α-actinin antibodies could not be eluted from glomerular deposits in mice with LN [ 20 ]. However, no previous study has compared anti-nucleosome and anti-α-actinin antibody levels in the same patients.…”

Co-Positivity for Anti-dsDNA, -Nucleosome and -Histone Antibodies in Lupus Nephritis Is Indicative of High Serum Levels and Severe Nephropathy

“…Furthermore, these antibodies are sensitive and specific for diagnosis of JSLE [ 6 ]. Meanwhile, serum anti-α actin antibody seems to be a reliable biomarker for renal involvement in SLE patients, yet relevant antibody is not found in renal biopsy [ 7 , 8 ]. We previously report that, in SLE patients, simultaneously positivity for anti-dsDNA, anti-nucleosome and anti-histone antibodies by Euroline ANA Profile (IgG) test is significantly relevant with LN onset and activity, and suggestive as a valuable indicator for renal involvement [ 9 ].…”

Precision medicine in lupus nephritis: can biomarkers get us there?

“…Non-autoimmune (BALB/c) mice immunized with alpha-actinin develop anti-alpha-actinin antibodies and develop immune complex glomerulonephritis and proteinuria [35]. Antibodies binding alpha-actinin have been identified in patients with LN [36–38].…”