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

Abstract

This study investigated the overall clinical impact of anti-alpha-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-alpha-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 alpha-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-alpha-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-alpha-actinin antibodies. Within the SLE cohort, anti-alpha-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-alpha-actinin antibodies. Of these, 36% had SLE, while 64% suffered from other, mostly autoimmune, disorders. Antibodies binding to alpha-actinin were detected in 20% of SLE patients but were not specific for SLE. They correlate with anti-dsDNA antibody levels, implying in vitro cross-reactivity of anti-dsDNA antibodies, which may explain the observed association with renal disease in SLE.

Figure 1

Scatterplots representing the relationship between α-actinin antibody (Ab) binding and levels of anti-double-stranded DNA (anti-dsDNA) Abs in the pre-selected diagnostic groups. The relationship of α-actinin Ab binding with anti-dsDNA Abs detected by enzyme-linked immunosorbent assay (ELISA) (a) or by EliA assay (b) and with overall disease activity (SLEDAI) (c). Broken lines indicate cutoff levels for the respective assays (see Materials and methods for analytical details). EliA, fluorescence enzyme immunoassay test for anti-dsDNA (Phadia GmbH); OD, optical density; Rs, Spearman's rho; SLEDAI, Systemic Lupus Erythematosus Disease activity index.

Figure 2

Box plot of the optical density (OD) of α-actinin binding in patients from pre-selected systemic lupus erythematosus group with and without renal flares. Thick bars indicate median values, and boxes border the interquartile range. Asterisks represent outliers.