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

Andrea Becker-Merok,Ole Rekvig,Kirsten Nilsen,Manar Kalaaji,Johannes C Nossent,Cathrin Nikolaisen,Kaia Haugbro

doi:10.1186/ar2070

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 cross-reactivity of anti-dsDNA antibodies, which may explain the observed association with renal disease in SLE.

Highlights

A wide spectrum of organ non-specific autoantibodies can be detected in sera of patients with systemic lupus erythematosus (SLE) [1]
To test for this, another approach was undertaken with patients selected purely on the basis of a positive anti-nuclear antibody (ANA) test
Because ANA may be present in a wide variety of conditions and among normal individuals, the bias toward SLE for this approach is insignificant [46]

Summary

Introduction

A wide spectrum of organ non-specific autoantibodies can be detected in sera of patients with systemic lupus erythematosus (SLE) [1]. The clinical significance of many of these autoantibodies remains unclear, anti-double-stranded DNA (anti-dsDNA) antibodies (Abs) are among the most SLEspecific autoantibodies and are involved in the pathogenesis of lupus nephritis (LN) [2,3,4,5,6,7]. Intraglomerular immune complex depositions are a hallmark of LN, and anti-dsDNA Abs can be eluted from affected kidneys in both human and experimental LN [8,9,10]. The glomerular target structures for anti-dsDNA Abs, are still controversial, and to determine structures that de facto bind Abs in vivo is more important than to determine potential cross-reactions of nephritogenic autoantibodies. Several models explain anti-dsDNA Ab binding in the glomeruli. Ab binds to externalised nucleosomes present in basement membranes and the mesangium of glomeruli [11,12], whereas other models focus on Ab binding

Methods

Results

Conclusion