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

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

Diagnostic value of antibodies against mutated citrullinated vimentin for rheumatoid arthritis

OBJECTIVES: To compare the diagnostic efficiency of anti-MCV, anti-CCP2 and RF detection for patients with RA. METHODS: Cross-sectional study of patients with established rheumatic disease: rheumatoid arthritis (RA; n=75), psoriatic arthritis (PsA; n=25), 27 patients with ankylosing spondylitis (AS; n=27) and connective tissue disease (CTD; n=17). Anti-CCP2, anti-MCV and RF were detected by enzyme-linked immunosorbent assays on stored serum according to the manufacturer`s instructions. RESULTS: IgM-RF had the highest sensitivity, but the positive likelihood ratio is just 1.43. The detection of anti-MCV has a higher sensitivity for RA (76%), a specificity similar to anti-CCP2 (96%) resulting in the lowest negative likelihood ratio (0.25). Anti-MCV levels correlate well with anti-CCP2 levels (R=0.74; p<0.01). The mean level of anti-MCV is significantly higher in RA than in other subgroups (395 U/ml versus 14.4 U/ml, χ2=61.0; p<0.001) and in each other subgroup (Mann-Whitney-Wilcoxon: U=239, p<0.001 for RA and PsA; U=215, p<0.001 for RA and AS; U=192, p<0.001 for RA and CTD). Among RA patients, anti-CCP2 levels have a dichotomous distribution whereas anti-MCV levels have a homogeneous distribution. CONCLUSIONS: Anti-MCV could be a better test for diagnosing RA than anti-CCP2

Should rheumatoid factor in rheumatoid arthritis be sent to Davy Jones's Locker?

This article reviews the characteristics and weaknesses of the rheumatoid factor (RF) assay compared with anticitrullinated peptide antibody (ACPA) testing in the work-up of patients with synovitis. This should lead physicians to change their ordering habits and replace RF by ACPA. For RA diagnosis, good clinical judgement based on clinical history, physical examination and routine laboratory work exceeds the value of RF and ACPA assays. In settings of both low and high pretest probability, the added value of each of these assays is low. In cases with intermediate probability, ACPA assays are superior to immunoglobulin (Ig)M-RF because of their higher specificity, and they should be the first choice in a RA diagnostic work-up. Dual testing brings few additional advantages and increases costs significantly. ACPA and IgM-RF are both imperfect tests; around 30% of patients with manifest RA will test negative in both assays and therefore caution needs to be exercised when interpreting negative results. Since 2009, the anti-cyclic citrullinated peptide (anti-CCP) antibody assay has been the only assay available at our institution for RA work-up, with IgM-RF available on a case-by-case basis for non-RA diseases. This has led to a 70% reduction in RF assays performed annually