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

Anti-PAD4 autoantibodies in rheumatoid arthritis: levels in serum over time and impact on PAD4 activity as measured with a small synthetic substrate

Isoform 4 of the human peptidylarginine deiminase (hPAD4) enzyme may be responsible for the citrullination of antigens in rheumatoid arthritis (RA) and has been shown to be itself the target of disease-specific autoantibodies. Here, we have tested whether the level of serum anti-hPAD4 antibodies in RA patients is stable over a period of 10 years and whether the antibodies influence hPAD4-mediated deimination of the small substrate N-α-Benzoyl-l-arginine ethyl ester. RA sera (n = 128) obtained at baseline and after 10 years were assessed for anti-hPAD4 antibodies by a specific immunoassay. For 118 RA patients, serum anti-hPAD4 IgG levels were stable over 10 years. Seven patients who were negative for anti-PAD4 IgG at baseline had become positive after 10 years. Further, total IgG from selected RA patients and controls were purified, and a fraction was depleted for anti-hPAD4 antibodies. Kinetic deimination assays were performed with total IgG and depleted fractions. The kcat and Km values of hPAD4-mediated deimination of N-α-Benzoyl-l-arginine ethyl ester were not affected by the depletion of the anti-hPAD4 antibodies from the total IgG pool. In conclusion, RA patients remain positive for anti-hPAD4 antibodies over time and some patients who are initially anti-hPAD4 negative become positive later in the disease course. The anti-hPAD4 antibodies did not affect the enzymatic activity of hPAD4 when the small substrate N-α-Benzoyl-l-arginine ethyl ester was used. However, this finding may not exclude an effect of these autoantibodies on citrullination of protein substrates in RA

Discovertebral (Andersson) lesions of the spine in ankylosing spondylitis revisited

A well-known complication in patients with ankylosing spondylitis (AS) is the development of localised vertebral or discovertebral lesions of the spine, which was first described by Andersson in 1937. Since then, many different terms are used in literature to refer to these localised lesions of the spine, including the eponym ‘Andersson lesion’ (AL). The use of different terms reflects an ongoing debate on the exact aetiology of the AL. In the current study, we performed an extensive review of the literature in order to align communication on aetiology, diagnosis and management between treating physicians. AL may result from inflammation or (stress-) fractures of the complete ankylosed spine. There is no evidence for an infectious origin. Regardless of the exact aetiology, a final common pathway exists, in which mechanical stresses prevent the lesion from fusion and provoke the development of pseudarthrosis. The diagnosis of AL is established on conventional radiography, but computed tomography and magnetic resonance imaging both provide additional information. There is no indication for a diagnostic biopsy. Surgical instrumentation and fusion is considered the principle management in symptomatic AL that fails to resolve from a conservative treatment. We advise to use the term Andersson lesion for these spinal lesions in patients with AS

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