Diagnostic potential of sarcoplasmic myxovirus resistance protein A expression in subsets of dermatomyositis.

AIMS: To elucidate the diagnostic value of sarcoplasmic expression of myxovirus resistance protein A (MxA) for dermatomyositis (DM) specifically analysing different DM subforms, and to test the superiority of MxA to other markers. METHODS: Immunohistochemistry for MxA and retinoic acid-inducible gene I (RIG-I) was performed on skeletal muscle samples and compared with the item presence of perifascicular atrophy (PFA) in 57 DM patients with anti-Mi-2 (n = 6), -transcription intermediary factor 1 gamma (n = 10), -nuclear matrix protein 2 (n = 13), -melanoma differentiation-associated gene 5 (MDA5) (n = 10) or -small ubiquitin-like modifier activating enzyme (n = 1) autoantibodies and with no detectable autoantibody (n = 17). Among the patients, nine suffered from cancer and 22 were juvenile-onset type. Disease controls included antisynthetase syndrome (ASS)-associated myositis (n = 30), immune-mediated necrotizing myopathy (n = 9) and inclusion body myositis (n = 5). RESULTS: Sarcoplasmic MxA expression featured 77% sensitivity and 100% specificity for overall DM patients, while RIG-I staining and PFA reached respectively 14% and 59% sensitivity and 100% and 86% specificity. In any subset of DM, sarcoplasmic MxA expression showed higher sensitivity than RIG-I and PFA. Some anti-MDA5 antibody-positive DM samples distinctively showed a scattered staining pattern of MxA. No ASS samples had sarcoplasmic MxA expression even though six patients had DM skin rash. CONCLUSIONS: Sarcoplasmic MxA expression is more sensitive than PFA and RIG-I expression for a pathological diagnosis of DM, regardless of the autoantibody-related subgroup. In light of its high sensitivity and specificity, it may be considered a pathological hallmark of DM per se. Also, lack of MxA expression in ASS supports the idea that ASS is a distinct entity from DM.

Testing for anti-nucleosome antibodies in daily practice: a monocentric evaluation in 1696 patients.

The objective was to report our experience of the detection of anti-nucleosome (anti-Nuc) antibodies (Ab) in a large series of consecutive patients, and to compare these results with those of anti-nuclear and anti-dsDNA Ab. In total, 1696 consecutive patients with suspected or confirmed autoimmune disease were tested over a two-year period. The biological investigation included detection of anti-nuclear, anti-dsDNA and anti-Nuc Ab. Among 1696 sera, 382 (23%) were negative for all Ab tested (anti-nuclear, anti-dsDNA and anti-Nuc) and 1314 (77%) were positive for at least one Ab. Anti-Nuc Ab were positive in 350/1314 patients. In this group, 249/350 (71%) also had positive anti-nuclear and anti-dsDNA, 97/350 (28%) had only positive anti-nuclear Ab without anti-dsDNA Ab and 4/350 (1%) had both anti-dsDNA and anti-Nuc Ab without anti-nuclear Ab. No patient had 'isolated' anti-Nuc Ab. Clinical data were available for 307/350 anti-Nuc positive patients. Systemic lupus erythematosus (SLE) was diagnosed in 240/307 (78%) patients, including 43 SLE patients with negative anti-dsDNA Ab. In conclusion, this study extends the relevance of anti-Nuc Ab to routine use for the diagnosis of connective tissue diseases, mainly anti-dsDNA Ab negative SLE.

IgA antineutrophil cytoplasmic antibodies in cutaneous vasculitis.

BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCA) of the IgA isotype have, for the most part, been detected in patients with Henoch-Schönlein purpura (HSP) or inflammatory bowel disease. OBJECTIVES: We have evaluated the prevalence of IgA ANCA in a series of patients with different causes of cutaneous vasculitis. METHODS: Forty consecutive patients with histologically proven leucocytoclastic vasculitis were included in the study: 18 had systemic vasculitis as well as cutaneous lesions, 10 of whom were diagnosed as having HSP, and 22 had only cutaneous vasculitis (with no identified cause in 10 cases). IgA ANCA were sought by indirect immunofluorescence using ethanol-fixed human neutrophil preparations as the substrate. RESULTS: IgA ANCA were detected in six of 40 patients (15%) (one each with HSP, ulcerative colitis, Sjögren's syndrome, hypergammaglobulinaemia associated with Castelman's disease, erythema elevatum diutinum and bacterial endocarditis). Three of these patients also had IgG ANCA whose target antigen remained unidentified. CONCLUSIONS: IgA ANCA are rarely observed in HSP (10%) and can be detected in a wide variety of other cutaneous vasculitides.