Raffaele Bendo

Anti-Mi-2 antibodies

Autoantibodies targeting the Mi-2 nuclear antigen represent one of the serologic hallmarks of idiopathic inflammatory myopathies, with a diagnostic sensitivity and specificity of approximately 4–18% and 98–100%, respectively. Mi-2 antigen is a component of the nuclesome remodeling-deacetylase (NuRD) complex involved in transcription regulation. Anti-Mi-2 antibodies are strongly associated with dermatomyositis (frequency up to 31%) and have a very high positive predictive value for such disease subset. A strong correlation with HLA-DR7 has been demonstrated. At the moment, optimal serologic testing is achieved by ELISA screening on ricombinant Mi-2 antigen and confirmation of positive results on immunoblot.

Clinical implications of autoantibody screening in patients with autoimmune myositis

Objective: To evaluate the clinical usefulness of serum autoantibody profiling in patients with autoimmune myositis. Methods: We retrospectively studied 74 consecutive patients: 68 had definite or probable myositis according to Bohan–Peter criteria, six suffered from antisynthetase syndrome with subclinical myopathy. Myositis specific antibodies (MSA) (anti-ARS, -SRP, -Mi-2) were determined by RNA immunoprecipitation or immunoblot, myositis associated antibodies (MAA) (anti-RoRNP, -U1RNP, -PM/Scl, -Ku) by immunoblot. Results: Forty-three patients (58%) were positive for MSA: anti-Jo-1 in 15/27 polymyositis (PM) (55%), 4/33 dermatomyositis (DM) (12%), 1/8 overlap (12%) and 2/6 antisynthetase syndrome (33%); anti-ARS non-Jo-1 in 1/27 PM (4%), 2/33 DM (6%) and 4/6 antisynthetase syndrome (67%); anti-Mi-2 in 1/27 PM (4%) and 11/33 DM (33%); anti-SRP in 3/27 PM (11%) and 1/33 DM (3%). One patient was anti-Jo-1/Mi-2 positive, one anti-Jo-1/SRP positive. Moreover, 27 patients (36%) were positive for MAA: anti-Ro/SSA in 8/27 PM (30%), 7/33 DM (21%), 1/8 overlap (12%), and 3/6 antisynthetase syndrome (50%); anti-U1RNP in 1/27 PM (3.7%), 1/33 DM (3%), and 2/8 overlap (25%); anti-PM/Scl in 2/8 overlap (25%), anti-Ku in 2/8 overlap (25%). Anti-Jo-1 was predominantly associated with PM, anti-Mi-2 was almost exclusively found in DM patients. Anti-ARS antibodies were closely associated with interstitial lung disease and polyarthritis; notably, anti-ARS non-Jo-1 was more frequent in patients without overt muscle alterations. Anti-Ro/SSA antibody was not associated with any disease subset, but significantly more frequent in antisynthetase syndrome. Conclusions: Searching for MSA and MAA in patients with autoimmmune myositis is recommended because of its diagnostic and clinical value. Anti-ARS non-Jo-1 antibodies seem to preferentially target patients with pulmonary fibrosis without overt myopathy.

Commercial blot assays in the diagnosis of systemic rheumatic diseases

Commercial blot assays are advanced applications of immunoblotting or dot immunobinding methodologies for the detection of specific autoantibodies in autoimmune diseases. Line(Dot) blots in particular have cost-effectively optimized a sort of multiparametric assay for simultaneous determination of several autoantibody reactivities. Efficient and wide-spectrum potentialities of recombinant DNA technology and proteomics are fruitfully employed by manufacturers in order to obtain highly purified antigens or novel targets to be spotted on blot matrices thus continuously implementing their multianalytic platforms. At present most widely used commercial blot assays for the diagnosis of connective tissue diseases can detect autoantibodies to several Extractable Nuclear Antigens or myositis and/or scleroderma associated autoantigens. They actually represent an important step-forward in the methodological panorama designed for the autoimmunity laboratory. However continuous effort in order to validate and improve clinical reliability of commercially available blot assays should be carried out. In this short review, our preliminary contribution on the validation of a commercial line blot assay for the laboratory diagnosis of autoimmune myositis is briefly reported.

Activated platelet‐derived and leukocyte‐derived circulating microparticles and the risk of thrombosis in heparin‐induced thrombocytopenia: A role for pf4‐bearing microparticles?

Though the presence of platelets‐derived microparticles (MPs) have previously been described in heparin‐induced thrombocytopenia (HIT), the mechanism of thrombosis in HIT remains poorly understood. We aimed to assess the presence and origin of MPs in patients with HIT and their possible contribution to HIT with thrombosis (HITT).