title: Heterogeneous pathogenic processes of thrombotic microangiopathies in patients with connective tissue diseases.
abstract: To clarify the pathogenic processes of thrombotic microangiopathies (TMAs) in patients with connective tissue disease (CTD), we analysed clinical characteristics and plasma ADAMTS13 levels in 127 patients with CTD-TMAs, including patients with systemic lupus erythematosus (SLE), systemic sclerosis, polymyositis/dermatomyositis, and rheumatoid arthritis (RA), and 64 patients with acquired idiopathic thrombotic thrombocytopenic purpura (ai-TTP). Plasma levels of ADAMTS13 activity, antigen, and inhibitors were determined by enzyme immunoassays. IgG type anti-ADAMTS13 antibodies were also detected by immunoblots using purified ADAMTS13. ADAMTS13 activity was significantly decreased in CTD-TMAs, regardless of the underlying disease, but the frequency of severe deficiency (defined as <0.5% of normal) was lower in CTD-TMA patients than in ai-TTP patients (16.5% vs. 70.3%, p < 0.01). Severe deficiency of ADAMTS13 activity was predominantly detected in patients with RA- and SLE-TMAs, and was closely associated with the presence of anti-ADAMTS13 IgG antibodies. CTD-TMA patients with severe deficiency of ADAMTS13 activity appeared to have lower platelet counts and better therapeutic outcomes. At least two phenotypic TMAs occur in patients with CTDs: a minor population with deficient ADAMTS13 activity caused by neutralising autoantibodies, and a major population with normal or moderately reduced activity. Classifying CTD-TMAs by ADAMTS13 activity may be useful in predicting the clinical course and therapeutic outcomes, as patients with moderately reduced activity are likely to have more prominent renal impairment and poor prognoses.
authors: Department of Blood Transfusion Medicine, Nara Medical University, Shijyo-cho 840, Kashihara city, Nara, 634-8522, Japan.
authors: Tomomi
authors: T
authors: Matsuyama
authors: Masataka
authors: M
authors: Kuwana
authors: Masanori
authors: M
authors: Matsumoto
authors: Ayami
authors: A
authors: Isonishi
authors: Shigeko
authors: S
authors: Inokuma
authors: Yoshihiro
authors: Y
authors: Fujimura
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors / Q000097:blood / Q000172:deficiency / Q000276:immunology; D000071120:ADAMTS13 Protein; D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000201:enzymology / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D016022:Case-Control Studies; D003240:Connective Tissue Diseases / Q000150:complications* / Q000201:enzymology / Q000276:immunology; D003882:Dermatomyositis / Q000150:complications / Q000201:enzymology / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000201:enzymology / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000150:complications / Q000201:enzymology / Q000276:immunology; D012595:Scleroderma, Systemic / Q000150:complications / Q000201:enzymology / Q000276:immunology; D013927:Thrombosis / Q000201:enzymology / Q000209:etiology* / Q000276:immunology; D014652:Vascular Diseases / Q000201:enzymology / Q000209:etiology* / Q000276:immunology; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human