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.

Flares of systemic lupus erythematosus during pregnancy and the puerperium: prevention, diagnosis and management

“…TTP may occur rarely in conjunction with systemic lupus [82]. This is usually associated with severe deficiency of ADAMTS13 activity and with the presence of anti-ADAMTS13 IgG antibodies [83].…”

Influenza A Infection Triggers Thrombotic Thrombocytopenic Purpura by Producing the Anti-ADAMTS13 IgG Inhibitor

“…Western blot studies of the patient's plasma, which had been stored at -80 , and the purified plasma-derived ADAMTS13, clearly identified that the immunoglobulin type of the inhibitor was IgG (6) (Fig. 1, inset).…”

A case of PR3–ANCA-positive anti-GBM disease associated with intrarenal arteritis and thrombotic microangiopathy

“…They concurrently occur in autoimmune diseases [28], and several cases associated with ANCA-associated vasculitis [29], ''pure'' anti-GBM antibody disease, and ''double positive'' disease have been reported [30]. In most of these cases, as well as present case, ADAMTS-13 activity is moderately decreased and the ADAMTS-13 inhibitor is negative [28][29][30]. Therefore, hemolytic uremic syndrome and thrombotic microangiopathy are supposed to develop following severe vascular endothelial damage [29].…”