| Research Abstract |
Our institution (Nara Medical University) has been analyzing for 783 patients with thrombotic microangiopathy (TMA) across Japan between 1998 and 2006. Of these, we found 258 patients (33%) with severely decreased ADAMTS13 activity (< 3% of normal control). There were 56 patients with congenital TMA and 727 patients with acquired TMA. In acquired TMA, 338 patients were diagnosed as idiopathic TMA because they developed TMA without discernible underlying diseases or pathological conditions. Ninety-four patients were classified as idiopathic HUS due to their predominance of nephrotropic clinical signs. None of the patients with idiopathic HUS showed severely decreased ADAMTS13 activity.
In secondary TMA, 187 patients were identified in the connective tissue disease (CTD) category. These patients suffered from: systemic lupus erythematosus (SLE, n=74), systemic sclerosis (SSc, n=44), polymyositis/dermatomyositis (PM/DM, n=12), rheumatoid arthritis (RA, n=8), mixed connective tissue disease
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(MCTD, n=7), Sjogren's syndrome (SJS, n=7), antiphosphoid syndrome (APS, n=6), anti-neutrophil cytoplasmic antibody related nephritis (ANCA-ARN, n=6), microscopic polyangitis (MPA, n=5), overlap syndrome (n=3), anti-glomerular basement membrane antibody related nephritis (BGM- GRN, n=3), and other CTD (n=12). Of these patients, 35 (19%) had severe deficiency of ADAMTS13 activity, The proportion of severely decreased ADAMTS13 activity in each disease was: SLE (n=18/74, 23%), SSc (n=2/44, 5.2%), PM/DM (n=2/12, 8.3%), RA (n=1/8, 17%), MCTD (n=5/7, 71%), SJS (n=3/7, 43%), APS (n=3/6, 50%), and ANCA-ARN (n=1/6, 17%). None of the remaining 23 patients with other CTDs had severely decreased ADAMTS13 activity.
Patients with predominant renal involvement are often termed atypical HUS. In these patients, genetic mutations in complementary regulatory factors, such as factor H, factor I, and MCP, were reported in western country, but not yet in Japan. We determined plasma factor H antigen using polyclonal antibody against factor H. However, no patient showed severely decreased factor H antigen. Next, we analyzed factor H gene in 2 patients and their families with congenital HUS. We did not found disease-causing mutations in factor H gene. Less
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