Anti–Factor H Autoantibodies Associated with Atypical Hemolytic Uremic Syndrome
Top Cited Papers
Open Access
- 1 February 2005
- journal article
- research article
- Published by Wolters Kluwer Health in Journal of the American Society of Nephrology
- Vol. 16 (2), 555-563
- https://doi.org/10.1681/asn.2004050380
Abstract
Several studies have demonstrated genetic predisposition in non–shigatoxin-associated hemolytic uremic syndrome (HUS), involving regulatory proteins of the complement alternative pathway: Factor H (FH) and membrane co-factor protein (CD46). Regarding the observations of thrombotic thrombocytopenic purpura patients, in whom a von Willebrand factor protease (ADAMST-13) deficiency may be inherited or acquired secondary to IgG antibodies, it was speculated that HUS might occur in a context of an autoimmune disease with the development of anti-FH antibodies leading to an acquired FH deficiency. The presence of FH autoantibodies was investigated by an ELISA method using coated purified human FH in a series of 48 children who presented with atypical HUS and were recruited from French university hospitals. Anti-FH IgG antibodies were detected in the plasma of three children who presented with recurrent HUS. The anti-FH specificity was conserved by the Fab′2 fraction. The plasma FH activity was found to be decreased, whereas plasma FH antigenic levels and FH gene analysis were normal, indicating that the presence of anti-FH antibodies led to an acquired functional FH deficiency. This report supports for the first time that HUS may occur in a context of an autoimmune disease with the development of anti-FH–specific antibody leading to an acquired FH deficiency. This new mechanism of functional FH deficiency may lead to the design of new approaches of diagnosis and treatment with a particular interest in plasma exchanges or immunosuppressive therapies.Keywords
This publication has 26 references indexed in Scilit:
- Severe ADAMTS13 Deficiency in Adult Idiopathic Thrombotic Microangiopathies Defines a Subset of Patients Characterized by Various Autoimmune Manifestations, Lower Platelet Count, and Mild Renal InvolvementMedicine, 2004
- Heterozygous and Homozygous Factor H Deficiencies Associated with Hemolytic Uremic Syndrome or Membranoproliferative GlomerulonephritisJournal of the American Society of Nephrology, 2004
- Nonneutralizing IgM and IgG antibodies to von Willebrand factor–cleaving protease (ADAMTS-13) in a patient with thrombotic thrombocytopenic purpuraBlood, 2003
- Haemolytic uraemic syndrome and mutations of the factor H gene: a registry-based study of German speaking countriesJournal of Medical Genetics, 2003
- Thrombotic MicroangiopathiesNew England Journal of Medicine, 2002
- Factor H Mutations in Hemolytic Uremic Syndrome Cluster in Exons 18–20, a Domain Important for Host Cell RecognitionAmerican Journal of Human Genetics, 2001
- Clustering of Missense Mutations in the C-Terminal Region of Factor H in Atypical Hemolytic Uremic SyndromeAmerican Journal of Human Genetics, 2001
- Genetic studies into inherited and sporadic hemolytic uremic syndromeKidney International, 1998
- Enteropathogens associated with childhood diarrhea in ItalyThe Pediatric Infectious Disease Journal, 1996
- Prevalence of nonthyroid specific autoantibodies in autoimmune thyroid diseasesJournal of Clinical Endocrinology & Metabolism, 1995