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Association of factor H autoantibodies with deletions of CFHR1, CFHR3, CFHR4, and with mutations in CFH, CFI, CD46, and C3 in patients with atypical hemolytic uremic syndrome
- Source :
- Blood. 115:379-387
- Publication Year :
- 2010
- Publisher :
- American Society of Hematology, 2010.
-
Abstract
- Factor H autoantibodies have been reported in approximately 10% of patients with atypical hemolytic uremic syndrome (aHUS) and are associated with deficiency of factor H–related proteins 1 and 3. In this study we examined the prevalence of factor H autoantibodies in the Newcastle cohort of aHUS patients, determined whether the presence of such autoantibodies is always associated with deficiency of factor H–related proteins 1 and 3, and examined whether such patients have additional susceptibility factors and/or mutations in the genes encoding complement regulator/activators. We screened 142 patients with aHUS and found factor H autoantibodies in 13 individuals (age 1-11 years). The presence of the autoantibodies was confirmed by Western blotting. By using multiplex ligation-dependent probe amplification we measured complement factor H–related (CFHR)1 and CFHR3 copy number. In 10 of the 13 patients there were 0 copies of CFHR1, and in 3 patients there were 2. In 3 of the patients with 0 copies of CFHR1 there was 1 copy of CFHR3, and these individuals exhibited a novel deletion incorporating CFHR1 and CFHR4. In 5 patients mutations were identified: 1 in CFH, 1 in CFI, 1 in CD46, and 2 in C3. The latter observation emphasizes that multiple concurrent factors may be necessary in individual patients for disease manifestation.
- Subjects :
- Male
Hemolytic anemia
Immunology
Gene Dosage
Complement factor I
medicine.disease_cause
Biochemistry
Autoimmunity
Cohort Studies
Membrane Cofactor Protein
Atypical hemolytic uremic syndrome
Complement C3b Inactivator Proteins
medicine
Humans
Child
Autoantibodies
Sequence Deletion
biology
CD46
business.industry
Autoantibody
Infant
Blood Proteins
Complement C3
Cell Biology
Hematology
medicine.disease
Apolipoproteins
Complement Factor I
Child, Preschool
Complement Factor H
Factor H
Hemolytic-Uremic Syndrome
biology.protein
Female
Antibody
business
Subjects
Details
- ISSN :
- 15280020 and 00064971
- Volume :
- 115
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....4b56e43b200ee76f8b7b736361a345db
- Full Text :
- https://doi.org/10.1182/blood-2009-05-221549