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Valoti, Elisabetta
(2018).
DOI: https://doi.org/10.21954/ou.ro.0000da2d
Abstract
Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy characterized by renal failure and determined by genetic and acquired defects of alternative pathway (AP) of the complement system. Autoantibodies against factor H (anti-FHs), a regulator of the AP, were reported in 10% of patients, and are associated with the deficiency of factor H related 1 (FHR1), a FH homologous protein.
The aim of this thesis was to evaluate the contribution of genetics to the development of anti-FHs in aHUS.
Thirty patients affected by aHUS resulted positive for anti-FHs (9.8%) and FHR1 deficiency was present in 83.3% of them. A healthy control also showed anti-FHs in concomitance with FHR1 deficiency documenting that the lack of FHR1 strongly predisposed to anti-FH development also in healthy subjects although this condition was not sufficient for the disease manifestation.
The presence of infectious prodromal signs and an age at the disease onset around 8 years indicated that common infections may trigger the development of autoantibodies in subjects with at risk genetic background.
Likely pathogenetic variants in complement genes were observed in 37% of our patients with anti-FHs. At variance, common variants in complement genes did not seem to contribute to the disease, as documented by comparing patients with super controls, unaffected subjects carrying FHR1 deficiency.
Finally, I report that the HLA-DRB1*11:04 allele could be a predisposing genetic variant for anti-FH associated aHUS. Further works will be necessary to confirm this finding and to explore the presence of other genetic susceptibility factors that, in combination with the HLA-DRB1*11:04 allele and the FHR1 deficiency, could increase the risk for anti-FHs.
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About
- Item ORO ID
- 55853
- Item Type
- PhD Thesis
- Academic Unit or School
-
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences - Associated Research Centre
- IRCCS Istituto di Ricerche Farmacologiche Mario Negri
- Copyright Holders
- © 2018 The Author
- Depositing User
- Elisabetta Valoti