{"id":{"repo_id":"the-open-u","oai_identifier":"oai:oro.open.ac.uk:55853"},"canonical_url":"https://search.dev.ndltd.org/etd/the-open-u/oai:oro.open.ac.uk:55853","repository":{"repo_id":"the-open-u","name":"The Open University","base_url":"https://oro.open.ac.uk/cgi/oai2"},"display":{"title":"Genetic Factors Associated with Anti-Factor H Autoantibodies in Atypical Hemolytic Uremic Syndrome (aHUS)","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. <br></br><br></br> The aim of this thesis was to evaluate the contribution of genetics to the development of anti-FHs in aHUS. <br></br><br></br> 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. <br></br><br></br> 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. <br></br><br></br> 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. <br></br><br></br> Finally, I report that the <i>HLA-DRB1*11:04</i> 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 <i>HLA-DRB1*11:04</i> allele and the FHR1 deficiency, could increase the risk for anti-FHs.","abstract_html":"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. &lt;br&gt;&lt;/br&gt;&lt;br&gt;&lt;/br&gt; The aim of this thesis was to evaluate the contribution of genetics to the development of anti-FHs in aHUS. &lt;br&gt;&lt;/br&gt;&lt;br&gt;&lt;/br&gt; 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. &lt;br&gt;&lt;/br&gt;&lt;br&gt;&lt;/br&gt; 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. &lt;br&gt;&lt;/br&gt;&lt;br&gt;&lt;/br&gt; 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. &lt;br&gt;&lt;/br&gt;&lt;br&gt;&lt;/br&gt; Finally, I report that the &lt;i&gt;HLA-DRB1*11:04&lt;/i&gt; 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 &lt;i&gt;HLA-DRB1*11:04&lt;/i&gt; allele and the FHR1 deficiency, could increase the risk for anti-FHs.","abstract_has_math":false,"creators":["Valoti, Elisabetta"],"institution":"The Open University","degree_name":"phd","degree_level":"doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2018,"date_issued":"2018-07","date_published":"2018-07","updated_at":"2026-07-24T05:02:52Z","subjects":[],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Valoti, Elisabetta"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2018-07-05"]},{"key":"dc:date.issued","label":"Date","values":["2018-07"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["ARRAY(0x7ffb9a36e1c8)"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["The Open University"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://oro.open.ac.uk/55853/"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["phd"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://oro.open.ac.uk/55853/1/PhD%20thesis_Valoti_2018_07_13.pdf","https://oro.open.ac.uk/55853/7/180725%20-%20Abstract.pdf","https://oro.open.ac.uk/55853/8/180725%20-%20Thesis%20Deposition%20form.pdf","https://oro.open.ac.uk/55853/9/GRADPROG%20memo.docx","https://oro.open.ac.uk/55853/21/Valoti%20-%20Library%20deposition%20memo.doc","https://oro.open.ac.uk/55853/25/180725%20-%20Abstract.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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. <br></br><br></br> The aim of this thesis was to evaluate the contribution of genetics to the development of anti-FHs in aHUS. <br></br><br></br> 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. <br></br><br></br> 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. <br></br><br></br> 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. <br></br><br></br> Finally, I report that the <i>HLA-DRB1*11:04</i> 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 <i>HLA-DRB1*11:04</i> allele and the FHR1 deficiency, could increase the risk for anti-FHs."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf","application/vnd.openxmlformats-officedocument.wordprocessingml.document","application/msword"]},{"key":"dc:title","label":"Title","values":["Genetic Factors Associated with Anti-Factor H Autoantibodies in Atypical Hemolytic Uremic Syndrome (aHUS)"]}]}],"canonical_facts":{"dc:creator":["Valoti, Elisabetta"],"dc:date":["2018-07-05"],"dc:date.issued":["2018-07"],"dc:description.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. <br></br><br></br> The aim of this thesis was to evaluate the contribution of genetics to the development of anti-FHs in aHUS. <br></br><br></br> 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. <br></br><br></br> 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. <br></br><br></br> 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. <br></br><br></br> Finally, I report that the <i>HLA-DRB1*11:04</i> 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 <i>HLA-DRB1*11:04</i> allele and the FHR1 deficiency, could increase the risk for anti-FHs."],"dc:format":["application/pdf","application/vnd.openxmlformats-officedocument.wordprocessingml.document","application/msword"],"dc:identifier.uri":["https://oro.open.ac.uk/55853/1/PhD%20thesis_Valoti_2018_07_13.pdf","https://oro.open.ac.uk/55853/7/180725%20-%20Abstract.pdf","https://oro.open.ac.uk/55853/8/180725%20-%20Thesis%20Deposition%20form.pdf","https://oro.open.ac.uk/55853/9/GRADPROG%20memo.docx","https://oro.open.ac.uk/55853/21/Valoti%20-%20Library%20deposition%20memo.doc","https://oro.open.ac.uk/55853/25/180725%20-%20Abstract.pdf"],"dc:language":["en"],"dc:publisher.department":["ARRAY(0x7ffb9a36e1c8)"],"dc:publisher.institution":["The Open University"],"dc:relation.isreferencedby":["https://oro.open.ac.uk/55853/"],"dc:title":["Genetic Factors Associated with Anti-Factor H Autoantibodies in Atypical Hemolytic Uremic Syndrome (aHUS)"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["doctoral"],"dc:type.qualificationname":["phd"]},"updated_at":"2026-07-24T05:02:52Z"}