{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T20:06:14Z","timestamp":1786133174090,"version":"build-2736575974"},"reference-count":24,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2021,5]]},"abstract":"\n Significance Statement<\/jats:title>\n Atypical hemolytic uremic syndrome (aHUS) is often related to complement dysregulation, but its pathophysiology remains unknown in at list 30% of patients. Anti-factor H autoantibodies of the IgG class are responsible for 10% of patients with aHUS; autoantibodies of IgM class have not been reported. The authors found anti-factor H IgM autoantibodies in seven of 186 patients with aHUS, with a frequency six-fold higher in patients with a history of hematopoietic stem cell transplantation. The purified IgM autoantibodies recognize the active site of the factor H molecule and inhibit its binding to C3b. These findings indicate that some forms of aHUS of unknown origin could be placed within the setting of autoimmune diseases, stemming from the presence of IgM autoantibodies specific for factor H\u2019s active site.<\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n Atypical hemolytic uremic syndrome (aHUS), a severe thrombotic microangiopathy, is often related to complement dysregulation, but the pathomechanisms remain unknown in at least 30% of patients. Researchers have described autoantibodies to complement factor H of the IgG class in 10% of patients with aHUS but have not reported anti-factor H autoantibodies of the IgM class.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n In 186 patients with thrombotic microangiopathy clinically presented as aHUS, we searched for anti-factor H autoantibodies of the IgM class and those of the IgG and IgA classes. We used immunochromatography to purify anti-factor H IgM autoantibodies and immunoenzymatic methods and a competition assay with mapping mAbs to characterize interaction with the target protein.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n We detected anti-factor H autoantibodies of the IgM class in seven of 186 (3.8%) patients with thrombotic microangiopathy presented as aHUS. No association was observed between anti-factor H IgM and homozygous deletions involving\n CFHR3-CFHR1<\/jats:italic>\n . A significantly higher proportion of patients with bone marrow transplant\u2013related thrombotic microangiopathy had anti-factor H IgM autoantibodies versus other patients with aHUS: three of 20 (15%) versus four of 166 (2.4%), respectively. The identified IgM autoantibodies recognize the SCR domain 19 of factor H molecule in all patients and interact with the factor H molecule, inhibiting its binding to C3b.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Detectable autoantibodies to factor H of the IgM class may be present in patients with aHUS, and their frequency is six-fold higher in thrombotic microangiopathy forms associated with bone marrow transplant. The autoantibody interaction with factor H\u2019s active site may support an autoimmune mechanism in some cases previously considered to be of unknown origin.<\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.2020081224","type":"journal-article","created":{"date-parts":[[2021,3,12]],"date-time":"2021-03-12T15:40:13Z","timestamp":1615563613000},"page":"1227-1235","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":22,"title":["IgM Autoantibodies to Complement Factor H in Atypical Hemolytic Uremic Syndrome"],"prefix":"10.1681","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9918-0763","authenticated-orcid":false,"given":"Massimo","family":"Cugno","sequence":"first","affiliation":[{"name":"Medicina Interna, Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Universit\u00e0 degli Studi di Milano, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca\u2019 Granda, Ospedale Maggiore Policlinico, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Berra","sequence":"additional","affiliation":[{"name":"L. Sacco Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Depetri","sequence":"additional","affiliation":[{"name":"Medicina Interna, Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Universit\u00e0 degli Studi di Milano, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca\u2019 Granda, Ospedale Maggiore Policlinico, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5272-8314","authenticated-orcid":false,"given":"Silvana","family":"Tedeschi","sequence":"additional","affiliation":[{"name":"Laboratorio di Genetica Medica, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca\u2019 Granda, Ospedale Maggiore Policlinico, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Griffini","sequence":"additional","affiliation":[{"name":"Medicina Interna, Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Universit\u00e0 degli Studi di Milano, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca\u2019 Granda, Ospedale Maggiore Policlinico, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Grovetti","sequence":"additional","affiliation":[{"name":"Medicina Interna, Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Universit\u00e0 degli Studi di Milano, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca\u2019 Granda, Ospedale Maggiore Policlinico, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0829-5379","authenticated-orcid":false,"given":"Sonia","family":"Caccia","sequence":"additional","affiliation":[{"name":"L. Sacco Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donata","family":"Cresseri","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa di Nefrologia, Dialisi e Trapianto Renale, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca\u2019 Granda, Ospedale Maggiore Policlinico, Universit\u00e0 degli Studi di Milano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piergiorgio","family":"Messa","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa di Nefrologia, Dialisi e Trapianto Renale, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca\u2019 Granda, Ospedale Maggiore Policlinico, Universit\u00e0 degli Studi di Milano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3062-8985","authenticated-orcid":false,"given":"Sara","family":"Testa","sequence":"additional","affiliation":[{"name":"Center for Hemolytic Uremic Syndrome Prevention, Control and Management, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca\u2019 Granda, Ospedale Maggiore Policlinico, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Giglio","sequence":"additional","affiliation":[{"name":"Hematology and Bone Marrow Transplantation Unit, Istituto di Ricovero e Cura a Carattere Scientifico S. Raffaele Scientific Institution, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flora","family":"Peyvandi","sequence":"additional","affiliation":[{"name":"Medicina Interna, Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Universit\u00e0 degli Studi di Milano, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca\u2019 Granda, Ospedale Maggiore Policlinico, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluigi","family":"Ardissino","sequence":"additional","affiliation":[{"name":"Center for Hemolytic Uremic Syndrome Prevention, Control and Management, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca\u2019 Granda, Ospedale Maggiore Policlinico, Milan, 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