{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:20:20Z","timestamp":1790911220608,"version":"4.1.0"},"reference-count":82,"publisher":"American Society of Hematology","issue":"24","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,12,12]]},"abstract":"<jats:sec>\n                  <jats:title>Abstract<\/jats:title>\n                  <jats:p>Complement-mediated thrombotic microangiopathy (CM-TMA) or hemolytic uremic syndrome, previously identified as atypical hemolytic uremic syndrome, is a TMA characterized by germ line variants or acquired antibodies to complement proteins and regulators. Building upon our prior experience with the modified Ham (mHam) assay for ex\u00a0vivo diagnosis of complementopathies, we have developed an array of cell-based complement \u201cbiosensors\u201d by selective removal of complement regulatory proteins (CD55 and CD59, CD46, or a combination thereof) in an autonomously bioluminescent HEK293 cell line. These biosensors can be used as a sensitive method for diagnosing CM-TMA and monitoring therapeutic complement blockade. Using specific complement pathway inhibitors, this model identifies immunoglobulin M (IgM)\u2013driven classical pathway stimulus during both acute disease and in many patients during clinical remission. This provides a potential explanation for \u223c50% of patients with CM-TMA who lack an alternative pathway \u201cdriving\u201d variant and suggests at least a subset of CM-TMA is characterized by a breakdown of IgM immunologic tolerance.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/blood.2024025850","type":"journal-article","created":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T20:59:27Z","timestamp":1727902767000},"page":"2528-2545","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":27,"title":["Complement biosensors identify a classical pathway stimulus in complement-mediated thrombotic microangiopathy"],"prefix":"10.1182","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0617-7256","authenticated-orcid":false,"given":"Michael A.","family":"Cole","sequence":"first","affiliation":[{"name":"1Division of Hematology, Department of Medicine, Johns Hopkins University, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0650-2928","authenticated-orcid":false,"given":"Nikhil","family":"Ranjan","sequence":"additional","affiliation":[{"name":"1Division of Hematology, Department of Medicine, Johns Hopkins University, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9855-0075","authenticated-orcid":false,"given":"Gloria F.","family":"Gerber","sequence":"additional","affiliation":[{"name":"1Division of Hematology, Department of Medicine, Johns Hopkins University, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang-Zuo","family":"Pan","sequence":"additional","affiliation":[{"name":"1Division of Hematology, Department of Medicine, Johns Hopkins University, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7194-805X","authenticated-orcid":false,"given":"Daniel","family":"Flores-Guerrero","sequence":"additional","affiliation":[{"name":"1Division of Hematology, Department of Medicine, Johns Hopkins University, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4155-0976","authenticated-orcid":false,"given":"George","family":"McNamara","sequence":"additional","affiliation":[{"name":"2Ross Fluorescence Imaging Center, Division of Gastroenterology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shruti","family":"Chaturvedi","sequence":"additional","affiliation":[{"name":"1Division of Hematology, Department of Medicine, Johns Hopkins University, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8409-0714","authenticated-orcid":false,"given":"C. John","family":"Sperati","sequence":"additional","affiliation":[{"name":"3Division of Nephrology, Department of Medicine, Johns Hopkins University, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7340-475X","authenticated-orcid":false,"given":"Keith R.","family":"McCrae","sequence":"additional","affiliation":[{"name":"4Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5741-1255","authenticated-orcid":false,"given":"Robert A.","family":"Brodsky","sequence":"additional","affiliation":[{"name":"1Division of Hematology, Department of Medicine, Johns Hopkins University, Baltimore, 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