{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T13:16:55Z","timestamp":1791206215217,"version":"4.1.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2014,12,1]],"date-time":"2014-12-01T00:00:00Z","timestamp":1417392000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The alternative pathway (AP) is critical for the efficient activation of complement regardless of the trigger. It is also a major player in pathogenesis, as illustrated by the long list of diseases in which AP activation contributes to pathology. Its relevance to human disease is further emphasized by the high prevalence of pathogenic inherited defects and acquired autoantibodies disrupting components and regulators of the AP C3-convertase. Because pharmacological downmodulation of the AP emerges as a broad-spectrum treatment alternative, there is a powerful interest in developing new molecules to block formation and\/or activity of the AP C3-convertase. In this paper, we describe the generation of a novel mAb targeting human factor B (FB). mAb FB48.4.2, recognizing with high affinity an evolutionary-conserved epitope in the Ba fragment of FB, very efficiently inhibited formation of the AP C3-proconvertase by blocking the interaction between FB and C3b. In vitro assays using rabbit and sheep erythrocytes demonstrated that FB28.4.2 was a potent AP inhibitor that blocked complement-mediated hemolysis in several species. Using ex vivo models of disease we demonstrated that FB28.4.2 protected paroxysmal nocturnal hemoglobinuria erythrocytes from complement-mediated hemolysis and inhibited both C3 fragment and C5b-9 deposition on ADP-activated HMEC-1 cells, an experimental model for atypical hemolytic uremic syndrome. Moreover, i.v. injection of FB28.4.2 in rats blocked complement activation in rat serum and prevented the passive induction of experimental autoimmune Myasthenia gravis. As a whole, these data demonstrate the potential value of FB28.4.2 for the treatment of disorders associated with AP complement dysregulation in man and animal models.<\/jats:p>","DOI":"10.4049\/jimmunol.1402013","type":"journal-article","created":{"date-parts":[[2014,10,30]],"date-time":"2014-10-30T03:03:14Z","timestamp":1414638194000},"page":"5567-5575","source":"Crossref","is-referenced-by-count":20,"title":["A Novel Antibody against Human Factor B that Blocks Formation of the C3bB Proconvertase and Inhibits Complement Activation in Disease Models"],"prefix":"10.1093","volume":"193","author":[{"given":"Marta","family":"Sub\u00edas","sequence":"first","affiliation":[{"name":"Centro de Investigaciones Biol\u00f3gicas, Consejo Superior de Investigaciones Cient\u00edficas , Madrid 28040 ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Enfermedades Raras , Madrid 28040 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agust\u00edn","family":"Tortajada","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biol\u00f3gicas, Consejo Superior de Investigaciones Cient\u00edficas , Madrid 28040 ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Enfermedades Raras , Madrid 28040 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Gastoldi","sequence":"additional","affiliation":[{"name":"IRCCS - Mario Negri Instituto for Pharmacological Research \u201cMario Negri,\u201d Clinical Research Center for Rare Diseases \u201cAldo e Cele Dacc\u00f2,\u201d Ranica , Bergamo 24020 ,","place":["Italy"]},{"name":"\u201cCentro Anna Maria Astori\u201d Parco Scientifico e Tecnologico Kilometro Rosso , Bergamo 24126 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Galbusera","sequence":"additional","affiliation":[{"name":"IRCCS - Mario Negri Instituto for Pharmacological Research \u201cMario Negri,\u201d Clinical Research Center for Rare Diseases \u201cAldo e Cele Dacc\u00f2,\u201d Ranica , Bergamo 24020 ,","place":["Italy"]},{"name":"\u201cCentro Anna Maria Astori\u201d Parco Scientifico e Tecnologico Kilometro Rosso , Bergamo 24126 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s","family":"L\u00f3pez-Perrote","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biol\u00f3gicas, Consejo Superior de Investigaciones Cient\u00edficas , Madrid 28040 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia de Juana","family":"Lopez","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biol\u00f3gicas, Consejo Superior de Investigaciones Cient\u00edficas , Madrid 28040 ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Enfermedades Raras , Madrid 28040 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando Ata\u00falfo","family":"Gonz\u00e1lez-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Hospital Cl\u00ednico San Carlos, Universidad Complutense de Madrid , Madrid 28040 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Villegas-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Hospital Cl\u00ednico San Carlos, Universidad Complutense de Madrid , Madrid 28040 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"Dominguez","sequence":"additional","affiliation":[{"name":"Servicio de Inmunolog\u00eda Microbiana, Centro Nacional de Microbiolog\u00eda, Instituto de Investigaci\u00f3n Carlos III , Madrid 28220 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Llorca","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biol\u00f3gicas, Consejo Superior de Investigaciones Cient\u00edficas , Madrid 28040 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Noris","sequence":"additional","affiliation":[{"name":"IRCCS - Mario Negri Instituto for Pharmacological Research \u201cMario Negri,\u201d Clinical Research Center for Rare Diseases \u201cAldo e Cele Dacc\u00f2,\u201d Ranica , Bergamo 24020 ,","place":["Italy"]},{"name":"\u201cCentro Anna Maria Astori\u201d Parco Scientifico e Tecnologico Kilometro Rosso , Bergamo 24126 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B Paul","family":"Morgan","sequence":"additional","affiliation":[{"name":"Institute of Infection and Immunity, School of Medicine, Cardiff University , Cardiff CF14 4XN ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6401-1874","authenticated-orcid":false,"given":"Santiago","family":"Rodr\u00edguez de C\u00f3rdoba","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biol\u00f3gicas, Consejo Superior de Investigaciones Cient\u00edficas , Madrid 28040 ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Enfermedades Raras , Madrid 28040 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,12,1]]},"reference":[{"key":"2025030707482624600_r1","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1056\/NEJM200104053441406","article-title":"Complement: first of two parts","volume":"344","author":"Walport","year":"2001","journal-title":"N. 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