{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:07:00Z","timestamp":1790514420860,"version":"4.1.0"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SCHM 3018 \/ 2-2"],"award-info":[{"award-number":["SCHM 3018 \/ 2-2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hemolytic disease driven by impaired complement regulation. Mutations in genes encoding the enzymes that build the GPI anchors are causative, with somatic mutations in the PIG-A gene occurring most frequently. As a result, the important membrane-bound complement regulators CD55 and CD59 are missing on the affected hematopoietic stem cells and their progeny, rendering those cells vulnerable to complement attack. Immune escape mechanisms sparing affected PNH stem cells from removal are suspected in the PNH pathogenesis, but molecular mechanisms have not been elucidated. We hypothesized that exuberant complement activity in PNH results in enhanced immune checkpoint interactions, providing a molecular basis for the potential immune escape in PNH. In a series of PNH patients, we found increased expression levels of the checkpoint ligand programmed death-ligand 1 (PD-L1) on granulocytes and monocytes, as well as in the plasma of PNH patients. Mechanistically, we demonstrate that complement activation leading to the decoration of particles\/cells with C3- and\/or C4-opsonins increased PD-L1 expression on neutrophils and monocytes as shown for different in vitro models of classical or alternative pathway activation. We further establish in vitro that complement inhibition at the level of C3, but not C5, inhibits the alternative pathway\u2013mediated upregulation of PD-L1 and show by means of soluble PD-L1 that this observation translates into the clinical situation when PNH patients are treated with either C3 or C5 inhibitors. Together, the presented data show that the checkpoint ligand PD-L1 is increased in PNH patients, which correlates with proximal complement activation.<\/jats:p>","DOI":"10.4049\/jimmunol.2100031","type":"journal-article","created":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T18:20:32Z","timestamp":1645035632000},"page":"1248-1258","source":"Crossref","is-referenced-by-count":5,"title":["Upregulation of Checkpoint Ligand Programmed Death-Ligand 1 in Patients with Paroxysmal Nocturnal Hemoglobinuria Explained by Proximal Complement Activation"],"prefix":"10.1093","volume":"208","author":[{"given":"Markus","family":"Anliker","sequence":"first","affiliation":[{"name":"Central Institute for Medical and Chemical Laboratory Diagnosis, University Hospital , Innsbruck,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3305-2945","authenticated-orcid":false,"given":"Daniela","family":"Drees","sequence":"additional","affiliation":[{"name":"Institute of Transfusion Medicine, University of Ulm , Ulm,","place":["Germany"]},{"name":"Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service, Baden-W\u00fcrttemberg-Hessen and University Hospital of Ulm , Ulm,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3677-6313","authenticated-orcid":false,"given":"Lorin","family":"Loacker","sequence":"additional","affiliation":[{"name":"Central Institute for Medical and Chemical Laboratory Diagnosis, University Hospital , Innsbruck,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0663-8382","authenticated-orcid":false,"given":"Susanne","family":"Hafner","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology of Natural Products and Clinical Pharmacology, Ulm University , Ulm,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Griesmacher","sequence":"additional","affiliation":[{"name":"Central Institute for Medical and Chemical Laboratory Diagnosis, University Hospital , Innsbruck,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregor","family":"Hoermann","sequence":"additional","affiliation":[{"name":"Central Institute for Medical and Chemical Laboratory Diagnosis, University Hospital , Innsbruck,","place":["Austria"]},{"name":"MLL Munich Leukemia Laboratory , Munich,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vilmos","family":"Fux","sequence":"additional","affiliation":[{"name":"Central Institute for Medical and Chemical Laboratory Diagnosis, University Hospital , Innsbruck,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Schennach","sequence":"additional","affiliation":[{"name":"Central Institute of Blood Transfusion and Immunology, University Hospital Innsbruck , Innsbruck,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9183-3320","authenticated-orcid":false,"given":"Paul","family":"H\u00f6rtnagl","sequence":"additional","affiliation":[{"name":"Central Institute of Blood Transfusion and Immunology, University Hospital Innsbruck , Innsbruck,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"Dopler","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology of Natural Products and Clinical Pharmacology, Ulm University , Ulm,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine V, Medical University of Innsbruck , Innsbruck,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5584-111X","authenticated-orcid":false,"given":"Rosa","family":"Bellmann-Weiler","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Innsbruck Medical University , Innsbruck,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0709-2158","authenticated-orcid":false,"given":"G\u00fcnter","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Innsbruck Medical University , Innsbruck,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Marx-Hofmann","sequence":"additional","affiliation":[{"name":"Institute of Transfusion Medicine, University of Ulm , Ulm,","place":["Germany"]},{"name":"Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service, Baden-W\u00fcrttemberg-Hessen and University Hospital of Ulm , Ulm,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sixten","family":"K\u00f6rper","sequence":"additional","affiliation":[{"name":"Institute of Transfusion Medicine, University of Ulm , Ulm,","place":["Germany"]},{"name":"Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service, Baden-W\u00fcrttemberg-Hessen and University Hospital of Ulm , Ulm,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britta","family":"H\u00f6chsmann","sequence":"additional","affiliation":[{"name":"Institute of Transfusion Medicine, University of Ulm , Ulm,","place":["Germany"]},{"name":"Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service, Baden-W\u00fcrttemberg-Hessen and University Hospital of Ulm , Ulm,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hubert","family":"Schrezenmeier","sequence":"additional","affiliation":[{"name":"Institute of Transfusion Medicine, University of Ulm , Ulm,","place":["Germany"]},{"name":"Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service, Baden-W\u00fcrttemberg-Hessen and University Hospital of Ulm , Ulm,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph Q","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology of Natural Products and Clinical Pharmacology, Ulm University , Ulm,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,3,1]]},"reference":[{"key":"2025021008564262700_r1","doi-asserted-by":"crossref","first-page":"5064","DOI":"10.4049\/jimmunol.179.8.5064","article-title":"PD-1 regulates self-reactive CD8+ T cell responses to antigen in lymph nodes and tissues","volume":"179","author":"Keir","year":"2007","journal-title":"J. Immunol."},{"key":"2025021008564262700_r2","doi-asserted-by":"crossref","first-page":"774","DOI":"10.3389\/fimmu.2019.00774","article-title":"Complementing the cancer-immunity cycle","volume":"10","author":"Pio","year":"2019","journal-title":"Front. Immunol."},{"key":"2025021008564262700_r3","doi-asserted-by":"crossref","first-page":"561","DOI":"10.3389\/fphar.2017.00561","article-title":"PD-1 and PD-L1 checkpoint signaling inhibition for cancer immunotherapy: mechanism, combinations, and clinical outcome","volume":"8","author":"Alsaab","year":"2017","journal-title":"Front. Pharmacol."},{"key":"2025021008564262700_r4","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1084\/jem.192.7.1027","article-title":"Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation","volume":"192","author":"Freeman","year":"2000","journal-title":"J. Exp. Med."},{"key":"2025021008564262700_r5","doi-asserted-by":"crossref","first-page":"e72249","DOI":"10.1371\/journal.pone.0072249","article-title":"IFN-\u03b3-stimulated neutrophils suppress lymphocyte proliferation through expression of PD-L1","volume":"8","author":"de Kleijn","year":"2013","journal-title":"PLoS One"},{"key":"2025021008564262700_r6","doi-asserted-by":"crossref","first-page":"e1003993","DOI":"10.1371\/journal.ppat.1003993","article-title":"Immune suppression by neutrophils in HIV-1 infection: role of PD-L1\/PD-1 pathway","volume":"10","author":"Bowers","year":"2014","journal-title":"PLoS Pathog."},{"key":"2025021008564262700_r7","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.clim.2008.05.009","article-title":"PDL-1 upregulation on monocytes and T cells by HIV via type I interferon: restricted expression of type I interferon receptor by CCR5-expressing leukocytes","volume":"129","author":"Boasso","year":"2008","journal-title":"Clin. Immunol."},{"key":"2025021008564262700_r8","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1097\/QAD.0b013e3282f4de23","article-title":"Upregulation of PD-L1 on monocytes and dendritic cells by HIV-1 derived TLR ligands","volume":"22","author":"Meier","year":"2008","journal-title":"AIDS"},{"key":"2025021008564262700_r9","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.cyto.2011.06.004","article-title":"Development of a sandwich ELISA for evaluating soluble PD-L1 (CD274) in human sera of different ages as well as supernatants of PD-L1+ cell lines","volume":"56","author":"Chen","year":"2011","journal-title":"Cytokine"},{"key":"2025021008564262700_r10","doi-asserted-by":"crossref","first-page":"e50256","DOI":"10.7554\/eLife.50256","article-title":"Soluble PD-L1 generated by endogenous retroelement exaptation is a receptor antagonist","volume":"8","author":"Ng","year":"2019","journal-title":"eLife"},{"key":"2025021008564262700_r11","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/s13046-015-0256-0","article-title":"Peritumoural neutrophils negatively regulate adaptive immunity via the PD-L1\/PD-1 signalling pathway in hepatocellular carcinoma","volume":"34","author":"He","year":"2015","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"2025021008564262700_r12","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1038\/ni.1655","article-title":"Modulation of the antitumor immune response by complement","volume":"9","author":"Markiewski","year":"2008","journal-title":"Nat. Immunol."},{"key":"2025021008564262700_r13","doi-asserted-by":"crossref","first-page":"4674","DOI":"10.4049\/jimmunol.1201654","article-title":"Anaphylatoxin C5a creates a favorable microenvironment for lung cancer progression","volume":"189","author":"Corrales","year":"2012","journal-title":"J. Immunol."},{"key":"2025021008564262700_r14","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/ni.1923","article-title":"Complement: a key system for immune surveillance and homeostasis","volume":"11","author":"Ricklin","year":"2010","journal-title":"Nat. Immunol."},{"key":"2025021008564262700_r15","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1084\/jem.188.12.2313","article-title":"Complement-dependent clearance of apoptotic cells by human macrophages","volume":"188","author":"Mevorach","year":"1998","journal-title":"J. Exp. Med."},{"key":"2025021008564262700_r16","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1084\/jem.20020263","article-title":"Opsonization of apoptotic cells by autologous iC3b facilitates clearance by immature dendritic cells, down-regulates DR and CD86, and up-regulates CC chemokine receptor 7","volume":"196","author":"Verbovetski","year":"2002","journal-title":"J. Exp. Med."},{"key":"2025021008564262700_r17","doi-asserted-by":"crossref","first-page":"2370","DOI":"10.1016\/j.molimm.2007.11.003","article-title":"The tick-over theory revisited: formation and regulation of the soluble alternative complement C3 convertase (C3(H2O)Bb)","volume":"45","author":"Bexborn","year":"2008","journal-title":"Mol. Immunol."},{"key":"2025021008564262700_r18","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1111\/imr.12475","article-title":"Protection of host cells by complement regulators","volume":"274","author":"Schmidt","year":"2016","journal-title":"Immunol. Rev."},{"key":"2025021008564262700_r19","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.exphem.2007.01.046","article-title":"The pathophysiology of paroxysmal nocturnal hemoglobinuria","volume":"35","author":"Parker","year":"2007","journal-title":"Exp. Hematol."},{"key":"2025021008564262700_r20","doi-asserted-by":"crossref","first-page":"2804","DOI":"10.1182\/blood-2014-02-522128","article-title":"Paroxysmal nocturnal hemoglobinuria","volume":"124","author":"Brodsky","year":"2014","journal-title":"Blood"},{"key":"2025021008564262700_r21","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/0092-8674(93)90250-T","article-title":"Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria","volume":"73","author":"Takeda","year":"1993","journal-title":"Cell"},{"key":"2025021008564262700_r22","doi-asserted-by":"crossref","first-page":"5123","DOI":"10.1172\/JCI123501","article-title":"Complement and inflammasome overactivation mediates paroxysmal nocturnal hemoglobinuria with autoinflammation","volume":"129","author":"H\u00f6chsmann","year":"2019","journal-title":"J. Clin. Invest."},{"key":"2025021008564262700_r23","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1172\/JCI105388","article-title":"Immune lysis of normal human and paroxysmal nocturnal hemoglobinuria (PNH) red blood cells. I. The sensitivity of PNH red cells to lysis by complement and specific antibody","volume":"45","author":"Rosse","year":"1966","journal-title":"J. Clin. Invest."},{"key":"2025021008564262700_r24","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1186\/s13045-017-0496-x","article-title":"Eculizumab treatment: stochastic occurrence of C3 binding to individual PNH erythrocytes","volume":"10","author":"Sica","year":"2017","journal-title":"J. Hematol. Oncol."},{"key":"2025021008564262700_r25","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1056\/NEJMoa031688","article-title":"Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria","volume":"350","author":"Hillmen","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"2025021008564262700_r26","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1056\/NEJMoa061648","article-title":"The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria","volume":"355","author":"Hillmen","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"2025021008564262700_r27","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1038\/nbt1344","article-title":"Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. [Published erratum appears in 2007 Nat. Biotechnol. 25: 1488.]","volume":"25","author":"Rother","year":"2007","journal-title":"Nat. Biotechnol."},{"key":"2025021008564262700_r28","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1182\/blood-2007-06-094136","article-title":"Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria","volume":"111","author":"Brodsky","year":"2008","journal-title":"Blood"},{"key":"2025021008564262700_r29","doi-asserted-by":"crossref","first-page":"4094","DOI":"10.1182\/blood-2008-11-189944","article-title":"Complement fraction 3 binding on erythrocytes as additional mechanism of disease in paroxysmal nocturnal hemoglobinuria patients treated by eculizumab","volume":"113","author":"Risitano","year":"2009","journal-title":"Blood"},{"key":"2025021008564262700_r30","doi-asserted-by":"crossref","first-page":"567","DOI":"10.3324\/haematol.2009.007229","article-title":"Eculizumab prevents intravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria and unmasks low-level extravascular hemolysis occurring through C3 opsonization","volume":"95","author":"Hill","year":"2010","journal-title":"Haematologica"},{"key":"2025021008564262700_r31","doi-asserted-by":"crossref","first-page":"6786","DOI":"10.1182\/blood-2011-02-333997","article-title":"Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival","volume":"117","author":"Kelly","year":"2011","journal-title":"Blood"},{"key":"2025021008564262700_r32","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1111\/j.1423-0410.2011.01530.x","article-title":"Paroxysmal nocturnal haemoglobinuria treatment with eculizumab is associated with a positive direct antiglobulin test","volume":"102","author":"H\u00f6chsmann","year":"2012","journal-title":"Vox Sang."},{"key":"2025021008564262700_r33","doi-asserted-by":"crossref","first-page":"230","DOI":"10.3324\/haematol.2019.236877","article-title":"Characterization of breakthrough hemolysis events observed in the phase 3 randomized studies of ravulizumab versus eculizumab in adults with paroxysmal nocturnal hemoglobinuria","volume":"106","author":"Brodsky","year":"2021","journal-title":"Haematologica"},{"key":"2025021008564262700_r34","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1021\/acs.bioconjchem.6b00369","article-title":"PASylated coversin, a C5-specific complement inhibitor with extended pharmacokinetics, shows enhanced anti-hemolytic activity in vitro","volume":"27","author":"Kuhn","year":"2016","journal-title":"Bioconjug. Chem."},{"key":"2025021008564262700_r35","doi-asserted-by":"crossref","first-page":"5712","DOI":"10.4049\/jimmunol.1203548","article-title":"Rational engineering of a minimized immune inhibitor with unique triple-targeting properties","volume":"190","author":"Schmidt","year":"2013","journal-title":"J. Immunol."},{"key":"2025021008564262700_r36","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nsmb.2018","article-title":"Structural basis for engagement by complement factor H of C3b on a self surface","volume":"18","author":"Morgan","year":"2011","journal-title":"Nat. Struct. Mol. Biol."},{"key":"2025021008564262700_r37","doi-asserted-by":"crossref","first-page":"e32187","DOI":"10.1371\/journal.pone.0032187","article-title":"Structural analysis of the C-terminal region (modules 18-20) of complement regulator factor H (FH)","volume":"7","author":"Morgan","year":"2012","journal-title":"PLoS One"},{"key":"2025021008564262700_r38","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1182\/blood-2016-08-732800","article-title":"Incomplete inhibition by eculizumab: mechanistic evidence for residual C5 activity during strong complement activation","volume":"129","author":"Harder","year":"2017","journal-title":"Blood"},{"key":"2025021008564262700_r39","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.3389\/fimmu.2019.01639","article-title":"Different levels of incomplete terminal pathway inhibition by eculizumab and the clinical response of PNH patients","volume":"10","author":"Harder","year":"2019","journal-title":"Front. Immunol."},{"key":"2025021008564262700_r40","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1182\/blood.2020005959","article-title":"Complement inhibition at the level of C3 or C5: mechanistic reasons for ongoing terminal pathway activity","volume":"137","author":"Mannes","year":"2021","journal-title":"Blood"},{"key":"2025021008564262700_r41","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1111\/trf.16384","article-title":"Multidisciplinary management of anti-PP1Pk or anti-P alloimmunization during pregnancy: a new case with anti-P and a literature review","volume":"61","author":"L\u00e9pine","year":"2021","journal-title":"Transfusion"},{"key":"2025021008564262700_r42","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"2025021008564262700_r43","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1182\/blood-2018-09-876136","article-title":"Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study","volume":"133","author":"Lee","year":"2019","journal-title":"Blood"},{"key":"2025021008564262700_r44","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1182\/blood-2018-09-876805","article-title":"Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients with PNH: the 302 study","volume":"133","author":"Kulasekararaj","year":"2019","journal-title":"Blood"},{"key":"2025021008564262700_r45","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1038\/s41598-017-01087-7","article-title":"Long lasting neutralization of C5 by SKY59, a novel recycling antibody, is a potential therapy for complement-mediated diseases","volume":"7","author":"Fukuzawa","year":"2017","journal-title":"Sci. Rep."},{"key":"2025021008564262700_r46","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/s40259-019-00401-1","article-title":"Second-generation C5 inhibitors for paroxysmal nocturnal hemoglobinuria","volume":"34","author":"Fattizzo","year":"2020","journal-title":"BioDrugs"},{"key":"2025021008564262700_r47","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1038\/nsmb.3427","article-title":"Regulator-dependent mechanisms of C3b processing by factor I allow differentiation of immune responses","volume":"24","author":"Xue","year":"2017","journal-title":"Nat. Struct. Mol. Biol."},{"key":"2025021008564262700_r48","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1111\/eci.12419","article-title":"Compstatin: a C3-targeted complement inhibitor reaching its prime for bedside intervention","volume":"45","author":"Mastellos","year":"2015","journal-title":"Eur. J. Clin. Invest."},{"key":"2025021008564262700_r49","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1056\/NEJMoa2029073","article-title":"Pegcetacoplan versus eculizumab in paroxysmal nocturnal hemoglobinuria","volume":"384","author":"Hillmen","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"2025021008564262700_r50","doi-asserted-by":"crossref","first-page":"4705","DOI":"10.1182\/blood-2011-06-359646","article-title":"Design and development of TT30, a novel C3d-targeted C3\/C5 convertase inhibitor for treatment of human complement alternative pathway-mediated diseases","volume":"118","author":"Fridkis-Hareli","year":"2011","journal-title":"Blood"},{"key":"2025021008564262700_r51","doi-asserted-by":"crossref","first-page":"2094","DOI":"10.1182\/blood-2013-11-536573","article-title":"Peptide inhibitors of C3 activation as a novel strategy of complement inhibition for the treatment of paroxysmal nocturnal hemoglobinuria. [Published erratum appears in 2017 Blood 129: 2205.]","volume":"123","author":"Risitano","year":"2014","journal-title":"Blood"},{"key":"2025021008564262700_r52","doi-asserted-by":"crossref","first-page":"eaam7729","DOI":"10.1126\/scitranslmed.aam7729","article-title":"Oncogenic JAK2V617F causes PD-L1 expression, mediating immune escape in myeloproliferative neoplasms","volume":"10","author":"Prestipino","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"2025021008564262700_r53","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1007\/s13577-020-00370-6","article-title":"Ectopic PD-L1 expression in JAK2 (V617F) myeloproliferative neoplasm patients is mediated via increased activation of STAT3 and STAT5","volume":"33","author":"Guru","year":"2020","journal-title":"Hum. Cell"},{"key":"2025021008564262700_r54","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.1182\/blood-2012-11-469353","article-title":"Glycosylphosphatidylinositol-specific, CD1d-restricted T cells in paroxysmal nocturnal hemoglobinuria","volume":"121","author":"Gargiulo","year":"2013","journal-title":"Blood"},{"key":"2025021008564262700_r55","doi-asserted-by":"crossref","first-page":"33346","DOI":"10.1038\/srep33346","article-title":"Complement C5a induces PD-L1 expression and acts in synergy with LPS through Erk1\/2 and JNK signaling pathways","volume":"6","author":"An","year":"2016","journal-title":"Sci. Rep."},{"key":"2025021008564262700_r56","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1158\/2159-8290.CD-16-1184","article-title":"A combined PD-1\/C5a blockade synergistically protects against lung cancer growth and metastasis","volume":"7","author":"Ajona","year":"2017","journal-title":"Cancer Discov."},{"key":"2025021008564262700_r57","doi-asserted-by":"crossref","first-page":"16426","DOI":"10.1073\/pnas.1311261110","article-title":"Structural insight on the recognition of surface-bound opsonins by the integrin I domain of complement receptor 3","volume":"110","author":"Bajic","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025021008564262700_r58","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1182\/blood-2015-02-625871","article-title":"Complement C3dg-mediated erythrophagocytosis: implications for paroxysmal nocturnal hemoglobinuria","volume":"126","author":"Lin","year":"2015","journal-title":"Blood"},{"key":"2025021008564262700_r59","doi-asserted-by":"crossref","first-page":"4586","DOI":"10.1073\/pnas.1202051109","article-title":"Molecular basis for complement recognition by integrin \u03b1X\u03b22","volume":"109","author":"Chen","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025021008564262700_r60","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1111\/cei.12952","article-title":"Production of complement components by cells of the immune system","volume":"188","author":"Lubbers","year":"2017","journal-title":"Clin. Exp. Immunol."},{"key":"2025021008564262700_r61","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/nri1994","article-title":"T-cell regulation: with complements from innate immunity","volume":"7","author":"Kemper","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"2025021008564262700_r62","doi-asserted-by":"crossref","first-page":"2808","DOI":"10.1016\/j.biocel.2013.09.016","article-title":"CD46: the \u2018multitasker\u2019 of complement proteins","volume":"45","author":"Yamamoto","year":"2013","journal-title":"Int. J. Biochem. Cell Biol."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/208\/5\/1248\/61465189\/ji2100031.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/208\/5\/1248\/61465189\/ji2100031.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T08:57:03Z","timestamp":1739177823000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/208\/5\/1248\/7924584"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,1]]},"references-count":62,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,3,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.2100031","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,3]]},"published":{"date-parts":[[2022,3,1]]}}}