{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:52:53Z","timestamp":1790711573794,"version":"4.1.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T00:00:00Z","timestamp":1687305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Australian Centre for Research Excellence"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,10,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Antibodies to variant surface antigens (VSAs) such as Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) may vary with malaria severity. The influence of ABO blood group on antibody development is not understood.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Immunoglobulin G antibodies to VSAs in Papua New Guinean children with severe (n = 41) or uncomplicated (n = 30) malaria were measured by flow cytometry using homologous P falciparum isolates. Isolates were incubated with ABO-matched homologous and heterologous acute and convalescent plasma. RNA was used to assess var gene transcription.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Antibodies to homologous, but not heterologous, isolates were boosted in convalescence. The relationship between antibody and severity varied by blood group. Antibodies to VSAs were similar in severe and uncomplicated malaria at presentation, higher in severe than uncomplicated malaria in convalescence, and higher in children with blood group O than other children. Six var gene transcripts best distinguished severe from uncomplicated malaria, including UpsA and 2 CIDR\u03b11 domains.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>ABO blood group may influence antibody acquisition to VSAs and susceptibility to severe malaria. Children in Papua New Guinea showed little evidence of acquisition of cross-reactive antibodies following malaria. Var gene transcripts in Papua New Guinean children with severe malaria were similar to those reported from Africa.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiad217","type":"journal-article","created":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T20:20:52Z","timestamp":1687465252000},"page":"1099-1107","source":"Crossref","is-referenced-by-count":5,"title":["Antibody to <i>Plasmodium falciparum<\/i> Variant Surface Antigens, <i>var<\/i> Gene Transcription, and ABO Blood Group in Children With Severe or Uncomplicated Malaria"],"prefix":"10.1093","volume":"228","author":[{"given":"Priyanka","family":"Barua","sequence":"first","affiliation":[{"name":"Department of Medicine, Peter Doherty Institute for Infection and Immunity, University of Melbourne , Melbourne"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael F","family":"Duffy","sequence":"additional","affiliation":[{"name":"Department of Medicine, Peter Doherty Institute for Infection and Immunity, University of Melbourne , Melbourne"},{"name":"Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, Bio21 Institute, University of Melbourne , Parkville, Victoria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4334-5351","authenticated-orcid":false,"given":"Laurens","family":"Manning","sequence":"additional","affiliation":[{"name":"Medical School, University of Western Australia , Perth"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moses","family":"Laman","sequence":"additional","affiliation":[{"name":"Vector Borne Diseases Unit, Papua New Guinea Institute of Medical Research , Madang"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy M E","family":"Davis","sequence":"additional","affiliation":[{"name":"Medical School, University of Western Australia , Perth"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivo","family":"Mueller","sequence":"additional","affiliation":[{"name":"Population Health and Immunity, Walter and Eliza Hall Institute , Parkville, Victoria , Australia"},{"name":"Department of Parasites and Insect Vector, Institut Pasteur , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Haghiri","sequence":"additional","affiliation":[{"name":"Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne , Parkville"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A","family":"Simpson","sequence":"additional","affiliation":[{"name":"Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne , Parkville"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1018-7898","authenticated-orcid":false,"given":"James G","family":"Beeson","sequence":"additional","affiliation":[{"name":"Malaria Immunity and Vaccines Laboratory, Burnet Institute , Melbourne"},{"name":"Central Clinical School and Department of Microbiology, Monash University , Clayton"},{"name":"Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, University of Melbourne , Melbourne, Victoria , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4287-1982","authenticated-orcid":false,"given":"Stephen J","family":"Rogerson","sequence":"additional","affiliation":[{"name":"Department of Medicine, Peter Doherty Institute for Infection and Immunity, University of Melbourne , Melbourne"},{"name":"Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, University of Melbourne , Melbourne, Victoria , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,6,21]]},"reference":[{"key":"2023101809352409300_jiad217-B1","doi-asserted-by":"crossref","first-page":"E1772","DOI":"10.1073\/pnas.1120461109","article-title":"A subset of group A-like var genes encodes the malaria parasite ligands for binding to human brain endothelial cells","volume":"109","author":"Claessens","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2023101809352409300_jiad217-B2","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1000386","article-title":"High throughput functional assays of the variant antigen PfEMP1 reveal a single domain in the 3D7 Plasmodium falciparum genome that binds ICAM1 with high affinity and is targeted by naturally acquired neutralizing antibodies","volume":"5","author":"Oleinikov","year":"2009","journal-title":"PLoS Pathogens"},{"key":"2023101809352409300_jiad217-B3","doi-asserted-by":"crossref","first-page":"49","DOI":"10.2307\/3281273","article-title":"Phagocytosis of Plasmodium falciparum\u2013parasitized erythrocytes by human polymorphonuclear leukocytes","volume":"69","author":"Celada","year":"1983","journal-title":"J Parasitol"},{"key":"2023101809352409300_jiad217-B4","doi-asserted-by":"crossref","first-page":"3227","DOI":"10.1172\/JCI62182","article-title":"Targets of antibodies against Plasmodium falciparum\u2013infected erythrocytes in malaria immunity","volume":"122","author":"Chan","year":"2012","journal-title":"J Clin Invest"},{"key":"2023101809352409300_jiad217-B5","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1016\/j.biocel.2008.12.012","article-title":"PfEMP1: an antigen that plays a key role in the pathogenicity and immune evasion of the malaria parasite Plasmodium falciparum","volume":"41","author":"Pasternak","year":"2009","journal-title":"Int J Biochem Cell Biol"},{"key":"2023101809352409300_jiad217-B6","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1046\/j.1365-2958.2003.03378.x","article-title":"Widespread functional specialization of Plasmodium falciparum erythrocyte membrane protein 1 family members to bind CD36 analysed across a parasite genome","volume":"47","author":"Robinson","year":"2003","journal-title":"Mol Microbiol"},{"key":"2023101809352409300_jiad217-B7","doi-asserted-by":"crossref","DOI":"10.1128\/IAI.00841-16","article-title":"The severity of Plasmodium falciparum infection is associated with transcript levels of var genes encoding endothelial protein C receptor\u2013binding P. falciparum erythrocyte membrane protein 1","volume":"85","author":"Mkumbaye","year":"2017","journal-title":"Infect Immun"},{"key":"2023101809352409300_jiad217-B8","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.chom.2017.02.009","article-title":"Structure-guided identification of a family of dual receptor-binding PfEMP1 that is associated with cerebral malaria","volume":"21","author":"Lennartz","year":"2017","journal-title":"Cell Host Microbe"},{"key":"2023101809352409300_jiad217-B9","doi-asserted-by":"crossref","first-page":"E1791","DOI":"10.1073\/pnas.1120455109","article-title":"Plasmodium falciparum erythrocyte membrane protein 1 domain cassettes 8 and 13 are associated with severe malaria in children","volume":"109","author":"Lavstsen","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2023101809352409300_jiad217-B10","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/nm0398-358","article-title":"Parasite antigens on the infected red cell surface are targets for naturally acquired immunity to malaria","volume":"4","author":"Bull","year":"1998","journal-title":"Nat Med"},{"key":"2023101809352409300_jiad217-B11","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.chom.2019.10.012","article-title":"Protective immunity against severe malaria in children is associated with a limited repertoire of antibodies to conserved PfEMP1 variants","volume":"26","author":"Tessema","year":"2019","journal-title":"Cell Host Microbe"},{"key":"2023101809352409300_jiad217-B12","doi-asserted-by":"crossref","first-page":"6281","DOI":"10.1038\/s41598-018-24462-4","article-title":"Children with cerebral malaria or severe malarial anaemia lack immunity to distinct variant surface antigen subsets","volume":"8","author":"Travassos","year":"2018","journal-title":"Sci Rep"},{"key":"2023101809352409300_jiad217-B13","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1093\/infdis\/jiy564","article-title":"Acquisition of antibodies against endothelial protein C receptor-binding domains of Plasmodium falciparum erythrocyte membrane protein 1 in children with severe malaria","volume":"219","author":"Rambhatla","year":"2019","journal-title":"J Infect Dis"},{"key":"2023101809352409300_jiad217-B14","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1093\/infdis\/jiy580","article-title":"Antibody targets on the surface of Plasmodium falciparum\u2013infected erythrocytes that are associated with immunity to severe malaria in young children","volume":"219","author":"Chan","year":"2019","journal-title":"J Infect Dis"},{"key":"2023101809352409300_jiad217-B15","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1186\/s12936-016-1296-4","article-title":"Differences in PfEMP1s recognized by antibodies from patients with uncomplicated or severe malaria","volume":"15","author":"Duffy","year":"2016","journal-title":"Malar J"},{"key":"2023101809352409300_jiad217-B16","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1038\/ng.3107","article-title":"Reappraisal of known malaria resistance loci in a large multicenter study","volume":"46","author":"Malaria Genomic Epidemiology Network","year":"2014","journal-title":"Nat Genet"},{"key":"2023101809352409300_jiad217-B17","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.blre.2018.07.002","article-title":"Effect of the ABO blood group on susceptibility to severe malaria: a systematic review and meta-analysis","volume":"33","author":"Degarege","year":"2019","journal-title":"Blood Rev"},{"key":"2023101809352409300_jiad217-B18","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0029203","article-title":"Features and prognosis of severe malaria caused by Plasmodium falciparum, Plasmodium vivax and mixed Plasmodium species in Papua New Guinean children","volume":"6","author":"Manning","year":"2011","journal-title":"PLoS One"},{"key":"2023101809352409300_jiad217-B19","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1093\/infdis\/jit646","article-title":"Low antibody levels to pregnancy-specific malaria antigens and heightened cytokine responses associated with severe malaria in pregnancy","volume":"209","author":"Chandrasiri","year":"2014","journal-title":"J Infect Dis"},{"key":"2023101809352409300_jiad217-B20","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/978-1-4939-2815-6_17","article-title":"Evaluating IgG antibody to variant surface antigens expressed on Plasmodium falciparum infected erythrocytes using flow cytometry","volume":"1325","author":"Teo","year":"2015","journal-title":"Methods Mol Biol"},{"key":"2023101809352409300_jiad217-B21","first-page":"1","article-title":"Mice: multivariate imputation by chained equations in R","volume":"45","author":"van Buuren","year":"2011","journal-title":"J Stat Softw"},{"key":"2023101809352409300_jiad217-B22","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1111\/j.1467-9868.2005.00503.x","article-title":"Regularization and variable selection via the elastic net","volume":"67","author":"Zou","year":"2005","journal-title":"J R Stat Soc Ser B (Stat Methodol)"},{"key":"2023101809352409300_jiad217-B23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v028.i05","article-title":"Building predictive models in R using the caret package","volume":"28","author":"Kuhn","year":"2008","journal-title":"J Stat Softw"},{"key":"2023101809352409300_jiad217-B24","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1128\/IAI.67.2.733-739.1999","article-title":"Antibody recognition of Plasmodium falciparum erythrocyte surface antigens in Kenya: evidence for rare and prevalent variants","volume":"67","author":"Bull","year":"1999","journal-title":"Infect Immun"},{"key":"2023101809352409300_jiad217-B25","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1086\/315652","article-title":"Plasmodium falciparum\u2013infected erythrocytes: agglutination by diverse Kenyan plasma is associated with severe disease and young host age","volume":"182","author":"Bull","year":"2000","journal-title":"J Infect Dis"},{"key":"2023101809352409300_jiad217-B26","doi-asserted-by":"crossref","DOI":"10.1074\/mcp.M111.008326","article-title":"The stability and complexity of antibody responses to the major surface antigen of Plasmodium falciparum are associated with age in a malaria endemic area","volume":"10","author":"Barry","year":"2011","journal-title":"Mol Cell Proteomics"},{"key":"2023101809352409300_jiad217-B27","doi-asserted-by":"crossref","first-page":"2124","DOI":"10.1002\/eji.201747032","article-title":"Patterns of protective associations differ for antibodies to P. falciparum\u2013infected erythrocytes and merozoites in immunity against malaria in children","volume":"47","author":"Chan","year":"2017","journal-title":"Eur J Immunol"},{"key":"2023101809352409300_jiad217-B28","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1086\/340420","article-title":"Plasmodium falciparum infections are associated with agglutinating antibodies to parasite-infected erythrocyte surface antigens among healthy Kenyan children","volume":"185","author":"Bull","year":"2002","journal-title":"J Infect Dis"},{"key":"2023101809352409300_jiad217-B29","doi-asserted-by":"crossref","first-page":"3444","DOI":"10.4049\/jimmunol.168.7.3444","article-title":"Plasmodium falciparum variant surface antigen expression varies between isolates causing severe and nonsevere malaria and is modified by acquired immunity","volume":"168","author":"Nielsen","year":"2002","journal-title":"J Immunol"},{"key":"2023101809352409300_jiad217-B30","doi-asserted-by":"crossref","first-page":"122","DOI":"10.4269\/ajtmh.1998.58.122","article-title":"Short report: severe malaria associated with blood group","volume":"58","author":"Fischer","year":"1998","journal-title":"Am J Trop Med Hyg"},{"key":"2023101809352409300_jiad217-B31","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1086\/515193","article-title":"The role of red blood cell polymorphisms in resistance and susceptibility to malaria","volume":"28","author":"Lell","year":"1999","journal-title":"Clin Infect Dis"},{"key":"2023101809352409300_jiad217-B32","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/1475-2875-5-72","article-title":"ABO phenotypes and malaria related outcomes in mothers and babies in The Gambia: a role for histo-blood groups in placental malaria?","volume":"5","author":"Loscertales","year":"2006","journal-title":"Malar J"},{"key":"2023101809352409300_jiad217-B33","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1179\/136485905X19946","article-title":"ABO-blood-group types and protection against severe, Plasmodium falciparum malaria","volume":"99","author":"Pathirana","year":"2005","journal-title":"Ann Trop Med Parasitol"},{"key":"2023101809352409300_jiad217-B34","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.1182\/blood-2007-03-077602","article-title":"The ABO blood group system and Plasmodium falciparum malaria","volume":"110","author":"Cserti","year":"2007","journal-title":"Blood"},{"key":"2023101809352409300_jiad217-B35","doi-asserted-by":"crossref","first-page":"149","DOI":"10.4269\/ajtmh.1993.48.149","article-title":"The effects of hemoglobin genotype and ABO blood group on the formation of rosettes by Plasmodium falciparum\u2013infected red blood cells","volume":"48","author":"Udomsangpetch","year":"1993","journal-title":"Am J Trop Med Hyg"},{"key":"2023101809352409300_jiad217-B36","doi-asserted-by":"crossref","first-page":"2971","DOI":"10.1128\/IAI.68.5.2971-2975.2000","article-title":"Blood group A antigen is a coreceptor in Plasmodium falciparum rosetting","volume":"68","author":"Barragan","year":"2000","journal-title":"Infect Immun"},{"key":"2023101809352409300_jiad217-B37","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1073\/pnas.0305306101","article-title":"A human complement receptor 1 polymorphism that reduces Plasmodium falciparum rosetting confers protection against severe malaria","volume":"101","author":"Cockburn","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2023101809352409300_jiad217-B38","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1086\/600071","article-title":"Analysis of Plasmodium falciparum var genes expressed in children from Papua New Guinea","volume":"200","author":"Falk","year":"2009","journal-title":"J Infect Dis"},{"key":"2023101809352409300_jiad217-B39","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1086\/503776","article-title":"Virulence of malaria is associated with differential expression of Plasmodium falciparum var gene subgroups in a case-control study","volume":"193","author":"Kaestli","year":"2006","journal-title":"J Infect Dis"},{"key":"2023101809352409300_jiad217-B40","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1084\/jem.20040274","article-title":"Plasmodium falciparum associated with severe childhood malaria preferentially expresses PfEMP1 encoded by group A var genes","volume":"199","author":"Jensen","year":"2004","journal-title":"J Exp Med"},{"key":"2023101809352409300_jiad217-B41","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.69040","article-title":"Common virulence gene expression in adult first-time infected malaria patients and severe cases","volume":"10","author":"Wichers","year":"2021","journal-title":"Elife"},{"key":"2023101809352409300_jiad217-B42","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.2004328","article-title":"The Plasmodium falciparum transcriptome in severe malaria reveals altered expression of genes involved in important processes including surface antigen-encoding var genes","volume":"16","author":"Tonkin-Hill","year":"2018","journal-title":"PLoS Biol"}],"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiad217\/50734568\/jiad217.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/228\/8\/1099\/52210004\/jiad217.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/228\/8\/1099\/52210004\/jiad217.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T09:36:39Z","timestamp":1697621799000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/article\/228\/8\/1099\/7204419"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,21]]},"references-count":42,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,6,21]]},"published-print":{"date-parts":[[2023,10,18]]}},"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiad217","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,10,15]]},"published":{"date-parts":[[2023,6,21]]}}}