{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T01:01:02Z","timestamp":1760576462499,"version":"build-2065373602"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Susceptibility to malaria can be influenced by host genetic factors, including immune response genes. Antibodies against Plasmodium antigens are known to play an important role in protection from clinical disease. Polymorphisms in these antibodies may result in different functional properties that could provide protection from malaria.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Immunoglobulin G1 (IgG1) and immunoglobulin G3 (IgG3) alleles and IgG3 hinge region were investigated by polymerase chain reaction and Sanger sequencing in a longitudinal cohort of children aged 1\u20133 years (N = 203) from the East Sepik region of Papua New Guinea. Linear regression was used to investigate associations between immunoglobulin alleles and Plasmodium infections.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Seventy-eight percent of the children were either heterozygous (n = 82 [40%]) or homozygous (n = 77 [38%]) for IGHG3*30 (G3m29), a novel IgG3 allele. G3m29 has a long hinge region of 4 exons. Significantly fewer Plasmodium spp infections were observed in children with the IGHG3*30 allele compared to children without the allele (\u03b2 = \u22121.736 [95% confidence interval {CI}, \u22123.39, \u2212.079]; P = .038). This effect was most noticeable for Plasmodium vivax asymptomatic infections as IGHG3*30 carriers had on average 1 fewer infection in the 18-month follow-up period compared with non-IGHG3*30 allele carriers (\u03b2 = \u22121.06 [95% CI, \u22122.01, \u2212.12]; P = .028). Additionally, IGHG3*30 allele carriers had significantly lower levels of IgG to P vivax vaccine candidate proteins compared to non-IGHG3*30 allele carriers.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The IGHG3*30 allele is highly prevalent in the East Sepik region and is associated with fewer Plasmodium spp infections.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiaf390","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T07:44:54Z","timestamp":1753688694000},"page":"e555-e564","source":"Crossref","is-referenced-by-count":0,"title":["Association of a Novel IgG3 Allele With Malaria in Children From the Sepik Region of Papua New Guinea"],"prefix":"10.1093","volume":"232","author":[{"given":"Maria","family":"Saeed","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, The Peter Doherty Institute for Infection and Immunity, University of Melbourne , Melbourne, Victoria ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2677-6208","authenticated-orcid":false,"given":"Elizabeth H","family":"Aitken","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Peter Doherty Institute for Infection and Immunity, University of Melbourne , Melbourne, Victoria ,","place":["Australia"]},{"name":"Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne , Melbourne, Victoria ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8595-4310","authenticated-orcid":false,"given":"Myo T","family":"Naung","sequence":"additional","affiliation":[{"name":"Infection and Global Health Division, Walter and Eliza Hall Institute , Parkville, Victoria ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4466-6563","authenticated-orcid":false,"given":"Caitlin","family":"Bourke","sequence":"additional","affiliation":[{"name":"Infection and Global Health Division, Walter and Eliza Hall Institute , Parkville, Victoria ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1889-396X","authenticated-orcid":false,"given":"Kenneth W","family":"Wu","sequence":"additional","affiliation":[{"name":"Infection and Global Health Division, Walter and Eliza Hall Institute , Parkville, Victoria ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rhea J","family":"Longley","sequence":"additional","affiliation":[{"name":"Infection and Global Health Division, Walter and Eliza Hall Institute , Parkville, Victoria ,","place":["Australia"]},{"name":"Department of Medical Biology, University of Melbourne , Melbourne, Victoria ,","place":["Australia"]},{"name":"Faculty of Tropical Medicine, Mahidol University , Bangkok ,","place":["Thailand"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0020-9704","authenticated-orcid":false,"given":"Amy W","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne , Melbourne, Victoria ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timon","family":"Damelang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Peter Doherty Institute for Infection and Immunity, University of Melbourne , Melbourne, Victoria ,","place":["Australia"]},{"name":"Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne , Melbourne, Victoria ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benson","family":"Kiniboro","sequence":"additional","affiliation":[{"name":"Vector Borne Disease Unit, Papua New Guinea Institute of Medical Research , Goroka ,","place":["Papua New Guinea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivo","family":"Mueller","sequence":"additional","affiliation":[{"name":"Infection and Global Health Division, Walter and Eliza Hall Institute , Parkville, Victoria ,","place":["Australia"]},{"name":"Department of Medical Biology, University of Melbourne , Melbourne, Victoria ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4287-1982","authenticated-orcid":false,"given":"Stephen J","family":"Rogerson","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Peter Doherty Institute for Infection and Immunity, University of Melbourne , Melbourne, Victoria ,","place":["Australia"]},{"name":"Department of Medicine, The Peter Doherty Institute for Infection and Immunity, University of Melbourne , Melbourne, Victoria ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,7,25]]},"reference":[{"year":"2024","author":"World Health Organization","key":"2025101515150804100_jiaf390-B1"},{"key":"2025101515150804100_jiaf390-B2","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1128\/CMR.15.4.564-594.2002","article-title":"Evolutionary and historical aspects of the burden of malaria","volume":"15","author":"Carter","year":"2002","journal-title":"Clin Microbiol Rev"},{"key":"2025101515150804100_jiaf390-B3","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1007\/s00439-020-02142-6","article-title":"Human genetics and malaria resistance","volume":"139","author":"Kariuki","year":"2020","journal-title":"Hum Genet"},{"key":"2025101515150804100_jiaf390-B4","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1038\/192733a0","article-title":"Gamma-globulin and acquired immunity to human malaria","volume":"192","author":"Cohen","year":"1961","journal-title":"Nature"},{"key":"2025101515150804100_jiaf390-B5","doi-asserted-by":"crossref","first-page":"33094","DOI":"10.1038\/srep33094","article-title":"The association between naturally acquired IgG subclass specific antibodies to the PfRH5 invasion complex and protection from Plasmodium falciparum malaria","volume":"6","author":"Weaver","year":"2016","journal-title":"Sci Rep"},{"key":"2025101515150804100_jiaf390-B6","doi-asserted-by":"crossref","first-page":"e65776","DOI":"10.7554\/eLife.65776","article-title":"Developing a multivariate prediction model of antibody features associated with protection of malaria-infected pregnant women from placental malaria","volume":"10","author":"Aitken","year":"2021","journal-title":"Elife"},{"key":"2025101515150804100_jiaf390-B7","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1080\/14760584.2021.1981864","article-title":"Multi-functional antibody profiling for malaria vaccine development and evaluation","volume":"20","author":"Opi","year":"2021","journal-title":"Expert Rev Vaccines"},{"key":"2025101515150804100_jiaf390-B8","doi-asserted-by":"crossref","first-page":"1304365","DOI":"10.3389\/fimmu.2023.1304365","article-title":"Impact of structural modifications of IgG antibodies on effector functions","volume":"14","author":"Damelang","year":"2024","journal-title":"Front Immunol"},{"key":"2025101515150804100_jiaf390-B9","first-page":"630","article-title":"Human Gm, Km, and Am allotypes and their molecular characterization: a remarkable demonstration of polymorphism","volume":"882","author":"Lefranc","year":"2012","journal-title":"Methods Mol Biol"},{"key":"2025101515150804100_jiaf390-B10","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/ncomms1608","article-title":"Competition for FcRn-mediated transport gives rise to short half-life of human IgG3 and offers therapeutic potential","volume":"2","author":"Stapleton","year":"2011","journal-title":"Nat Commun"},{"key":"2025101515150804100_jiaf390-B11","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1111\/trf.12334","article-title":"H435-containing immunoglobulin G3 allotypes are transported efficiently across the human placenta: implications for alloantibody-mediated diseases of the newborn","volume":"54","author":"Einarsdottir","year":"2014","journal-title":"Transfusion (Paris)"},{"key":"2025101515150804100_jiaf390-B12","doi-asserted-by":"crossref","first-page":"e1002403","DOI":"10.1371\/journal.pmed.1002403","article-title":"Associations between an IgG3 polymorphism in the binding domain for FcRn, transplacental transfer of malaria-specific IgG3, and protection against Plasmodium falciparum malaria during infancy: a birth cohort study in Benin","volume":"14","author":"Dechavanne","year":"2017","journal-title":"PLoS Med"},{"key":"2025101515150804100_jiaf390-B13","doi-asserted-by":"crossref","first-page":"520","DOI":"10.3389\/fimmu.2014.00520","article-title":"IgG subclasses and allotypes: from structure to effector functions","volume":"5","author":"Vidarsson","year":"2014","journal-title":"Front Immunol"},{"key":"2025101515150804100_jiaf390-B14","doi-asserted-by":"crossref","first-page":"1008064","DOI":"10.1371\/journal.ppat.1008064","article-title":"IgG3 enhances neutralization potency and Fc effector function of an HIV V2-specific broadly neutralizing antibody","volume":"15","author":"Richardson","year":"2019","journal-title":"PLoS Pathog"},{"key":"2025101515150804100_jiaf390-B15","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.it.2019.01.005","article-title":"Role of IgG3 in infectious diseases","volume":"40","author":"Damelang","year":"2019","journal-title":"Trends Immunol"},{"key":"2025101515150804100_jiaf390-B16","doi-asserted-by":"crossref","first-page":"740","DOI":"10.3389\/fimmu.2020.00740","article-title":"Fc\u03b3r binding and ADCC activity of human IgG allotypes","volume":"11","author":"de Taeye","year":"2020","journal-title":"Front Immunol"},{"key":"2025101515150804100_jiaf390-B17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00251-022-01272-7","article-title":"Functional consequences of allotypic polymorphisms in human immunoglobulin G subclasses","volume":"75","author":"Crowley","year":"2022","journal-title":"Immunogenetics"},{"author":"Damelang","key":"2025101515150804100_jiaf390-B18","doi-asserted-by":"publisher","DOI":"10.2139\/ssrn.4287904"},{"key":"2025101515150804100_jiaf390-B19","doi-asserted-by":"crossref","first-page":"6098","DOI":"10.1074\/jbc.M113.541813","article-title":"Dynamics of inter-heavy chain interactions in human immunoglobulin G (IgG) subclasses studied by kinetic Fab arm exchange","volume":"289","author":"Rispens","year":"2014","journal-title":"Biol Chem"},{"key":"2025101515150804100_jiaf390-B20","doi-asserted-by":"crossref","first-page":"9047","DOI":"10.1371\/journal.pone.0009047","article-title":"Differential patterns of infection and disease with P. falciparum and P. vivax in young Papua New Guinean children","volume":"5","author":"Lin","year":"2010","journal-title":"PLoS One"},{"key":"2025101515150804100_jiaf390-B21","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1128\/JCM.42.6.2403-2410.2004","article-title":"Development of a multiplex PCR-ligase detection reaction assay for diagnosis of infection by the four parasite species causing malaria in humans","volume":"42","author":"McNamara","year":"2004","journal-title":"J Clin Microbiol"},{"key":"2025101515150804100_jiaf390-B22","doi-asserted-by":"crossref","first-page":"29203","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":"2025101515150804100_jiaf390-B23","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1074\/mcp.M116.064733","article-title":"Human immunoglobulin heavy gamma chain polymorphisms: molecular confirmation of proteomic assessment","volume":"16","author":"Dambrun","year":"2017","journal-title":"Mole Cell Proteomics"},{"key":"2025101515150804100_jiaf390-B24","first-page":"88","article-title":"Determination of allotypes G1m(f) and G1m(z) at the genomic level by subclass-specific amplification of DNA and use of allele-specific probes","volume":"8","author":"Balbin","year":"1991","journal-title":"Exp Clin Immunogenet"},{"key":"2025101515150804100_jiaf390-B25","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1080\/19420862.2015.1128605","article-title":"A comparison of the ability of the human IgG1 allotypes G1m3 and G1m1,17 to stimulate T-cell responses from allotype matched and mismatched donors","volume":"8","author":"Webster","year":"2016","journal-title":"MAbs"},{"key":"2025101515150804100_jiaf390-B26","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1093\/infdis\/jiab548","article-title":"Association of immunoglobulin G3 hinge region length polymorphism with cerebral malaria in Ghanaian children","volume":"225","author":"Kyei-Baafour","year":"2022","journal-title":"J Infect Dis"},{"key":"2025101515150804100_jiaf390-B27","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1038\/s41591-020-0841-4","article-title":"Development and validation of serological markers for detecting recent Plasmodium vivax infection","volume":"26","author":"Longley","year":"2020","journal-title":"Nat Med"},{"key":"2025101515150804100_jiaf390-B28","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1111\/j.1365-3024.2007.00938.x","article-title":"Significant differences in GM allotype frequencies between two sympatric tribes with markedly differential susceptibility to malaria","volume":"29","author":"Pandey","year":"2007","journal-title":"Parasite Immunol"},{"key":"2025101515150804100_jiaf390-B29","first-page":"5","article-title":"Natural selection, genetic drift, and gene flow do not act in isolation in natural populations","volume":"3","author":"Andrews","year":"2010","journal-title":"Nat Educ Knowledge"},{"key":"2025101515150804100_jiaf390-B30","doi-asserted-by":"crossref","first-page":"102526","DOI":"10.1016\/j.parint.2021.102526","article-title":"Plasmodium vivax\u2014how hidden reservoirs hinder global malaria elimination","volume":"87","author":"Angrisano","year":"2022","journal-title":"Parasitol Int"},{"key":"2025101515150804100_jiaf390-B31","first-page":"81","article-title":"Direct antiglobulin reactions in Gambian children with P. falciparum malaria III. Expression of IgG subclass determinants and genetic markers and association with anaemia","volume":"41","author":"Facer","year":"1980","journal-title":"Clin Exp Immunol"},{"key":"2025101515150804100_jiaf390-B32","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1186\/s12936-022-04361-w","article-title":"Naturally acquired antibodies from Beninese infants promote Plasmodium falciparum merozoite-phagocytosis by human blood leukocytes: implications for control of asymptomatic malaria infections","volume":"21","author":"Fall","year":"2022","journal-title":"Malar J"},{"key":"2025101515150804100_jiaf390-B33","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1038\/301720a0","article-title":"An idiotypic determinant formed by both immunoglobulin constant and variable regions","volume":"301","author":"Morahan","year":"1983","journal-title":"Nature"},{"key":"2025101515150804100_jiaf390-B34","doi-asserted-by":"crossref","first-page":"13917","DOI":"10.1074\/jbc.M700661200","article-title":"The immunoglobulin heavy chain constant region affects kinetic and thermodynamic parameters of antibody variable region interactions with antigen","volume":"282","author":"Torres","year":"2007","journal-title":"J Biol Chem"},{"key":"2025101515150804100_jiaf390-B35","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.cellimm.2010.03.006","article-title":"Fc\u03b3 receptors exhibit different phagocytosis potential in human neutrophils","volume":"263","author":"Rivas-Fuentes","year":"2010","journal-title":"Cell Immunol"},{"key":"2025101515150804100_jiaf390-B36","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1038\/s41467-021-21998-4","article-title":"Mechanisms and targets of Fc\u03b3-receptor mediated immunity to malaria sporozoites","volume":"12","author":"Feng","year":"2021","journal-title":"Nat Commun"},{"key":"2025101515150804100_jiaf390-B37","doi-asserted-by":"crossref","first-page":"e1008083","DOI":"10.1371\/journal.ppat.1008083","article-title":"Hinge length contributes to the phagocytic activity of HIV-specific IgG1 and IgG3 antibodies","volume":"16","author":"Chu","year":"2020","journal-title":"PLoS Pathog"},{"key":"2025101515150804100_jiaf390-B38","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.4049\/jimmunol.110.6.1642","article-title":"The effect of Gm (23) on the concentration of IgG2 and IgG4 in normal human serum","volume":"110","author":"Steinberg","year":"1973","journal-title":"J Immunol"},{"key":"2025101515150804100_jiaf390-B39","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/BF00918793","article-title":"Allotype-associated differences in concentrations of human IgG subclasses","volume":"11","author":"Sarvas","year":"1991","journal-title":"J Clin Immunol"},{"key":"2025101515150804100_jiaf390-B40","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0198-8859(96)00205-4","article-title":"GM phenotypes influence the concentrations of the four subclasses of immunoglobulin G in normal human serum","volume":"51","author":"Pandey","year":"1996","journal-title":"Hum Immunol"},{"key":"2025101515150804100_jiaf390-B41","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/j.1365-3083.1993.tb01750.x","article-title":"Serum IgG and IgG subclass contents in different Gm phenotypes","volume":"37","author":"Oxelius","year":"1993","journal-title":"Scand J Immunol"}],"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\/jiaf390\/63858138\/jiaf390.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/232\/4\/e555\/63858138\/jiaf390.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/232\/4\/e555\/63858138\/jiaf390.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T19:17:29Z","timestamp":1760555849000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/article\/232\/4\/e555\/8214313"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,25]]},"references-count":41,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,7,25]]},"published-print":{"date-parts":[[2025,10,15]]}},"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiaf390","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"type":"print","value":"0022-1899"},{"type":"electronic","value":"1537-6613"}],"subject":[],"published-other":{"date-parts":[[2025,10,15]]},"published":{"date-parts":[[2025,7,25]]}}}