{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T07:40:23Z","timestamp":1778744423967,"version":"3.51.4"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,11,30]],"date-time":"2024-11-30T00:00:00Z","timestamp":1732924800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2024,11,30]],"date-time":"2024-11-30T00:00:00Z","timestamp":1732924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["Proc.# 2017\/12924-3"],"award-info":[{"award-number":["Proc.# 2017\/12924-3"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["Proc. # 312654\/2021-9"],"award-info":[{"award-number":["Proc. # 312654\/2021-9"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Immunogenetics"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1007\/s00251-024-01362-8","type":"journal-article","created":{"date-parts":[[2024,11,30]],"date-time":"2024-11-30T01:43:29Z","timestamp":1732931009000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Analysis of Complement Factor H gene polymorphisms and their association with clinical manifestations ofleptospirosis"],"prefix":"10.1007","volume":"77","author":[{"given":"Lazara Elena","family":"Santiesteban-Lores","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonardo Moura","family":"Midon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ThirsaAlvares","family":"Franco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciano Marcondes","family":"de Oliveira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sumire","family":"Hibi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yosena","family":"Chiani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"GdayllonCavalcante","family":"Meneses","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"De Francesco Daher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denise Moraes","family":"Fonseca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Pontillo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lourdes","family":"Isaac","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,11,30]]},"reference":[{"key":"1362_CR1","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1007\/s13353-018-0444-7","volume":"59","author":"A Anna","year":"2018","unstructured":"Anna A, Monika G (2018) Splicing mutations in human genetic disorders: examples, detection, and confirmation. J Appl Genet 59:253\u2013268. https:\/\/doi.org\/10.1007\/s13353-018-0444-7","journal-title":"J Appl Genet"},{"key":"1362_CR2","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1128\/IAI.01310-08","volume":"77","author":"AS Barbosa","year":"2009","unstructured":"Barbosa AS, Abreu PAE, Vasconcellos SA et al (2009) Immune Evasion of Leptospira Species by Acquisition of Human Complement Regulator C4BP. Infect Immun 77:1137\u20131143. https:\/\/doi.org\/10.1128\/IAI.01310-08","journal-title":"Infect Immun"},{"key":"1362_CR3","doi-asserted-by":"publisher","first-page":"3207","DOI":"10.1128\/IAI.00279-10","volume":"78","author":"AS Barbosa","year":"2010","unstructured":"Barbosa AS, Monaris D, Silva LB et al (2010) Functional Characterization of LcpA, a Surface-Exposed Protein of Leptospira spp. That Binds the Human Complement Regulator C4BP. Infect Immun 78:3207\u20133216. https:\/\/doi.org\/10.1128\/IAI.00279-10","journal-title":"Infect Immun"},{"key":"1362_CR4","doi-asserted-by":"publisher","unstructured":"Bharti AR, Nally JE, Ricaldi JN et al (2003) Leptospirosis: A zoonotic disease of global importance. Lancet Infect Dis 3(12):757\u2013771. https:\/\/doi.org\/10.1016\/s1473-3099(03)00830-2","DOI":"10.1016\/s1473-3099(03)00830-2"},{"key":"1362_CR5","doi-asserted-by":"publisher","unstructured":"Castiblanco-Valencia MM, Fraga TR, Silva LB Da et al (2012) Leptospiral immunoglobulin-like proteins interact with human complement regulators factor H, FHL-1, FHR-1, and C4BP. J Infect Dis 205. https:\/\/doi.org\/10.1093\/infdis\/jir875","DOI":"10.1093\/infdis\/jir875"},{"key":"1362_CR6","doi-asserted-by":"publisher","unstructured":"Castiblanco-Valencia M, Fraga T, Isaac L et al (2016) Plasmin cleaves fibrinogen and the human complement proteins C3b and C5 in the presence of Leptospira interrogans proteins: A new role of LigA and LigB in invasion and complement immune evasion. Immunobiology 221. https:\/\/doi.org\/10.1016\/j.imbio.2016.01.001","DOI":"10.1016\/j.imbio.2016.01.001"},{"key":"1362_CR7","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.actatropica.2015.03.007","volume":"146","author":"M C\u00e9dola","year":"2015","unstructured":"C\u00e9dola M, Chiani Y, Pretre G et al (2015) Association of Toll-like receptor 2 Arg753Gln and Toll-like receptor 1 Ile602Ser single-nucleotide polymorphisms with leptospirosis in an Argentinian population. Acta Trop 146:73\u201380. https:\/\/doi.org\/10.1016\/j.actatropica.2015.03.007","journal-title":"Acta Trop"},{"key":"1362_CR8","doi-asserted-by":"publisher","first-page":"2049","DOI":"10.4049\/jimmunol.1201751","volume":"190","author":"SJ Clark","year":"2013","unstructured":"Clark SJ, Ridge LA, Herbert AP et al (2013) Tissue-Specific Host Recognition by Complement Factor H Is Mediated by Differential Activities of Its Glycosaminoglycan-Binding Regions. J Immunol 190:2049\u20132057. https:\/\/doi.org\/10.4049\/jimmunol.1201751","journal-title":"J Immunol"},{"key":"1362_CR9","unstructured":"Contreras AV, Zenteno JC, Fern\u00e1ndez-L\u00f3pez JC et al (2014) CFH haplotypes and ARMS2, C2, C3, and CFB alleles show association with susceptibility to age-related macular degeneration in Mexicans. Mol Vis 20:105\u2013116"},{"key":"1362_CR10","doi-asserted-by":"publisher","unstructured":"Costa F, Hagan JE, Calcagno J et al (2015) Global Morbidity and Mortality of Leptospirosis: A Systematic Review. PLoSNegl Trop Dis 9. https:\/\/doi.org\/10.1371\/journal.pntd.0003898","DOI":"10.1371\/journal.pntd.0003898"},{"key":"1362_CR32","doi-asserted-by":"publisher","unstructured":"da Silva LB, Miragaia LDS, Dantas Breda LC et al (2015) Pathogenic Leptospira species acquire factor H and vitronectin via the surface protein LcpA. Infect Immun 83. https:\/\/doi.org\/10.1128\/IAI.02844-14","DOI":"10.1128\/IAI.02844-14"},{"key":"1362_CR11","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1001\/jama.296.3.301","volume":"296","author":"DDG Despriet","year":"2006","unstructured":"Despriet DDG, Klaver CCW, Witteman JCM et al (2006) Complement Factor H Polymorphism, Complement Activators, and Risk of Age-Related Macular Degeneration. JAMA 296:301. https:\/\/doi.org\/10.1001\/jama.296.3.301","journal-title":"JAMA"},{"key":"1362_CR12","doi-asserted-by":"publisher","first-page":"e108534","DOI":"10.1371\/journal.pone.0108534","volume":"9","author":"LM Esteves","year":"2014","unstructured":"Esteves LM, Bulh\u00f5es SM, Branco CC et al (2014) Human Leptospirosis: Seroreactivity and Genetic Susceptibility in the Population of S\u00e3o Miguel Island (Azores, Portugal). PLoS ONE 9:e108534. https:\/\/doi.org\/10.1371\/journal.pone.0108534","journal-title":"PLoS ONE"},{"key":"1362_CR13","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1016\/j.humimm.2009.08.007","volume":"70","author":"RN Fialho","year":"2009","unstructured":"Fialho RN, Martins L, Pinheiro JP et al (2009) Role of human leukocyte antigen, killer-cell immunoglobulin-like receptors, and cytokine gene polymorphisms in leptospirosis. Hum Immunol 70:915\u2013920. https:\/\/doi.org\/10.1016\/j.humimm.2009.08.007","journal-title":"Hum Immunol"},{"key":"1362_CR14","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.bpj.2018.12.007","volume":"116","author":"RES Harrison","year":"2019","unstructured":"Harrison RES, Morikis D (2019) Molecular Mechanisms of Macular Degeneration Associated with the Complement Factor H Y402H Mutation. Biophys J 116:215\u2013226. https:\/\/doi.org\/10.1016\/j.bpj.2018.12.007","journal-title":"Biophys J"},{"key":"1362_CR15","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1128\/jb.91.4.1403-1409.1966","volume":"91","author":"RC Johnson","year":"1966","unstructured":"Johnson RC, Muschel LH (1966) Antileptospiral Activity of Serum I. Normal Immune Serum J Bacteriol 91:1403\u20131409. https:\/\/doi.org\/10.1128\/jb.91.4.1403-1409.1966","journal-title":"Normal Immune Serum J Bacteriol"},{"key":"1362_CR16","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.exger.2008.10.006","volume":"44","author":"J Jylh\u00e4v\u00e4","year":"2009","unstructured":"Jylh\u00e4v\u00e4 J, Eklund C, Jylh\u00e4 M et al (2009) Complement factor H 402His variant confers an increased mortality risk in Finnish nonagenarians: The Vitality 90+ study. ExpGerontol 44:297\u2013299. https:\/\/doi.org\/10.1016\/j.exger.2008.10.006","journal-title":"ExpGerontol"},{"key":"1362_CR17","doi-asserted-by":"publisher","unstructured":"Langford-Smith A, Day AJ, Bishop PN, Clark SJ (2015) Complementing the Sugar Code: Role of GAGs and Sialic Acid in Complement Regulation. Front Immunol 6. https:\/\/doi.org\/10.3389\/fimmu.2015.00025","DOI":"10.3389\/fimmu.2015.00025"},{"key":"1362_CR18","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1128\/CMR.14.2.296-326.2001","volume":"14","author":"PN Levett","year":"2001","unstructured":"Levett PN (2001) Leptospirosis. Clinmicrobiol Rev 14:296\u2013326. https:\/\/doi.org\/10.1128\/CMR.14.2.296-326.2001","journal-title":"Clinmicrobiol Rev"},{"key":"1362_CR19","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/sj.gene.6364058","volume":"5","author":"J Lingappa","year":"2004","unstructured":"Lingappa J, Kuffner T, Tappero J et al (2004) HLA-DQ6 and ingestion of contaminated water: possible gene\u2013environment interaction in an outbreak of Leptospirosis. Genes Immun 5:197\u2013202. https:\/\/doi.org\/10.1038\/sj.gene.6364058","journal-title":"Genes Immun"},{"key":"1362_CR20","first-page":"1","volume":"71","author":"S Meri","year":"1990","unstructured":"Meri S, Morgan BP, Davies A et al (1990) Human protectin (CD59), an 18000\u201320000 MW complement lysis restricting factor, inhibits C5b\u20138 catalysed insertion of C9 into lipid bilayers. Immunology 71:1\u20139","journal-title":"Immunology"},{"key":"1362_CR21","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.micpath.2005.07.003","volume":"39","author":"T Meri","year":"2005","unstructured":"Meri T, Murgia R, Stefanel P et al (2005) Regulation of complement activation at the C3-level by serum resistant leptospires. MicrobPathog 39:139\u2013147. https:\/\/doi.org\/10.1016\/j.micpath.2005.07.003","journal-title":"MicrobPathog"},{"key":"1362_CR22","doi-asserted-by":"publisher","unstructured":"Neumann HPH, Salzmann M, Bohnert-Iwan B et al (2003) Haemolyticuraemic syndrome and mutations of the factor H gene: A registry-based study of German speaking countries. J Med Genet 40 https:\/\/doi.org\/10.1136\/jmg.40.9.676","DOI":"10.1136\/jmg.40.9.676"},{"key":"1362_CR23","doi-asserted-by":"publisher","first-page":"2464","DOI":"10.4049\/jimmunol.1701695","volume":"200","author":"AJ Osborne","year":"2018","unstructured":"Osborne AJ, Breno M, Borsa NG et al (2018) Statistical Validation of Rare Complement Variants Provides Insights into the Molecular Basis of Atypical Hemolytic Uremic Syndrome and C3 Glomerulopathy. J Immunol 200:2464\u20132478. https:\/\/doi.org\/10.4049\/jimmunol.1701695","journal-title":"J Immunol"},{"key":"1362_CR24","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1084\/jem.146.1.257","volume":"146","author":"MK Pangburn","year":"1977","unstructured":"Pangburn MK, Schreiber RD, M\u00fcller-Eberhard HJ (1977) Human complement C3b inactivator: isolation, characterization, and demonstration of an absolute requirement for the serum protein beta1H for cleavage of C3b and C4b in solution. J Exp Med 146:257\u2013270. https:\/\/doi.org\/10.1084\/jem.146.1.257","journal-title":"J Exp Med"},{"key":"1362_CR25","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1007\/s00018-016-2418-4","volume":"74","author":"R Parente","year":"2017","unstructured":"Parente R, Clark SJ, Inforzato A, Day AJ (2017) Complement factor H in host defense and immune evasion. Cell Mol Life Sci 74:1605\u20131624. https:\/\/doi.org\/10.1007\/s00018-016-2418-4","journal-title":"Cell Mol Life Sci"},{"key":"1362_CR26","doi-asserted-by":"publisher","unstructured":"Pereira MM, Schneider MC, Munoz-Zanzi C et al (2017) A road map for leptospirosis research and health policies based on country needs in Latin America. Rev Panam Salud P\u00fablica 1\u20139. https:\/\/doi.org\/10.26633\/RPSP.2017.131","DOI":"10.26633\/RPSP.2017.131"},{"key":"1362_CR27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.medmal.2012.11.005","volume":"43","author":"M Picardeau","year":"2013","unstructured":"Picardeau M (2013) Diagnosis and epidemiology of leptospirosis. M\u00e9decine Mal Infect 43:1\u20139. https:\/\/doi.org\/10.1016\/j.medmal.2012.11.005","journal-title":"M\u00e9decine Mal Infect"},{"key":"1362_CR28","doi-asserted-by":"publisher","first-page":"2277","DOI":"10.1084\/jem.20071069","volume":"204","author":"BE Prosser","year":"2007","unstructured":"Prosser BE, Johnson S, Roversi P et al (2007) Structural basis for complement factor H\u2013linked age-related macular degeneration. J Exp Med 204:2277\u20132283. https:\/\/doi.org\/10.1084\/jem.20071069","journal-title":"J Exp Med"},{"key":"1362_CR29","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1086\/318203","volume":"68","author":"A Richards","year":"2001","unstructured":"Richards A, Buddles MR, Donne RL et al (2001) Factor H Mutations in Hemolytic Uremic Syndrome Cluster in Exons 18\u201320, a Domain Important for Host Cell Recognition. Am J Hum Genet 68:485\u2013490. https:\/\/doi.org\/10.1086\/318203","journal-title":"Am J Hum Genet"},{"key":"1362_CR30","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1042\/bj2490593","volume":"249","author":"J Ripoche","year":"1988","unstructured":"Ripoche J, Day AJ, Harris TJR, Sim RB (1988) The complete amino acid sequence of human complement factor H. Biochem J 249:593\u2013602. https:\/\/doi.org\/10.1042\/bj2490593","journal-title":"Biochem J"},{"key":"1362_CR31","unstructured":"Minist\u00e9rio da Sa\u00fade, Minist\u00e9rio da Saude (n.d.). https:\/\/www.gov.br\/saude\/pt-br\/pagina-inicial. Accessed 14 June 2024"},{"key":"1362_CR33","doi-asserted-by":"publisher","unstructured":"Silva A (2011) Interaction of human complement factor H variants Tyr402 and His402 with Leptospira spp. Front Immunol 2 https:\/\/doi.org\/10.3389\/fimmu.2011.00044","DOI":"10.3389\/fimmu.2011.00044"},{"key":"1362_CR34","doi-asserted-by":"publisher","unstructured":"Teixeira AG, Silva AS, Lin FLH, et al (2010) Association of complement factor H Y402H polymorphism and age-related macular degeneration in Brazilian patients. ActaOphthalmol 88 https:\/\/doi.org\/10.1111\/j.1755-3768.2010.01932.x","DOI":"10.1111\/j.1755-3768.2010.01932.x"},{"key":"1362_CR35","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1016\/j.survophthal.2020.10.008","volume":"66","author":"N Tzoumas","year":"2021","unstructured":"Tzoumas N, Hallam D, Harris CL et al (2021) Revisiting the role of factor H in age-related macular degeneration: Insights from complement-mediated renal disease and rare genetic variants. SurvOphthalmol 66:378\u2013401. https:\/\/doi.org\/10.1016\/j.survophthal.2020.10.008","journal-title":"SurvOphthalmol"},{"key":"1362_CR36","doi-asserted-by":"publisher","first-page":"3268","DOI":"10.1073\/pnas.73.9.3268","volume":"73","author":"JM Weiler","year":"1976","unstructured":"Weiler JM, Daha MR, Austen KF, Fearon DT (1976) Control of the amplification convertase of complement by the plasma protein beta1H. Proc Natl AcadSci 73:3268\u20133272. https:\/\/doi.org\/10.1073\/pnas.73.9.3268","journal-title":"Proc Natl AcadSci"},{"key":"1362_CR37","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1086\/431426","volume":"77","author":"S Zareparsi","year":"2005","unstructured":"Zareparsi S, Branham KEH, Li M et al (2005) Strong Association of the Y402H Variant in Complement factor H at 1q32 with Susceptibility to Age-Related Macular Degeneration. Am J Hum Genet 77:149\u2013153. https:\/\/doi.org\/10.1086\/431426","journal-title":"Am J Hum Genet"}],"container-title":["Immunogenetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00251-024-01362-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00251-024-01362-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00251-024-01362-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T22:01:41Z","timestamp":1768341701000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00251-024-01362-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,30]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["1362"],"URL":"https:\/\/doi.org\/10.1007\/s00251-024-01362-8","relation":{},"ISSN":["0093-7711","1432-1211"],"issn-type":[{"value":"0093-7711","type":"print"},{"value":"1432-1211","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,30]]},"assertion":[{"value":"5 August 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 November 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 November 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The present study was conducted in accordance with the Declaration of Helsinki. Ethical approval was provided by the Ethical Committee of the Institute of Biomedical Sciences University of S\u00e3o Paulo\/USP (identification code: 78969417.5.1001.5467; December 14th, 2017) and the Ethical Committee of the Municipal Health Secretariat from S\u00e3o Paulo State Government (Identification code: 78969417.5.3001.0086; January 2nd, 2019).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"4"}}