{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T08:55:27Z","timestamp":1781513727025,"version":"3.54.1"},"reference-count":32,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T00:00:00Z","timestamp":1770422400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T00:00:00Z","timestamp":1770422400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2026,5]]},"abstract":"ABSTRACT<\/jats:title>\n \n Introduction<\/jats:title>\n \n Inhibitor development remains one of the most serious complications of replacement therapy in patients with hemophilia. Tumour necrosis factor\u2010alpha (TNF\u2010\n \u03b1<\/jats:italic>\n ) is a key pro\u2010inflammatory cytokine, and its genetic variants have been implicated in immune\u2010related conditions. The association between TNF\u2010\n \u03b1<\/jats:italic>\n gene polymorphisms and inhibitor formation in hemophilia has been explored.\n <\/jats:p>\n <\/jats:sec>\n \n Aim<\/jats:title>\n \n To systematically review and quantitatively synthesize available evidence on the association between TNF\u2010\n \u03b1<\/jats:italic>\n gene polymorphisms and the development of inhibitors in patients with hemophilia.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n A comprehensive literature search was conducted in PubMed and SciELO from inception to 11 February 2025. Eligible studies evaluated TNF\u2010\n \u03b1<\/jats:italic>\n polymorphisms in patients with hemophilia and reported data on inhibitor status. Data extraction and quality assessment (using the Q\u2010Genie tool) were performed independently by two reviewers. Meta\u2010analyses were conducted using the Mantel\u2010Haenszel method, where pooled odds ratios (\n ORs<\/jats:italic>\n ) with 95% confidence intervals (\n CIs<\/jats:italic>\n ) were calculated.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Nineteen studies met the inclusion criteria for the systematic review, and ten were included in the meta\u2010analysis. A significant association was observed between the rs1800629 (\u2212308\n G>A<\/jats:italic>\n ) polymorphism and inhibitor development under the A\u2010recessive model (\n OR<\/jats:italic>\n = 2.00; 95%\n CI<\/jats:italic>\n : 1.13\u20133.54). No significant associations were found for other TNF\u2010\n \u03b1<\/jats:italic>\n polymorphisms.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n This meta\u2010analysis suggests that the TNF\u2010\n \u03b1<\/jats:italic>\n rs1800629 polymorphism may be associated with an increased risk of inhibitor development in patients with hemophilia. These findings highlight the potential role of inflammatory genetic variants in modulating the immune response to replacement therapy. Further large\u2010scale, multi\u2010ethnic studies are needed to confirm these results and better understand the underlying mechanisms.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/hae.70223","type":"journal-article","created":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T16:44:52Z","timestamp":1770482692000},"page":"671-679","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["TNF\u2011\n \u03b1<\/i>\n Gene Polymorphisms as Determinants of Alloantibody Emergence in Hemophilia: A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1111","volume":"32","author":[{"given":"Alessandra Faustino da Concei\u00e7\u00e3o","family":"Bezerra","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio De Biologia Integrativa Grupo De Pesquisa em Bioestat\u00edstica e Epidemiologia Molecular Departamento De Gen\u00e9tica Ecologia e Evolu\u00e7\u00e3o Instituto De Ci\u00eancias Biol\u00f3gicas Universidade Federal de Minas Gerais Belo Horizonte Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nat\u00e3 Abner Andrade Carito","family":"de Sousa","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio De Biologia Integrativa Grupo De Pesquisa em Bioestat\u00edstica e Epidemiologia Molecular Departamento De Gen\u00e9tica Ecologia e Evolu\u00e7\u00e3o Instituto De Ci\u00eancias Biol\u00f3gicas Universidade Federal de Minas Gerais Belo Horizonte Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suely Meireles","family":"Rezende","sequence":"additional","affiliation":[{"name":"Departamento De Cl\u00ednica M\u00e9dica Faculdade De Medicina Universidade Federal de Minas Gerais Belo Horizonte, Minas Gerais Belo Horizonte Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renan Pedra de","family":"Souza","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio De Biologia Integrativa Grupo De Pesquisa em Bioestat\u00edstica e Epidemiologia Molecular Departamento De Gen\u00e9tica Ecologia e Evolu\u00e7\u00e3o Instituto De Ci\u00eancias Biol\u00f3gicas Universidade Federal de Minas Gerais Belo Horizonte Brazil"},{"name":"Instituto Ren\u00e9 Rachou Funda\u00e7\u00e3o Oswaldo Cruz Belo Horizonte Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2006.01361.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph15080911"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.14182"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep32677"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0029(20000801)50:3<216::AID-JEMT5>3.0.CO;2-Q"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20180143"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/jocd.14940"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.70048"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6483490"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2019.05.005"},{"issue":"6","key":"e_1_2_9_13_1","article-title":"Risk 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