{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T21:00:23Z","timestamp":1789678823462,"version":"4.0.1"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T00:00:00Z","timestamp":1599177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"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\/501100008123","name":"Centre Scientifique de Monaco","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008123","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"DOI":"10.3389\/fimmu.2020.02041","type":"journal-article","created":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T13:48:49Z","timestamp":1599227329000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Polymorphisms in Inflammatory Genes Modulate Clinical Complications in Patients With Sickle Cell Disease"],"prefix":"10.3389","volume":"11","author":[{"given":"Karina","family":"Tozatto-Maio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Girot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indou Deme","family":"Ly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Cristina","family":"Silva Pinto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanderson","family":"Rocha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Fernandes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahima","family":"Diagne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahia","family":"Benzerara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla L.","family":"Dinardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia Pavan","family":"Soler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Kashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itau\u00e1 Leston","family":"Araujo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Kenzey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme H. H.","family":"Fonseca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evandra S.","family":"Rodrigues","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"Volt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana","family":"Jarduli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Ruggeri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Mariaselvam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra F. M.","family":"Gualandro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanadi","family":"Rafii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Cappelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe Melo","family":"Nogueira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graziana Maria","family":"Scigliuolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato Luiz","family":"Guerino-Cunha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelen Cristina Ribeiro","family":"Malmegrim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belinda P.","family":"Sim\u00f5es","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliane","family":"Gluckman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryad","family":"Tamouza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,9,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2018","DOI":"10.1016\/S0140-6736(10)61029-X","article-title":"Sickle-cell disease","volume":"376","author":"Rees","year":"2010","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.1056\/NEJMra1510865","article-title":"Sickle cell disease","volume":"376","author":"Piel","year":"2017","journal-title":"N Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1056\/NEJM199202273260905","article-title":"The use of transcranial ultrasonography to predict stroke in sickle cell disease","volume":"326","author":"Adams","year":"1992","journal-title":"N Engl J Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"263","DOI":"10.3233\/CH-189012","article-title":"Inflammation in sickle cell disease","volume":"68","author":"Conran","year":"2018","journal-title":"Clin Hemorheol Microcirc"},{"key":"B5","doi-asserted-by":"publisher","first-page":"18010","DOI":"10.1038\/nrdp.2018.10","article-title":"Sickle cell disease","volume":"4","author":"Kato","year":"2018","journal-title":"Nat Rev Dis Primers"},{"key":"B6","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1182\/blood-2013-04-495887","article-title":"Heme triggers TLR4 signaling leading to endothelial cell activation and vaso-occlusion in murine sickle cell disease","volume":"123","author":"Belcher","year":"2014","journal-title":"Blood"},{"key":"B7","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1016\/S0022-3476(96)70334-7","article-title":"Relationship between Fc receptor IIA polymorphism and infection in children with sickle cell disease","volume":"128","author":"Norris","year":"1996","journal-title":"J Pediatr"},{"key":"B8","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1038\/sj.ejhg.5200360","article-title":"Genetic polymorphism of the mannose-binding protein gene in children with sickle cell disease: identification of three new variant alleles and relationship to infections","volume":"7","author":"Neonato","year":"1999","journal-title":"Eur J Hum Genet"},{"key":"B9","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/S0198-8859(01)00378-0","article-title":"Infectious complications in sickle cell disease are influenced by HLA class II alleles","volume":"63","author":"Tamouza","year":"2002","journal-title":"Hum Immunol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2391","DOI":"10.1182\/blood-2003-09-3015","article-title":"Gene interactions and stroke risk in children with sickle cell anemia","volume":"103","author":"Hoppe","year":"2004","journal-title":"Blood"},{"key":"B11","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1586\/ehm.10.44","article-title":"Genomic polymorphisms in sickle cell disease: implications for clinical diversity and treatment","volume":"3","author":"Fertrin","year":"2010","journal-title":"Expert Rev Hematol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.humimm.2015.10.010","article-title":"Protective effect of HLA-DQB1 alleles against alloimmunization in patients with sickle cell disease","volume":"77","author":"Tatari-Calderone","year":"2016","journal-title":"Hum Immunol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1111\/trf.13920","article-title":"Red blood cell alloimmunization in patients with sickle cell disease: correlation with HLA and cytokine gene polymorphisms","volume":"57","author":"Sippert","year":"2017","journal-title":"Transfusion"},{"key":"B14","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1007\/s00251-017-1013-7","article-title":"Variants in the non-coding region of the TLR2 gene associated with infectious subphenotypes in pediatric sickle cell anemia","volume":"70","author":"David","year":"2018","journal-title":"Immunogenetics"},{"key":"B15","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1111\/bjh.15875","article-title":"A Toll-like receptor 2 genetic variant modulates occurrence of bacterial infections in patients with sickle cell disease","volume":"185","author":"Tozatto-Maio","year":"2019","journal-title":"Br J Haematol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1111\/iji.12334","article-title":"\u2212318C\/T polymorphism of the CTLA-4 gene is an independent risk factor for RBC alloimmunization among sickle cell disease patients","volume":"44","author":"Oliveira","year":"2017","journal-title":"Int J Immunogenet"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.1182\/blood.V89.5.1787.1787_1787_1792","article-title":"Acute chest syndrome in sickle cell disease: clinical presentation and course. Cooperative Study of Sickle Cell Disease","volume":"89","author":"Vichinsky","year":"1997","journal-title":"Blood"},{"key":"B18","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1089\/ped.2017.0814","article-title":"Acute chest syndrome in children with sickle cell disease","volume":"30","author":"Jain","year":"2017","journal-title":"Pediatr Allergy Immunol Pulmonol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1093\/nar\/16.3.1215","article-title":"A simple salting out procedure for extracting DNA from human nucleated cells","volume":"16","author":"Miller","year":"1988","journal-title":"Nucleic Acids Res"},{"key":"B20","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1186\/1471-2164-8-124","article-title":"Comparative sequence analysis of leucine-rich repeats (LRRs) within vertebrate toll-like receptors","volume":"8","author":"Matsushima","year":"2007","journal-title":"BMC Genomics"},{"key":"B21","doi-asserted-by":"publisher","first-page":"e0119702","DOI":"10.1371\/journal.pone.0119702","article-title":"Combined effect of TLR2 gene polymorphism and early life stress on the age at onset of bipolar disorders","volume":"10","author":"Oliveira","year":"2015","journal-title":"PLoS ONE"},{"key":"B22","unstructured":"1000 Genomes|A Deep Catalog of Human Genetic Variation"},{"key":"B23","volume-title":"The Basics of Item Response Theory","author":"Baker","year":"2001"},{"key":"B24","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1007\/BF02296153","article-title":"Generalized latent trait models","volume":"65","author":"Moustaki","year":"2000","journal-title":"Psychometrika"},{"key":"B25","unstructured":"Vienna: R Foundation for Statistical Computing"},{"key":"B26","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1016\/j.tracli.2019.01.003","article-title":"Association between MTHFR 677C>T polymorphism and vascular complications in sickle cell disease: a meta-analysis","volume":"26","author":"Lakkakula","year":"2019","journal-title":"Transfus Clin Biol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1158\/2326-6066.CIR-15-0098","article-title":"NKG2D receptor and its ligands in host defense","volume":"3","author":"Lanier","year":"2015","journal-title":"Cancer Immunol Res"},{"key":"B28","doi-asserted-by":"publisher","first-page":"5481","DOI":"10.4049\/jimmunol.181.8.5481","article-title":"NKG2D is critical for NK cell activation in host defense against Pseudomonas aeruginosa respiratory infection","volume":"181","author":"Wesselkamper","year":"2008","journal-title":"J Immunol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1038\/ni929","article-title":"NKG2D-DAP10 triggers human NK cell-mediated killing via a Syk-independent regulatory pathway","volume":"4","author":"Billadeau","year":"2003","journal-title":"Nat Immunol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"9452","DOI":"10.1073\/pnas.1632807100","article-title":"Stimulation of T cell autoreactivity by anomalous expression of NKG2D and its MIC ligands in rheumatoid arthritis","volume":"100","author":"Groh","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"key":"B31","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1016\/j.immuni.2008.02.016","article-title":"NKG2D-deficient mice are defective in tumor surveillance in models of spontaneous malignancy","volume":"28","author":"Guerra","year":"2008","journal-title":"Immunity"},{"key":"B32","doi-asserted-by":"publisher","first-page":"e30","DOI":"10.1371\/journal.ppat.0040030","article-title":"A role for NKG2D in NK cell-mediated resistance to poxvirus disease","volume":"4","author":"Fang","year":"2008","journal-title":"PLoS Pathog"},{"key":"B33","doi-asserted-by":"publisher","first-page":"27","DOI":"10.3389\/fimmu.2014.00027","article-title":"NK cell autoreactivity and autoimmune diseases","volume":"5","author":"Poggi","year":"2014","journal-title":"Front Immunol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1038\/sj.jid.5701183","article-title":"Maintenance of hair follicle immune privilege is linked to prevention of NK cell attack","volume":"128","author":"Ito","year":"2008","journal-title":"J Invest Dermatol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1111\/bjh.13326","article-title":"Immune parameter analysis of children with sickle cell disease on hydroxycarbamide or chronic transfusion therapy","volume":"169","author":"Nickel","year":"2015","journal-title":"Br J Haematol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1182\/blood-2009-02-205492","article-title":"NKT cells mediate pulmonary inflammation and dysfunction in murine sickle cell disease through production of IFN-gamma and CXCR3 chemokines","volume":"114","author":"Wallace","year":"2009","journal-title":"Blood"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1913","DOI":"10.1002\/eji.200940278","article-title":"NKG2D performs two functions in invariant NKT cells: direct TCR-independent activation of NK-like cytolysis and co-stimulation of activation by CD1d","volume":"41","author":"Kuylenstierna","year":"2011","journal-title":"Eur J Immunol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1158\/0008-5472.CAN-05-2776","article-title":"Identification of the NKG2D haplotypes associated with natural cytotoxic activity of peripheral blood lymphocytes and cancer immunosurveillance","volume":"66","author":"Hayashi","year":"2006","journal-title":"Cancer Res"},{"key":"B39","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1111\/bjh.15617","article-title":"Elevated fetal haemoglobin levels are associated with decreased incidence of retinopathy in adults with sickle cell disease","volume":"183","author":"Mian","year":"2018","journal-title":"Br J Haematol"},{"key":"B40","first-page":"150","article-title":"Incidence of ocular abnormalities in patients with sickle hemoglobinopathies","volume":"18","author":"Friberg","year":"1986","journal-title":"Ann Ophthalmol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/S0268-960X(03)00003-1","article-title":"The paradox of hemoglobin SC disease","volume":"17","author":"Nagel","year":"2003","journal-title":"Blood Rev"},{"key":"B42","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/j.survophthal.2009.11.004","article-title":"Sickle cell disease and the eye: old and new concepts","volume":"55","author":"Elagouz","year":"2010","journal-title":"Surv Ophthalmol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"CD002202","DOI":"10.1002\/14651858.CD002202.pub2","article-title":"Hydroxyurea (hydroxycarbamide) for sickle cell disease","volume":"4","author":"Nevitt","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"key":"B44","doi-asserted-by":"publisher","first-page":"50","DOI":"10.3324\/haematol.2017.177360","article-title":"Inflammatory molecule reduction with hydroxyurea therapy in children with sickle cell anemia","volume":"103","author":"Penkert","year":"2018","journal-title":"Haematologica"},{"key":"B45","doi-asserted-by":"publisher","first-page":"1480","DOI":"10.15252\/emmm.201505246","article-title":"The MICA-129 dimorphism affects NKG2D signaling and outcome of hematopoietic stem cell transplantation","volume":"7","author":"Isernhagen","year":"2015","journal-title":"EMBO Mol Med"},{"key":"B46","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1007\/s002510100325","article-title":"Interactions of human NKG2D with its ligands MICA, MICB, and homologs of the mouse RAE-1 protein family","volume":"53","author":"Steinle","year":"2001","journal-title":"Immunogenetics"},{"key":"B47","doi-asserted-by":"publisher","first-page":"588","DOI":"10.3389\/fimmu.2016.00588","article-title":"Impact of the MICA-129Met\/Val dimorphism on NKG2D-mediated biological functions and disease risks","volume":"7","author":"Isernhagen","year":"2016","journal-title":"Front Immunol"},{"key":"B48","doi-asserted-by":"publisher","first-page":"67","DOI":"10.2174\/187152808785107615","article-title":"HLA-G and inflammatory diseases","volume":"7","year":"2008","journal-title":"Inflamm Allergy Drug Targets"},{"key":"B49","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1111\/j.1399-0039.2009.01331.x","article-title":"HLA-G polymorphism influences the susceptibility to HCV infection in sickle cell disease patients","volume":"74","author":"Cordero","year":"2009","journal-title":"Tissue Antigens"},{"key":"B50","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.ijid.2009.03.010","article-title":"Infection in sickle cell disease: a review","volume":"14","author":"Booth","year":"2010","journal-title":"Int J Infect Dis"},{"key":"B51","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1016\/j.jaci.2003.12.374","article-title":"Toll-like receptor 2 as a major gene for asthma in children of European farmers","volume":"113","author":"Eder","year":"2004","journal-title":"J Allergy Clin Immunol"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1608","DOI":"10.1111\/j.1398-9995.2009.02066.x","article-title":"Association of the toll-like receptor 2 A-16934T promoter polymorphism with severe atopic dermatitis","volume":"64","author":"Oh","year":"2009","journal-title":"Allergy"},{"key":"B53","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1136\/thx.2009.119636","article-title":"Toll-like receptor 2 and 4 genes influence susceptibility to adverse effects of traffic-related air pollution on childhood asthma","volume":"65","author":"Kerkhof","year":"2010","journal-title":"Thorax"},{"key":"B54","doi-asserted-by":"publisher","first-page":"e98815","DOI":"10.1371\/journal.pone.0098815","article-title":"Polymorphisms in the inflammatory pathway genes TLR2, TLR4, TLR9, LY96, NFKBIA, NFKB1, TNFA, TNFRSF1A, IL6R, IL10, IL23R, PTPN22, and PPARG are associated with susceptibility of inflammatory bowel disease in a Danish cohort","volume":"9","author":"Bank","year":"2014","journal-title":"PLoS ONE"},{"key":"B55","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/s12879-018-2943-x","article-title":"Correlation between polymorphisms in toll-like receptor genes and the activity of hepatitis B virus among treatment-na\u00efve patients: a case-control study in a Han Chinese population","volume":"18","author":"Lin","year":"2018","journal-title":"BMC Infect Dis"},{"key":"B56","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1038\/tpj.2017.31","article-title":"Associations between functional polymorphisms and response to biological treatment in Danish patients with psoriasis","volume":"18","author":"Loft","year":"2018","journal-title":"Pharmacogenomics J"},{"key":"B57","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1056\/NEJMoa1611770","article-title":"Crizanlizumab for the prevention of pain crises in sickle cell disease","volume":"376","author":"Ataga","year":"2017","journal-title":"N Engl J Med"},{"key":"B58","unstructured":"Phase-I study of ETA receptor antagonist ambrisentan in sickle cell Disease\n            KutlarA\n          2019"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2020.02041\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,9]],"date-time":"2020-09-09T12:25:32Z","timestamp":1599654332000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2020.02041\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,4]]},"references-count":58,"alternative-id":["10.3389\/fimmu.2020.02041"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2020.02041","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,4]]},"article-number":"2041"}}