{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T04:32:03Z","timestamp":1777264323766,"version":"3.51.4"},"reference-count":19,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HLA"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The HLA system plays a crucial role in immune recognition, with genetic variability influencing disease susceptibility. This study examines the association between HLA evolutionary divergence (HED) scores and paediatric haematological malignancies, aiming to determine whether locus\u2010specific HED profiles correlate with disease risk. A cohort of 89 paediatric patients (age\u2009\u2264\u200920) with high\u2010resolution HLA typing (A, B, C loci) was analysed. HED scores were categorised into eight distinct profiles (H\u2009=\u2009High, L\u2009=\u2009Low divergence). Statistical associations were assessed using Fisher's exact test and binary logistic regression to adjust for potential confounders, including age and sex. The LHH profile (low divergence at Locus A, high at B and C) emerged as a significant risk factor for Acute Lymphoblastic Leukaemia (ALL), showing a three\u2010fold increase in risk (OR\u2009=\u20093.24;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0481). Conversely, high divergence at Locus B alone showed a trend toward ALL susceptibility (OR\u2009=\u20092.17;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.056). Multivariable regression confirmed that HED is an independent biological variable, with no significant influence from age (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.689) or sex (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.756). Furthermore, HED profiles significantly influenced the age at diagnosis (clinical latency); for instance, patients with the HHL profile exhibited a delayed onset compared to HHH profiles (mean age 12.47 vs. 6.58\u2009years), suggesting that specific HED configurations may modulate the kinetics of immune evasion. These findings demonstrate that HED, particularly at the HLA\u2010A locus, is a critical determinant of leukaemia susceptibility. The identification of the HLA\u2010A \u2018bottleneck\u2019 (LHH profile) suggests a selective failure in antigen presentation, potentially leading to compromised anti\u2010tumour surveillance. The independence of HED from standard clinical variables and its impact on disease latency highlight its potential as a robust immunogenetic biomarker for risk stratification and personalised monitoring in paediatric oncology.\n                  <\/jats:p>","DOI":"10.1111\/tan.70721","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T10:59:43Z","timestamp":1777028383000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>HLA<\/scp>\n                    Evolutionary Divergence and Paediatric Disease Risk: Unveiling Genetic Associations"],"prefix":"10.1111","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9971-7313","authenticated-orcid":false,"given":"Donato","family":"Madalese","sequence":"first","affiliation":[{"name":"UOSD Ba.S.C.O., Manipolazione Cellulare ed Immunogenetica \u2013 Department of Oncology Haematology and Cell Therapies, AORN Santobono\u2010Pausilipon  Naples Italy"},{"name":"Stem Cell Transplantation and Cell Therapy Unit, Department of Oncology Haematology and Cell Therapies, AORN Santobono\u2010Pausilipon  Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Auriemma","sequence":"additional","affiliation":[{"name":"UOSD Ba.S.C.O., Manipolazione Cellulare ed Immunogenetica \u2013 Department of Oncology Haematology and Cell Therapies, AORN Santobono\u2010Pausilipon  Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Esposito","sequence":"additional","affiliation":[{"name":"UOSD Ba.S.C.O., Manipolazione Cellulare ed Immunogenetica \u2013 Department of Oncology Haematology and Cell Therapies, AORN Santobono\u2010Pausilipon  Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Toriello","sequence":"additional","affiliation":[{"name":"UOSD Ba.S.C.O., Manipolazione Cellulare ed Immunogenetica \u2013 Department of Oncology Haematology and Cell Therapies, AORN Santobono\u2010Pausilipon  Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Nappo","sequence":"additional","affiliation":[{"name":"UOSD Ba.S.C.O., Manipolazione Cellulare ed Immunogenetica \u2013 Department of Oncology Haematology and Cell Therapies, AORN Santobono\u2010Pausilipon  Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Lama","sequence":"additional","affiliation":[{"name":"UOSD Ba.S.C.O., Manipolazione Cellulare ed Immunogenetica \u2013 Department of Oncology Haematology and Cell Therapies, AORN Santobono\u2010Pausilipon  Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Topo","sequence":"additional","affiliation":[{"name":"UOSD Ba.S.C.O., Manipolazione Cellulare ed Immunogenetica \u2013 Department of Oncology Haematology and Cell Therapies, AORN Santobono\u2010Pausilipon  Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Gallo","sequence":"additional","affiliation":[{"name":"UOSD Ba.S.C.O., Manipolazione Cellulare ed Immunogenetica \u2013 Department of Oncology Haematology and Cell Therapies, AORN Santobono\u2010Pausilipon  Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Castellano","sequence":"additional","affiliation":[{"name":"UOSD Ba.S.C.O., Manipolazione Cellulare ed Immunogenetica \u2013 Department of Oncology Haematology and Cell Therapies, AORN Santobono\u2010Pausilipon  Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natasha","family":"Martino","sequence":"additional","affiliation":[{"name":"UOSD Ba.S.C.O., Manipolazione Cellulare ed Immunogenetica \u2013 Department of Oncology Haematology and Cell Therapies, AORN Santobono\u2010Pausilipon  Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa","family":"Colucci","sequence":"additional","affiliation":[{"name":"Servizio Immunotrasfusionale, Ospedale Madonna delle Grazie \u2013 ASM Matera  Matera Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8473-202X","authenticated-orcid":false,"given":"Roberto","family":"Crocchiolo","sequence":"additional","affiliation":[{"name":"Immunohematology and Transfusion Medicine Service, ASST Grande Ospedale Metropolitano Niguarda  Milano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco Paolo","family":"Tambaro","sequence":"additional","affiliation":[{"name":"Stem Cell Transplantation and Cell Therapy Unit, Department of Oncology Haematology and Cell Therapies, AORN Santobono\u2010Pausilipon  Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Penta de Vera d\u2019Aragona","sequence":"additional","affiliation":[{"name":"UOSD Ba.S.C.O., Manipolazione Cellulare ed Immunogenetica \u2013 Department of Oncology Haematology and Cell Therapies, AORN Santobono\u2010Pausilipon  Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/9710376"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/SJI.12329"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.12688\/F1000RESEARCH.10990.1"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.HUMIMM.2017.11.002"},{"key":"e_1_2_13_6_1","unstructured":"P.Cruz\u2010Tapias J.Castiblanco andJ.\u2010M.Anaya \u201cMajor Histocompatibility Complex: Antigen Processing and Presentation \u201daccessed April 16 2025 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