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Interaction between maternal killer immunoglobulin-like receptors and offspring HLAs and susceptibility of childhood ALL

Acute lymphoblastic leukemia (ALL) in children is associated with a distinct neonatal cytokine profile. The basis of this neonatal immune phenotype is unknown but potentially related to maternal-fetal immune receptor interactions. We conducted a case-control study of 226 case child-mother pairs and...

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Autores principales: Feng, Qianxi, Zhou, Mi, Li, Shaobo, Morimoto, Libby, Hansen, Helen, Myint, Swe Swe, Wang, Rong, Metayer, Catherine, Kang, Alice, Fear, Anna Lisa, Pappas, Derek, Erlich, Henry, Hollenbach, Jill A., Mancuso, Nicholas, Trachtenberg, Elizabeth, de Smith, Adam J., Ma, Xiaomei, Wiemels, Joseph L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Hematology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9631572/
https://www.ncbi.nlm.nih.gov/pubmed/35500222
http://dx.doi.org/10.1182/bloodadvances.2021006821
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author Feng, Qianxi
Zhou, Mi
Li, Shaobo
Morimoto, Libby
Hansen, Helen
Myint, Swe Swe
Wang, Rong
Metayer, Catherine
Kang, Alice
Fear, Anna Lisa
Pappas, Derek
Erlich, Henry
Hollenbach, Jill A.
Mancuso, Nicholas
Trachtenberg, Elizabeth
de Smith, Adam J.
Ma, Xiaomei
Wiemels, Joseph L.
author_facet Feng, Qianxi
Zhou, Mi
Li, Shaobo
Morimoto, Libby
Hansen, Helen
Myint, Swe Swe
Wang, Rong
Metayer, Catherine
Kang, Alice
Fear, Anna Lisa
Pappas, Derek
Erlich, Henry
Hollenbach, Jill A.
Mancuso, Nicholas
Trachtenberg, Elizabeth
de Smith, Adam J.
Ma, Xiaomei
Wiemels, Joseph L.
author_sort Feng, Qianxi
collection PubMed
description Acute lymphoblastic leukemia (ALL) in children is associated with a distinct neonatal cytokine profile. The basis of this neonatal immune phenotype is unknown but potentially related to maternal-fetal immune receptor interactions. We conducted a case-control study of 226 case child-mother pairs and 404 control child-mother pairs to evaluate the role of interaction between HLA genotypes in the offspring and maternal killer immunoglobulin-like receptor (KIR) genotypes in the etiology of childhood ALL, while considering potential mediation by neonatal cytokines and the immune-modulating enzyme arginase-II (ARG-II). We observed different associations between offspring HLA-maternal KIR activating profiles and the risk of ALL in different predicted genetic ancestry groups. For instance, in Latino subjects who experience the highest risk of childhood leukemia, activating profiles were significantly associated with a lower risk of childhood ALL (odds ratio [OR] = 0.59; 95% confidence interval [CI], 0.49-0.71) and a higher level of ARG-II at birth (coefficient = 0.13; 95% CI, 0.04-0.22). HLA-KIR activating profiles were also associated with a lower risk of ALL in non-Latino Asians (OR = 0.63; 95% CI, 0.38-1.01), although they had a lower tumor necrosis factor-α level (coefficient = −0.27; 95% CI, −0.49 to −0.06). Among non-Latino White subjects, no significant association was observed between offspring HLA-maternal KIR interaction and ALL risk or cytokine levels. The current study reports the association between offspring HLA-maternal KIR interaction and the development of childhood ALL with variation by predicted genetic ancestry. We also observed some associations between activating profiles and immune factors related to cytokine control; however, cytokines did not demonstrate causal mediation of the activating profiles on ALL risk.
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spelling pubmed-96315722022-11-04 Interaction between maternal killer immunoglobulin-like receptors and offspring HLAs and susceptibility of childhood ALL Feng, Qianxi Zhou, Mi Li, Shaobo Morimoto, Libby Hansen, Helen Myint, Swe Swe Wang, Rong Metayer, Catherine Kang, Alice Fear, Anna Lisa Pappas, Derek Erlich, Henry Hollenbach, Jill A. Mancuso, Nicholas Trachtenberg, Elizabeth de Smith, Adam J. Ma, Xiaomei Wiemels, Joseph L. Blood Adv Clinical Trials and Observations Acute lymphoblastic leukemia (ALL) in children is associated with a distinct neonatal cytokine profile. The basis of this neonatal immune phenotype is unknown but potentially related to maternal-fetal immune receptor interactions. We conducted a case-control study of 226 case child-mother pairs and 404 control child-mother pairs to evaluate the role of interaction between HLA genotypes in the offspring and maternal killer immunoglobulin-like receptor (KIR) genotypes in the etiology of childhood ALL, while considering potential mediation by neonatal cytokines and the immune-modulating enzyme arginase-II (ARG-II). We observed different associations between offspring HLA-maternal KIR activating profiles and the risk of ALL in different predicted genetic ancestry groups. For instance, in Latino subjects who experience the highest risk of childhood leukemia, activating profiles were significantly associated with a lower risk of childhood ALL (odds ratio [OR] = 0.59; 95% confidence interval [CI], 0.49-0.71) and a higher level of ARG-II at birth (coefficient = 0.13; 95% CI, 0.04-0.22). HLA-KIR activating profiles were also associated with a lower risk of ALL in non-Latino Asians (OR = 0.63; 95% CI, 0.38-1.01), although they had a lower tumor necrosis factor-α level (coefficient = −0.27; 95% CI, −0.49 to −0.06). Among non-Latino White subjects, no significant association was observed between offspring HLA-maternal KIR interaction and ALL risk or cytokine levels. The current study reports the association between offspring HLA-maternal KIR interaction and the development of childhood ALL with variation by predicted genetic ancestry. We also observed some associations between activating profiles and immune factors related to cytokine control; however, cytokines did not demonstrate causal mediation of the activating profiles on ALL risk. American Society of Hematology 2022-06-24 /pmc/articles/PMC9631572/ /pubmed/35500222 http://dx.doi.org/10.1182/bloodadvances.2021006821 Text en © 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.
spellingShingle Clinical Trials and Observations
Feng, Qianxi
Zhou, Mi
Li, Shaobo
Morimoto, Libby
Hansen, Helen
Myint, Swe Swe
Wang, Rong
Metayer, Catherine
Kang, Alice
Fear, Anna Lisa
Pappas, Derek
Erlich, Henry
Hollenbach, Jill A.
Mancuso, Nicholas
Trachtenberg, Elizabeth
de Smith, Adam J.
Ma, Xiaomei
Wiemels, Joseph L.
Interaction between maternal killer immunoglobulin-like receptors and offspring HLAs and susceptibility of childhood ALL
title Interaction between maternal killer immunoglobulin-like receptors and offspring HLAs and susceptibility of childhood ALL
title_full Interaction between maternal killer immunoglobulin-like receptors and offspring HLAs and susceptibility of childhood ALL
title_fullStr Interaction between maternal killer immunoglobulin-like receptors and offspring HLAs and susceptibility of childhood ALL
title_full_unstemmed Interaction between maternal killer immunoglobulin-like receptors and offspring HLAs and susceptibility of childhood ALL
title_short Interaction between maternal killer immunoglobulin-like receptors and offspring HLAs and susceptibility of childhood ALL
title_sort interaction between maternal killer immunoglobulin-like receptors and offspring hlas and susceptibility of childhood all
topic Clinical Trials and Observations
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9631572/
https://www.ncbi.nlm.nih.gov/pubmed/35500222
http://dx.doi.org/10.1182/bloodadvances.2021006821
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