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  1. Article ; Online: Polyclonal lymphoid expansion drives paraneoplastic autoimmunity in neuroblastoma

    Miriam I. Rosenberg / Erez Greenstein / Martin Buchkovich / Ayelet Peres / Eric Santoni-Rugiu / Lei Yang / Martin Mikl / Zalman Vaksman / David L. Gibbs / Dan Reshef / Amy Salovin / Meredith S. Irwin / Arlene Naranjo / Igor Ulitsky / Pedro A. de Alarcon / Katherine K. Matthay / Victor Weigman / Gur Yaari / Jessica A. Panzer /
    Nir Friedman / John M. Maris

    Cell Reports, Vol 42, Iss 8, Pp 112879- (2023)

    2023  

    Abstract: Summary: Neuroblastoma is a lethal childhood solid tumor of developing peripheral nerves. Two percent of children with neuroblastoma develop opsoclonus myoclonus ataxia syndrome (OMAS), a paraneoplastic disease characterized by cerebellar and brainstem- ... ...

    Abstract Summary: Neuroblastoma is a lethal childhood solid tumor of developing peripheral nerves. Two percent of children with neuroblastoma develop opsoclonus myoclonus ataxia syndrome (OMAS), a paraneoplastic disease characterized by cerebellar and brainstem-directed autoimmunity but typically with outstanding cancer-related outcomes. We compared tumor transcriptomes and tumor-infiltrating T and B cell repertoires from 38 OMAS subjects with neuroblastoma to 26 non-OMAS-associated neuroblastomas. We found greater B and T cell infiltration in OMAS-associated tumors compared to controls and showed that both were polyclonal expansions. Tertiary lymphoid structures (TLSs) were enriched in OMAS-associated tumors. We identified significant enrichment of the major histocompatibility complex (MHC) class II allele HLA-DOB∗01:01 in OMAS patients. OMAS severity scores were associated with the expression of several candidate autoimmune genes. We propose a model in which polyclonal auto-reactive B lymphocytes act as antigen-presenting cells and drive TLS formation, thereby supporting both sustained polyclonal T cell-mediated anti-tumor immunity and paraneoplastic OMAS neuropathology.
    Keywords CP: Cancer ; CP: Immunology ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2023-08-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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  2. Article ; Online: Family-based exome-wide association study of childhood acute lymphoblastic leukemia among Hispanics confirms role of ARID5B in susceptibility.

    Natalie P Archer / Virginia Perez-Andreu / Ulrik Stoltze / Michael E Scheurer / Anna V Wilkinson / Ting-Nien Lin / Maoxiang Qian / Charnise Goodings / Michael D Swartz / Nalini Ranjit / Karen R Rabin / Erin C Peckham-Gregory / Sharon E Plon / Pedro A de Alarcon / Ryan C Zabriskie / Federico Antillon-Klussmann / Cesar R Najera / Jun J Yang / Philip J Lupo

    PLoS ONE, Vol 12, Iss 8, p e

    2017  Volume 0180488

    Abstract: We conducted an exome-wide association study of childhood acute lymphoblastic leukemia (ALL) among Hispanics to confirm and identify novel variants associated with disease risk in this population. We used a case-parent trio study design; unlike more ... ...

    Abstract We conducted an exome-wide association study of childhood acute lymphoblastic leukemia (ALL) among Hispanics to confirm and identify novel variants associated with disease risk in this population. We used a case-parent trio study design; unlike more commonly used case-control studies, this study design is ideal for avoiding issues with population stratification bias among this at-risk ethnic group. Using 710 individuals from 323 Guatemalan and US Hispanic families, two inherited SNPs in ARID5B reached genome-wide level significance: rs10821936, RR = 2.31, 95% CI = 1.70-3.14, p = 1.7×10-8 and rs7089424, RR = 2.22, 95% CI = 1.64-3.01, p = 5.2×10-8. Similar results were observed when restricting our analyses to those with the B-ALL subtype: ARID5B rs10821936 RR = 2.22, 95% CI = 1.63-3.02, p = 9.63×10-8 and ARID5B rs7089424 RR = 2.13, 95% CI = 1.57-2.88, p = 2.81×10-7. Notably, effect sizes observed for rs7089424 and rs10821936 in our study were >20% higher than those reported among non-Hispanic white populations in previous genetic association studies. Our results confirmed the role of ARID5B in childhood ALL susceptibility among Hispanics; however, our assessment did not reveal any strong novel inherited genetic risks for acute lymphoblastic leukemia among this ethnic group.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2017-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

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