Dataset Information

Ena-DATASET-DKFZ-IBIOS-17-08-2015-09:13:01:216-19 - samples

ABSTRACT: PAR-CLIP was performed on the Argonaute-2 protein (AGO2) in four lymphoma cell lines: Namalwa Raji SU-DHL-4 SU-DHL-6

PROVIDER: EGAD00001001468 | EGA |

REPOSITORIES: EGA

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Alterations of microRNA and microRNA-regulated messenger RNA expression in germinal center B-cell lymphomas determined by integrative sequencing analysis.

Hezaveh Kebria K Kloetgen Andreas A Bernhart Stephan H SH Mahapatra Kunal Das KD Lenze Dido D Richter Julia J Haake Andrea A Bergmann Anke K AK Brors Benedikt B Burkhardt Birgit B Claviez Alexander A Drexler Hans G HG Eils Roland R Haas Siegfried S Hoffmann Steve S Karsch Dennis D Klapper Wolfram W Kleinheinz Kortine K Korbel Jan J Kretzmer Helene H Kreuz Markus M Küppers Ralf R Lawerenz Chris C Leich Ellen E Loeffler Markus M Mantovani-Loeffler Luisa L López Cristina C McHardy Alice C AC Möller Peter P Rohde Marius M Rosenstiel Philip P Rosenwald Andreas A Schilhabel Markus M Schlesner Matthias M Scholz Ingrid I Stadler Peter F PF Stilgenbauer Stephan S Sungalee Stéphanie S Szczepanowski Monika M Trümper Lorenz L Weniger Marc A MA Siebert Reiner R Borkhardt Arndt A Hummel Michael M Hoell Jessica I JI

Haematologica 20160706 11

MicroRNA are well-established players in post-transcriptional gene regulation. However, information on the effects of microRNA deregulation mainly relies on bioinformatic prediction of potential targets, whereas proof of the direct physical microRNA/target messenger RNA interaction is mostly lacking. Within the International Cancer Genome Consortium Project "Determining Molecular Mechanisms in Malignant Lymphoma by Sequencing", we performed miRnome sequencing from 16 Burkitt lymphomas, 19 diffus ...[more]

PMID: 27390358

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Project description:BackgroundHLA-E interaction with inhibitory receptor, NKG2A attenuates NK-mediated cytotoxicity. NKG2A overexpression by SARS-CoV-2 exhausts NK cells function, whereas virus-induced down-regulation of MHC-Ia reduces its derived-leader sequence peptide levels required for proper binding of HLA-E to NKG2A. This leads HLA-E to become more complex with viral antigens and delivers them to CD8+ T cells, which facilitates cytolysis of infected cells. Now, the fact that alleles of HLA-E have different levels of expression and affinity for MHC Ia-derived peptide raises the question of whether HLA-E polymorphisms affect susceptibility to COVID-19 or its severity.Methods104 COVID-19 convalescent plasma donors with/without history of hospitalization and 18 blood donors with asymptomatic COVID-19, all were positive for anti-SARS-CoV-2 IgG antibody as well as a group of healthy control including 68 blood donors with negative antibody were subjected to HLA-E genotyping. As a privilege, individuals hadn't been vaccinated against COVID-19 and therefore naturally exposed to the SARS-CoV-2.ResultsThe absence of HLA-E*01:03 allele significantly decreases the odds of susceptibility to SARS-CoV-2 infection [p = 0.044; OR (95 %CI) = 0.530 (0.286 - 0.983)], suggesting that HLA-E*01:01 + HLA-E*01:01 genotype favors more protection against SARS-CoV-2 infection. HLA-E*01:03 + HLA-E*01:03 genotype was also significantly associated with more severe COVID-19 [p = 0.020; 2.606 (1.163 - 5.844) CONCLUSION: Here, our observation about lower susceptibility of HLA-E*01:01 + HLA-E*01:01 genotype to COVID-19 could be clinical evidence in support of some previous studies suggesting that the lower affinity of HLA-E*01:01 to peptides derived from the leader sequence of MHC class Ia may instead shift its binding to virus-derived peptides, which then facilitates target recognition by restricted conventional CD8+ T cells and leads to efficient cytolysis. On the other hand, according to other studies, less reactivity of HLA-E*01:01 with NKG2A abrogates NK cells or T cells inhibition, which may also lead to a greater cytotoxicity against SARS-CoV-2 infected cells compared to HLA-E*01:03. Taken together given HLA-E polymorphisms, the data presented here may be useful in identifying more vulnerable individuals to COVID-19 for better care and management. Especially since along with other risk factors in patients, having HLA-E*01:03 + HLA-E*01:03 genotype may also be associated with the possibility of severe cases of the disease.

Dataset Information

Ena-DATASET-DKFZ-IBIOS-17-08-2015-09:13:01:216-19 - samples

Publications

Alterations of microRNA and microRNA-regulated messenger RNA expression in germinal center B-cell lymphomas determined by integrative sequencing analysis.

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