Journal article
Host microRNAs are decreased in pediatric solid-organ transplant recipients during EBV plus Post-transplant Lymphoproliferative Disorder
Frontiers in immunology, Vol.13, 994552
10/07/2022
DOI: 10.3389/fimmu.2022.994552
PMCID: PMC9595046
PMID: 36304469
Abstract
Post-transplant lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation. Predisposing factors include primary Epstein-Barr virus (EBV) infection, reactivation of EBV in recipient B cells, and decreased T cell immunity due to immunosuppression. In our previous studies EBV infection was demonstrated to markedly alter the expression of host B cell microRNA (miR). Specifically, miR-194 expression was uniquely suppressed in EBV+ B cell lines from PTLD patients and the 3'untranslated region of IL-10 was determined to be targeted by miR-194. Although EBV has been shown to regulate host miR expression in B cell lymphoma cell lines, the expression of miRs in the circulation of patients with EBV-associated PTLD has not been studied. The objective of this study was to determine if changes in miR expression are associated with EBV+ PTLD. In this study, we have shown that miR-194 is significantly decreased in EBV+PTLD tumors and that additional miRs, including miRs-17, 19 and 106a are also reduced in EBV+PTLD as compared to EBV-PTLD. We quantitated the levels of miRs-17, 19, 106a, 155, and 194 in the plasma and extracellular vesicles (EV; 50-70 nm as determined by nanoparticle tracking analysis) from pediatric recipients of solid organ transplants with EBV+ PTLD+ that were matched 1:2 with EBV+ PTLD- pediatric transplant recipients as part of the NIH-sponsored Clinical Trials in Organ Transplantation in Children, (CTOTC-06) study. Levels of miRs-17, 19, 106a, and 194 were reduced in the plasma and extracellular vesicles (EV) of EBV+ PTLD+ group compared to matched controls, with miRs-17 (p = 0.034; plasma), miRs-19 (p = 0.029; EV) and miR-106a (p = 0.007; plasma and EV) being significantly reduced. Similar levels of miR-155 were detected in the plasma and EV of all pediatric SOT recipients. Importantly, similar to 90% of the cell-free miR were contained within the EV supporting that EBV+ PTLD tumor miR are detected in the circulation and suggesting that EVs, containing miRs, may have the potential to target and regulate cells of the immune system. Further development of diagnostic, mechanistic and potential therapeutic uses of the miRs in PTLD is warranted.
Details
- Title: Subtitle
- Host microRNAs are decreased in pediatric solid-organ transplant recipients during EBV plus Post-transplant Lymphoproliferative Disorder
- Creators
- Ayantika Sen - Stanford UniversityJeanna Enriquez - Stanford UniversityMahil Rao - Stanford UniversityMarla Glass - Stanford UniversityYarl Balachandran - Stanford UniversitySharjeel Syed - Stanford UniversityClare J. Twist - Roswell Park Comprehensive Cancer CenterKenneth Weinberg - Stanford UniversityScott D. Boyd - Stanford UniversityDaniel Bernstein - Stanford UniversityAmber W. Trickey - Stanford UniversityDita Gratzinger - Stanford UniversityBrent Tan - Stanford UniversityMary Gay Lapasaran - Stanford UniversityMark A. Robien - National Institute of Allergy and Infectious DiseasesMerideth Brown - National Institute of Allergy and Infectious DiseasesBrian Armstrong - RhoDev Desai - The University of Texas Southwestern Medical CenterGeorge Mazariegos - University of Pittsburgh Medical CenterClifford Chin - Cincinnati Children's Hospital Medical CenterThomas M. Fishbein - Georgetown UniversityRobert S. Venick - University of California, Los AngelesAkin Tekin - University of MiamiHeiner Zimmermann - Evangelisches DiakoniekrankenhausRalf U. Trappe - Charité - Universitätsmedizin BerlinIoannis Anagnostopoulos - University of WürzburgCarlos O. Esquivel - Stanford UniversityOlivia M. Martinez - Stanford UniversitySheri M. Krams - Stanford University
- Resource Type
- Journal article
- Publication Details
- Frontiers in immunology, Vol.13, 994552
- DOI
- 10.3389/fimmu.2022.994552
- PMID
- 36304469
- PMCID
- PMC9595046
- NLM abbreviation
- Front Immunol
- ISSN
- 1664-3224
- eISSN
- 1664-3224
- Publisher
- Frontiers Media Sa
- Number of pages
- 12
- Grant note
- Stanford Maternal and Child Health Research Institute fellowship T32 AI007290; A1UO1AI104342; UM2AI117870 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Stanford Transplant and Tissue Engineering Center of Excellence fellowship Stanford University Jackson Vaughan Critical Care Research Fund
- Language
- English
- Date published
- 10/07/2022
- Academic Unit
- Critical Care; Stead Family Department of Pediatrics
- Record Identifier
- 9984775024102771
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