Miren Vallejo Ruiz, a predoctoral researcher in the Navarrabiomed Hematological Oncology Unit – Navarre Health Research Institute (IdiSNA), will defend her doctoral dissertation from the Universidad Pública de Navarra on Tuesday, 17 November at 11 a.m. The event will be held in the Navarrabiomed Assembly Hall. Due to current COVID-19 restrictions, attendance is limited, but a videoconference of the defense will be available.

The dissertation, “Evaluation of functional immune response developed against cytomegalovirus, Epstein-Barr virus and adenovirus and their regulatory elements in allogeneic hematopoietic stem cell transplantation recipients,” was developed at Navarrabiomed under the direction of Natalia Ramírez Huerto, Head of the Hematological Oncology Unit.

Research focused on describing the main biological and genetic variables that affect the development of a protective immune response to infections caused by cytomegalovirus (CMV), Epstein-Barr virus (VEB) or adenovirus (AdV) in patients who have received an allogeneic hematopoietic stem cell transplantation (allo-HSCT), i.e., those requiring the administration of healthy stem cells to increase bone marrow function.

One of the results of this study shows that the analysis of the functionality of the subpopulation of virus-specific T cells in patients who have received an allo-HSCT can be used to predict CMV infection in the post-transplantation period. T cells help destroy tumor cells and control immune responses.

With regard to the parameters that regulate the workings of this immune response, the study also used samples from healthy donors to show that gliotoxin (GT), the fungal toxin in Aspergillus fumigatus (AF), inhibits the function of subpopulations of T cells and natural killer (NK) cells, whose mission is to destroy infected cells and cancer cells, and to regulate immune responses.

In vitro observations also confirmed that the presence of GT in combination with the drugs ciclosporin A and methotrexate triggers a mechanism that impedes immune response. These drugs are used as a prophylactic against graft-versus-host disease (GvHD) in these patients. This experimental result was corroborated in patients after HSCT, when the presence of bis-methyl-gliotoxin (bmGT), the GT metabolite, in combination with the administration of cyclophosphamide, negatively modulated specific immune response against CMV/VEB/AdV.

Finally, the study confirmed that that the evaluation of certain polymorphisms in cytokine and chemokine genes and their receptors in patients and their respective donors can be used to predict the individual risk of developing CMV infection after HSCT. Analysis of these polymorphisms was used to generate an equation and a practical score for early identification of patients with a high risk of CMV infection after allo-HSCT.

These results were presented at three events: the International Conference of the European Society for Clinical Cell Analysis held in Valencia in September 2018, the 24th Congress of the European Hematology Association held in Amsterdam in June 2019, and the 61st National Conference of the Spanish Society of Hematology and Hemotherapy (SEHH/SETH) held in Valencia in October 2019. The research study was also on display in October 2020 at the 62nd edition of the SEHH/SETH conference. 

In order to prepare her dissertation, Miren Vallejo was a beneficiary of the Government of Navarre’s 2017-2019 Industrial Doctoral Students financial aid program, issued in 2016, for research and knowledge-sharing companies and organizations to hire doctoral students. While preparing her dissertation, Miren Vallejo also participated in an internship from June to December 2018 in the group “Genetic and clinical analysis of hematological neoplasms and stem cell transplantation” at Gregorio Marañón General University Hospital.