Genetic Background of Immune Complications after Allogeneic Hematopoietic Stem Cell Transplantation in Children.

Wojciech Strojny,Jacek J. Pietrzyk,Kamil Fijorek,Walentyna Balwierz,Agnieszka Grabowska,Szymon Skoczen,Miroslaw Bik-Multanowski,Kinga Klus-Kwiecinska,Maciej Siedlar

doi:10.1155/2016/2626081

Abstract

Immune reactions are among the most serious complications observed after hematopoietic stem cell transplantation (HSCT) in children. Microarray technique allows for simultaneous assessment of expression of nearly all human genes. The objective of the study was to compare the whole genome expression in children before and after HSCT. A total of 33 children referred for HSCT were enrolled in the study. In 70% of the patients HSCT was performed for the treatment of neoplasms. Blood samples were obtained before HSCT and six months after the procedure. Subsequently, the whole genome expression was assessed in leukocytes using GeneChip Human Gene 1.0 ST microarray. The analysis of genomic profiles before and after HSCT revealed altered expression of 124 genes. Pathway enrichment analysis revealed upregulation of five pathways after HSCT: allograft rejection, graft-versus-host disease, type I diabetes mellitus, autoimmune thyroid disease, and viral myocarditis. The activation of those pathways seems to be related to immune reactions commonly observed after HSCT. Our results contribute to better understanding of the genomic background of the immunologic complications of HSCT.

Highlights

Allogeneic hematopoietic stem cell transplantation (HSCT) has progressed from a risky experimental therapy to a safe and life-saving treatment modality in a relatively short span of five decades [1]
50% of patients treated with HSCT subsequently develop Acute graft-versus-host disease (aGvHD) and require systemic treatment [12]
Chronic graft-versushost disease occurs in 40% of patients treated with HSCT from an HLA-identical sibling and in more than 50% of patients treated with HSCT from an HLAnonidentical related donor and in 70% of patients treated with HSCT from an HLA-matched unrelated donor

Summary

Introduction

Allogeneic hematopoietic stem cell transplantation (HSCT) has progressed from a risky experimental therapy to a safe and life-saving treatment modality in a relatively short span of five decades [1]. Transplant recipients still require prolonged treatment with multiple, nonspecific, and toxic immunosuppressive drugs and are at a constant risk of immune reactions which may lead to graft-versus-host disease (GvHD) or graft rejection (GR). Immune reactions result from the activation of donor lymphocytes with subsequent recognition of the host’s antigens, emergence of effector T cells, production of alloantibodies, and infiltration of tissues by alloreactive cells [2].

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