Abstract
Autologous hematopoietic stem cell transplantation (aHSCT) has been used as a therapeutic approach in multiple sclerosis (MS). However, it is still unclear if the immune system that emerges from autologous CD34+ hematopoietic progenitor cells (HPC) of MS patients is pre-conditioned to re-develop the proinflammatory phenotype. The objective of this article is to compare the whole genome gene and microRNA expression signature in CD34+ HPC of MS patients and healthy donors (HD). CD34+ HPC were isolated from peripheral blood of eight MS patients and five HD and analyzed by whole genome gene expression and microRNA expression microarray. Among the differentially expressed genes (DEGs) only TNNT1 reached statistical significance (logFC=3.1, p<0.01). The microRNA expression was not significantly different between MS patients and HD. We did not find significant alterations of gene expression or microRNA profiles in CD34+ HPCs of MS patients. Our results support the use of aHSCT for treatment of MS.
Highlights
Intense immunosuppression followed by autologous hematopoietic stem cell transplantation is a potential treatment for patients suffering from aggressive multiple sclerosis (MS).[1] aHSCT is able to induce a long-lasting remission of inflammatory disease activity, which can persist years beyond complete immune reconstitution
We found 2801 differentially expressed genes (DEGs) in CD34+ and 9440 DEGs in CD34- cells comparing MS patients mobilized with granulocyte colony-stimulating factor (G-CSF) only or Cy/G-CSF, respectively
Comparing DEGs in CD34+ hematopoietic progenitor cells (HPC) of MS patients and healthy donors (HD), both mobilized with G-CSF only, we found 297 DEGs, but the TNNT1 gene was the only DEG with statistical significance after Benjamini-Hochberg correction
Summary
Intense immunosuppression followed by autologous hematopoietic stem cell transplantation (aHSCT) is a potential treatment for patients suffering from aggressive multiple sclerosis (MS).[1] aHSCT is able to induce a long-lasting remission of inflammatory disease activity, which can persist years beyond complete immune reconstitution. The rationale for aHSCT in MS is based on the concept that lympho-/myeloablative conditioning eliminates pathogenic autoreactive immune cells and facilitates the regeneration of a new and tolerant immune system from CD34+ hematopoietic progenitor cells (HPC). Thorough analysis of the T cell repertoire in the regenerating immune system after aHSCT in MS supports that a new and antigen-naïve T cell repertoire develops from the HPC compartment via thymic regeneration.[2] To date, it remains unresolved whether autoimmunity in MS is merely a consequence of loss of peripheral immune tolerance or whether it results from immune dysregulation, which is already predetermined in HPC. Approach this key point we compared the global gene- and miRNA expression profiles of CD34+ and CD34- cells collected from MS patients and healthy donors (HD)
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