Autologous hematopoietic stem cell transplantation significantly alters circulating ceramides in peripheral blood of relapsing-remitting multiple sclerosis patients

• Published in: Lipids in health and disease 2023-07, Vol.22 (1), p.97-97, Article 97
• Main Authors: Vaivade, Aina, Wiberg, Anna, Khoonsari, Payam Emami, Carlsson, Henrik, Herman, Stephanie, Al-Grety, Asma, Freyhult, Eva, Olsson-Strömberg, Ulla, Burman, Joachim, Kultima, Kim
• Format: Article
• Language: English
• Subjects: Acids; Analysis; Autografts; Autologous hematopoietic stem cell transplantation; Care and treatment; Central nervous system; Ceramide; Ceramides; Chromatography; Cyclophosphamide; Diagnosis; Disease; Glycerophosphoinositol; Health aspects; Hematopoietic stem cells; Immune system; Inflammatory diseases; Ions; Lipid metabolism; Lipidomics; Lipids; Mass spectrometry; Mass spectroscopy; Metabolomics; Multiple sclerosis; Neurodegeneration; Patients; Peripheral blood; Relapsing-remitting multiple sclerosis; Scientific imaging; Stem cell transplantation; Transplantation
• ISSN: 1476-511X; 1476-511X
• DOI: 10.1186/s12944-023-01863-7

The common inflammatory disease multiple sclerosis (MS) is a disease of the central nervous system. For more than 25 years autologous hematopoietic stem cell transplantation (AHSCT) has been used to treat MS. It has been shown to be highly effective in suppressing inflammatory activity in relapsing-remitting MS (RRMS) patients. This treatment is thought to lead to an immune system reset, inducing a new, more tolerant system; however, the precise mechanism behind the treatment effect in MS patients is unknown. In this study, the effect of AHSCT on the metabolome and lipidome in peripheral blood from RRMS patients was investigated. Peripheral blood samples were collected from 16 patients with RRMS at ten-time points over the five months course of AHSCT and 16 MS patients not treated with AHSCT. Metabolomics and lipidomics analysis were performed using liquid-chromatography high-resolution mass spectrometry. Mixed linear models, differential expression analysis, and cluster analysis were used to identify differentially expressed features and groups of features that could be of interest. Finally, in-house and in-silico libraries were used for feature identification, and enrichment analysis was performed. Differential expression analysis found 657 features in the lipidomics dataset and 34 in the metabolomics dataset to be differentially expressed throughout AHSCT. The administration of cyclophosphamide during mobilization and conditioning was associated with decreased concentrations in glycerophosphoinositol species. Thymoglobuline administration was associated with an increase in ceramide and glycerophosphoethanolamine species. After the conditioning regimen, a decrease in glycerosphingoidlipids concentration was observed, and following hematopoietic stem cell reinfusion glycerophosphocholine concentrations decreased for a short period of time. Ceramide concentrations were strongly associated with leukocyte levels during the procedure. The ceramides Cer(d19:1/14:0) and Cer(d20:1/12:0) were found to be increased (P