Immunomonitoring of MSC-Treated GvHD Patients Reveals Only Moderate Potential for Response Prediction but Indicates Treatment Safety

Abstract

<p><a title="Learn more about Mesenchyme" href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/mesenchyme"><u>Mesenchymal</u></a> <a title="Learn more about Stromal cell" href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/stromal-cell"><u>stromal cells</u></a> (MSCs) are used as salvage therapy to treat steroid-refractory acute graft-versus-host disease (aGvHD). We studied the immunological response to MSC treatment in 16 aGvHD patients by assessing <a title="Learn more about Lymphocyte" href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/lymphocyte"><u>lymphocyte</u></a> profiles and three proposed aGvHD serum markers during the MSC treatment. Surprisingly, there were no obvious differences in the lymphocyte profiles between the responders and non-responders. The numbers of T, <a title="Learn more about B cell" href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/b-cell"><u>B, and NK cells</u></a> were below the normal reference interval in all patients. CD4⁺ <a title="Learn more about T helper cell" href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/t-helper-cell"><u>T helper</u></a> (Th) cell levels remained particularly low throughout the follow-up period. The relative proportion of Th1 cells decreased, while <a title="Learn more about Regulatory T cell" href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/regulatory-t-cell"><u>regulatory T cells</u></a> remained unaltered, and only very few Th2 and Th17 cells could be detected. Serum concentrations of regenerating islet-derived protein 3-alpha, <a title="Learn more about Keratin 18" href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/keratin-18"><u>cytokeratin-18</u></a> fragments (CK18F), and <a title="Learn more about Elafin" href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/elafin"><u>elafin</u></a> were significantly elevated in patient samples compared with healthy controls, but only CK18F showed any potential in the prediction of patients’ response to <a title="Learn more about MSC (gene)" href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/msc-gene"><u>MSCs</u></a>. No obvious markers for MSC therapy response were revealed in this study, but the results suggest that allogeneic MSCs do not provoke overt T cell-mediated immune responses at least in immunosuppressed aGvHD patients. The results advocate for the safety of MSC therapy and bring new insights in MSC immunomodulation mechanisms.<br /></p>