Long-Term Suppression of Circulating Proinflammatory Cytokines in Multiple Sclerosis Patients Following Autologous Haematopoietic Stem Cell Transplantation

• Published in: Frontiers in immunology Vol. 12; p. 782935
• Main Authors: Hendrawan, Kevin, Khoo, Melissa L M, Visweswaran, Malini, Massey, Jennifer C, Withers, Barbara, Sutton, Ian, Ma, David D F, Moore, John J
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 19.01.2022
• Subjects: Adult; Aged; AHSCT; cytokines; Cytokines - blood; Female; Hematopoietic Stem Cell Transplantation - adverse effects; Humans; Immunology; Interleukin-12 - blood; Interleukins - blood; long-term suppression; Lymphoma, Non-Hodgkin - blood; Male; Middle Aged; multiple sclerosis; Multiple Sclerosis - blood; T helper 17; Th17 Cells - metabolism; Transplantation, Autologous - adverse effects; Young Adult; AHSCT; cytokines; T helper 17; multiple sclerosis; long-term suppression
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.782935

Autologous haematopoietic stem cell transplantation (AHSCT) is a therapeutic option for haematological malignancies, such as non-Hodgkin's lymphoma (NHL), and more recently, for autoimmune diseases, such as treatment-refractory multiple sclerosis (MS). The immunological mechanisms underlying remission in MS patients following AHSCT likely involve an anti-inflammatory shift in the milieu of circulating cytokines. We hypothesised that immunological tolerance in MS patients post-AHSCT is reflected by an increase in anti-inflammatory cytokines and a suppression of proinflammatory cytokines in the patient blood. We investigated this hypothesis using a multiplex-ELISA assay to compare the concentrations of secreted cytokine in the peripheral blood of MS patients and NHL patients undergoing AHSCT. In MS patients, we detected significant reductions in proinflammatory T helper (Th)17 cytokines interleukin (IL)-17, IL-23, IL-1β, and IL-21, and Th1 cytokines interferon (IFN)γ and IL-12p70 in MS patients from day 8 to 24 months post-AHSCT. These changes were not observed in the NHL patients despite similar pre-conditioning treatment for AHSCT. Some proinflammatory cytokines show similar trends in both cohorts, such as IL-8 and tumour necrosis factor (TNF)-α, indicating a probable treatment-related AHSCT response. Anti-inflammatory cytokines (IL-10, IL-4, and IL-2) were only transiently reduced post-AHSCT, with only IL-10 exhibiting a significant surge at day 14 post-AHSCT. MS patients that relapsed post-AHSCT exhibited significantly elevated levels of IL-17 at 12 months post-AHSCT, unlike non-relapse patients which displayed sustained suppression of Th17 cytokines at all post-AHSCT timepoints up to 24 months. These findings suggest that suppression of Th17 cytokines is essential for the induction of long-term remission in MS patients following AHSCT.