Effects of High Efficacy Multiple Sclerosis Disease Modifying Drugs on the Immune Synapse: A Systematic Review

• Published in: Current pharmaceutical design Vol. 30; no. 7; p. 536
• Main Authors: Deftereos, Spyros N, Vavougios, George D, Bakirtzis, Christos, Hadjigeorgiou, George, Grigoriadis, Nikolaos
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.01.2024
• Subjects: Animals; Cell Adhesion Molecules - antagonists & inhibitors; Cell Adhesion Molecules - immunology; Cell Adhesion Molecules - metabolism; Humans; Immunological Synapses - drug effects; Immunological Synapses - immunology; Immunological Synapses - metabolism; Multiple Sclerosis - drug therapy; Multiple Sclerosis - immunology; disease modifying drugs; autoimmune disorders; Multiple sclerosis; co-signaling molecules; adhesion molecules; immune synapse
• ISSN: 1873-4286
• DOI: 10.2174/0113816128288102240131053205

Co-signaling and adhesion molecules are important elements for creating immune synapses between T lymphocytes and antigen-presenting cells; they positively or negatively regulate the interaction between a T cell receptor with its cognate antigen, presented by the major histocompatibility complex. We conducted a systematic review on the effects of High Efficacy Disease Modifying Drugs (HEDMDs) for Multiple Sclerosis (MS) on the co-signaling and adhesion molecules that form the immune synapse. We searched EMBASE, MEDLINE, and other sources to identify clinical or preclinical reports on the effects of HEDMDs on co-signaling and adhesion molecules that participate in the formation of immune synapses in patients with MS or other autoimmune disorders. We included reports on cladribine tablets, anti- CD20 monoclonal antibodies, S1P modulators, inhibitors of Bruton's Tyrosine Kinase, and natalizumab. In 56 eligible reports among 7340 total publications, limited relevant evidence was uncovered. Not all co-signaling and adhesion molecules have been studied in relation to every HEDMD, with more data being available on the anti-CD20 monoclonal antibodies (that affect CD80, CD86, GITR and TIGIT), cladribine tablets (affecting CD28, CD40, ICAM-1, LFA-1) and the S1P modulators (affecting CD86, ICAM-1 and LFA-1) and less on Natalizumab (affecting CD80, CD86, CD40, LFA-1, VLA-4) and Alemtuzumab (affecting GITR and CTLA-4). The puzzle of HEDMD effects on the immune synapse is far from complete. The available evidence suggests that distinguishing differences exist between drugs and are worth pursuing further.