Title:Effects of High Efficacy Multiple Sclerosis Disease Modifying Drugs on the Immune
Synapse: A Systematic Review
Volume: 30
Issue: 7
Author(s): Spyros N. Deftereos, George D. Vavougios, Christos Bakirtzis, George Hadjigeorgiou and Nikolaos Grigoriadis*
Affiliation:
- Second Department of Neurology, Special Unit for Biomedical Research and Education (S.U.B.R.E.), School of Medicine, Aristotle
University of Thessaloniki, Thessaloniki, Greece
Keywords:
Multiple sclerosis, autoimmune disorders, disease modifying drugs, immune synapse, co-signaling molecules, adhesion molecules.
Abstract:
Background: 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.
Objectives: 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.
Methods: 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.
Results: 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).
Conclusion: 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.