A recent study has discovered that B cells mediate spontaneous T cell proliferation through the HLA-DR15 haplotype, and this interaction between T cells and B cells may serve as a key factor in understanding the pathogenesis of multiple sclerosis (MS).
A recent study has discovered that B cells mediate spontaneous T cell proliferation through the HLA-DR15 haplotype, and this interaction between T cells and B cells may serve as a key factor in understanding the pathogenesis of multiple sclerosis (MS).1
A complex neurological disease involving the immune system, MS affects approximately 2.5 million people worldwide. The genetic associations of MS are still not fully understood, with the HLA-DR 15 haplotype, adoptive immunity, and CD4-positive T cells being the genetic affiliations most connected with MS pathogenesis. However, recent reports have shown that CD8-positive T cells, proinflammatory B cells, and autoantibodies may also be involved in MS. An interesting phenomenon associated with MS was increased spontaneous T-cell proliferation, known as autoproliferation (AP). Jelcic et al recently published an article on the potential cellular interactions that lead to increased AP and its role in MS.
The first objective that the investigators had was to determine if AP in patients with MS surpasses that in healthy patients. In a previous study conducted by Mohme et al in 2013, investigators validated an increased AP in patients with MS compared with healthy donors.2 Interestingly, other autoimmune diseases, such as psoriasis and Crohn disease, did not have the same increases in AP compared with MS. This development was believed to be caused by the reduced autologous mixed lymphocyte reaction that occurred in MS but not in the other diseases. Next, the researchers analyzed the association between AP and the different disease states of MS, such as relapse and remission. An unexpected observation was where patients with MS in remission had higher AP than patients with relapse or active disease.
How can machines predict the RR phase in MS?
Another finding was an association between HLA-DR15 and AP. B cells were studied because they upregulate HLA-DR expression. In patients with MS, the AP of both B and T cells were higher in HLA-DR15—positive patients. The role of B cells was significant AP because following B cell depletion or separation from T cells, reduced T cell AP and interferon-γ secretion was observed. The clinical efficacy of B cell depletion for the treatment of MS with anti-CD20 antibodies has shown to be effective in reducing MS relapses. Patients on rituximab, a monoclonal antibody targeting CD20, had reduced AP of T cells and proinflammatory cytokine responses.
Activated T cells in the blood also exhibited an ability to migrate toward the brain upon recognition of specific antigens. One antigen that stood out was RASGRP2, a peptide with high antigen expressed on B cells. “Our findings not only explain how new MS drugs take effect, but also pave the way for novel approaches in basic research and therapy for MS,” said Ronald Martin, MD, director of the Clinical Research Priority Program Multiple Sclerosis at the University of Zurich in Switzerland, in a statement.
Previous studies and data presented from this study have shown that there may be a connection between B and T cells with MS. Future research should be done to learn more about the specificity of B and T cells in MS pathogenesis, and may serve as a foundation in creating new drug therapies that patients with MS may benefit from.
References
Dr Dalia Rotstein: Physicians Must Be Aware MS Affects People of All Backgrounds
April 24th 2024Dalia Rotstein, MD, MPH, emphazises the importance of awareness that multiple sclerosis (MS) impacts patients from various backgrounds as clinicians think through ways to improve access to care and research efforts in MS.
Read More
FDA Issues CRL for Glatiramer Acetate Depot for Relapsing Forms of MS
March 11th 2024The FDA has declined to approve glatiramer acetate (GA) depot in the treatment of relapsing types of multiple sclerosis (MS), issuing a complete response letter (CRL) for the long-acting, injectable form of GA.
Read More
Choroid Plexus Indicated in MS Pathology
February 9th 2024A longitudinal, observational study found that the choroid plexus, a network of blood vessels in each ventricle of the brain, plays a potential role in the neurodegenerative and chronic inflammatory process experienced by patients with relapsing remitting multiple sclerosis (MS).
Read More