Immunology

Immune reconstitution–pathology and pathway

The keynote lecture highlights the immune reconstitution therapies in MS, which are explored as a way to reset rather than simply suppress the immune system. By depleting and then reshaping T- and B-cell populations, especially memory and regulatory subsets, these approaches aim to restore immune tolerance and achieve more durable disease control.

In this keynote from Athens presented by Bart Van Wijmeersch, the concept of immune reconstitution therapy (IRT) in multiple sclerosis is examined from a mechanistic and clinical perspective. The presentation focuses on how targeted depletion and controlled repopulation of immune cells may rebalance dysregulated immunity, enhance tolerance, and reshape long-term disease activity.

Key Insights from the Lecture:

Immune reconstitution as a goal: restoring immune balance and tolerance is presented as a core objective in MS, by resetting dysregulated regulatory and effector cells.
The “3R” concept: immune reconstitution therapies are described as following three phases: Reduction (depletion), Repopulation, and Reconstitution (long-term reshaping of the immune repertoire).
Profound T- and B-cell depletion is followed by rapid B-cell rebound and slower T-cell recovery, with a relative increase in regulatory T cells but risk of secondary autoimmunity.
Selective lymphocyte depletion is shown, with sustained reduction of memory B cells and a relative enrichment of regulatory B, T and NK subsets over time.
Near-complete immune ablation is followed by regeneration of a new naïve T- and B-cell repertoire, with a higher relative proportion of regulatory cells.
Common pattern, different depth: all IRTs share depletion → homeostatic proliferation → rebalancing, but differ in depth, duration and impact on memory and regulatory compartments.
Towards tolerance, a dampened myelin-specific reactivity and a shift toward a more anti-inflammatory profile are reported, especially after HSCT, supporting the concept of partial immune “reset”.

“Immune reconstitution – pathology and pathway“.

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About the speaker:

Bart Van Wijmeersch

Associate Professor of Neurology at the University of Hasselt

Bart Van Wijmeersch is a neurologist specialized in Multiple Sclerosis. He is medical director of the Rehabilitation and MS Center in Pelt where he leads the multidisciplinary MS-team. Furthermore, he is an associate professor of Neurology at the University of Hasselt, affiliated with the Biomedical Institute, where he’s involved in pre-clinical as well as the clinical research on MS at the biomedical institute (BIOMED). He has a supporting role in all the immunological research on blood- and CSF samples of persons with MS and in EAE-animal models, as well as in the rehabilitation research at REVAL. Immunological, Biomarker, MRI, Electrophysiological and Rehabilitation research in MS come together in this way. He has an educational role in the faculty of medicine and physiotherapy.

He’s a member of the Belgian Study Group of Multiple Sclerosis, first President of ParadigMS and a member of advisory boards of different pharmaceutical companies with interest in Multiple Sclerosis.

As acknowledgment of his scientific work, he received an honorary award of the Flemish government in the summer of 2019.