Learning MS pathogenesis from anti-CD20 therapy
Posted: Tue Sep 12, 2023 3:59 am
Learning multiple sclerosis immunopathogenesis from anti-CD20 therapy
https://www.pnas.org/doi/full/10.1073/pnas.2221544120
Summary:
1) By analyzing blood immune profiles of patients receiving disease-modifying immune therapies, we can learn how therapy impacts the immune system (“mode of action” type of investigations) and gain a deeper understanding of the underlying pathogenesis in a reverse translational approach. Those approaches will become even more powerful by incorporating novel single-cell omic technologies and multiple compartments,
2) CD20dim T cells, particularly CD20dim CD8+ T cells, may leave the circulation into the CNS already before the start of anti-CD20 therapy and contribute to relapse biology. This finding implies that anti-CD20 treatment is a highly effective therapy, but already-ongoing relapse biology cannot be modified, a notion that basically all used disease-modifying treatments share (even fast-acting leukocyte trafficking-inhibition agents). Moreover, those findings imply that CD20-expressing T cells should be depleted by a further dose of anti-CD20 therapy. Therapy should therefore not be discontinued too early because an insufficient effect is mistakenly assumed.
3) Early repopulating B cells exhibit a transitional anti-inflammatory phenotype and are probably not related to early MS disease activity after anti-CD20 therapy. However, effects would be expected to be reversible because B cell depletion therapy is not a reconstitution therapy in the sense that it fully restores a new immune system. Consequently, proinflammatory memory B cells might reappear in the absence of continuous B cell depletion.
4) Frequency of pretreatment CD20dim CD8+ T cells may have the potential in predicting early disease activity after anti-CD20 therapy. Yet, this would clearly necessitate larger multicenter biomarker studies in well-curated, longitudinal cohorts.
In the near future, similar approaches will hopefully make personalized neuroimmunology not only wishful thinking, but also practical reality.
https://www.pnas.org/doi/full/10.1073/pnas.2221544120
Summary:
1) By analyzing blood immune profiles of patients receiving disease-modifying immune therapies, we can learn how therapy impacts the immune system (“mode of action” type of investigations) and gain a deeper understanding of the underlying pathogenesis in a reverse translational approach. Those approaches will become even more powerful by incorporating novel single-cell omic technologies and multiple compartments,
2) CD20dim T cells, particularly CD20dim CD8+ T cells, may leave the circulation into the CNS already before the start of anti-CD20 therapy and contribute to relapse biology. This finding implies that anti-CD20 treatment is a highly effective therapy, but already-ongoing relapse biology cannot be modified, a notion that basically all used disease-modifying treatments share (even fast-acting leukocyte trafficking-inhibition agents). Moreover, those findings imply that CD20-expressing T cells should be depleted by a further dose of anti-CD20 therapy. Therapy should therefore not be discontinued too early because an insufficient effect is mistakenly assumed.
3) Early repopulating B cells exhibit a transitional anti-inflammatory phenotype and are probably not related to early MS disease activity after anti-CD20 therapy. However, effects would be expected to be reversible because B cell depletion therapy is not a reconstitution therapy in the sense that it fully restores a new immune system. Consequently, proinflammatory memory B cells might reappear in the absence of continuous B cell depletion.
4) Frequency of pretreatment CD20dim CD8+ T cells may have the potential in predicting early disease activity after anti-CD20 therapy. Yet, this would clearly necessitate larger multicenter biomarker studies in well-curated, longitudinal cohorts.
In the near future, similar approaches will hopefully make personalized neuroimmunology not only wishful thinking, but also practical reality.