Abstract
It is uncertain as to whether similar or different mechanisms contribute to different subtypes of multiple sclerosis (MS). A unifying concept proposes that patients with both relapsing-remitting MS (RRMS) and primary progressive MS (PPMS) have premature thymic involution, which alters peripheral T-cell homeostasis and leads to T-cell alterations that contribute to the pathogenesis of both MS subtypes.
Highlights
Multiple sclerosis is a complex, heterogeneous disorder of the CNS
Cumulative data from various investigators suggest an alternate, unifying concept, that premature thymic involution leads to a shift in peripheral T-cell homeostasis, which contributes to the pathogenesis of both relapsing-remitting MS (RRMS) and primary progressive MS (PPMS) [5]
In a study of T-cell receptor excision circles (TRECs) that excluded proliferation, we found that young patients with RRMS and PPMS have thymic export of naive CD4 Tcells/day that is reduced to a level similar to controls 30-40 years older [10]
Summary
Multiple sclerosis is a complex, heterogeneous disorder of the CNS. An unresolved issue is whether similar or different mechanisms contribute to the different MS subtypes. Most think that peripheral immune mechanisms contribute to attacks in RRMS but not in PPMS [1]. Cumulative data from various investigators suggest an alternate, unifying concept, that premature thymic involution leads to a shift in peripheral T-cell homeostasis, which contributes to the pathogenesis of both RRMS and PPMS [5].
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