Given that most cited immunomodulatory effects are drawn from adult studies or inferred from preclinical data, how do the authors justify generalizing these findings to the pediatric population? Moreover, since immune tolerance breakdown is central in chronic pediatric ITP, wouldn’t more emphasis on longitudinal immunological monitoring be essential before concluding that TPO-RAs restore immune homeostasis in children? The review risks overstating mechanistic conclusions without sufficient pediatric-specific evidence, could the authors clarify this point?
