Until programmed death do us tolerant

David W. Scott*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Healthy individuals are generally immunologically tolerant to proteins derived from one’s self (termed self proteins). However, patients with monogenic clotting disorders, like hemophilia A (HemA), lack central tolerance to the absent self protein. Thus, when exposed to replacement therapy, such as procoagulant factor VIII, they may mount an immune response against the very self protein that is missing. In the current issue of the JCI, Becker-Gotot, Meissner, et al. present data on a possible mechanism for tolerance to factor VIII in healthy individuals and the immune response in patients, involving a role of PD-1 and T regulatory cells. The findings suggest that treatment with PD-1– and PD-1L–specific reagents may induce tolerance in patients with autoimmune disease, especially those with HemA who also possess inhibiting antibodies.

Original languageEnglish
Article numbere164858
JournalJournal of Clinical Investigation
Issue number22
StatePublished - 15 Nov 2022
Externally publishedYes


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