Progress toward inducing immunologic tolerance to factor VIII

David W. Scott*, Kathleen P. Pratt, Carol H. Miao

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

51 Scopus citations

Abstract

A major problem in treating hemophilia A patients with therapeutic factor VIII (FVIII) is that 20% to 30% of these patients produce neutralizing anti-FVIII antibodies. These antibodies block (inhibit) the procoagulant function of FVIII and thus are termed "inhibitors." The currently accepted clinical method to attempt to eliminate inhibitors is immune tolerance induction (ITI) via a protocol requiring intensive FVIII treatment until inhibitor titers drop. Although often successful, ITI is extremely costly and is less likely to succeed in patients with high-titer inhibitors. During the past decade, significant progress has been made in clarifying mechanisms of allo- and autoimmune responses to FVIII and in suppression of these responses. Animal model studies are suggesting novel, less costlymethods to induce tolerance to FVIII. Complementary studies of anti-FVIII T-cell responses using blood samples from human donors are identifying immunodominant T-cell epitopes in FVIII and possible targets for tolerogenic efforts. Mechanistic experiments using human T-cell clones and lines are providing a clinically relevant counterpoint to the animal model studies. This review highlights recent progress toward the related goals of lowering the incidence of anti-FVIII immune responses and promoting durable, functional immune tolerance to FVIII in patients with an existing inhibitor.

Original languageEnglish
Pages (from-to)4449-4456
Number of pages8
JournalBlood
Volume121
Issue number22
DOIs
StatePublished - 30 May 2013
Externally publishedYes

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