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Review
. 2025 Nov:74:101328.
doi: 10.1016/j.blre.2025.101328. Epub 2025 Aug 5.

Targeting the neonatal Fc receptor (FcRn) in hematologic conditions with a focus on warm autoimmune hemolytic anemia

Affiliations
Review

Targeting the neonatal Fc receptor (FcRn) in hematologic conditions with a focus on warm autoimmune hemolytic anemia

Bruno Fattizzo et al. Blood Rev. 2025 Nov.

Abstract

Warm autoimmune hemolytic anemia (wAIHA) is the most prevalent form of autoimmune hemolytic anemia, where in most patients extravascular hemolysis is driven by immunoglobulin G (IgG) autoantibodies, with or without complement activation. While standard-of-care treatment with corticosteroids provides a high initial response rate, relapses are frequent, and most patients require additional immunosuppressive therapies. A high unmet medical need remains for patients with refractory or chronic relapsing wAIHA. Neonatal Fc receptor (FcRn) blockers are novel biologic therapies designed to provide a rapid, sustained decrease in circulating concentrations of IgG antibodies, including autoantibodies, and have been investigated in hematologic conditions like immune thrombocytopenia and hemolytic anemia of the fetus and newborn and other autoimmune conditions, such as generalized myasthenia gravis. FcRn blockade is currently under evaluation in patients with wAIHA to determine its potential as a safe, effective treatment option.

Keywords: FcRn blocker; Hemolytic anemia of the fetus and newborn; IgG autoantibody; Immune thrombocytopenia; Neonatal Fc receptor; Warm autoimmune hemolytic anemia.

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Conflict of interest statement

Declaration of competing interest BF received consultancy and speaker's honoraria from Alexion, Novartis, Roche, Sobi, Sanofi, Johnson & Johnson; and received research funding from Agios and Zenas. LEL is an employee of and holds stock/stock options in Johnson & Johnson. WB served as a consultant and/or advisory board member for Agios, Alexion, Alpine, argenx, BioCryst, Incyte, Johnson & Johnson, Momenta Pharmaceuticals, Novartis, Recordati, Roche, and Sobi; received lecture fees and/or congress support from Alexion, Incyte, Novartis, and Sanofi; and received research grant support from Alexion.

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