Hyperoxidized Species of Heme Have a Potent Capacity to Induce Autoreactivity of Human IgG Antibodies - Sorbonne Université Access content directly
Journal Articles International Journal of Molecular Sciences Year : 2023

Hyperoxidized Species of Heme Have a Potent Capacity to Induce Autoreactivity of Human IgG Antibodies

Abstract

The interaction of some human antibodies with heme results in posttranslational acquisition of binding to various self-and pathogen-derived antigens. The previous studies on this phenomenon were performed with oxidized heme (Fe 3+). In the present study, we elucidated the effect of other pathologically relevant species of heme, i.e., species that were formed after contact of heme with oxidizing agents such as hydrogen peroxide, situations in which heme's iron could acquire higher oxidation states. Our data reveal that hyperoxidized species of heme have a superior capacity to heme (Fe 3+) in triggering the autoreactivity of human IgG. Mechanistic studies demonstrated that oxidation status of iron was of critical importance for the heme's effect on antibodies. We also demonstrated that hyperoxidized heme species interacted at higher affinities with IgG and that this binding occurred through a different mechanism as compared to heme (Fe 3+). Regardless of their profound functional impact on the antigen-binding properties of antibodies, hyperoxidized species of heme did not affect Fc-mediated functions of IgG, such as binding to the neonatal Fc receptor. The obtained data contribute to a better understanding of the pathophysiological mechanism of hemolytic diseases and of the origin of elevated antibody autoreactivity in patients with some hemolytic disorders.
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Dates and versions

hal-03988064 , version 1 (14-02-2023)

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Marie Wiatr, Maya Hadzhieva, Maxime Lecerf, Rémi Noé, Sune Justesen, et al.. Hyperoxidized Species of Heme Have a Potent Capacity to Induce Autoreactivity of Human IgG Antibodies. International Journal of Molecular Sciences, 2023, 24, ⟨10.3390/ijms24043416⟩. ⟨hal-03988064⟩
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