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Oxidized hemoglobin triggers polyreactivity and autoreactivity of human IgG via transfer of heme.

ABSTRACT: Intravascular hemolysis occurs in diverse pathological conditions. Extracellular hemoglobin and heme have strong pro-oxidative and pro-inflammatory potentials that can contribute to the pathology of hemolytic diseases. However, many of the effects of extracellular hemoglobin and heme in hemolytic diseases are still not well understood. Here we demonstrate that oxidized hemoglobin (methemoglobin) can modify the antigen-binding characteristics of human immunoglobulins. Thus, incubation of polyclonal or some monoclonal human IgG in the presence of methemoglobin results in an appearance of binding reactivities towards distinct unrelated self-proteins, including the protein constituent of hemoglobin i.e., globin. We demonstrate that a transfer of heme from methemoglobin to IgG is indispensable for this acquisition of antibody polyreactivity. Our data also show that only oxidized form of hemoglobin have the capacity to induce polyreactivity of antibodies. Site-directed mutagenesis of a heme-sensitive human monoclonal IgG1 reveals details about the mechanism of methemoglobin-induced antigen-binding polyreactivity. Further here we assess the kinetics and thermodynamics of interaction of a heme-induced polyreactive human antibody with hemoglobin and myoglobin. Taken together presented data contribute to a better understanding of the functions of extracellular hemoglobin in the context of hemolytic diseases.

SUBMITTER: Planchais C

PROVIDER: S-EPMC9922299 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Oxidized hemoglobin triggers polyreactivity and autoreactivity of human IgG via transfer of heme.

Planchais Cyril C Noe Remi R Gilbert Marie M Lecerf Maxime M Kaveri Srini V SV Lacroix-Desmazes Sébastien S Roumenina Lubka T LT Dimitrov Jordan D JD

Communications biology 20230211 1

Intravascular hemolysis occurs in diverse pathological conditions. Extracellular hemoglobin and heme have strong pro-oxidative and pro-inflammatory potentials that can contribute to the pathology of hemolytic diseases. However, many of the effects of extracellular hemoglobin and heme in hemolytic diseases are still not well understood. Here we demonstrate that oxidized hemoglobin (methemoglobin) can modify the antigen-binding characteristics of human immunoglobulins. Thus, incubation of polyclon ...[more]

PMID: 36774392

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Oxidized hemoglobin triggers polyreactivity and autoreactivity of human IgG via transfer of heme.

Publications

Oxidized hemoglobin triggers polyreactivity and autoreactivity of human IgG via transfer of heme.

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