Induced antigen-binding polyreactivity in human serum IgA

Gorshkova, E. N.; Lecerf, Maxime; Astrakhantseva, Irina V.; Vasilenko, E. A.; Starkina, Olga V.; Ilyukina, Natalya A.; Dimitrova, Petya; Dimitrov, Jordan D.; Vassilev, Tchavdar

doi:10.1016/j.imbio.2022.152213

Cited by 4 publications

(2 citation statements)

References 38 publications

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“…Experiments with monoclonal Abs had shown that the contact of the Fab fragment with heme triggers polyreactivity [ 30 , 32 , 33 ]. This phenomenon was reported to occur in 10–20% of Abs in a normal immune repertoire and described for IgG, IgM, IgA, and IgE Abs [ 27 , 28 , 30 , 31 , 32 , 33 , 55 , 56 , 57 ]. Notably, certain heme-treated monoclonal Abs recognized their newly acquired target antigens with high binding affinity (K D ~1–2 nM) [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

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

Wiatr

Hadzhieva

Lecerf

et al. 2023

IJMS

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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 (Fe3+). 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 (Fe3+) 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 (Fe3+). 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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Section: Discussionmentioning

confidence: 99%

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

Wiatr

Hadzhieva

Lecerf

et al. 2023

IJMS

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“…The interaction between heme and band 1 was predominant, while a very low signal could be found in band 1 s tail, and at around 13 min tailing into band 3 (Figure 4, inset). These signals can be attributed to SA aggregates, hemopexin, and HDL [56][57][58] and other type of immunoglobulins such as IgA and IgM [59,60]. Interestingly, no interaction was observed in correspondence of band 2, attributed to IgG.…”

Section: Serum-heme Binding Studymentioning

confidence: 94%

Tracking Heme-Protein Interactions in Healthy and Pathological Human Serum in Native Conditions by Miniaturized FFF-Multidetection

et al. 2022

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The interaction of heme with blood serum proteins plays an important role in many physiological and pathological processes involving enzyme activity, gene expression and cell proliferation. The mechanisms underlying these interactions are; however, not yet fully understood. New analytical methods able to investigate protein-heme binding in native, biologically representative conditions are thus required. In this work, we present a method based on miniaturized, hollow-fiber flow field-flow fractionation with multiple spectrophotometric and light-scattering detection for size separation of high-abundance serum proteins and selective detection of heme-bound subpopulations. Heme is found to mainly interact with serum albumin, whereas a low amount also binds to other proteins such as IgM. The ability to bind heme in physiological conditions is also investigated for individual serum proteins. IgG is found unable to bind heme at clinically relevant concentrations. The proposed method allows separation, quantitation, and mass/size characterization of serum high-abundance proteins, providing information of heme-protein complex stability and preferred heme-clearing pathways. The same approach could be in perspective extended to the investigation of specific heme-antibody binding, and to further studies involving other molecules of pharmaceutical/clinical interest.

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Serum IgA contributes to the comprehension of Anisakis simplex associated chronic urticaria

González-Fernández,

Ullate,

Fernández-Fígares

et al. 2024

International Immunopharmacology

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Induced antigen-binding polyreactivity in human serum IgA

Cited by 4 publications

References 38 publications

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

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

Tracking Heme-Protein Interactions in Healthy and Pathological Human Serum in Native Conditions by Miniaturized FFF-Multidetection

Serum IgA contributes to the comprehension of Anisakis simplex associated chronic urticaria

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