Unveiling chronic spontaneous urticaria pathophysiology through systems biology

Segú-Vergés, Cristina; Gómez, Jessica; Terradas, Pau; Artigas, Laura; Smeets, Serge J.; Ferrer, Marta; Savic, Sinisa

doi:10.1016/j.jaci.2022.12.809

Cited by 7 publications

(4 citation statements)

References 68 publications

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“…Rapid reduction of free IgE by OMZ in patients with autoallergic CSU leads to a rapid depletion of IgE AAb and thus a rapid response to treatment, 155 whereas a slow response could be explained by FcεRI downregulation by skin mast cells, which may take months, 156 and the action of anti‐IgE IgG AAb on remaining occupied FcεRI 157 . Complete non‐response, seen in up to 20% of CSU patients, 158 suggests the existence of other endotype(s), with a pathogenesis not involving IgE or FcεRI 154 …”

Section: Targeting Ige In Non‐allergic Diseasesmentioning

confidence: 99%

“…155 Rapid reduction of free IgE by OMZ in patients with autoallergic CSU leads to a rapid depletion of IgE AAb and thus a rapid response to treatment, 155 whereas a slow response could be explained by FcεRI downregulation by skin mast cells, which may take months, 156 and the action of anti-IgE IgG AAb on remaining occupied FcεRI. 157 Complete non-response, seen in up to 20% of CSU patients, 158 suggests the existence of other endotype(s), with a pathogenesis not involving IgE or FcεRI. 154 LGZ was found to outperform OMZ efficacy, in terms of rate of complete responders and longer lasting effects, in a multicenter randomized, controlled, phase IIb study including 382 patients with inadequately controlled CSU.…”

Section: Chronic Spontaneous Urticariamentioning

confidence: 99%

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Autoreactive IgE: Pathogenic role and therapeutic target in autoimmune diseases

Charles

Krohn

Kocatürk

et al. 2023

Allergy

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Autoimmunity is the break of tolerance to self‐antigens that leads to organ‐specific or systemic diseases often characterized by the presence of pathogenic autoreactive antibodies (AAb) produced by plasmablast and/or plasma cells. AAb are prevalent in the general population and not systematically associated with clinical symptoms. In contrast, in some individuals, these AAb are pathogenic and drive the development of signs and symptoms of antibody‐mediated autoimmune diseases (AbAID). AAb production, isotype profiles, and glycosylations are promoted by pro‐inflammatory triggers linked to genetic, environmental, and hormonal parameters. Recent evidence supports a role for pathogenic AAb of the IgE isotype in a number of AbAID. Autoreactive IgE can drive the activation of mast cells, basophils, and other types of FcεRI‐bearing cells and may play a role in promoting autoantibody production and other pro‐inflammatory pathways. In this review, we discuss the current knowledge on the pathogenicity of autoreactive IgE in AbAID and their status as therapeutic targets. We also highlight unresolved issues including the need for assays that reproducibly quantify IgE AAbs, to validate their diagnostic and prognostic value, and to further study their pathophysiological contributions to AbAID.

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Section: Targeting Ige In Non‐allergic Diseasesmentioning

confidence: 99%

Section: Chronic Spontaneous Urticariamentioning

confidence: 99%

Autoreactive IgE: Pathogenic role and therapeutic target in autoimmune diseases

Charles

Krohn

Kocatürk

et al. 2023

Allergy

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show abstract

“…Rapid reduction of free IgE by OMZ in patients with autoallergic CSU leads to a rapid depletion of IgE AAb and thus a rapid response to treatment 153 , whereas a slow response could be explained by FcεRI downregulation by skin mast cells, which may take months 154 , and the action of anti-IgE IgG AAb on remaining occupied FcεRI 155 . Complete non-response, seen in up to 20% of CSU patients 156 , suggests the existence of other endotype(s), with a pathogenesis not involving IgE or FcεRI 152 .…”

Section: Chronic Spontaneous Urticariamentioning

confidence: 99%

Autoreactive IgE: pathogenic role and therapeutic target in autoimmune diseases

Charles

Krohn

Kocatürk

et al. 2023

Preprint

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Autoimmunity is the break of tolerance to self-antigens that leads to organ-specific or systemic diseases characterized by the presence of pathogenic autoreactive antibodies (AAb) produced by plasmablast and/or plasma cells. AAb are prevalent in the general population and not systematically associated with clinical symptoms. In contrast, in some individuals, these AAb are pathogenic and drive the development of signs and symptoms of antibody-mediated autoimmune diseases (AbAID). AAb production, isotype profiles, and glycosylations are promoted by pro-inflammatory triggers linked to genetic, environmental, and hormonal parameters. Recent evidence supports a role for pathogenic AAb of the IgE isotype in a number of AbAID. Autoreactive IgE can drive the activation of mast cells, basophils and other types of FcεRI-bearing cells and may play a role in promoting autoantibody production and other pro-inflammatory pathways. In this review, we discuss the current knowledge on the pathogenicity of autoreactive IgE in AbAID and their status as therapeutic targets. We also highlight unresolved issues including the need for assays that reproducibly quantify IgE AAbs, to validate their diagnostic and prognostic value, and to further study their pathophysiological contributions to AbAID.

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“…In silico modeling has previously been used to unravel the MoA of multifactorial pathologies and their treatments [26][27][28]. Here, we report the use of a systems biology modeling approach, based on a previously applied algorithm similar to a Multilayer Perceptron of an Artificial Neural Network over the human protein-protein interaction network (where proteins are represented as neurons and the edges of the network are used to transfer the information) [29][30][31].…”

Section: Introductionmentioning

confidence: 99%

Aflibercept Off-Target Effects in Diabetic Macular Edema: An In Silico Modeling Approach

Blanot,

Casaroli-Marano,

Mondéjar-Medrano

et al. 2024

IJMS

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Intravitreal aflibercept injection (IAI) is a treatment for diabetic macular edema (DME), but its mechanism of action (MoA) has not been completely elucidated. Here, we aimed to explore IAI’s MoA and its multi-target nature in DME pathophysiology with an in silico (computer simulation) disease model. We used the Therapeutic Performance Mapping System (Anaxomics Biotech property) to generate mathematical models based on the available scientific knowledge at the time of the study, describing the relationship between the modulation of vascular endothelial growth factor receptors (VEGFRs) by IAI and DME pathophysiological processes. We also undertook an enrichment analysis to explore the processes modulated by IAI, visualized the effectors’ predicted protein activity, and specifically evaluated the role of VEGFR1 pathway inhibition on DME treatment. The models simulated the potential pathophysiology of DME and the likely IAI’s MoA by inhibiting VEGFR1 and VEGFR2 signaling. The action of IAI through both signaling pathways modulated the identified pathophysiological processes associated with DME, with the strongest effects in angiogenesis, blood–retinal barrier alteration and permeability, and inflammation. VEGFR1 inhibition was essential to modulate inflammatory protein effectors. Given the role of VEGFR1 signaling on the modulation of inflammatory-related pathways, IAI may offer therapeutic advantages for DME through sustained VEGFR1 pathway inhibition.

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Unveiling chronic spontaneous urticaria pathophysiology through systems biology

Cited by 7 publications

References 68 publications

Autoreactive IgE: Pathogenic role and therapeutic target in autoimmune diseases

Autoreactive IgE: Pathogenic role and therapeutic target in autoimmune diseases

Autoreactive IgE: pathogenic role and therapeutic target in autoimmune diseases

Aflibercept Off-Target Effects in Diabetic Macular Edema: An In Silico Modeling Approach

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