Fc receptors in immune thrombocytopenias: a target for immunomodulation?

Psaila, Bethan; Bussel, James B.

doi:10.1172/jci36451

Cited by 19 publications

(20 citation statements)

References 26 publications

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“…In contrast, blocking antibodies for the medium affinity receptor FcγRIV resulted in an impaired platelet clearance. Similar results were obtained in human ITP patients where blocking antibodies to FcγRIIIA, which is the human ortholog of murine FcγRIV [23,42], but not to human FcγRI were very efficient in blocking platelet depletion [43][44][45][46]. Thus, FcγRs are instrumental for IgG-mediated platelet depletion for murine and human ITP and are an attractive target for therapeutic intervention.…”

Section: Effector Pathways Involved In Murine Itpsupporting

confidence: 73%

The role of Fcγ receptors in murine autoimmune thrombocytopenia

et al. 2010

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International audienceImmune thrombocytopenia (ITP) can become a life-threatening condition that requires immediate medical attention. The loss in platelet numbers during ITP can be induced by a variety of triggers. Anti-platelet antibodies of several isotypes and subclasses are a major cause for ITP and are a hallmark of many complex autoimmune diseases such as systemic lupus erythematosus. Mouse models have been important to understand the effector pathways involved in antibody-mediated platelet depletion. Therapeutic interventions based on these results have been proven successful in treating human ITP, thus validating the use of these model systems. One major problem that remains to be answered is which cell populations are crucial for platelet removal. Targeting these cells directly might be a novel therapeutic strategy and will also be important to understand the underlying biological mechanisms

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Section: Effector Pathways Involved In Murine Itpsupporting

confidence: 73%

The role of Fcγ receptors in murine autoimmune thrombocytopenia

et al. 2010

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“…[7][8][9] Encouragingly, .50% of ITP patients refractory to other treatments responded with significantly improved platelet counts. 8,10 However, its continued therapeutic application was stalled by adverse events, including vomiting, nausea, and fever. 8,10,11 One major hypothesis behind the adverse events involves the (antiFcgRIIIA antibody) Fc-mediated interaction with FcgRIIIA in addition to its antigen-binding fragment (Fab) domain-induced cross-linking.…”

Section: Introductionmentioning

confidence: 99%

“…8,10 However, its continued therapeutic application was stalled by adverse events, including vomiting, nausea, and fever. 8,10,11 One major hypothesis behind the adverse events involves the (antiFcgRIIIA antibody) Fc-mediated interaction with FcgRIIIA in addition to its antigen-binding fragment (Fab) domain-induced cross-linking. The cross-linking of FcgRIIIA triggers phosphorylation of the signaling components of this receptor, leading to proinflammatory responses.…”

Section: Introductionmentioning

confidence: 99%

“…6 However, uncontrolled cross-linking of FcgRs, such as by an anti-FcgRIIIA antibody, can lead to an anaphylactic reaction, 6,12,13 as evidenced by the 3G8 trial. 8,10 One potential means of reducing unwanted adverse events involves abolishing Fc-mediated effector function. A deglycosylated version of 3G8 (called GMA161), known to have abrogated Fc function, 14 had thus been developed by Fc engineering.…”

Section: Introductionmentioning

confidence: 99%

“…15 Consistent with the humanized mouse model, GMA161 improved platelet counts in refractory patients but failed to reverse adverse events exhibited by its parent 3G8. 10,11 The outcome of the pilot trial of GMA161 suggested to us that the bivalent Fab domain likely triggers the adverse events. We have speculated here that a monovalent Fab fragment would represent a suitable therapeutic candidate.…”

Section: Introductionmentioning

confidence: 99%

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Monovalent Fc receptor blockade by an anti–Fcγ receptor/albumin fusion protein ameliorates murine ITP with abrogated toxicity

Menard

Prechl

et al. 2016

Blood

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Bioinformatic identification of key pathways, hub genes, and microbiota for therapeutic intervention in Helicobacter pylori infection

Chen

et al. 2020

Journal Cellular Physiology

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The pathogenic mechanisms of Helicobacter pylori infection remain to be defined, and potential interventional microbiota are just beginning to be identified. In this study, gene-set enrichment analysis (GSEA) was used to integrate three H. pylori infection microarray data sets from the gene expression omnibus database and identified ten hallmark gene sets and 35 Kyoto encyclopedia of genes and genomes (KEGG) pathways that differed between healthy and Helicobacter pylori-infected individuals. Weighted gene co-expression network analysis (WGCNA) performed on two of the data sets identified three key gene coexpression modules. These modules contained 54 enriched KEGG pathways, 25 of which overlapped with the GSEA analysis, suggesting potentially important roles in H. pylori-infection. We selected 116 hub genes from the three key modules for in vitro validation at the transcriptional level using H. pylori Sydney Strain 1 and verified the upregulation of 80. WGCNA of the microbiomes based on 20 mucosal samples and a sequence read archive data set revealed four microbiota modules correlated with H. pylori infection. The negatively correlated modules contained 11 microbiome families. These findings provide new insight into the pathogenesis of H. pylori infection and systematically identify 25 key pathways, 80 upregulated hub genes, and 11 families of candidate interventional microbiota for further research.

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Fc receptors in immune thrombocytopenias: a target for immunomodulation?

Cited by 19 publications

References 26 publications

The role of Fcγ receptors in murine autoimmune thrombocytopenia

The role of Fcγ receptors in murine autoimmune thrombocytopenia

Monovalent Fc receptor blockade by an anti–Fcγ receptor/albumin fusion protein ameliorates murine ITP with abrogated toxicity

Bioinformatic identification of key pathways, hub genes, and microbiota for therapeutic intervention in Helicobacter pylori infection

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