- |||||||||| Journal: BCR ligation selectively inhibits IgE class switch recombination. (Pubmed Central) - Sep 30, 2024
BCR ligation also inhibited CSR to IgE in human tonsillar B cells, and this inhibition was also synergistic with IL-21. These findings establish that IgE CSR is uniquely susceptible to inhibition by BCR signaling in mouse and human B cells, with important implications for the regulation and pathogenesis of allergic disease.
- |||||||||| Journal, IO biomarker: Formononetin inhibits IgE by huPlasma/PBMCs and mast cells/basophil activation via JAK/STAT/PI3-Akt pathways. (Pubmed Central) - Sep 2, 2024
In basophils KU812 cells, formononetin significantly increased the gene expression of NFKBIA, TP53, and BCL-2 while decreasing the gene expression of BTK, TYK, CASP8, STAT3, CCND1, STAT1, NFKB1, IL7R. These findings comprehensively present formononetin's mechanisms in regulating IgE production in plasma cells and degranulation in mast cells.
- |||||||||| Jakafi (ruxolitinib) / Incyte
Journal: The JAK1/JAK2 inhibitor ruxolitinib inhibits mediator release from human basophils and mast cells. (Pubmed Central) - Aug 27, 2024
Ruxolitinib also inhibited anti-IgE- and IL-3-mediated cytokine (IL-4 and IL-13) release from basophils, as well as the secretion of preformed mediators (histamine, tryptase, and chymase) from substance P-activated HSMCs. These results indicate that ruxolitinib, inhibiting the release of several mediators from human basophils and mast cells, is a potential candidate for the treatment of inflammatory disorders.
- |||||||||| Journal: Allosteric inhibition of IgE-Fc?RI interactions by simultaneous targeting of IgE F(ab')2 epitopes. (Pubmed Central) - Aug 24, 2024
Consequently, HMK-12 Fab-mediated targeting of C?2 reduced the binding affinity of Fc domains and resulted in rapid removal of IgE from the receptor complex. This unexpected finding of allosteric inhibition of IgE-Fc?RI interactions by simultaneous targeting of two epitope sites on the C?2 homodimer domain of IgE F(ab')2 may have implications for the development of novel therapies for allergic disease.
- |||||||||| Journal: Sulfur dioxide inhibits mast cell degranulation by sulphenylation of galectin-9 at cysteine 74. (Pubmed Central) - Jul 2, 2024
Sulfenylation of the 74th cysteine of Gal-9 protein was required in the SO2-inhibited MC degranulation under both physiological and pathophysiological conditions. These findings elucidated that SO2 inhibited MC degranulation via sulfenylating Gal-9 under both physiological and pathophysiological conditions, which might provide a novel treatment approach for MC activation-related diseases.
- |||||||||| Journal, IO biomarker: Heterogenous Induction of Blocking Antibodies against Ragweed Allergen Molecules by Allergen Extract-Based Immunotherapy Vaccines. (Pubmed Central) - Jun 27, 2024
The high levels of allergen-specific IgG levels were associated with their ability to prevent the recognition of allergens by patients' IgE and allergen-induced basophil activation, indicating that the measurement of allergen-induced IgG could be a useful surrogate marker for the immunological efficacy of vaccines. Accordingly, the results of our study may be helpful for the selection of personalized AIT vaccination strategies for ragweed-allergic patients.
- |||||||||| Review, Journal: Treatment strategies for ANCA-associated vasculitides: from standard protocols to future horizons. (Pubmed Central) - Jun 16, 2024
There is hope that the new treatment targets currently under study in AAV may enable a faster and more lasting clinical response, ensuring the reduction of possible side effects from therapies. Moreover, numerous aspects necessitate further exploration in the future, such as tailoring of GCs, integration of GCs-sparing agents, efficacy of combination therapy, optimal maintenance therapy, to reduce organ-damage and improve quality of life.
- |||||||||| IGNX001 / IgGenix
IGNX001 Inhibits Peanut-Mediated Mast Cell Activation in a Translational Spike-In Assay (Poster Zone) - May 25, 2024 - Abstract #EAACI2024EAACI_2851;
Conclusion A preclinical translational spike-in MAT was developed to recapitulate the time dependent concentration of an IgG4-based antibody therapeutic in circulation. IGNX001, which competitively inhibits IgE interaction with allergen, demonstrated potent inhibition of cellular activation and provided a case study of how this assay could serve as a valuable pharmacodynamic marker in clinical trials.
- |||||||||| Cross-reactivity and co-sensitization among allergenic enolases (Poster Zone) - May 25, 2024 - Abstract #EAACI2024EAACI_2813;
This suggests that IgE-reactivity might be caused by independent co-sensitization to enolases from distantly related organisms. Our findings will contribute to an improvement of allergy diagnosis and patient-tailored prevention strategies.
- |||||||||| ligelizumab (QGE031) / Novartis
Characterization of anti-IgE molecules to inhibit IgE:receptor interactions and suppress IgE production in B-cells (Poster Zone) - Apr 21, 2024 - Abstract #EAACI2024EAACI_2589;
Interestingly, KIH_E07_79 suppressed IgE production in a similar range as previously described for the anti-IgE antibody ligelizumab and reduced the number of IgE+ cells in primary human B-cells in vitro comparable to the anti-IgE antibody quilizumab...In addition to active desensitization of allergic effector cells, KIH_E07_79 also inhibits IgE production and reduces IgE+ cells in primary human B-cell cultures. These additional modes-of-action could potentially be of clinical relevance and might increase the efficacy of such a multi-level IgE targeting approach.
- |||||||||| Allergic reaction to a commercially available insect snack caused by house cricket (Acheta domesticus) tropomyosin (Poster Zone) - Apr 21, 2024 - Abstract #EAACI2024EAACI_1936;
Our findings emphasize the necessity for clear declaration of insect contents in foodstuffs since tropomyosins represent a pan-allergen in (edible) insects present in e.g. crickets, cockroaches, silkworm and mealworm. Furthermore, allergic patients and allergologists should be aware of the potential cross-reactivity between tropomyosins in edible insects, shrimps, molluscs and house dust mite.
- |||||||||| Development of a specific IgE immunoassay for rAra h 18 (Poster Zone) - Apr 21, 2024 - Abstract #EAACI2024EAACI_1816;
The results suggest that cyclophilins may have a similar role as profilins in IgE testing. Conclusion An ImmunoCAP rAra h 18 RUO test was developed which may be helpful for clarifying cross-reactivity between cyclophilin containing allergen sources such as pollen, peanut and other plant derived foods and for gaining a fuller understanding of the clinical and diagnostic implications of cyclophilin sensitization.
- |||||||||| Cross-reactivity and co-sensitization among allergenic enolases (Bilbao) - Apr 5, 2024 - Abstract #EAACI2024EAACI_764;
This suggests that IgE-reactivity might be caused by independent co-sensitization to enolases from distantly related organisms. Our findings will contribute to an improvement of allergy diagnosis and patient-tailored prevention strategies.
- |||||||||| IGNX001 / IgGenix
IGNX001 Inhibits Peanut-Mediated Mast Cell Activation in a Translational Spike-In Assay (Bilbao) - Apr 5, 2024 - Abstract #EAACI2024EAACI_687;
Conclusion A preclinical translational spike-in MAT was developed to recapitulate the time dependent concentration of an IgG4-based antibody therapeutic in circulation. IGNX001, which competitively inhibits IgE interaction with allergen, demonstrated potent inhibition of cellular activation and provided a case study of how this assay could serve as a valuable pharmacodynamic marker in clinical trials.
- |||||||||| AK006 / Allakos, ucenprubart (LY3454738) / Eli Lilly, lirentelimab (AK002) / Allakos
Review, Journal: Mast cell silencing: A novel therapeutic approach for urticaria and other mast cell-mediated diseases. (Pubmed Central) - Jan 2, 2024
MC silencers, such as agonist monoclonal antibodies that engage inhibitory receptors (e.g., sialic acid-binding immunoglobulin-like lectin8 -[Siglec-8] [lirentelimab/AK002], Siglec-6 [AK006], and CD200R [LY3454738]), have reached preclinical and clinical stages of development. In this review, we (1) describe the role of MCs in the pathogenesis of CU, highlighting similarities with other MC diseases in disease mechanisms and response to treatment; (2) explore current therapeutic strategies, categorized by nonspecific immunosuppression, targeted inhibition of MC activation or mediators, and targeted modulation of MC activity; and (3) introduce the concept of MC silencing as an emerging strategy that could selectively block activation of MCs without eliciting or exacerbating on- or off-target, immunosuppressive adverse effects.
- |||||||||| Jingzhuda (entinostat) / EOC Pharma, EddingPharm
Journal: HDAC1 inhibits beige adipocyte-mediated thermogenesis through histone crotonylation of Pgc1a/Ucp1. (Pubmed Central) - Oct 6, 2023
Herein, we report that class I histone deacetylases (HDAC) inhibitor MS275 increased PGC1?/UCP1 protein levels in inguinal white adipose tissue (iWAT) concomitant with elevated energy expenditure, reduced obesity and ameliorated glucose tolerance compared to control littermates...Taken together, HDAC1 inhibits beige adipocyte-mediated thermogenesis through histone crotonylation of Pgc1a/Ucp1. This finding may provide a therapeutic strategy through increasing energy expenditure in obesity and related metabolic disorders.
- |||||||||| Journal: Allergy to cypress and olive pollen: Clinical phenotypes and allergen recognition. (Pubmed Central) - Aug 4, 2023
Importantly, FGTI-2734 was effective in The exclusive C+O allergy results from co-sensitization to Cup s 1 and Ole e 1, and to cross-reactivity due to Ole e 1-like, Ole e 9-like and Ole e 11-like allergens not described previously, and translates into 4 clinical phenotypes of winter and/or spring or perennial rhinoconjunctivitis with and without asthma.
- |||||||||| Dupixent (dupilumab) / Sanofi, Regeneron, Xolair (omalizumab) / Roche, Novartis
Review, Journal: Treatment of food allergy: oral immunotherapy, biologics and beyond. (Pubmed Central) - Jul 4, 2023
Biologics such as omalizumab and dupulimab, which already have FDA approval for other atopic conditions have been the most studied, but additional biologics and novel strategies are emerging. In this review we discuss therapeutic strategies including IgE inhibitors, IgE disruptors, IL-4 and IL-13 inhibitors, anti-alarmins, JAK1 and BTK inhibitors, and nanoparticles and the data surrounding their application in food allergy and highlight their potential.
- |||||||||| Xolair (omalizumab) / Roche, Novartis
Omalizumab Induced Photosensitivity In A Patient With Chronic Spontaneous Urticaria () - Jul 3, 2023 - Abstract #WCD2023WCD_6560;
OBSERVATION: A 42 year old man with past history of urticaria on exposure to shellfish, non-steroidal antiinflamatory drugs and fentanyl developed chronic spontaneous urticaria...He developed symptomatic high blood pressure with cyclosporin while azathioprine caused drug induced liver injury...KEY MESSAGE: Photosensitivity is a rare adverse reaction of omalizumab. Therapy may be continued with adequate photoprotection measures
- |||||||||| CH-223191 / BMS
Journal: Ethyl Caffeate Can Inhibit Aryl Hydrocarbon Receptor (AhR) Signaling and AhR-Mediated Potentiation of Mast Cell Activation. (Pubmed Central) - Jul 2, 2023
Notably, both EC and CH-223191, a well-established AhR antagonist, inhibited IgE-mediated degranulation in BMMCs grown in a cell culture medium containing significant amounts of AhR ligands...Collectively, EC inhibited AhR signaling and AhR-mediated potentiation of mast cell activation due to the intrinsic AhR activity in both the culture medium and normal mouse skin. Given the AhR control of inflammation, these findings suggest a novel mechanism for the anti-inflammatory activity of EC.
- |||||||||| Review, Journal: IgG4 Antibodies Induced by Repeated Vaccination May Generate Immune Tolerance to the SARS-CoV-2 Spike Protein. (Pubmed Central) - May 27, 2023
However, emerging evidence suggests that the reported increase in IgG4 levels detected after repeated vaccination with the mRNA vaccines may not be a protective mechanism; rather, it constitutes an immune tolerance mechanism to the spike protein that could promote unopposed SARS-CoV2 infection and replication by suppressing natural antiviral responses. Increased IgG4 synthesis due to repeated mRNA vaccination with high antigen concentrations may also cause autoimmune diseases, and promote cancer growth and autoimmune myocarditis in susceptible individuals.
- |||||||||| Journal: Circadian clock control of MRTF/SRF pathway suppresses beige adipocyte thermogenic recruitment. (Pubmed Central) - May 15, 2023
Selective ablation of Bmal1 induces beigeing with improved glucose homeostasis, whereas its targeted overexpression attenuates thermogenic induction resulting in obesity. Collectively, our findings identify the clock-MRTF/SRF regulatory axis as an inhibitory mechanism of beige fat thermogenic recruitment with significant contribution to systemic metabolic homeostasis.
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