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Allergology International : Official... Jul 2023Chronic spontaneous urticaria (CSU) is a common skin disease without an etiology in the vast majority of cases. The similarity of symptoms and pathology to... (Review)
Review
Chronic spontaneous urticaria (CSU) is a common skin disease without an etiology in the vast majority of cases. The similarity of symptoms and pathology to allergen-induced skin reactions supports that skin mast cell IgE receptor activation is also involved in CSU. Accumulating evidence also supports a role for blood basophils in disease expression. Blood basopenia is noted in active CSU disease with the recruitment of blood basophils to skin lesion sites. Blood basophils further display altered IgE receptor mediated degranulation patterns in two phenotypes that improve in remission. In active CSU subjects, changes in IgE receptor signaling molecule expression levels accompany the altered degranulation function in blood basophils. The success of therapies targeting IgE in CSU patients have also shown that altered blood basophil phenotypes and enumeration have potential use as a disease biomarker.
Topics: Humans; Basophils; Receptors, IgE; Chronic Disease; Urticaria; Chronic Urticaria
PubMed: 37221123
DOI: 10.1016/j.alit.2023.05.001 -
The Journal of Allergy and Clinical... May 2024Chronic spontaneous urticaria (CSU) is an inflammatory skin disorder that manifests with itchy wheals, angioedema, or both for more than 6 weeks. Mast cells and... (Review)
Review
Chronic spontaneous urticaria (CSU) is an inflammatory skin disorder that manifests with itchy wheals, angioedema, or both for more than 6 weeks. Mast cells and basophils are the key pathogenic drivers of CSU; their activation results in histamine and cytokine release with subsequent dermal inflammation. Two overlapping mechanisms of mast cell and basophil activation have been proposed in CSU: type I autoimmunity, also called autoallergy, which is mediated via IgE against various autoallergens, and type IIb autoimmunity, which is mediated predominantly via IgG directed against the IgE receptor FcεRI or FcεRI-bound IgE. Both mechanisms involve cross-linking of FcεRI and activation of downstream signaling pathways, and they may co-occur in the same patient. In addition, B-cell receptor signaling has been postulated to play a key role in CSU by generating autoreactive B cells and autoantibody production. A cornerstone of FcεRI and B-cell receptor signaling is Bruton tyrosine kinase (BTK), making BTK inhibition a clear therapeutic target in CSU. The potential application of early-generation BTK inhibitors, including ibrutinib, in allergic and autoimmune diseases is limited owing to their unfavorable benefit-risk profile. However, novel BTK inhibitors with improved selectivity and safety profiles have been developed and are under clinical investigation in autoimmune diseases, including CSU. In phase 2 trials, the BTK inhibitors remibrutinib and fenebrutinib have demonstrated rapid and sustained improvements in CSU disease activity. With phase 3 studies of remibrutinib ongoing, it is hoped that BTK inhibitors will present an effective, well-tolerated option for patients with antihistamine-refractory CSU, a phenotype that presents a considerable clinical challenge.
Topics: Humans; Agammaglobulinaemia Tyrosine Kinase; Chronic Urticaria; Signal Transduction; Mast Cells; Animals; Receptors, IgE; Basophils; Protein Kinase Inhibitors
PubMed: 38141832
DOI: 10.1016/j.jaci.2023.12.008 -
Virology Journal Jun 2023The relationship between chronic hepatitis B (CHB) and Coronavirus disease 2019 (COVID-19) has been inconsistent in traditional observational studies.
BACKGROUND
The relationship between chronic hepatitis B (CHB) and Coronavirus disease 2019 (COVID-19) has been inconsistent in traditional observational studies.
METHODS
We explored the total causal and direct causal associations between CHB and the three COVID-19 outcomes using univariate and multivariate Mendelian randomization (MR) analyses, respectively. Genome-wide association study datasets for CHB and COVID-19 were obtained from the Japan Biobank and the COVID-19 Host Genetics Initiative, respectively.
RESULTS
Univariate MR analysis showed that CHB increased the risk of SARS-CoV-2 infection (OR = 1.04, 95% CI 1.01-1.07, P = 3.39E-03), hospitalized COVID-19 (OR = 1.10, 95% CI 1.06-1.13, P = 7.31E-08), and severe COVID-19 (OR = 1.16, 95%CI 1.08-1.26, P = 1.43E-04). A series of subsequent sensitivity analyses ensured the stability and reliability of these results. In multivariable MR analyses adjusting for type 2 diabetes, body mass index, basophil count, and smoking, genetically related CHB is still positively associated with increased risk of SARS-CoV-2 infection (OR = 1.06, 95% CI 1.02-1.11, P = 1.44E-03) and hospitalized COVID-19 (OR = 1.12, 95% CI 1.07-1.16, P = 5.13E-07). However, the causal link between CHB and severe COVID-19 was attenuated after adjustment for the above variables. In addition, the MR analysis did not support the causal effect of COVID-19 on CHB.
CONCLUSIONS
This study provides evidence that CHB increases COVID-19 susceptibility and severity among individuals of East Asian ancestry.
Topics: Humans; COVID-19; East Asian People; Genome-Wide Association Study; Hepatitis B, Chronic; Reproducibility of Results
PubMed: 37264390
DOI: 10.1186/s12985-023-02081-4