Pathogenesis and Treatment of Anaphylaxis

我们对112例特发性过敏反应（IA）和抗原特异性过敏反应（SA）患者进行了评估，以探讨发病机制并确定克隆肥大细胞病患者。总体而言，22%被诊断为克隆肥大细胞病，13.4%被诊断为IA， 7.1%被诊断为毒液过敏反应，1.8%被诊断为食物或药物性过敏反应。此外，8.9%的患者被诊断为α -gal综合征，13.4%的患者被诊断为遗传性α -胰蛋白酶血症综合征。

We have evaluated 112 patients referred for idiopathic anaphylaxis (IA) and antigen-specific anaphylaxis (SA) to explore pathogenesis and identify patients with clonal mast cell disease. Overall, 22% have been diagnosed with a clonal mast cell disease, 13.4% with IA, 7.1% with venom anaphylaxis and 1.8% with food or drug-induced anaphylaxis. In addition, 8.9% were diagnosed with alpha-gal syndrome, and 13.4% were diagnosed with hereditary alpha-tryptasemia syndrome. Among patients with antigen-induced anaphylaxis, those with venom anaphylaxis in European cohorts have been reported to have a higher prevalence of clonal mast cell disease. In our cohort of patients referred for venom anaphylaxis to date (n=10), seven (80%) have been diagnosed with clonal mast cell disease. Of the ten patients enrolled with food or drug-induced anaphylaxis, thus far, two (20%) have been diagnosed with clonal mast cell disease. In FY 2023, we continue to admit patients with IA and antigen-specific anaphylaxis (SA). Most patients are admitted to the inpatient unit and undergo a bone marrow procedure in an attempt to elucidate the etiology and evaluate the pathogenesis of their disease. In collaboration with the NIH Clinical Center's myeloid core facility, we assess all patient bone marrow aspirates and biopsies obtained based on the current WHO criteria to diagnose systemic mastocytosis. This cohort was also used to contribute to the validation of mast cell activation syndromes and further elucidate pathways of activation for targeted therapy and thus, important for management strategies. In FY 2023, we contributed to manuscripts utilizing our anaphylaxis patient cohort. Our patient cohort of patients with IA were compared to patients with mastocytosis highlighting specific biomarkers of GI permeability that were elevated in both cohorts. Serum concentrations of zonulin, intestinal fatty acid binding protein (I-FABP), and soluble CD14 (sCD14) measured in 54 patients with IA were compared with concentrations in healthy controls (HCs); and correlated with clinical and laboratory parameters. The I-FABP and sCD14 are elevated in the serum of patients with IA. We found both an overlap and a divergence in the microbial translocation markers (MTM) profiles associated with IA versus mastocytosis, Elevations in both intestinal fatty acid binding protein (I-FABP) and soluble CD14 (sCD14) are thus observed in both conditions. However, the MTM profile of IA diverges from that of mastocytosis, with a lack of zonulin elevation in those with IA. One conclusion appears to be that various mast cell disorders carry specific profiles of MTMs. Elevations in these biomarkers of IA provides evidence that increased GI permeability, as is observed in other allergic conditions such as food allergy, is a common finding in those with IA and offers possible insight into the pathogenesis of this disease. I was the co-Editor for a themed issue on Anaphylaxis in the Journal of Allergy and Clinical Immunology: In Practice. I also contributed to a manuscript in this journal with authors from Canada and Germany regarding the role of intrinsic and extrinsic modulators in anaphylaxis.