<p>IgE-Mediated Systemic Anaphylaxis And Its Association With Gene Polymorphisms Of ACE, Angiotensinogen And Chymase</p>

Abstract

BackgroundThe renin-angiotensin system (RAS) protects the circulation against sudden falls in systemic blood pressure via generation of angiotensin II (AII). Previously, we demonstrated that patients with anaphylaxis involving airway angioedema and cardiovascular collapse (AACVS) had significantly increased “I” gene polymorphisms of the angiotensin-converting-enzymes (ACE). This is associated with lower serum ACE and AII levels and was not seen in anaphylaxis without collapse nor atopics and healthy controls.ObjectivesTo examine the angiotensinogen (AGT-M235T) and chymase gene (CMA-1 A1903G) polymorphisms in these original subjects.Method122 patients with IgE-mediated anaphylaxis, 119 healthy controls and 52 atopics had polymorphisms of the AGT gene and chymase gene examined by polymerase chain reactions and gel electrophoresis. Their previous ACE genotypes were included for the analysis.ResultsAGT-MM genes (associated with low AGT levels) were significantly increased in anaphylaxis (Terr’s classification). When combined with ACE, anaphylaxis showed increased MM/II gene pairing (p<0.0013) consistent with lower RAS activity. For chymase, there was increased pairing of MM/AG (p<0.005) and AG/II and AG/ID (p<0.0073) for anaphylaxis consistent with lower RAS activity. A tri-allelic ensemble of the 6 commonest gene combinations for the healthy controls and anaphylaxis confirmed this difference (p=0.0001); for anaphylaxis, genes were predominately MM/AG/II or ID, while healthy controls were DD/MT/AG or GG patterns.ConclusionOur gene polymorphisms show lower RAS activity for anaphylaxis especially AACVS. Animal models of anaphylaxis are focused on endothelial nitric oxide (eNO) which is shown to be the mediator of fatal shock and prevented by eNO-blockade. The interaction of AII and eNO controls the microcirculation in man. High serum AII levels reduce eNO activity, so higher RAS-activity could protect against shock. Our data shows low RAS activity in anaphylaxis especially AACVS, suggesting the influence of these genes on shock are via AII levels and its effects on eNO.

The Role of Mast Cells in the Induction and Maintenance of Inflammation in Selected Skin Diseases

“…So far, the best-known pathophysiological mechanisms of MCs in skin diseases are those related to their clonal neoplastic growth (mastocytosis group), as well as allergic diseases proceeding in the IgE-dependent mechanism (allergies to foods, pollen, drugs, etc.) [ 19 , 38 , 131 , 140 ]. In recent years, more and more papers have been published indicating the key role of MCs in inflammatory skin diseases, including those of autoimmune origin [ 13 , 147 ].…”

Mast Cell Activation Syndromes: Collegium Internationale Allergologicum Update 2022

“…Several of the affected genes encode proteins physiologically involved in the regulation of MC development, such as KIT, IL-4, or IL-6, the production of IgE, and/or the regulation of expression of the IgE receptor on MC, where IL-4, the IL-4 receptors, and IL-13 may play a role [ 54 , 55 , 56 ]. Other genes (variants) encode for proteins that are produced in MC and/or other immune cells and are involved in the regulation of vascular stability or dysfunction, such as angiotensinogen, angiotensin-converting enzymes, or chymase [ 8 , 20 , 57 , 58 ].…”

Tree nut allergy

“…Analysis of prick tests from 1286 allergy sufferers aged 2–79 years in southern Iran showed positive walnut tests in as many as 21.4%, which was the second most frequent allergy after hen’s egg white (30.3%). Cases of anaphylaxis induced by ACEi after consumption of walnuts were also observed [ 50 , 51 ].…”