Brief Summary: This clinical trial aims to evaluate and compare novel and commercially available diagnostic assays through blood tests for the differential diagnosis and comprehensive assessment of patients experiencing recurrent angioedema attacks, including both urticarial and non-urticarial angioedema. The primary objective is to assess the efficiency of novel diagnostic assays, both individually and in combination, in comparison to currently available commercial tests. The ultimate goal is to establish the feasibility of developing an affordable and accurate laboratory test capable of diagnosing the diverse etiological manifestations of angioedema.

Detailed Description: Purpose: The purpose of this prospective non-interventional non-randomized diagnostic study is to first identify patients with recurrent angioedema attacks, then collect their blood samples (venipuncture) and ultimately send the samples to specialized laboratories to perform multiple diagnostic assays, novel and traditional, that can distinguish the various forms of angioedema (urticaria and non-urticarial symptoms and signs), and healthy subjects. Methods and Materials: Blood specimen collection from a total of 300 patients with recurrent angioedema attacks, and 300 healthy volunteers without a history of angioedema attacks. Laboratory testing will include assays on multiple platforms. Complement testing via immunoassay and biochemistry techniques. Flow Cytometry using multiple markers. Mass Spectrometry that includes bradykinin metabolite and histamine detection. Molecular Genetics include Sanger sequencing, Next Generation Sequencing (NGS), and digital PCR. Patient population: Study participants to be screened who have a history of recurrent angioedema incidents as well as a population of healthy subjects. A medical history will be documented after obtaining informed patient consent to enter into the clinical trial. Each enrolled participant will have blood collected as whole blood, plasma and serum via venipuncture. Eligibility criteria (inclusion) for sample collection (angioedema subject): * Understand and sign the informed consent form before starting any study procedure. * Adult or Child: aged 12 years of age or older (consent must be signed by a single parent or legal guardian). * Angioedema symptoms and signs by medical history, or previous laboratory diagnostic testing, or genetically proven cases (e.g. SERPING1 or other mutation). Patients can be on active medication for the treatment and prophylaxis of angioedema. Angioedema cases must be verified by a clinician from IAA. * Able to perform and endure safely the collection of peripheral blood samples (venipuncture), or optionally agree to have additional testing via a skin punch biopsy. Eligibility criteria (inclusion) for sample collection (for healthy participant/subject): * Understand and sign the informed consent form before starting any study procedure. * Adult or Child: aged 12 years of age or older (consent must be signed by a single parent or legal guardian). * No history of any angioedema symptoms and signs, previous laboratory diagnostic testing, or genetically proven cases. * Able to perform and endure safely the collection of peripheral blood samples (venipuncture), or optionally agree to have additional testing via a skin punch biopsy. * Not on ACE inhibitors and if on blood pressure medication, to indicate the drug(s). Exclusion Criteria (for all participants): * Minor: 11 years of age or younger. * Cannot read or understand the informed consent form and instructions. * Unable to perform the peripheral blood sample collection. * Taking medications contraindicated for testing. * History of excessive bleeding after phlebotomy, e.g. Hemophilia. * Contraindication due to other health-related issues.