Significance of Mast Cell Formed Extracellular Traps in Microbial Defense
AbstractMast cells (MCs) are critically involved in microbial defense by releasing antimicrobial peptides (such as cathelicidin LL-37 and defensins) and phagocytosis of microbes. In past years, it has become evident that in addition MCs may eliminate invading pathogens by ejection of web-like structures of DNA strands embedded with proteins known together as extracellular traps (ETs). Upon stimulation of resting MCs with various microorganisms, their products (including superantigens and toxins), or synthetic chemicals, MCs become activated and enter into a multistage process that includes disintegration of the nuclear mem...
Source: Clinical Reviews in Allergy and Immunology - May 22, 2021 Category: Allergy & Immunology Source Type: research

Mitigating Disparity in Health-care Resources Between Countries for Management of Hereditary Angioedema
AbstractHereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent episodes of skin and mucosal edema. The main treatment goal is to enable a “normal life” for all patients. However, due to high costs, there are limited options for the management of HAE in most developing and low-income countries. As a result, most of the recommended first-line treatments are not available. In this review, we attempt to highlight the disparities in he alth-care resources for the management of patients with HAE amongst different countries. Data was collected from HAE experts in countries who provide tabulated info...
Source: Clinical Reviews in Allergy and Immunology - May 18, 2021 Category: Allergy & Immunology Source Type: research

Blood Clotting and the Pathogenesis of Types I and II Hereditary Angioedema
AbstractThe plasma contact system is the initiator of the intrinsic pathway of coagulation and the main producer of the inflammatory peptide bradykinin. When plasma is exposed to a negatively charged surface the two enzymes factor XII (FXII) and plasma prekallikrein (PK) bind to the surface alongside the co-factor high molecular weight kininogen (HK), where PK is non-covalently bound to. Here, FXII and PK undergo a reciprocal activation feedback loop that leads to full contact system activity in a matter of seconds. Although naturally occurring negatively charged surfaces have shown to be involved in the role of the contac...
Source: Clinical Reviews in Allergy and Immunology - May 6, 2021 Category: Allergy & Immunology Source Type: research

Perspective: Application of the American College of Medical Genetics Variant Interpretation Criteria to Common Variable Immunodeficiency Disorders
AbstractCommon variable immunodeficiency disorders (CVIDs) are rare primary immunodeficiency diseases (PIDs) mostly associated with late onset antibody failure leading to immune system failure. Patients with CVID are predisposed to disabling complications such as bronchiectasis and systemic autoimmunity. In recent years a large number of genetic defects have become associated with these disorders. Patients with a causative mutation are deemed to have CVID-like disorders, while those with mutations predisposing to or modifying disease severity remain within the spectrum of CVID as defined by current diagnostic criteria. Nex...
Source: Clinical Reviews in Allergy and Immunology - April 5, 2021 Category: Allergy & Immunology Source Type: research

The Global Registry for Hereditary Angioedema due to C1-Inhibitor Deficiency
In conclusion, the establishment of a registry for C1-INH-HAE allowed collection of a large amount of data that may help to better understand the clinica l characteristics of this disease. This information may enhance patient care and guide future therapeutic decisions. (Source: Clinical Reviews in Allergy and Immunology)
Source: Clinical Reviews in Allergy and Immunology - March 31, 2021 Category: Allergy & Immunology Source Type: research

Unnecessary Abdominal Surgeries in Attacks of Hereditary Angioedema with Normal C1 Inhibitor
AbstractHereditary angioedema (HAE) is an autosomal dominant disease mostly due to the deficiency of C1 inhibitor (C1-INH). HAE with normal C1-INH was first described in 2000 and associated with mutations in the coagulation factor XII in 2006. Both diseases are associated with high bradykinin production, resulting in increased vascular permeability. Gastrointestinal edema due to HAE can be misdiagnosed as acute abdomen and unnecessary surgical procedures may be performed. The present study evaluates the prevalence of surgical procedures and/or acute abdomen in HAE patients with the coagulation factor XII mutation. It is a ...
Source: Clinical Reviews in Allergy and Immunology - March 23, 2021 Category: Allergy & Immunology Source Type: research

Thrombin in the Activation of the Fluid Contact Phase in Patients with Hereditary Angioedema Carrying the F12 P.Thr309Lys Variant
Abstract Hereditary angioedema due to pathogenic FXII variants (HAE-FXII) is a rare dominant disease caused by increased activation of the plasma contact system. The most prevalent HAE-FXII variant, c.1032C  >  A p.Thr309Lys (FXII309Lys), results in a smaller FXII protein with increased sensitivity to fluid-phase activation by poorly understood mechanisms. We aimed to investigate the functionality of the FXII309Lys variant in 33 HAE-FXII  patients, 25 healthy controls and 46 patients with congenital disorders of glycosylation (CDG). Activation of the plasma contact system was assessed by western blot and amidoly...
Source: Clinical Reviews in Allergy and Immunology - March 16, 2021 Category: Allergy & Immunology Source Type: research

Long-term Outcome of Children Born to Women with Autoimmune Rheumatic Diseases: A Multicentre, Nationwide Study on 299 Randomly Selected Individuals
AbstractThe concern about the offspring ’s health is one of the reasons for a reduced family size of women with rheumatic diseases (RD). Increased risk of autoimmune diseases (AD) and neurodevelopmental disorders (ND) has been reported in children born to patients with RD. Within a nationwide survey about reproductive issues of women wi th RD, we aimed at exploring the long-term outcome of their children. By surveying 398 patients who received their diagnosis of RD during childbearing age (before the age of 45), information about the offspring were obtained from 230 women who declared to have had children. A total of 148...
Source: Clinical Reviews in Allergy and Immunology - March 16, 2021 Category: Allergy & Immunology Source Type: research

Molecular Dambusters: What Is Behind Hyperpermeability in Bradykinin-Mediated Angioedema?
AbstractIn the last few decades, a substantial body of evidence underlined the pivotal role of bradykinin in certain types of angioedema. The formation and breakdown of bradykinin has been studied thoroughly; however, numerous questions remained open regarding the triggering, course, and termination of angioedema attacks. Recently, it became clear that vascular endothelial cells have an integrative role in the regulation of vessel permeability. Apart from bradykinin, a great number of factors of different origin, structure, and mechanism of action are capable of modifying the integrity of vascular endothelium, and thus, ma...
Source: Clinical Reviews in Allergy and Immunology - March 16, 2021 Category: Allergy & Immunology Source Type: research

Next-Generation Sequencing in the Field of Primary Immunodeficiencies: Current Yield, Challenges, and Future Perspectives
AbstractPrimary immunodeficiencies comprise a group of inborn errors of immunity that display significant clinical and genetic heterogeneity. Next-generation sequencing techniques and predominantly whole exome sequencing have revolutionized the understanding of the genetic and molecular basis of genetic diseases, thereby also leading to a sharp increase in the discovery of new genes associated with primary immunodeficiencies. In this review, we discuss the current diagnostic yield of this generic diagnostic approach by evaluating the studies that have employed next-generation sequencing techniques in cohorts of patients wi...
Source: Clinical Reviews in Allergy and Immunology - March 5, 2021 Category: Allergy & Immunology Source Type: research

Correction to: Serum Immunoglobulin G Levels Predict Biochemical and Histological Remission of Autoimmune Hepatitis Type 1: A Single ‑Center Experience and Literature Review
Correction to: Clinical Reviews in Allergy& Immunology (Source: Clinical Reviews in Allergy and Immunology)
Source: Clinical Reviews in Allergy and Immunology - March 5, 2021 Category: Allergy & Immunology Source Type: research

How Angioedema Quality of Life Questionnaire Can Help Physicians in Treating C1-Inhibitor Deficiency Patients?
AbstractThe Angioedema Quality of Life Questionnaire (AE-QoL) is an angioedema (AE)-specific validated questionnaire, which surveys the quality of life of diagnosed patients. The questionnaire has been used in multiple clinical trials. Our aim was to investigate how the questionnaire can assist physicians in the everyday practice of following up and managing C1-inhibitor deficiency patients. In a prospective trial conducted in our center between 2016 and 2018, 125 hereditary angioedema and 10 diagnosed with acquired angioedema completed an AE-QoL during their annual follow-up visit. Laboratory indices (i.e., complement lev...
Source: Clinical Reviews in Allergy and Immunology - March 3, 2021 Category: Allergy & Immunology Source Type: research

Systematic Review and Meta-analysis on the Association of Occupational Exposure to Free Crystalline Silica and Rheumatoid Arthritis
AbstractKey messages•Occupational exposure to free crystalline silica and tobacco smoking are associated with an increased risk rheumatoid arthritis, with the evidence of an interaction in seropositive subjects.•Further studies in the field are needed to support such associationWe carried out a systematic search for all published epidemiological studies concerning the association between occupational exposure to free crystalline silica (FCS) and subsequent development of rheumatoid arthritis (RA). A meta-analysis was conducted on relevant studies. We searched PubMed and Embase, search engines, for original articles pub...
Source: Clinical Reviews in Allergy and Immunology - March 2, 2021 Category: Allergy & Immunology Source Type: research

A Review of Persistent Post-COVID Syndrome (PPCS)
AbstractPersistent post-COVID syndrome, also referred to aslong COVID, is a pathologic entity, which involves persistent physical, medical, and cognitive sequelae following COVID-19, including persistent immunosuppression as well as pulmonary, cardiac, and vascular fibrosis. Pathologic fibrosis of organs and vasculature leads to increased mortality and severely worsened quality of life. Inhibiting transforming growth factor beta (TGF- β), an immuno- and a fibrosis modulator, may attenuate these post-COVID sequelae. Current preclinical and clinical efforts are centered on the mechanisms and manifestations of COVID-19 and i...
Source: Clinical Reviews in Allergy and Immunology - February 20, 2021 Category: Allergy & Immunology Source Type: research

Pathways of Neutrophil Granulocyte Activation in Hereditary Angioedema with C1 Inhibitor Deficiency
AbstractHereditary angioedema (HAE) with C1-inhibitor deficiency belongs to bradykinin-mediated angioedemas. It is characterized by recurrent subcutaneous and/or submucosal swelling episodes (HAE attacks) and erythema marginatum skin rash as a pre-attack (prodromal) phase. HAE attacks were shown to be accompanied by peripheral blood neutrophilia. We aimed to find molecular mechanisms that may explain the distinct role of neutrophil granulocytes in HAE. Plasma levels of blood cells and factors related to neutrophil activation (cytokines, chemokines, chemotactic factors, enzymes, and neutrophil extracellular trap) were measu...
Source: Clinical Reviews in Allergy and Immunology - February 19, 2021 Category: Allergy & Immunology Source Type: research