European Society for Immunodeficiencies (ESID) and European Reference Network on Rare Primary Immunodeficiency, Autoinfl
- PDF / 1,357,215 Bytes
- 16 Pages / 595.276 x 790.866 pts Page_size
- 50 Downloads / 219 Views
ORIGINAL ARTICLE
European Society for Immunodeficiencies (ESID) and European Reference Network on Rare Primary Immunodeficiency, Autoinflammatory and Autoimmune Diseases (ERN RITA) Complement Guideline: Deficiencies, Diagnosis, and Management Nicholas Brodszki 1 & Ashley Frazer-Abel 2 & Anete S. Grumach 3 & Michael Kirschfink 4 & Jiri Litzman 5 & Elena Perez 6 & Mikko R. J. Seppänen 7 & Kathleen E. Sullivan 8 & Stephen Jolles 9 Received: 5 June 2019 / Accepted: 20 January 2020 # The Author(s) 2020
Abstract This guideline aims to describe the complement system and the functions of the constituent pathways, with particular focus on primary immunodeficiencies (PIDs) and their diagnosis and management. The complement system is a crucial part of the innate immune system, with multiple membrane-bound and soluble components. There are three distinct enzymatic cascade pathways within the complement system, the classical, alternative and lectin pathways, which converge with the cleavage of central C3. Complement deficiencies account for ~5% of PIDs. The clinical consequences of inherited defects in the complement system are protean and include increased susceptibility to infection, autoimmune diseases (e.g., systemic lupus erythematosus), age-related macular degeneration, renal disorders (e.g., atypical hemolytic uremic syndrome) and angioedema. Modern complement analysis allows an in-depth insight into the functional and molecular basis of nearly all complement deficiencies. However, therapeutic options remain relatively limited for the majority of complement deficiencies with the exception of hereditary angioedema and inhibition of an overactivated complement system in regulation defects. Current management strategies for complement disorders associated with infection include education, family testing, vaccinations, antibiotics and emergency planning. Keywords Complement . complement deficiencies . classical pathway . alternative pathway . mannan-binding lectin
Introduction Most complement deficiencies have a combined estimated prevalence of 0.03% in the general population, meaning that they meet the criteria for rare diseases (< 0.05% in the EU and
< 200,000 individuals in the USA [i.e., approximately < 0.06%]) [1]. A small number of deficiencies are more common: mannose-binding lectin (MBL) deficiency has a prevalence of ~5%, and deficiencies of C4A and C4B have prevalence rates of 11–22% and 30–45%, respectively [2, 3].
* Stephen Jolles [email protected]
5
Department of Clinical Immunology and Allergology, St Anne’s University Hospital, and Faculty of Medicine, Masaryk University, Brno, Czech Republic
1
Department of Pediatrics, Children’s Hospital, Skåne University Hospital, Lund, Sweden
6
Allergy Associates of the Palm Beaches, North Palm Beach, FL, USA
2
7
Division of Rheumatology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA
3
Clinical Immunology, Reference Center on Rare Diseases, University Center Health ABC, Santo Andre, SP, Brazil
Rare Disease Center,
Data Loading...
