Hereditary Systemic Autoinflammatory Diseases: Therapeutic Stratification

Frontiers in Pediatrics

article

Ovgu Kul Cinar¹  Amber Putland¹  Karen Wynne¹  Despina Eleftheriou¹  Paul A. Brogan¹ 

[1] Department of Paediatric Rheumatology, Great Ormond Street Hospital for Children NHS Foundation Trust;Division of Medicine, National Amyloidosis Centre and Centre for Acute Phase Proteins, University College London, Royal Free Campus;Section of Infection, Immunity and Inflammation, Institute of Child Health, University College London Great Ormond Street;Paediatric Rheumatology, ARUK Centre for Adolescent Rheumatology, Institute of Child Health, University College London ,(UCL) Great Ormond Street Hospital

关键词: genomics;    IL-1 inhibitors;    innate immunity;    interferonopathies;    JAK 1/2 inhibitors;    periodic fever;    systemic autoinflammation;   

DOI  :  10.3389/fped.2022.867679

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Hereditary systemic autoinflammatory diseases (SAIDs) are rare, often severe conditions characterised by mutations in the key regulators of innate immune responses. Dramatic advances in the molecular genetics and next-generation sequencing in the past decade enabled identification of novel mutations that play a pivotal role in the mechanistic pathways of inflammation. Although genetic testing may not always provide straightforward guidance in diagnosis and clinical decision making, through translational research, it sheds light into molecular immunopathogenesis, particularly in IL-1 inflammasome and cytokine signalling pathways. These remarkable insights provided a better understanding of autoinflammatory conditions and their association with the innate and adaptive immune systems, as well as leading to development of cytokine-targetted biologic treatments. Use of targetted therapeutics not only helps control disease flares, reduce acute-phase responses and prevent devastating complications such as amyloidosis, but also improves health-related quality of lives and support patients to pursue almost a normal life. Herein, we discuss the commonest monogenic SAIDs, describe their immunopathology, and summarise the approaches in the management and targetted treatment of these conditions, including presentation of novel data based on a cohort of children with these rare diseases from a single quaternary referral centre in London.

【 授权许可】

CC BY