Autoinflammation and autoimmunity across rheumatic and musculoskeletal diseases

• Published in: Nature reviews. Rheumatology 2021-10, Vol.17 (10), p.585-595
• Main Authors: Szekanecz, Zoltán, McInnes, Iain B., Schett, Georg, Szamosi, Szilvia, Benkő, Szilvia, Szűcs, Gabriella
• Format: Article
• Language: English
• Subjects: 631/250/38; 692/4023/1670; Adaptive immunity; Antiphospholipid syndrome; Autoimmune diseases; Autoimmune Diseases - genetics; Autoimmune Diseases - immunology; Autoimmunity; Autoimmunity - genetics; Autoimmunity - immunology; Cytokines; Development and progression; Health aspects; Humans; Immune response; Immunity, Innate - genetics; Immunity, Innate - immunology; Inflammasomes; Inflammation; Inflammation - genetics; Inflammation - immunology; Inflammatory diseases; Innate immunity; Medicine; Medicine & Public Health; Musculoskeletal diseases; Musculoskeletal Diseases - genetics; Musculoskeletal Diseases - immunology; Review Article; Rheumatic diseases; Rheumatic Diseases - genetics; Rheumatic Diseases - immunology; Rheumatoid arthritis; Rheumatology; Systemic lupus erythematosus
• ISSN: 1759-4790; 1759-4804
• DOI: 10.1038/s41584-021-00652-9

Most rheumatic and musculoskeletal diseases (RMDs) can be placed along a spectrum of disorders, with autoinflammatory diseases (including monogenic systemic autoinflammatory diseases) and autoimmune diseases (such as systemic lupus erythematosus and antiphospholipid syndrome) representing the two ends of this spectrum. However, although most autoinflammatory diseases are characterized by the activation of innate immunity and inflammasomes and classical autoimmunity typically involves adaptive immune responses, there is some overlap in the features of autoimmunity and autoinflammation in RMDs. Indeed, some ‘mixed-pattern’ diseases such as spondyloarthritis and some forms of rheumatoid arthritis can also be delineated. A better understanding of the pathogenic pathways of autoinflammation and autoimmunity in RMDs, as well as the preferential cytokine patterns observed in these diseases, could help us to design targeted treatment strategies. Most rheumatic and musculoskeletal diseases (RMDs) fall along a spectrum of disorders from autoinflammatory diseases to autoimmune diseases, with ‘mixed-pattern’ RMDs having features of autoinflammation and autoimmunity. A better understanding of the pathogenic pathways of autoinflammation and autoimmunity in RMDs should enhance targeted treatment strategies. Key points Rheumatic and musculoskeletal diseases (RMDs) form a continuum between classical autoimmune and autoinflammatory conditions. Classical autoinflammatory and autoimmune diseases are associated with the activation of innate immunity and adaptive immune responses, respectively. There are some ‘mixed-pattern’ disorders that carry the features of both autoimmune and autoinflammatory conditions, and one disorder might have autoimmune and autoinflammatory characteristics at different stages of disease development. The autoimmune, autoinflammatory or mixed phenotype of RMDs might help us to develop and administer therapies targeted to specific disease phenotypes.