Current landscape of monogenic autoinflammatory actinopathies: A literature review

First author : P. Mertz

Review: Autoimmunity Reviews

Link to article: https://doi.org/10.1016/j.autrev.2024.103715

Autoinflammatory diseases (AID) are conditions leading to a hyperactivation of innate immunity without any underlying infection, and may be poly- (e.g. Still's disease) or monogenic. The number of monogenic AID is continuously expanding, with the discovery of novel pathologies and pathophysiological mechanisms, facilitated in part by easier access to pangenomic sequencing. Actinopathies with autoinflammatory manifestations represent a newly emerging subgroup of AID, associated with defects in the regulation of actin cytoskeleton dynamics. These diseases typically manifest in the neonatal period and variably combine a primary immunodeficiency of varying severity, cytopenia (particularly thrombocytopenia), autoinflammatory manifestations primarily affecting the skin and digestive system, as well as atopic and autoimmune features.

Diagnosis should be considered primarily when encountering an early-onset autoinflammatory skin and digestive disorder, along with a primary immunodeficiency and either thrombocytopenia or a bleeding tendency. Some of these diseases exhibit specific features, such as a risk of macrophage activation syndrome (MAS) or a predisposition to atopy or lymphoproliferation. The complete pathophysiology of these diseases is not yet fully understood, and further studies are required to elucidate the underlying mechanisms, which could guide therapeutic choices. In most cases, the severity of the conditions necessitates allogeneic marrow transplantation as a treatment option.

In this review, we discuss these novel diseases, providing a practical approach based on the main associated biological abnormalities and specific clinical characteristics, with a special focus on the newly described actinopathies DOCK11 and ARPC5 deficiency. Nonetheless, genetic testing remains essential for definitive diagnosis, and various differential diagnoses must be considered.

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An update on autoinflammatory diseases

First author: S. Georgin-Lavialle

Abstract:

Autoinflammatory diseases (AIDs) are defined as disorders of innate immunity. They were initially defined in opposition to autoimmune diseases, due to the absence of involvement of the adaptive immune system and circulating autoantibodies. The 4 IADs first described are known as the “historic” IADs and include: familial Mediterranean fever (associated with mutations in the MEFV gene), cryopyrinopathies (associated with mutations in NLRP3), tumor necrosis factor receptor-associated periodic syndrome (associated with mutations in TNFRSF1A) and mevalonate kinase deficiency (associated with mutations in MVK). Over the past 10 years, more than 50 new monogenic IBDs have been discovered thanks to advances in genetics. Diagnosis is facilitated by personal and family history-taking and detailed analysis of the signs and symptoms associated with febrile attacks, which must be associated with the presence of elevated blood biomarkers of inflammation. Increasingly powerful genetic analysis techniques can help refine the diagnosis. This chapter describes the main types of IJD, and helps to guide the clinician in the suspicion and diagnosis of IJD.

MAi en français.pdf

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