Autoinflammatory diseases. Part 3: NLRP and NLRC inflammasomopathies. Biologic therapies for inflammasomopathies

Inflammasomopathies and other enhanced interleukin (IL)-1 signaling syndromes represent a significant cluster of systemic autoinflammatory diseases (SAIDs) which are monogenic disorders characterized by episodic spontaneous multisystemic inflammation mediated by innate immunity and resulting mainly from inappropriate activation of antigen-independent inflammatory mechanisms without production of autoantibodies. Autoinflammation is currently considered a distinct category of immune dysfunction along with autoimmunity/allergy and immunodeficiency. This scientific review is the third in a series of publications aimed at raising awareness among healthcare professionals regarding the diagnosis and management of SAIDs in children. The review highlights the immunobiological features of inflammasomes containing nucleotide-binding domain, leucine-rich repeat-containing proteins (NLRs). It also presents the clinical and pathogenetic features of the currently genetically defined NLRP3-, NLRP12-, NLRP1- and NLRC4-associated inflammasomopathies. The paper also discusses the potential of biologic-targeted therapies for inflammasomopathies which are now considered a key trend in the treatment of SAIDs and based on the molecular immunopathogenesis of the disease. Furthermore, we summarized the current experience of using available biological agents in the treatment of specific inflammasomopathies, namely agents blocking the effects of IL-1, IL-6, IL-17, IL-12/23, interferon-gamma, and tumor necrosis factor. Data were collected through a focused search over the Web of Science, Scopus, PubMed Central®, Google Scholar databases for the past 10 years using the keywords “autoinflammatory diseases”, “autoinflammation”, “inflammasomopathies”, “NLRP”, “NLRC”, “biologic therapies”.