Autoinflammatory manifestations in adult patients

Abstract

Autoinflammatory diseases represent a family of immune-mediated conditions characterized by the unchecked activation of innate immunity. These conditions share common clinical features such as recurrent fever, inflammatory arthritis, and elevation of acute phase reactants, in the absence of an identified infectious etiology, generally without detectable serum autoantibodies, with variable response to glucocorticoids and in some cases colchicine, which represented the mainstay of treatment until cytokine blockade therapies became available. The first autoinflammatory diseases to be described were monogenic disorders caused by missense mutations in inflammasome components and were recognized predominantly during childhood or early adulthood. However, the progress of genetic analyses and a more detailed immunological phenotyping capacity led to the discovery a wide spectrum of diseases, often becoming manifest or being diagnosed in the adult population. The beneficial role of targeting hyperinflammation via interleukin 1 in complex non-immune-mediated diseases is a field of growing clinical interest. We provide an overview of the autoinflammatory diseases of interest to physicians treating adult patients and to analyze the contribution of hyperinflammation in non-immune-mediated diseases; the result is intended to provide a roadmap to orient scientists and clinicians in this broad area.

Keywords: COVID-19; anakinra; canakinumab; inflammasome; interleukin-1; myocarditis.

Graphical Abstract

Figure 1:

inflammasome assembly and activation. (A) PAMPs and DAMPs phagocytosis directly and, mainly, indirectly induces the intracellular assembly of the inflammasome (B), which catalyzes the proteolytic cleavage of pro-interleukin-1 and pro-interleukin18 (C). In the meantime, TLR binding activates intracellular pathways that culminate in the nuclear synthesis of NFkB, which in turn induces increased synthesis of inflammasome components, and pro-IL-1 and pro-IL18 (D). Activated proinflammatory cytokines mediate multiorgan inflammation with characteristic clinical features.