Rare Autoinflammatory Diseases

Abstract

Systemic autoinflammatory diseases are disorders caused by dysregulation of the innate immune system leading to systemic inflammation. Since the first gene had been identified causing Familial Mediterranean Fever, the most common hereditary systemic autoinflammatory disease, advances in genomic techniques and awareness of the diseases have led to identifying more genes causing autoinflammatory conditions affecting different parts of the innate immune system. The aim of this review is to provide an update on some recently discovered autoinflammatory conditions and raise awareness for the clinicians. We focused on the actinopathies, interferonopathies, and NF-κB-mediated autoinflammatory diseases.

Figure 1.

The interferon pathway. Gain-of-function mutations causing the constitutive activation STING drive SAVI. For CANDLE disease, after IFN activation, cells with mutated proteasome will not be able to remove waste proteins. Misfolded proteins will accumulate and this cellular stress leads to excessive type 1 IFNs secretion. SAVI, STING-associated vasculopathy with onset in infancy; STING, stimulator of interferon genes protein; CANDLE, chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature; IFN, interferon.

Figure 2.

NF-κB pathway and mechanisms of pathogenesis in haploinsufficiency of A20 (HA20) and otulipenia. Decreased expression of A20 or OTULIN in patients will lead to activation of the NF-κB pathway, increased proinflammatory cytokine transcripts in immune cells, and systemic inflammation.NF-κB, nuclear factor kappa light-chain enhancer of activated B cells.