An Autoinflammatory Disease Due to Homozygous Deletion of theIL1RNLocus

Abstract

SUMMARY We describe a patient with an autoinflammatory disease in which the main clinical features are pustular rash, marked osteopenia, lytic bone lesions, respiratory insufficiency, and thrombosis. Genetic studies revealed a 175-kb homozygous deletion at chromosome 2q13, which encompasses several interleukin-1 family members, including the gene encoding the interleukin-1–receptor antagonist (IL1RN). Mononuclear cells, obtained from the patient and cultured, produced large amounts of inflammatory cytokines, with increasing amounts secreted after stimulation with lipopolysaccharide. A similar increase was not observed in peripheral-blood mononuclear cells from a patient with neonatal-onset multisystem inflammatory disorder (NOMID). Treatment with anakinra completely resolved the symptoms and lesions.

Mice deficient in hepatocyte‐specific IL‐1Ra show delayed resolution of concanavalin A‐induced hepatitis

“…IL-1Ra binds to IL-1 receptors without inducing intracellular signals and acts as a natural competitive IL-1 inhibitor [2]. Genetic IL-1Ra deficiency leads to excessive IL-1 signaling and exaggerated inflammatory responses in several animal models and in humans [1,[3][4][5][6][7][8][9].…”

“…IL-1Ra binds to IL-1 receptors without inducing intracellular signals and acts as a natural competitive IL-1 inhibitor [2]. Genetic IL-1Ra deficiency leads to excessive IL-1 signaling and exaggerated inflammatory responses in several animal models and in humans [1,[3][4][5][6][7][8][9].IL-1β has been proposed as an important mediator in the pathophysiology of hepatic diseases. Indeed, a significant increase of circulating IL-1β levels has been reported in patients with fulminant hepatic failure and chronic liver diseases [10][11][12][13].…”

Autoinflammatory diseases and the inflammasome: mechanisms of IL-1β activation leading to neutrophil-rich skin disorders

“…This rare disease is defined by an association of CRMO with congenital dyserythropoietic anemia and neutrophilic dermatosis, although the role of lipin 2 in bone and skin-localized inflammation remains unknown. Multifocal osteomyelitis associated with pustulosis has also been described as deficiency of an IL-1Ra (DIRA; MIM #612852) [30][31] . This newly described member of the autoinflammatory diseases showed dramatically improved clinical symptoms after the administration of an IL-1Ra.…”

Síndromes autoinflamatórias hereditárias na faixa etária pediátrica

“…126 The syndrome, which was described in 10 patients, was given the name "deficiency of interleukin-1 receptor antagonist" (DIRA) and is characterized by early onset of symptoms, most frequently in the neonatal period. 126,127 Patients with DIRA present with pustulosis, multifocal aseptic osteomyelitis, and markedly elevated ESR and CRP levels. 126,127 Skin involvement may range from sparse pustules to generalized pustular dermatitis or ichthyosiform lesions.…”

“…126,127 Patients with DIRA present with pustulosis, multifocal aseptic osteomyelitis, and markedly elevated ESR and CRP levels. 126,127 Skin involvement may range from sparse pustules to generalized pustular dermatitis or ichthyosiform lesions. 126 Skin biopsy may reveal neutrophilic infiltration of the epidermis and dermis, pustules in the stratum corneum, acanthosis, and hyperkeratosis.…”