Interleukin 36 receptor antagonist

Interleukin 36 receptor antagonist belongs to the interleukin-1 cytokine family. It inhibits the activity of interleukin-36 (IL36A, IL36B, and IL36G) by binding to the receptor IL1RL2 and preventing its association with the co-receptor IL1RAP for signal transduction. Cytokines of this family play an essential role in epithelial barrier function as well as inflammatory processes.

Mutations of the IL36RN gene are causative for the rare forms of familial psoriasis pustulosa generalisata (PPG). They induce an autoinflammatory enhanced inflammatory response.

Such mutations are also detected in a high percentage of acquired PPG without signs of psoriasis vulgaris.

In 5 unrelated subjects with generalized pustular psoriasis (GPP), Onoufriadis et al. (2011) found missense mutations in the IL36RN gene in 3 of the subjects. The two mutation-negative patients had palmoplantar pustulosis . Setta-Kaffetzi et al (2013) identified mutations in the IL36RN gene in patients with generalized pustular psoriasis and in patients with acrodermatitis continua suppurativa Hallopeau.

Korber et al (2013) identified mutations in the IL36RN gene in 8 of 19 patients with GPP. Analysis of the CARD14 gene (607211) revealed that 3 patients also carried CARD14 variants.

With the IL36 receptor inhibitor spesolimab (Spevigo®⁾), an efficient drug for the indication "psoriasis pustulosa generalisata" has been available since January 2023 (Choon SE et al. 2021).

1. Choon SE et al (2021) Study protocol of the global Effisayil 1 phase II, multicentre, randomised, double-blind, placebo-controlled trial of spesolimab in patients with generalized pustular psoriasis presenting with an acute flare. BMJ Open 11:e043666.

2. Li M et al. (2013) Prevalent and rare mutations in IL-36RN gene in Chinese patients with generalized pustular psoriasis and psoriasis vulgaris. (Letter) J Invest Derm 133: 2637-2639.
3. Onoufriadis A et al (2011) Mutations in IL36RN/IL1F5 are associated with the severe episodic inflammatory skin disease known as generalized pustular psoriasis. Am J Hum Genet 89: 432-437.
4. Setta-Kaffetzi N et al (2013) Rare pathogenic variants in IL36RN underlie a spectrum of psoriasis-associated pustular phenotypes. (Letter) J Invest Derm 133: 1366-1369.
5. Sugiura K et al (2012) Novel IL36RN/IL1F5 homozygous nonsense mutation, p.Arg10X, in a Japanese patient with adult-onset generalized pustular psoriasis. Brit J Derm167: 699-701
6. Sugiura K eet al. (2013) The majority of generalized pustular psoriasis without psoriasis vulgaris is caused by deficiency of interleukin-36 receptor antagonist. J Invest Derm 133: 2514-2521