Correlation of IL36RN mutation with different clinical features of pustular psoriasis in Chinese patients

Abstract

Different studies have reported various values for the percentage of patients with IL36RN mutations, and it has also been reported that the sites of these mutations differ among different ethnicities. The current study was a cross-sectional study conducted to investigate the risk factors predicting IL36RN mutation in Chinese patients with different clinical features of pustular psoriasis. 57 Han Chinese patients, including 32 with generalized pustular psoriasis, 14 with palmoplantar pustulosis, 9 with plaque-type psoriasis with pustules, and 2 with erythrodermic psoriasis, were enrolled between March 2013 and July 2014. Blood samples were collected, genomic DNA was extracted from leukocytes, and polymerase chain reaction (PCR)-based Sanger sequencing was used to analyze the coding exons and flanking introns of the IL36RN gene. The patients with generalized pustular psoriasis exhibited the highest IL36RN mutation rate (75 %) among the aforementioned patient types, with the subgroup consisting of those patients who had features of acrodermatitis continua of Hallopeau exhibiting the highest c.115+6T>C mutation rate (93.8 %). In addition, early onset, ever generalized pustular psoriasis (more than two attacks), ever acrodermatitis continua of Hallopeau, inverse psoriasis, and a family history of pustular psoriasis were associated with IL36RN mutation. The c.115+6T>C mutation was the most common and the most important variant in all subtypes of pustular psoriasis with IL36RN mutations among our sample of Chinese patients.

Pustular psoriasis and related pustular skin diseases

“…Likewise, our group and others have identified homozygous or composite heterozygous loss‐of‐function mutations the IL36RN gene in consanguineous families from southern Tunisia (Fig. b), and also in sporadic or familial cases of GPP from Europe and from Asia …”

“…1b), and also in sporadic or familial cases of GPP from Europe and from Asia. 11,[18][19][20][21][22][23] These mutations, which are most commonly identified in patients with GPP without plaque psoriasis, impair structure and/or expression and ultimately the regulatory function of the encoded interleukin (IL)-36Ra protein, leading to an enhanced inflammatory cascade downstream of the interaction between the IL-36a, IL-36b and IL-36c agonistic ligands and their specific receptor. This results, mainly in keratinocytes and macrophages, to the upregulated expression and extracellular release of inflammatory mediators such as CXCL8/IL-8, tumour necrosis factor (TNF)-a, IL-1 and IL-23.…”

“…Studies have also unveiled the presence of mutations of the same gene in a minority of patients with PPPP, with ACH and with AGEP, but not in patients with plaque psoriasis without pustular lesions. [21][22][23][24][25] Even more striking is the detection of a common mutation across the different pustular subtypes. 22 Likewise, it has been shown that so-called null mutations (e.g.…”

442 European consensus statement on phenotypes of pustular psoriasis

“…The same pattern was confirmed by a European study finding IL36RN mutations in 46% of GPP patients without PV and 17% in GPP with PV [15]. Finally, an interesting study from China found that about 93% of patients with GPP and features of ACH had a damaging IL36RN mutation [16].…”

Successful treatment of refractory juvenile generalized pustular psoriasis with secukinumab monotherapy: A case report and review of published work

“…Although GPP in childhood has been regarded as less recalcitrant with a more benign course, higher rates of spontaneous resolution and long‐term remission compared with adult patients, it still can be life‐threatening in children . Homozygous or compound heterozygous mutations in the IL‐36 receptor antagonist gene IL36RN is present in 75% of GPP cases, and the most common mutation is c.115+6T>C in the Han Chinese patients in Taiwan …”