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The genetic background of generalized pustular psoriasis: IL36RN mutations and CARD14 gain-of-function variants

      Abstract

      Generalized pustular psoriasis (GPP) is often present in patients with existing or prior psoriasis vulgaris (PV; “GPP with PV”). However, cases of GPP have been known to arise without a history of PV (“GPP alone”). There has long been debate over whether GPP alone and GPP with PV are distinct subtypes that are etiologically different from each other. We recently reported that the majority of GPP alone cases is caused by recessive mutations of IL36RN. In contrast, only a few exceptional cases of GPP with PV were found to have recessive IL36RN mutations. Very recently, we also reported that CARD14 p.Asp176His, a gain-of-function variant, is a predisposing factor for GPP with PV; in contrast, the variant is not associated with GPP alone in the Japanese population. These results suggest that GPP alone is genetically different from GPP with PV. IL36RN mutations are also found in some patients with severe acute generalized exanthematous pustulosis, palmar-plantar pustulosis, and acrodermatitis continua of hallopeau. CARD14 mutations and variants are causal or disease susceptibility factors of PV, GPP, or pityriasis rubra pilaris, depending on the mutation or variant position of CARD14. It is clinically important to analyze IL36RN mutations in patients with sterile pustulosis. For example, identifying recessive IL36RN mutations leads to early diagnosis of GPP, even at the first episode of pustulosis. In addition, individuals with IL36RN mutations are very susceptible to GPP or GPP-related generalized pustulosis induced by drugs (e.g., amoxicillin), infections, pregnancy, or menstruation.

      Keywords

      Abbreviations:

      ACH (acrodermatitis continua of hallopeau), AGEP (acute generalized exanthematous pustulosis), CARD14 (caspase recruitment domain family, member 14), DITRA (deficiency of IL-36 receptor antagonist), FGPP (familial generalized pustular psoriasis), GPP (generalized pustular psoriasis), GPP with PV (generalized pustular psoriasis often presents in patients with existing or prior psoriasis vulgaris), GPP alone (generalized pustular psoriasis have been known to arise without a history of psoriasis vulgaris), GMA (I granulocyte monocyte plasma apheresis), IL-36RN (L-36 receptor antagonist), IL-36A (interleukin-36α), IL-36B (interleukin-36β), IL-36G (interleukin-36γ), KC (keratinocyte), PPP (palmoplantar pustulosis), PRP (pityriasis rubra pilaris), PV (psoriasis vulgaris)
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      Biography

      Kazumitsu Sugiura graduated from Nagoya University and received his MD degree in 1994. He trained for 2 years in molecular biology under the supervision of Professor Masatoshi Hagiwara in the Department of Anatomy III, Nagoya University Graduate School of Medicine. In 1999, he received his Ph.D. from the Department of Dermatology, Nagoya University Graduate School of Medicine. He studied autoimmunity under the supervision of Professor Eng M. Tan at the Autoimmune Disease Center of The Scripps Research Institute as a research fellow for 3 years. He moved to the Department of Biochemistry II, Nagoya University Graduate School of Medicine, as an assistant professor for a year (under Professor Koichi Furukawa). In 2002, he returned to Nagoya University Graduate School of Medicine, in the Department of Dermatology, where he has been since then. Since 2008, he has been an associate professor in the Department of Dermatology at Nagoya University Graduate School of Medicine in that department (under Emeritus Professor Yasushi Tomita and Professor Masashi Akiyama). His research interests include genodermatoses, psoriasis, and autoimmune diseases.