A Pellino-2 variant is associated with constitutive NLRP3 inflammasome activation in a family with ocular pterygium–digital keloid dysplasia

• Autores: Cristea, Ileana, Abarca, Hugo, Christensen Mellgren, Anne E., Trubnykova, Milana, Mehrasa, Roya, Peters, Dorien J.M., Houge, Gunnar, Hennekam, Raoul C.M., Rødahl, Eyvind, Bruland, Ove, Bredrup, Cecilie
• Formato: artículo
• Fecha de Publicación: 2023
• Institución: Universidad Peruana de Ciencias Aplicadas
• Repositorio: UPC-Institucional
• Lenguaje: inglés
• OAI Identifier: oai:repositorioacademico.upc.edu.pe:10757/667780
• Enlace del recurso: http://hdl.handle.net/10757/667780
• Nivel de acceso: acceso embargado
• Materia: corneal vascularization; keloids; NLRP3 inflammasome; OPDKD; PELI2; pterygium; Ocular pterygium–digital keloid dysplasia (OPDKD); Hereditary disease; Corneal ingrowth; Vascularized conjunctival tissu; Keloids; De novo c.770C > T, p.(Thr257Ile) variant; E3 ubiquitin ligase Pellino-2; Transgenic U87MG cells; Intracellular localization; PELI2-associated OPDKD.

Ocular pterygium–digital keloid dysplasia (OPDKD) is a rare hereditary disease characterized by corneal ingrowth of vascularized conjunctival tissue early in life. Later, patients develop keloids on fingers and toes but are otherwise healthy. In a recently described family with OPDKD, we report the presence of a de novo c.770C > T, p.(Thr257Ile) variant in PELI2 in the affected individual. PELI2 encodes for the E3 ubiquitin ligase Pellino-2. In transgenic U87MG cells overexpressing Pellino-2 with the p.(Thr257Ile) amino acid substitution, constitutive activation of the NLRP3 inflammasome was observed. However, the Thr257Ile variant did not affect Pellino-2 intracellular localization, its binding to known interaction partners, nor its stability. Our findings indicate that constitutive autoactivation of the NLRP3 inflammasome contributes to the development of PELI2-associated OPDKD.