Tiphaine Arlabosse, Marie Materna, Orbicia Riccio, Caroline Schnider, Federica Angelini, Matthieu Perreau, Isabelle Rochat, Andrea Superti-Furga, Belinda Campos-Xavier, Sébastien Héritier, Anaïs Pereira, Caroline Deswarte, Romain Lévy, Marco Distefano, Jacinta Bustamante, Marie Roelens, Raphaël Borie, Mathilde Le Brun, Bruno Crestani, Jean-Laurent Casanova, Anne Puel, Michaël Hofer, Claire Fieschi, Katerina Theodoropoulou, Vivien Béziat, Fabio Candotti
Patients with autosomal dominant (AD) hyper-IgE syndrome (HIES) suffer from a constellation of manifestations including recurrent bacterial and fungal infections, severe atopy, and skeletal abnormalities. This condition is typically caused by monoallelic dominant-negative (DN) STAT3 variants. In 2020, we described 12 patients from eight kindreds with DN IL6ST variants resulting in a new form of AD HIES. These variants encoded truncated GP130 receptors, with intact extracellular and transmembrane domains, but lacking the intracellular recycling motif and the four STAT3-binding residues, resulting in an inability to recycle and activate STAT3...
June 5, 2023: Journal of Clinical Immunology