Marco Distefano
A5089772413- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunodeficiency and Autoimmune Disorders
- Cytomegalovirus and herpesvirus research
- Immune Response and Inflammation
Inserm
2022-2023
Institut des Maladies Génétiques Imagine
2022-2023
Université Paris Cité
2022-2023
Patients with inherited CARMIL2 or CD28 deficiency have defective T cell signaling, but their immunological and clinical phenotypes remain largely unknown. We show that only one of three isoforms is produced functional across leukocyte subsets. Tested mutant alleles from 89 patients 52 families impair canonical NF-κB not AP-1 NFAT activation in cells stimulated via CD28. Like CD28-deficient patients, CARMIL2-deficient display recalcitrant warts low blood counts CD4+ CD8+ memory TREGs. Unlike...
Abstract Patients with autosomal dominant (AD) hyper-IgE syndrome (HIES) suffer from a constellation of manifestations including recurrent bacterial and fungal infections, severe atopy, skeletal abnormalities. This condition is typically caused by monoallelic dominant-negative (DN) STAT3 variants. In 2020, we described 12 patients eight kindreds DN IL6ST variants resulting in new form AD HIES. These encoded truncated GP130 receptors, intact extracellular transmembrane domains, but lacking...