Expanding Clinical Phenotype and Novel Insights into the Pathogenesis of ICOS Deficiency.

ABSTRACT:

Background

Inducible T cell co-stimulator (ICOS) deficiency has been categorized as a combined immunodeficiency often complicated by enteropathies, autoimmunity, lymphoproliferation, and malignancy. We report seven new patients and four novel ICOS mutations resulting in a common variable immunodeficiency (CVID)-like phenotype and show that dysregulated IL-12 release, reduced cytotoxic T lymphocyte-associated protein 4 (CTLA4) expression, and skewing towards a Th1-dominant phenotype are all associated with inflammatory complications in this condition.

Methods

A combination of whole exome and Sanger sequencing was used to identify novel mutations. Standard clinical and immunological evaluation was performed. FACS and ELISA-based assays were used to study cytokine responses and

SUBMITTER: Abolhassani H 

PROVIDER: S-EPMC7082411 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature