Immune Dysregulation in Human Subjects with Heterozygous Germline Mutations in

We identified germline heterozygous mutations in CTLA4 in members of four families with severe immune dysregulation. Human CTLA4 haploinsufficiency caused dysregulation of FoxP3+ regulatory T (Treg) cells and lymphocytic infiltration of target organs, mimicking Ctla4 homozygous mice. Patients also exhibited a B cell phenotype, with progressive loss of B cells and accumulation of autoreactive CD21^lo B cells. This study demonstrates a critical quantitative role for CTLA-4 in human immune homeostasis.

• Type: Case Set
• Archiver: The database of Genotypes and Phenotypes (dbGaP)