CTLA4 haploinsufficiency and immune dysregulation

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 CD21lo B cells. This study demonstrates a critical quantitative role for CTLA-4 in human immune homeostasis.]]> Inclusion criteria: Combination of hypogammaglobulinemia and/or CD4 lymphopenia, and infiltration of at least one non-lymphoid organ [brain, lungs and gastrointestinal tract] with lymphocytic aggregates, autoimmune cytopenia. Exclusion criteria: Any known previously identified genetic defects for immune dysregulation and lymphoproliferation]]>