Immune Dysregulation Syndrome With Ctla4 Haploinsufficiency: Clinical and Immunological Phenotype and Therapeutic Approaches

Abstract

CTLA4 haploinsufficiency with autoimmune infiltration (CHAI – CTLA4 haploinsufficiency with autoimmune infiltration) is a rare primary immunodeficiency diseases (PIDDs) that belongs to the group of T-regopathy or PIDDs with immune dysregulation. Monoallelic mutations in the CTLA4 gene cause haploinsufficiency of the homonymous protein and lead to multiple autoimmune complications, such as lymphoproliferation, immune cytopenias, lymphocytic interstitial pneumonia (LIP), inflammatory diseases of the gut, CNS damage, etc., combined with increased susceptibility to infections. Algorithms for the treatment of patients with CHAI have not yet been developed, however, there are promising therapeutic options for targeted therapy with a biologically modified CTLA4 abatacept drug. Hematopoietic stem cell transplantation is indicated for patients with a severe course of the disease, however, in order to draw conclusions about the efficacy and safety of this method of treatment, long period observations and large groups of patients are required.