A Patient with CTLA-4 Haploinsufficiency with Multiple Autoimmune Presentations: A Case Report

Increased susceptibility to autoimmunity, malignancy, and allergy in addition to recurrent infections are the main characteristics suggesting primary immunodeficiency diseases (PID). CTLA-4 is predominantly expressed on activated T-cells and regulatory T-cells, which can bind to CD80/CD86 molecules on antigen presenting cells as a negative regulator. In this article, we describe a patient with heterozygous CTLA-4 mutation who presented with multiple autoimmunities. A 24-year-old male patient from consanguineous parents referred to our clinic with multiple autoimmunities. His past clinical history revealed alopecia areata at four years old and subsequently, he developed Evans syndrome, type 1 diabetes mellitus, hypothyroidism, and chronic diarrhea while chronic rhinosinusitis and cytomegalovirus (CMV) colitis were the only infectious manifestations. Immunologic investigations revealed: low B cell count, abnormal Lymphocyte transformation test (LTT) to phytohemagglutinin (PHA) and hypogammaglobulinemia. Although all available treatments such as Intravenous Immunoglobulin (IVIG) therapy, immunosuppressive drugs, and antibiotic therapy were applied, diarrhea was not controlled due to colitis, which remained challenging and made us seek for genetic study. Whole exome sequencing showed heterozygous variant CHR2.204,735,635 G>A in the CTLA-4 gene, which was confirmed by the Sanger method. CTLA4 haploinsufficiency leads to autoimmune disorders, recurrent respiratory infections, hypo-gammaglobulinemia, lymphoproliferation with organ infiltration and lymphocytic interstitial lung disease.