Iranian Journal of Immunology

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

Document Type : Case Report

Authors

Fatemeh Zaremehrjardi 1
Leila Baniadam 1
Farhad Seif 2
Saba Arshi 1
Mohamad Hasan Bemanian 3
Sima Shokri 1
Afshin Rezaeifar 1
Morteza Fallahpour 4
Mohammad Nabavi 1

1 1- Department of Allergy and Clinical Immunology, Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran

2 Academic center for edication,Tehran University of Medical Sciences, Tehran,Iran

3 Allergy department, Rasool e Akram Hospital, Iran University of Medical Sciences, Tehran, Iran

4 Department of Clinical Immunology and Allergy, Rasoul Akram Hospital, IUMS, Tehran, Iran

https://doi.org/10.22034/iji.2020.85641.1721
Abstract
Increased susceptibility to autoimmunity, malignancy, and allergy in addition to recurrent infections are the main characteristics suggesting for the primary immunodeficiency diseases (PID). CTLA-4 is predominantly expressed on activated and regulatory T-cells, which can bind to CD80/CD86 molecules on antigen-presenting cells as a negative regulator. Here, we describe a 24-year-old male born from consanguineous parents with heterozygous CTLA-4 mutation who presented with multiple autoimmune diseases. 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. Whole exome sequencing was performed and the result 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, hypogammaglobulinemia, lymphoproliferation with organ infiltration, and lymphocytic interstitial lung disease.

Keywords

Abatacept
CTLA-4 Deficiency
Haploinsufficiency
Immunodeficiency
Multiple Autoimmunities
Iranian Journal of Immunology
Volume 17, Issue 3
Summer 2020
Pages 244-249

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