Category: Immunodeficiency: primary or acquired
Autoimune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome is a rare autosomal recessive disorder caused by a mutation in the AIRE gene that is responsible for immune regulation. We present a patient with clinical APECED and a single pathogenic AIRE mutation. Whole exome sequencing identified a mutation in BTNL2 gene that we propose may have also contributed to his disease.
15-year-old male patient presents with multiple autoimmune disorders including adrenal and pancreatic insufficiency, vitiligo, Sjogren’s syndrome, celiac disease, as well as hypothyroidism, hypoparathyroidism, candida onychomycosis, recurrent nasal sinus and ear polyps. He developed acute autoimmune hepatitis requiring systemic corticosteroids and tacrolimus. Genetic sequencing identified a monoallelic pathogenic variant p.Arg257Ter in the AIRE gene at the c.769 C>T coding DNA. An IL7 receptor heterozygous mutation was also reported but the patient did not have laboratory findings suggestive of its associated disease. Whole exome sequencing identified a frameshift deletion mutation at the promoter/enhancer region of the BTNL2 gene at the 32370969,TG>T site.
AIRE is critical for self-antigen expression in the thymus, allowing for destruction of self-reactive T cells by negative selection. Butyrophilin-like 2 (BTNL2) is a butyrophilin family member with immunoregulatory properties. It is found in gut tissue and Peyer’s patches and is thought to be involved in immune surveillance, serving as a negative T-cell regulator. We suggest that the unique combination of mutations in each of these genes contributed to the development of severe autoimmune disease in our patient.