D1.327 - A Rare Primary Immunodeficency Hidden in Autoimmunity: Heterozygote CD3G variant in a 49-year-old Female Patient

The T-cell receptor (TCR)/CD3 complex plays a crucial role in T-cell development and immune regulation. CD3G gene encodes one of the CD3 subunits named CD3γ, and its deficiency can cause autoimmune disorders, immunodeficiency and recurrent infections. To date, only 13 patients with CD3G variants have been reported. Autoimmunity in patients with CD3γ deficiency may involve many organs and systems: the thyroid, hematologic system, the liver, lung, kidney, bowel and skin. Symptoms usually start in childhood or early adulthood, however, late adulthood onset CD3γ deficiency has not been previously described.  Our case was a 46 years old female from a consanguineous marriage when she was referred to our tertiery center. She was misdiagnosed as CVID complicated with GLILD and probable CVID associated enteropathy. Previous colonoscopy specimens were compatible with ulcerative colitis and protein losing enteropathy. She had severe interstitial lung disease and bronchiectasis and severe O2 dependent pulmonary hypertension, right heart failure and cardiac ascites. She was put on Rituximab for severe GLILD. She was under IGRT and prophylactic antibiotherapy, and she was not having frequent infections. Heterozygous c.213dup(p.Trp72Metfs*6) variant in the CD3G(NM_000073.3) gene was identified via whole exome sequencing. The variant was classified as pathogenic. Although CD3γ deficiency is an autosomal recessive disorder, autoimmunity has been described in heterozygous individuals (PMID: 24910257). Our patient, who has more severe symptoms than the heterozygotes described before, demonstrates a compelling case providing basis for further research.