Five Patients With Two Novel Homozygous Variants in CD3 Subunits and Comprehensive Review of the Literature

CD3 subunit deficiency (CD3SD) causes combined immunodeficiency (CID) and severe CID (SCID).

To elucidate the clinical, laboratory, and genetic features of patients with different CD3SD subtypes.

We evaluated the data of five patients with CD3ε (two), CD3γ (two), and CD3δ (one) deficiencies from our institution. In addition, we reviewed the medical literature for cases of CD3SD.

We identified two novel homozygous CD3 variants. In addition, we identified 44 CD3SD cases in the literature. In total, we analyzed the results of 49 patients. Our review of the medical literature revealed 11, 12, 18, and three patients with CD3ε, CD3γ, CD3δ, and CD3ζ deficiency, respectively. Of the 49 patients, 40 had an SCID profile, whereas nine with CD3γ variants had a CID profile. The patients with SCID presented with typical symptoms, including recurrent infections (18 of 40; 45%), diarrhea (13 of 40; 33%), and candidiasis (12 of 40, 30%). Recurrent sinopulmonary infections (four of nine; 45%), thyroiditis (four of nine; 45%), and bronchiectasis (four of nine; 45%) were common in patients with CID. Almost 70% of patients with SCID (27 of 40) underwent hematopoietic stem cell transplantation.

Our results show that patients with CD3δ, CD3ε, and CD3ζ deficiencies typically present with a classic SCID phenotype. In contrast, patients with CD3γ deficiency may either show an SCID phenotype or a milder, less severe CID phenotype. Importantly, autoimmunity may be the sole manifestation of CD3γ deficiency.