Immunodeficiency 25D84.8

Alarcon et al. (1988)

Alarcon et al (1988) first described 2 brothers who had low expression of the antigen receptor on the surface of their T lymphocytes. Functional analyses of their T cells showed an impaired immune response to alloantigens, tetanus toxoid, and mitogens. Immunodeficiency-25 (IMD25) is caused by a homozygous mutation in the CD247 (CD3Z) gene (186780) on chromosome 1q24.

Rieux-Laucat et al (2006) described a boy of Caribbean origin with primary T-cell immunodeficiency. He presented at 4 months of age with erythroderma, protracted diarrhea, and lung abscesses caused by Pseudomonas aeruginosa. Over the next 2 years, recurrent herpes simplex viral infections of the mouth and skin, 2 oral and skin infections with Candida albicans, and 2 pulmonary infections occurred.

Lab: The patient's T-cell counts were very low, B-cell counts were normal, and there was eosinophilia. When the patient was 30 months old, a haploidentical bone marrow transplant was performed with the mother as donor. The transplantation resulted in persistent donor-recipient chimerism and correction of the immunodeficiency.

Rieux-Laucat et al (2006) demonstrated homozygosity for a germline mutation Q70X in the CD247 gene (186780.0001) in a boy with primary T-cell immunodeficiency. Some patient T cells had low levels of the T-cell receptor-CD3 complex and carried the Q70X mutation on both alleles of the CD3Z gene, whereas other T cells had normal levels of the complex and carried the Q70X mutation on only one allele of CD3Z, as well as one of three heterozygous somatic mutations of CD3Z on the other allele (186780.0002-186780.0004), which allowed expression of poorly functioning T-cell receptor-CD3 complexes. Thus, the patient had both inherited and somatic CD3Z mutations as the basis for T-cell deficiency.

1. Alarcon B et al (1988) Familial defect in the surface expression of the T-cell receptor-CD3 complex. New Eng. J Med 319: 1203-1208.
2. Arnaiz-Villena A et al.(1991) iochemical basis of a novel T lymphocyte receptor immunodeficiency by immunohistochemistry: a possible CD3-gamma abnormality. Lab Invest 64: 675-681.
3. Rieux-Laucat F et al (2006) Inherited and somatic CD3-zeta mutations in a patient with T-cell deficiency. New Eng J Med 354: 1913-1921.
4. Asgardoon MH et al (2020). Monogenic primary immunodeficiency disorder associated with common variable immunodeficiency and autoimmunity. Int Arch Allergy Immunol 181:706-714.