Immunodeficiency 18D81.0

Immunodeficiency-18 is an autosomal recessive primary immunodeficiency characterized by the onset of recurrent infections in infancy or early childhood. It is caused by mutations in the CD3D gene. The severity is variable and includes both mild immunodeficiency and severe combined immunodeficiency(SCID), leading to early death without bone marrow transplantation in some patients. Immunological examination of IMD18-SCID patients reveals a T-cell negative, B-cell positive, and NK-cell positive phenotype, while T-cell development is unaffected in the mild form of IMD18.

Le Deist et al (1991) reported on a 4-year-old boy who presented at 2 years of age with mild immunodeficiency that manifested as recurrent bacterial pneumonia and otitis media. Lymphocyte counts were normal, and serum Ig levels were elevated during the infection but later returned to normal. There was some evidence of impaired antibody production with absent antibodies to poliovirus or isohemagglutinin, but antibody levels to tetanus and diphtheria toxoids were normal. The patient's lymphocytes showed markedly decreased CD3 expression on T cells (approximately 10% of normal) and decreased numbers of CD4 (186940)-positive T cells. B cells were normal and NK cells were increased. Functional studies showed defects in proliferation of T cells in response to CD2 (186990) stimulation, and cytotoxic T cell activity was absent.

Severe combined immunodeficiency (SCID) comprises a group of rare monogenic primary immunodeficiency disorders characterized by a deficiency of functional peripheral T lymphocytes, leading to early-onset severe respiratory infections and failure to thrive. They are divided into SCID with absent T cells but present B cells (T-B+ SCID) or SCID with absent T cells (T-B- SCID), depending on the immunologic phenotype. Both groups include multiple forms with or without natural killer (NK) cells. The clinical symptoms are only gradually different.

1. Le Deist F et al (1991) Immunodeficiency with low expression of the T cell receptor/CD3 complex: effect on T lymphocyte activation. Europ J Immun 21: 1641-1647.
2. Natkunam Y et al (2018) Immunodeficiency-associated lymphoproliferative disorders: time for reappraisal? Blood 132:1871-1878.
3. Soudais C et al.(1993) Independent mutations of the human CD3-epsilon gene resulting in a T cell receptor/CD3 complex immunodeficiency. Nature Genet 3: 77-81.