Abstract
The patients with CD3γ deficiency can present with different clinical findings despite having the same homozygous mutation. We report three new CD3gamma-deficient siblings from a consanguineous family with a combined T-B+NK+ immunodeficiency and their variable clinical and cellular phenotypes despite the same homozygous mutation of the CD3G gene (c.80-1G>C). We also re-evaluate a previously reported non-consanguineous family with two CD3gamma-deficient siblings with the same mutation. The median age at diagnosis was 11 years (14 months-20 years). We found all five patients to display autoimmunity: autoimmune thyroiditis (n = 5), autoimmune haemolytic anaemia (n = 2), immune thrombocytopenia (n = 1), autoimmune hepatitis (n = 1), minimal change nephrotic syndrome (n = 1), vitiligo (n = 1) and positive antinuclear antibodies (n = 3) as well as high IgE (n = 2) and atopic eczema (n = 2). While CD3(+) TCRαβ+T cell percentages were low in all patients, only one had lymphopenia and 3 had CD3(+) T cell lymphopenia. Strikingly, we report frequent and multiple autoimmunity in tested heterozygous carriers in both families (n = 6; in 67%), and frequent autoimmunity in family members not available for testing (n = 5, in 80%). The results suggest that CD3G should be studied as a candidate gene for autoimmunity and that CD3gamma deficiency should be considered among other primary immunodeficiencies with predominantly autoimmune manifestations.
Original language | English |
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Pages (from-to) | 354-61 |
Number of pages | 8 |
Journal | Scandinavian Journal of Immunology |
Volume | 80 |
Issue number | 5 |
DOIs | |
Publication status | Published - Nov 2014 |
Keywords
- Adult
- Anemia, Hemolytic, Autoimmune
- Antibodies, Antinuclear
- Antigens, CD3
- Autoimmunity
- B-Lymphocytes
- Child
- Dermatitis, Atopic
- Female
- Genetic Association Studies
- Genetic Predisposition to Disease
- Hepatitis, Autoimmune
- Humans
- Immunoglobulin E
- Infant
- Killer Cells, Natural
- Lymphopenia
- Male
- Nephrosis, Lipoid
- Pedigree
- Purpura, Thrombocytopenic, Idiopathic
- T-Lymphocytes
- Thyroiditis, Autoimmune
- Vitiligo
- Young Adult