General Information
• There is T cell dysfunction. For this reason, patients with disorders in the T-cell system often also have B-cell deficiency.
• T cells have an important regulatory effect on the differentiation and function of B cells.
General Clinical Features
• Recurrent infections with fungi, viruses, mycobacteria and protozoa (Pneumocystis carinii infections are common).
• Systemic illness or death with live viral vaccines or BCG.
• If blood and blood products are given without irradiation, Graft-Versus-Host reaction develops.
• Some viral diseases (measles, chicken pox) have a severe and complicated course.
• There is anergy.
• There is marked growth retardation, malabsorption and diarrhea.
• The thymus shadow is not seen on the x-ray.
• There is a high risk of malignancy.
• Children's chances of surviving to old age are low.
General Diagnostic Methods
• If the absolute lymphocyte count (less than 1500/mm3 is lymphopenia) is normal, a T cell defect is most likely to be ruled out.
- CD4; If it is below 1000/mm3 under 4 months and below 500/mm3 over 2 years of age, T cell failure is considered.
- CD3; indicates total T cell. It should be at least 50%.
- CD4; The absolute value of T helper in infancy is quite high. It should be between 30-50%.
- CD5; T suppressor is between 20-25%.
• Sheep erythrocyte and T-cell rosette formation are reduced.
• Candida skin test: It is examined with an intradermal test using candida albicans extract diluted 1:1000 over the age of 6 years.
• Delayed hypersensitivity tests (PPD) are negative.
Treatment
• Thymus transplantation or MHC compatible sibling or haploidentical (semi-matched) parental stem cell transplantation or bone marrow transplantation can be performed in patients with primary T cell defects.
Congenital Thymic Aplasia (Di George Syndrome)
• There is a 22q11 deletion. Also known as velo-cardio-facial syndrome.
• Clinical findings occur before 1 year of age.
Complete Di George Syndrome
• The numbers and functions of CD3 T lymphocytes are decreased.
Incomplete Di George Syndrome
• CD3 T cells are few in number but their functions are normal.
phenotypic traits
• Abnormal facial appearance: Dropped ears, deformity of the auricle, hypertelorism, fish mouth, small chin (hypoplasia of the mandible), microcephaly, short filtrum
• Speech disorder
• Hypoparathyroidism; Ca↓, P↑, ALP normal or ↓, PTH↓
• Congenital heart diseases (conotruncal anomalies)
- Transposition of the great arteries
- Truncus arteriosus
- tetralogy of Fallot
- VSD + pulmonary atresia
• Some patients may have GIS malformations (esophageal atresia, bifid uvula), eye anomalies, renal anomalies and mental retardation.
• Thymus is hypoplastic (75%) or aplasic (1%). There is cellular immunodeficiency.
There are recurrent or chronic infections caused by different viral, bacterial, fungal or protozoal agents. Pneumonia, chronic candida infection of the mucous membranes, diarrhea and growth retardation are seen.
Congenital heart disease + moniliasis (oral candida) = Di George syndrome
Diagnosis
• Complete type lymphocyte count is usually below 1500/mm3.
• The thymus shadow cannot be detected in the anterior mediastinum on the lateral radiograph.
• T-cell rosette formation is reduced.
• The diagnosis of hypoparathyroidism is made with low calcium, high phosphorus and absence of parathyroid hormone.
• Rarely, severe combined immunodeficiency may be seen with complete absence of B and T cell immunity.
• There is a lack of response to delayed hypersensitivity skin tests.
• Peripheral lymphocytes have no response to phytohemagglutinin and allogeneic cells.
Treatment
• Fetal thymus (12-14 weeks) transplantation provides permanent correction.
• Bone marrow transplantation, treatment of hypoparathyroidism and frequent infections are performed.
CHRONIC MUCOCUTANEOUS CANDIDIASIS
• The primary defect in the disease is the insufficient cellular immune response to the candida antigen.
• It shows autosomal recessive (iL-17 receptor A deficiency) or autosomal dominant (IL-17F cytokine deficiency) inheritance.
• Findings become evident after 6 months. It is characterized by persistent candida infection of the mucosa, skin, hair and nails. In some cases, susceptibility to non-candida infections is also observed.
• Candida most commonly affects the oral mucosa and often the toenails.
• Systemic candida infection is not usually seen (Systemic infection may occur only in CARD9 gene mutations).
• Other autoimmune diseases may accompany.
• Systemic antifungal drugs (ketoconazole, fluconazole, amphotericin-B) are used in the treatment.
• Coexisting endocrine disorders are treated.
Autoimmune polyglandular syndrome (OPS) Type-1 (APECED syndrome)
AIRE gene mutation
Mucocutaneous candidiasis
· Hypoparathyroidism
Adrenal insufficiency