TEXTBOOK OF IMMUNOLOGY - Mercury Podillya 2013

CONGENITAL IMMUNE DEFICIENCY

Deficiency of Cellular (T-cell) Immunity

Class="center">DiGeorge syndrome (thymic hypoplasia or aplasia).

(ICD-10 Code D 82.1)

DiGeorge syndrome (DGS) is an isolated T-Cell immunodeficiency characterized by a clinical triad of thymic and/or parathyroid hypoplasia and Congenital Heart defects. It accounts for 5-10% of all Primary immunodeficiencies.

Specific defect. Dysembriogenesis: maldevelopment of the third and fourth pharyngeal pouches occurring between the sixth and tenth weeks of gestation, leading to impaired Development of the Thymus, thyroid, and Parathyroid glands, facial structural anomalies, and congenital heart defects involving the aortic arch.

Chromosomal localization of the defect: 22q11.

Clinical Features. Most patients exhibit dysmorphic facial features. The most characteristic findings include dysplastic auricles, hypertelorism, a wide nasal bridge, "carp Mouth", and antimongoloid slant of the eyes. Some children present with more severe anomalies, such as micrognathia and cleft Hard and Soft palate. Hypocalcemia of varying severity and the absence of a thymic shadow on chest radiography are frequent manifestations. Hypoparathyroidism presents with hypocalcemic seizures occurring from the first days of life. All patients exhibit developmental delay. Congenital heart defects and Anomalies of the great vessels are among the most characteristic and severe signs of the disease. T-cell immunodeficiency leads to recurrent viral, parasitic, and bacterial infections, as well as mycoses. However, serum immunoglobulin levels in such patients are unaffected. Children may experience unusual, potentially fatal reactions following vaccination with live attenuated measles, polio, or BCG Vaccines (Table 51).

Immunological studies: 1) lymphocytopenia; 2) decreased count and proliferative activity of T-lymphocytes; 3) dissociation between decreased levels of T- and NK-Cells and elevated B-lymphocyte counts; 4) normal or elevated antibody levels; 5) diminished delayed-type hypersensitivity Skin reactions. The ability to produce Antibodies against specific Antigens is impaired due to the absence of T-helper cells.

Treatment. Approaches include thymus transplantation; replacement therapy with thymic Hormones; and symptomatic therapy. In the presence of severe malformations that primarily determine the prognosis for life, thymus transplantation is considered insufficiently substantiated. If the patient survives beyond 6 months of age, a gradual spontaneous recovery of T-cell Immunity is observed.

As an example of the Immune Response in cellular (T-cell) immune deficiency, we present the case history of Patient K., 8 years old, suffering from isolated T-cell immunodeficiency (DiGeorge syndrome), who is under follow-up at the City Pediatric Immunology Center (Table 54).

Patient K., 8 years old, has a history of frequent viral infections since early childhood, suffering from acute respiratory viral infections 3-4 times a year. He received treatment for measles in the intensive care unit of a pediatric infectious diseases hospital, suffered from mononucleosis, and presents with chronic recurrent herpetic skin lesions of the face, with Candida species isolated from stool samples. At 4 months of age, he underwent surgery for a Congenital Heart defect (ventricular septal defect). He was diagnosed with DiGeorge syndrome.

The presented immunogram of Patient K. at 10 years of age demonstrates a profound suppression of the T-cell immune response, lymphocytopenia, reduced T-lymphocyte counts; dissociation between decreased levels of T- and NK-cells and elevated B-lymphocyte counts; neutrophilic leukocytosis accompanied by incomplete phagocytosis and decreased phagocytic activity; and a slight elevation in IgM levels.

Treatment:

1) famciclovir 0.25 g orally twice daily for 8-12 months; Herpovir ointment applied to affected skin areas and labial mucosa 4 times daily for 7 days during disease exacerbation;

2) Viferon-2 (500,000 IU of interferon) 1 suppository twice daily for 10 days, followed by 2 suppositories daily 3 times a week for up to 2.5 months; Virogel applied to affected skin areas and labial mucosa twice daily for 5-7 days;

3) during herpes exacerbations, specific (anti-herpetic) immunoglobulin is prescribed: 3.0 ml twice daily for the first 2 days, followed by 1.5-3.0 ml daily intramuscularly. The course of treatment ranges from 15 to 45 ml.

4) Polyoxidonium 6 mg daily for the first 5 days, then every other day, total 10 doses. This is followed by maintenance therapy of 6 mg twice weekly for one month;

5) itraconazole (Intrungal) 100 mg twice weekly for 1 month.

Immunorehabilitation:

6) Roncoleukin intravenous infusion over 4-6 hours at a dose of 500,000 IU with an interval of 2-3 days, total 2-3 doses during the remission period;

Thymalin 1 ml subcutaneously every other day, total 10 doses;

7) Cycloferon (an interferon inducer) - 12.5% solution for injection - 2 ml, single dose 0.25 g intramuscularly on days 1, 2, 4, 6, 8, 11, 14, 17, 20, 23, 26, and 29. Administered following Interferon Therapy.

Table 54. Immunogram of Patient K., 8 years old

Lymphocytic dysgenesia

(Nezelof syndrome, French type). (ICD-10 code D81.4)

Lymphocytic dysgenesia (Nezelof syndrome) is a quantitative and qualitative deficiency of the T-cell system resulting from thymic and lymph node atrophy. Impaired maturation of T-lymphocyte precursors leads to their functional inadequacy; Autosomal Recessive Inheritance. It is characterized by the absence of cellular immune defense reactions in the presence of normal plasma immunoglobulin levels. Manifesting in the first weeks and months of life, it presents with a rudimentary thymus, low thymocyte count, and the absence of Hassall's corpuscles.

Clinical manifestations: growth and developmental delay in the child, protracted septic process with purulent-inflammatory foci in Internal Organs and skin; recurrent Pneumonia, diarrhea, eczema, lymphadenitis, and lymphoid tissue hyperplasia.

Marked susceptibility to infectious agents: Bacteria (tuberculosis, listeria, Escherichia coli, salmonella), Viruses (herpes, Epstein-Barr, Adenoviruses, enteroviruses), Protozoa (Pneumocystis, Toxoplasma, Cryptosporidium), and Fungi (Candida, Cryptococcus, Nocardia).

Immunological studies: peripheral Blood reveals lymphocytopenia, extremely low T-lymphocyte levels; B-lymphocytes are within normal limits; lymphocyte blastogenesis is sharply suppressed; delayed-type hypersensitivity reaction is poorly expressed. Immunoglobulin levels of all classes in the blood are within normal limits or elevated. The production of specific IMMUNOGLOBULINS is reduced.

Children most frequently die in the first months of life from Sepsis.

Treatment: stem cell transplantation.

Chronic mucocutaneous candidiasis

Specific defect. Selective T-cell response deficiency to Candida antigen. Humoral response is unimpaired.

Clinical features. Characterized by chronic lesions of the skin, Nails, scalp, and mucous membranes caused by Candida albicans. The underlying pathology is a unique defect in T-cell-mediated immune response: against the Background of a normal T-lymphocyte count and normal proliferative response to phytohemagglutinin, There is a sharp decrease in the ability of T-lymphocytes to become activated and produce lymphokines (specifically, macrophage migration inhibitory factor) in the presence of Candida albicans antigen. Meanwhile, responses to other antigens may remain intact. Delayed-type hypersensitivity skin tests to Candida antigen are also negative. At the same time, the humoral response to Candida antigen is unimpaired. Autoimmune endocrine disorders are characteristic (Tables 50, 51).

Treatment involves symptomatic antifungal therapy. There are reports on The Use of transfer factor and thymus transplantation.