Congenital immunodeficiencies

Congenital immunodeficiency is a group of diseases that are based on genetically determined disorders of the immune system, most of which manifest themselves at birth or in early childhood. 

The pathology is characterized by a partial or complete absence of certain components of the body’s immune defense, which significantly increases susceptibility to various infections and also determines an increased risk of developing autoimmune and oncological diseases.

The impact of the disease on the immune system is multifaceted and affects various links in the defense mechanisms:

  1. dysfunction of B-lymphocytes, which leads to insufficient production of antibodies;
  2. T-cell defects that weaken cellular immunity;
  3. dysfunction of phagocytes, which reduces the body’s ability to fight bacterial and fungal infections;
  4. Defects in the complement system increase vulnerability to certain pathogens.

Early detection and initiation of therapy can significantly improve the quality of life of patients and prevent the development of severe complications. Genetic counseling of families with identified cases of primary immunodeficiencies plays a special role.

Types of primary immunodeficiency

Let’s take a closer look at the types of primary immunodeficiencies in children. They represent a diverse group of genetic pathologies that significantly affect the functioning of the immune system. 

  1. Immunoglobulin A deficiencyis the most common form of immunodeficiency. This condition is characterized by a critical decrease or complete absence of IgA in the bloodstream and on the surface of the body’s mucous membranes. 
  2. X-linked agammaglobulinemia(Bruton’s disease) is predominantly diagnosed in males. The pathology is caused by a genetic defect that blocks the maturation of B cells, which leads to a virtually complete absence of all classes of immunoglobulins in the body. 
  3. Severe combined immune deficiencyis a critical form of immunodeficiency with disruption of the functioning of the main links of immunity. It is characterized by a profound defect in both cellular and humoral immune responses, which makes the body extremely vulnerable to various pathogens.
  4. Congenital DiGeorge syndromeis manifested by a complex of dysfunctions, including hypoplasia or aplasia of the thymus, cardiovascular defects, specific facial dysmorphia. In addition, there is a dysfunction of calcium metabolism, as well as dysfunction of the T-cell link of immunity.
  5. Wiskott-Aldrich complex immunodeficiencyis characterized by a triad of major symptoms:
  • hemorrhagic syndrome due to thrombocytopenia;
  • atopic dermatitis;
  • recurrent infectious diseases.
  1. Complement system deficiency, despite its relative rarity, forms a special group of immunodeficiencies. Their clinical manifestations may include increased susceptibility to specific pathogens, a tendency to develop autoimmune reactions, and inflammation. 

Causes and risk factors

The main role in the development of these conditions is played by genetic mutations affecting genes responsible for the formation and functioning of the immune system.

The hereditary nature of transmission is a key factor in the development of PID. Different types of inheritance include:

  1. autosomal recessive;
  2. autosomal dominant;
  3. X-linked, determines the likelihood of the disease occurring in offspring. 

The risk is particularly high in families where there are already cases of primary immunodeficiency or there is a consanguineous marriage.

An important risk factor is the influence of unfavorable factors during pregnancy. Impact:

  1. toxic substances;
  2. radiation;
  3. some medications;
  4. Viral infections during intrauterine development increase the likelihood of genetic mutations leading to the development of immunodeficiencies.

Ethnicity also influences the development of certain types of disease. Some forms of immunodeficiency are more common in certain ethnic groups due to differences in the genetic pool of these populations. For example, some antibody deficiencies are more common in Caucasians.

Symptoms and manifestations

The main PIDs are characterized by a wide range of clinical manifestations, which depend on the type of immunological defect and the age of the patient. Let’s consider the main groups of symptoms:

  1. Infectious manifestations, which include frequent recurrences of upper and lower respiratory tract infections, chronic sinusitis and otitis, recurring pneumonia, protracted intestinal infections. Fungal lesions of the skin and mucous membranes may occur. 
  2. Non-infectious manifestations, which include delayed physical development, growth and weight retardation, problems with tooth formation, skin manifestations (eczema, rashes), autoimmune damage to the endocrine system (endocrinopathy), neurological abnormalities, etc. 
  3. Gastrointestinal symptoms include chronic diarrhea, malabsorption syndrome, weight loss, inflammatory bowel disease.

Also, let us highlight autoimmune manifestations separately:

  1. autoimmune anemia;
  2. thrombocytopenia;
  3. vasculitis;
  4. endocrine disruptions;
  5. systemic pathologies of connective tissue.

The following statistics are interesting: the ratio of men to women suffering from PID is on average 6:1. The most frequently diagnosed primary immunodeficiencies are severe combined immunodeficiency (SCID) (28.6%) and hyper-IgM syndrome (HIGM) (24.1%).

Diagnostics

Diagnosis of primary immunodeficiencies is a complex process that includes several successive stages of examination. 

When collecting anamnesis, special attention is paid to the frequency and severity of infectious diseases, the presence of unusual infections, and the effectiveness of the therapy. 

An important point remains control of family history, since many forms have a genetic nature. The age of onset of manifestations, the nature of the course of the disease and the presence of concomitant pathologies are taken into account.

Physical examination includes:

  1. assessment of the general condition of the patient;
  2. identification of signs of chronic infections;
  3. determination of the state of lymphoid tissue;
  4. presence of skin manifestations;
  5. skeletal deformities and other characteristic features. 

Particular attention is paid to assessing physical development, especially in children. Laboratory diagnostics begin with a general blood test to determine the number and ratio of different types of leukocytes. 

Biochemical analysis helps to assess the general condition of the body and identify possible complications. The study of the level of immunoglobulins is a mandatory component of diagnostics and includes the determination of IgA, IgM, IgG and IgE.

Cellular immunity is assessed by determining the quantity and functional activity of T-lymphocytes and their subpopulations. The phagocytic activity of neutrophils and macrophages is studied. An important component of diagnostics is the assessment of the complement system.

Instrumental research methods may include chest X-ray, CT scan of the paranasal sinuses, ultrasound of the abdominal organs and other visualization methods to assess the condition of various organs and systems.

Treatment of pathology

The therapeutic strategy is developed individually for each patient, taking into account the type of PID, the severity of the condition and the presence of complications.

The treatment program is developed strictly individually, taking into account the specifics of the immunodeficiency, the severity of clinical manifestations and associated complications.

  1. Antimicrobial therapyis a fundamental element in the complex treatment of primary immunodeficiencies. Rational use of antibacterial drugs is necessary both to stop current infectious processes and to prevent recurrent bacterial complications. 
  2. Immunosupplement therapyis a key element in the treatment of many types of primary immunodeficiencies, especially in cases of antibody formation disorders. Modern immunoglobulin preparations are available for intravenous and subcutaneous administration, which allows choosing the optimal method of administration for each clinical case.
  3. Blood stem cell transplantationis a radical method of treating certain forms of primary immunodeficiency. This therapeutic approach demonstrates the greatest effectiveness in severe combined immunodeficiency states and a number of other specific forms of PID. 
  4. Gene therapyis an innovative treatment method. This approach is based on the introduction of a functional gene into the patient’s cells to correct a genetic defect. Although the technology is still in active development, encouraging results have already been obtained in the treatment of some forms of severe combined immunodeficiency.

Living with PID

Living with immunodeficiency requires a special approach to organizing daily activities and constant attention to your health. Despite the seriousness of the diagnosis, with proper treatment and adherence to recommendations, many patients can lead a fairly active lifestyle.

Particular attention is paid to preventive measures, including vaccination (taking into account the type of pathology and contraindications), compliance with hygiene rules, and correction of the diet. Regular monitoring of the condition allows for timely correction of therapy and prevention of complications.

Psychological support and social adaptation are important components of complex treatment. Working with the patient and his family helps improve adherence to therapy and quality of life.

Modern treatment methods are constantly being improved. New drugs are being developed, stem cell transplant protocols are being improved, and innovative approaches to gene therapy are emerging. This allows for an improvement in the prognosis and quality of life for various forms of the disease.

Conclusion

To sum up, we emphasize that early diagnostics of primary immunodeficiencies plays a decisive role in the fate of the patient. Timely detection of the disease allows preventing the development of serious complications and significantly improving the quality of his life.

If you notice signs in yourself or your loved ones that indicate possible immunodeficiency, do not delay a visit to the doctor. Early diagnosis and timely therapy can radically change the course of the disease and the quality of life.

By contacting the Republican Scientific and Practical Center for Children’s Oncology, Hematology and Immunology, you will receive:

  1. accurate diagnostics using modern equipment;
  2. effective treatment according to modern protocols;
  3. professional support;
  4. consultations with the best oncologists.

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