Immunodeficiency in children

Immunodeficiency states (immunodeficiency) develop as a result of damage to one or more links of the immune system. A typical manifestation of immunodeficiency is recurrent, severe infections. However, many types of immunodeficiency states are also characterized by an increased frequency of autoimmune manifestations and/or tumor diseases. Some conditions may be accompanied by allergic pathology. Thus, the traditional understanding of immunodeficiency states as conditions with increased sensitivity to infections has expanded to include non-infectious pathology.

Immunodeficiency states (immunodeficiencies) are divided into primary and secondary. Secondary immunodeficiency states are characterized by pronounced immunological defects that arise as a consequence of another disease or exposure.

Primary immunodeficiency states (PIDS) are much less common and belong to a group of severe genetically determined diseases caused by a disruption of one or more immune defense mechanisms.

The first described primary immunodeficiency states were named after the researcher, the country of discovery, or the main features of pathogenesis. It happened that one state had several names. Currently, an international classification of immunodeficiencies has been adopted, which seeks to combine diseases depending on the main affected link of immunity. The main role in the classification of immunodeficiencies is played by the international group of experts on immunodeficiencies created in 1970 on the initiative of the WHO (currently - the group of experts at the IUIS - International Union of Immunodeficiency Societies). The group meets every 2-3 years and updates the classification. Over the past years, the main changes in the classification are associated with the discovery of new types of primary immunodeficiencies and changes in ideas about the mechanisms of their development, as well as the identification of the genetic basis of many primary immunodeficiency states.

The latest classification of 2006, mainly based on the predominant damage to one or another link of the immune system, divides primary immunodeficiencies into the following main groups:

• combined immunodeficiencies with damage to T and B lymphocytes;
• predominantly humoral immunodeficiencies;
• clearly defined immunodeficiency states;
• states of immune dysregulation;
• phagocytosis defects;
• defects of innate immunity;
• autoinflammatory diseases;
• complement system defects.

The main causes of secondary immunodeficiency states

• Premature newborns
• Congenital and metabolic diseases
  • Chromosomal abnormalities (Down syndrome, etc.)
  • Uremia
  • Nephritic syndrome
  • Energeopathy
• Immunosuppressive agents
  • Irradiation
  • Cytostatics
  • Glucocorticosteroids
  • Antithymocyte globulin
  • Aiti-T and B monoclonal antibodies
• Infections
  • HIV
  • VEB
  • Congenital rubella
• Hematological diseases
  • Histiocytosis
  • Leukemia
  • Myeloid disease
• Surgical interventions and injuries
  • Splenectomy
  • Burn disease
  • Hypothermia

Defects in antibody production (humoral defects) account for the majority of all cases of primary immunodeficiency states. Patients with the most severe manifestations of primary immunodeficiency states are in the group of combined cellular states, they account for 20%.

Primary immunodeficiencies are the most important natural models that allow us to fully understand the functions of certain components of the immune system. Over the past years, the approach to diagnostics and therapy of primary immunodeficiency states has changed fundamentally. If initially the diagnosis was based on clinical manifestations, then increasingly complex laboratory tests later became an integral part of diagnostics. Now, diagnosis is unthinkable without subsequent detection of a mutation in the suspected gene. Genes whose defects lead to the development of primary immunodeficiency states are localized only in the cells of the immune system (for example, the RAG defect) or are expressed in other tissues. In this case, immunodeficiency states are accompanied by other, non-immunological defects (for example, Nijmigen syndrome).

Most immunodeficiency disorders are inherited in an X-linked or autosomal recessive manner. A small group of immunodeficiency disorders are inherited in an autosomal dominant manner. Some primary immunodeficiency disorders are caused by mutations in a single gene (e.g., ataxia-telangiectasia), but many clinically identical disorders are caused by mutations in different genes (severe combined immunodeficiency, chronic granulomatous disease). In addition, as molecular genetic methods for diagnosing primary immunodeficiency disorders have become more widespread, it has become possible to identify that different mutations in the same gene can lead to clinically different disorders (WASP mutations).

Most primary immunodeficiency states debut in early childhood. Early diagnosis and adequate therapy of primary immunodeficiency states allows achieving recovery or stable general condition of patients with most of these diseases. The frequency of occurrence of primary immunodeficiency states on average is 1:10,000 people - a frequency comparable to phenylketonuria or cystic fibrosis. However, there is a pronounced spodiagnostic of these states. The consequence of this is an unjustifiably high disability and mortality of children with primary immunodeficiency states caused by infectious and other complications. Unfortunately, due to the heterogeneity of primary immunodeficiency states, their screening in newborns is practically impossible.

However, there is hope that increased alertness of pediatricians and general practitioners towards primary immunodeficiencies and greater public awareness will improve diagnostics and, accordingly, the overall prognosis for this group of patients.

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