Immunodeficiency in children

Immunodeficiency states (immunodeficiency) develop due to the defeat of one or more links of immunity. A characteristic manifestation of immunodeficiencies are recurrent, severe infections. However, for many types of immunodeficient conditions, an increased frequency of autoimmune manifestations and / or tumor diseases is also characteristic. Some conditions may be accompanied by an allergic pathology. Thus, the traditional understanding of immunodeficiency states as conditions with increased sensitivity to infections has expanded, including 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 result of another disease or gyuzdeystviya.

Primary immunodeficiency states (PIDC) are much less common and belong to the group of severe genetically determined diseases caused by violation 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 used to happen that one state of melody has several names. Currently, the international classification of immunodeficiencies is adopted , which seeks to combine diseases depending on the main affected immune system. The main role in the classification of immunodeficiencies is played by the international group of experts on immunodeficiency (currently the IUIS - International Union of Immunodeficiency Societies), created in 1970 on the initiative of WHO. The group meets every 2-3 years and updates the classification. Over the 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 last classification of 2006 "and mainly based on the primary defeat of one or another link of immunity, subdivides the primary immunodeficiency into the following main groups:

• combined immunodeficiencies with T and B lymphocyte damage;
• predominantly humoral immunodeficiencies;
• clearly delineated immunodeficiency states;
• the state of immune dysregulation;
• defects of phagocytosis;
• defects of innate immunity;
• auto-inflammatory diseases;
• defects of the complement system.

The main causes of secondary immunodeficiency status

• Premature neonates
• Congenital and metabolic diseases
  • Chromosomal abnormalities (Down's syndrome, etc.)
  • Uremia
  • Nephritic syndrome
  • Engeropathy
• Immunosuppressive agents
  • Irradiation
  • Cytotoxic agents
  • Glucocorticosteroids
  • Antitimocytic globulin
  • Aichi-T and B monoclonal antibodies
• Infections
  • HIV
  • VEB
  • Congenital rubella
• Hematological diseases
  • Histiocytosis
  • Leukemia
  • Myelogenous disease
• Surgical interventions and injuries
  • Splenctomy
  • Burn disease
  • Hypothermia

Defects of antibody production (humoral defects) constitute the greater part of all cases of primary immunodeficiency states. Patients with the most severe manifestations of primary immunodeficiency states are in the group of combined cell states, they are 20%.

Primary immunodeficiencies are the most important natural models that allow one to fully understand the functions of certain components of the immune system. Over the past years, the approach to diagnosis and therapy of primary immunodeficient conditions has fundamentally changed. If initially the diagnosis was based on clinical manifestations, then further increasingly complex laboratory studies became an integral part of the diagnosis. Now the diagnosis is unthinkable without the subsequent detection of the mutation of 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 the express and are also managed in other tissues. In this case, immunodeficiency states are accompanied by other, non-immunological defects (for example, Nijmigen syndrome).

Most immunodeficiency states are inherited by X-linked or autosomally recessive. A small group of immunodeficient states has an autosomal dominant path of inheritance. Some primary immunodeficiency states are caused by mutations of one gene (for example, ataxia-telangiectasia), but many clinically identical states result from mutations of different genes (severe combined immune deficiency, chronic granulomatous disease). In addition, as molecular genetic methods for the diagnosis of primary immunodeficiency states have spread widely, it has been possible to identify that different mutations of the same gene can lead to clinically different states (mutations of the WASP gene ).

Most of the primary immunodeficiency states debut in early childhood. Early diagnosis and adequate therapy of primary immunodeficiency states allows to achieve recovery or stable general condition of patients with the majority of these diseases. The frequency of occurrence of primary immunodeficiencies averages from 1: 10,000 people - a frequency comparable to phenylketonuria or cystic fibrosis. However, marked shpodiagnostika these conditions. The consequence of this is unreasonably high disability and mortality of children with primary immunodeficiency states caused by infectious and other complications. Unfortunately, in connection with the heterogeneity of primary immunodeficiency states, their screening in newborns is practically impossible.

However, there is a hope that increasing the alertness of pediatricians and general practitioners towards primary immunodeficiencies, greater awareness of the population, will improve the diagnosis and, accordingly, the overall prognosis of this group of patients. 

[1], [2], [3], [4], [5]