Clinical picture of SCID

Class

Primary and secondary immunodeficiencies

Immunodeficiency states (IDS) are permanent (persistent) or temporary (transient) states characterized by an inadequate immune response to antigens of microbial or any other origin.

There are primary or genetically determined IDS, physiological IDS (in newborns, pregnant women, the elderly) and secondary IDS (against the background of other diseases and conditions).

Primary immunodeficiencies (PIDS)

Primary immunodeficiencies are congenital disorders of the immune system associated with a genetic defect in one or more parts of the immune system. The prevalence of PIDS is 1:10,000 births.

Currently, about 250 forms of PIDS have been described, and genetic defects are known for 170 of them. Due to the limited availability of molecular genetic methods in everyday practice, the diagnosis of PIDS is dominated by a phenotypic approach based on clinical and immunological signs.

  1. Phenotypic classification of primary immunodeficiencies
  2. Combined T- and B-cell immunodeficiencies (severe combined immunodeficiency syndrome – SCID ).
  3. Predominantly cellular (lymphoid) immunity defects.
  4. Antibody deficiency syndromes ( humoral immunodeficiencies ).
  5. defects in phagocytosis.
  6. Complement defects.
  7. Primary IDS associated with other defects ( other well-defined PIDS ).

Primary immunodeficiencies are most often detected in children, since a significant proportion of patients do not live up to 20 years. Their typical manifestations are severe infections , an increased tendency to develop neoplasia .

Infections in primary IDS have a number of features:

  1. Chronic or relapsing course, tendency to progression.
  2. opportunistic character.
  3. Polytopic (multiple lesions of various organs).
  4. Polyetiology (susceptibility to many pathogens at the same time).
  5. Incomplete rehabilitation, incomplete effect of treatment.

The type of infection may facilitate the diagnosis of IDS (Table 1).

Table 1

Failure Associated disease
T- and B-lymphocytes (combined immune deficiency) Acute and chronic infections – viral, bacterial, fungal, protozoal
T-lymphocytes (mainly cell failure) Increased susceptibility to viral, fungal and protozoal infections)
B-lymphocytes (humoral IDS) Recurrent bacterial infections (otitis media, sinusitis, pneumonia)
Phagocytes Pyogenic infections, impaired pus formation, poor wound healing, systemic opportunistic infections
Complement components Bacterial infections, autoimmune diseases

6% of patients develop autoimmune processes , 17% develop allergic diseases.

Allergic manifestations are mandatory for the Wiskott-Aldrich syndrome and hyper-IgE syndrome (Job’s syndrome), and are more frequent with selective IgA deficiency.

Autoimmune diseases (rheumatoid arthritis, hemolytic anemia, autoimmune endocrinopathies) occur with increased frequency in CVID, chronic mucocutaneous candidiasis, selective IgA deficiency.

Almost all cases of neoplasia occur in Wiskott-Aldrich, Louis-Bar, and CVID syndromes.

Many forms of PIDS are extremely dangerous, difficult to treat, and therefore, a significant proportion of patients die in childhood (SCID, ataxia-telangiectasia, hyper-IgE syndrome, Wiskott-Aldrich syndrome, etc.). However, advances in the treatment of PIDS in recent decades have resulted in an increasing number of patients surviving into adulthood.

1. Combined deficiency of cellular and humoral immunity (severe combined immunodeficiency – SCID). It makes up 20-25% of all primary immunodeficiencies. This group includes diseases caused by impaired proliferation and differentiation of T- and B-lymphocytes. Age of manifestation: the first weeks and months of life.

TCID Options

T B + – (↓CD3 + <10%, ↑CD19 + >75%, B-lymphocytes do not function )

  1. X-linked SCID (up to 50% of all SCID) (mutation of the γ-chain gene , defect in cytokine receptors – IL2, IL-4, IL-7, etc., impaired response to many cytokines).
  2. Autosomal recessive SCID ( mutation of the JAK3 tyrosine kinase gene on the short arm of chromosome 19, no signal transduction from the γ-chain of cytokine receptors, impaired response to many cytokines).

T B – (↓CD3 + <20%, severe lymphopenia <3000/mm 3 )

1. Deficiency of adenosine deaminase – ADA (up to 20% of all SCID) (mutation of the ADA gene on the long arm of chromosome 20, deficiency of the ADA enzyme leads to the accumulation of toxic products and the destruction of lymphocytes).

2. Deficiency of RAG1 RAG2 (mutation of the RAG1 RAG2 genes on the short arm of chromosome 11 leads to a defect in gene rearrangement, maturation of T- and B-lymphocytes stops)

Clinical picture of SCID

  1. Early onset, cessation of weight gain, increasing dystrophy
  2. Complications after BCG vaccination, up to disseminated infection
  3. Persistent diarrhea at 2-6 months of age that does not respond to therapy
  4. Recurrent candidiasis of the skin and mucous membranes
  5. Interstitial pneumonia – fungal and pneumocystis
  6. Unexplained skin rash (graft-versus-host disease)

7. Severe forms of viral infections (herpetic, CMV, EBV, adenovirus)

  1. Hypoplasia of lymphoid tissue

Laboratory signs:

1. lymphopenia, a sharp decrease in CD3 + (<10-20%), CD4 + , CD8 + ,

2. violation of the synthesis of immunoglobulins,

3. The level of CD19 + may be normal or elevated, but their function is impaired.

Treatment: maintenance therapy – antibacterial, antifungal, antiviral , administration of intravenous immunoglobulins . The use of live vaccines is contraindicated. Without immunoreconstruction, children with SCID die within the first 2-3 years. The main method of treatment to achieve the restoration of immune functions is bone marrow transplantation (BMT) or transfusion of hematopoietic stem cells. It is preferable to perform BMT shortly after birth before the onset of clinical manifestations. Another method of treatment is gene therapy with the replacement of a defective gene.

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