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Defects of the interferon-y / interleukin-12 dependent pathway: symptoms, diagnosis, treatment
Last reviewed: 23.04.2024
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Defects that lead to a violation of interferon-gamma (INF-y) and interleukin-12 (11-12) -dependent pathway are characterized by hypersensitivity to mycobacterial and some other infections (Salmonella, viruses).
Pathogenesis of defects of interferon-y / interleukin-12 dependent pathway
Absorbed by macrophages, mycobacteria stimulate production of IL-12. IL-12 stimulates T-lymphocytes and NK cells and induces INF-y production. The latter activates macrophages and enhances the killing of mycobacteria. Defects of these cytokines, cellular receptors to them, as well as proteins that transmit signals from the receptor into the cell, lead to a specific sensitivity to certain pathogens.
Symptoms of defects of interferon-y / interleukin-12 dependent pathway
Clinical manifestations in patients with various genetic defects are largely similar. After vaccination BCG patients develop disseminated infection. If there is no vaccination at an older age (1-3 years), pulmonary or generalized infections caused by methicobacterial mycobacteria or Salmonella are noted.
In all cases of mycobacterial infection, patients had fever, weight loss, lymphadenopathy, hepatosplenomegaly, chronic anemia. Many patients had a lesion of specific organs. In addition, several patients described such conditions as bronchial asthma, vasculitis, glomerulonephritis. However, it is not possible to establish a reliable pathogenetic association of these conditions with the defect of the INF-y / IL-12 pathway at this stage.
Diagnostics
In patients with the above defects, there are no quantitative and qualitative laboratory changes in the cellular and humoral units of immunity. The diagnosis is confirmed by the identification of an appropriate mutation in patients with a typical clinical picture.
Treatment of defects of interferon-y / interleukin-12 dependent pathway
TSCA is potentially a therapy of choice in these patients, but the relevant world experience is extremely limited. Patients should avoid contact with people suffering from tuberculosis, leprosy and other infections caused by intracellular pathogens. Possible the appointment of preventive anti-tuberculosis therapy. BCG vaccination to such patients is strictly contraindicated. When infected with mycobacteria, therapy is administered by 4 drugs. With special care, it is necessary to determine the sensitivity of the pathogen, due to the high level of resistance in this group of pathogens. There are reports of the use of INF-alpha, as well as INF-a, IL-12 with a partial clinical effect.
Forecast
When infection with BCG or mycobacteria, the prognosis is extremely unfavorable. In many ways, the prognosis depends on the dose of the infectious pathogen and early diagnosis.
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