Interferon-gamma receptor deficiency in children

Introduction to pediatric interferon-gamma receptor deficiency disease Interferon-gamma receptor (IFN-R1) deficiency is an autosomal recessive hereditary disease characterized by severe mycobacteria, Salmonella infection, and disseminated infection caused by BCG vaccination. basic knowledge The proportion of illness: 0.005% Susceptible people: children Mode of infection: non-infectious Complications: Asthma Glomerulonephritis Vasculitis

Pediatric interferon-gamma receptor deficiency disease etiology

(1) Causes of the disease

The IFN-R1 gene is located at 6q23~24 and contains 7 exons: exons 1 to 5 encode the extracellular region of IFN-R1, exon 6 is the transmembrane region, and exon 7 is the intracellular region. The transcript of the IFNGR1 gene is IFN-R1 or chain. The IFNGR1 gene mutations have been found to include the 116th nucleotide mutation of exon 3 (TCATAA), the 131th C deletion of exon 2, and the exon. Insertion of 107 at 4 nucleotides (TTAC) and splicing mutation of exon 3 (GA).

In addition, mutations in the INFGR2 gene result in dysregulation of IFN-R2, which prevents intracellular signaling from being blocked by STATS phosphorylation. IL-12 subunit p40 gene deletion leads to decreased IL-12 activity, and IL-12 receptor deficiency is significantly hindered. IFN- mediates macrophage and T cell immune function, and the clinical manifestations of these gene mutations are similar to those of interferon-gamma receptor deficiency.

(two) pathogenesis

IFN-R1 is widely present in a variety of immunocompetent cells. Non-tuberculous mycobacteria (NTM) stimulates phagocytic cells to secrete IL-12, IL-18 and IFN-, induce Th1 cell differentiation, promote CTL killing of BCG and NTM, and cytokines. IFN- and TNF- also directly inhibit BCG and NTM, therefore, IFN- is the most critical factor against NTM and BCG.

Mutation of IFNGR1 gene and defective expression of IFN-R1 ( chain) cause obstacles to the above-mentioned killing mechanism, resulting in severe NTM infection or disseminated BCG.

Prevention of interferon-gamma receptor deficiency in children

Pregnant woman health care

It is known that the occurrence of some immunodeficiency diseases is closely related to embryonic dysplasia. If pregnant women are exposed to radiation, receive certain chemical treatments or develop viral infections (especially rubella virus infections), they can damage the fetal immune system. Especially in the early pregnancy, it can affect multiple systems including the immune system. Therefore, it is very important to strengthen the health care of pregnant women, especially in the early pregnancy. Pregnant women should avoid receiving radiation, use some chemical drugs with caution, and inject rubella vaccine to prevent as much as possible. Virus infection, but also to strengthen the nutrition of pregnant women, timely treatment of some chronic diseases.

2. Genetic counseling and family survey

Although most diseases cannot determine the genetic pattern, genetic counseling for diseases with defined genetic patterns is valuable if genetically immunodeficiency in adults will provide the developmental risk of their children; if a child has autosomals Recessive genetic or sexually linked immunodeficiency disease, it is necessary to tell parents that their next child is likely to be sick, for patients with antibodies or complement deficiency patients should check the antibody and complement levels to determine the family disease For some diseases that can be genetically mapped, such as chronic granulomatosis, parents, siblings and their children should be genetically tested. If a patient is found, it should also be performed among his or her family members. Check that the child's child should be carefully observed at the beginning of the birth for any disease.

3. Prenatal diagnosis

Some immunodeficiency diseases can be prenatally diagnosed, such as cultured amniotic fluid cell enzymology can diagnose adenosine deaminase deficiency, nucleoside phosphorylase deficiency and some combined immunodeficiency diseases; fetal blood cell immunological test can be Diagnosis of CGD, X-linked no-gammaglobulinemia, severe combined immunodeficiency disease, thereby terminating pregnancy and preventing the birth of children, the diagnosis of interferon-gamma receptor deficiency disease depends on IFNGR1 gene deletion or IFN-R1 molecular function Confirmation of defects, early and accurate diagnosis, early delivery of specific treatment and provision of genetic counseling (prenatal diagnosis or even intrauterine treatment) are very important.

Pediatric interferon-gamma receptor deficiency disease complications Complications Asthma glomerulonephritis vasculitis

Repeated severe infections often occur, and BCG and non-tuberculous mycobacterial infections can lead to the spread of lethal infections; lead to hepatosplenomegaly; other causes of allergic diseases such as asthma, glomerulonephritis and blood vessels Inflammation and so on.

Symptoms of interferon-gamma receptor deficiency in children Common symptoms Unexplained fever, swollen lymph nodes, night sweats, liver splenomegaly

If BCG is given at the time of birth, disseminated BCG may occur in March; the age of onset of natural infection of mycobacteria is 2 months to 3 years after birth, and infection with non-typhoid Salmonella is also low. Clinical manifestations of fever, night sweats, swollen lymph nodes, hepatosplenomegaly, infection can spread to the whole body, including skin, soft tissue, bone marrow and meninges, caused by inoculation of BCG, initially with lymphadenopathy and ulceration nearby, followed by whole body Sexual spread, similar to the natural non-tuberculous mycobacterial infection process, most children die within a few years.

Children's sensitivity to viral infections did not increase, others showed allergies and asthma, immune complex glomerulonephritis and vasculitis.

Examination of pediatric interferon-gamma receptor deficiency disease

There was no abnormality in the general immune function. Further examination revealed that the ability of exogenous IFN- to induce TNF- in peripheral blood mononuclear cells of children with and without clinical manifestations was decreased, and the proliferation of NTM in children was normal. However, the amount of IFN- produced is reduced.

Natural NTM-infected lymph nodes and hepatic lesion histology are often non-specific inflammatory granulomatous changes, including neutrophils, macrophages and foam cell infiltration, polynuclear giant cells are rare or absent, and a large number of branches are seen in the diseased tissue. Bacteria have a poor prognosis.

There are two types of histopathological changes in disseminated BCG: tuberculous granuloma (type I) and leprosy-like granuloma (type II), children with type I granulomas have a greater chance of survival, while type II granulation The prognosis of swollen is very poor, and anti-mycobacterial drug treatment can not change the nature of granulomatous lesions.

The use of specific antibodies to detect the expression of IFN-R1 on the cell surface can initially diagnose the disease, but can not completely rule out the IFN-R1 molecular function defects caused by partial mutation, gene sequencing and the response of children's cells to IFN- stimulation. Clear diagnosis.

Routine chest X-ray, B-ultrasound examination, found liver and spleen lymph node enlargement, pneumonia and other diseases.

Diagnosis and differential diagnosis of interferon-gamma receptor deficiency in children

In cases of natural NTM infection, the clinical manifestations are similar to those of general inflammatory diseases. The results of repeated mycobacterial culture are often negative. The histological examination of the lesions is non-specific. The results of tuberculin or NTM skin tests are different, so the diagnosis is extremely difficult. Unexplained fever, liver and spleen and lymphadenopathy should be considered in this disease. Repeatedly do a variety of diseased tissue and mycobacterial culture and section staining to find acid-fast bacilli, BCG vaccination is easier to find, the disease The diagnosis depends on the confirmation of IFNGR1 gene deletion or IFN-R1 molecular function defect.

Identification with hematogenous disseminated tuberculosis, laboratory tests can help identify.

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