Pediatric autoimmune lymphoproliferative syndrome

Introduction to pediatric autoimmune lymphocytosis syndrome Autoimmunelymphoproliferative syndrome (ALPS) is a mutation in the body's CD95/Fas gene APT1, a large number of activated lymphocytes continue to survive, resulting in lymphocyte proliferation and autoimmune phenomenon, known as lymphocytosis syndrome with itself Immunization (lymphoproliferativesyndromewithautoimmunity) and Canale-Smith syndrome. basic knowledge The proportion of sickness: 0.00001% Susceptible people: children Mode of infection: non-infectious Complications: hypersplenism, spleen rupture, hemolytic anemia

Causes of childhood autoimmune lymphocytosis syndrome

(1) Causes of the disease

The APT1 gene is located at 10q23, exons 2, 3, 4 and 5 occupy Fas in the three extracellular regions of the cysteine, exon 6 is localized in the transmembrane region of Fas; exons 7, 8 and 9 It is an intracellular part in which exon 9 is homologous to the intracellular part of TNF receptor-1 and is a cell death determining region. The 5-terminal single peptide directs its expression on the cell membrane. The transcription product of APT1 gene is CD95/Fas. /Apo-1 protein belongs to the TNF receptor (TNFR) family.

The common mutation site is the 290-bp deletion in exon 9 (cell death determining region), and the others are single nucleotide changes, including nonsense mutation, missense mutation, insertion, frameshift and splicing, APT1 gene. The relationship between mutations and clinical phenotypes is not completely consistent.

(two) pathogenesis

When normal human lymphocytes are activated, they begin to express their own Fas molecules, and FasL binds to Fas, which transmits signals to the intracellular death determining region of Fas molecules, which triggers the protease system caspases, which ultimately leads to lymphocyte apoptosis. Occurrence, APT1 gene mutation can not express CD95/Fas/APO-1, which causes FasL-Fas-induced apoptosis pathway, and a large number of activated lymphocytes can not enter the apoptosis program, resulting in lymphocyte proliferation and autoimmune response.

Pediatric autoimmune lymphocytosis syndrome prevention

1. Maternal 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 have viral infections (especially rubella virus infection), they may be damaged. The fetal immune system, especially in the first trimester, can involve multiple systems including the immune system. Therefore, it is important to strengthen maternal health care, especially in early pregnancy. Pregnant women should avoid radiation, use some chemical drugs with caution, and inject rubella vaccine. Wait, try to prevent viral infections, but also to strengthen the nutrition of pregnant women, and timely treatment of some chronic diseases.

2. Genetic counseling and family surveys: Although most diseases cannot determine the genetic pattern, it is valuable to conduct genetic counseling for diseases with defined genetic patterns. If adults have hereditary immunodeficiency diseases, they will provide the developmental risks of their children. If a child has an autosomal recessive or sexually linked immunodeficiency disease, tell the parents how likely they are to have the next child, and the immediate family members of the antibody or complement deficiency should check for antibodies and The level of complement determines the family's disease pattern. For some diseases that can be genetically located, such as chronic granulomatosis, the patient's parents, siblings and their children should be tested for localization. If a patient is found, the same should be given to him. The family members of (her) are examined and the child's children should be carefully observed at the beginning of the birth for any disease.

3. Prenatal diagnosis: Some immunodeficiency diseases can be used for prenatal diagnosis. For example, cultured amniotic fluid cell enzymology can diagnose adenosine deaminase deficiency, nucleoside phosphorylase deficiency and some combined immunodeficiency diseases; Fetal blood cell immunology test can diagnose CGD, X-linked no-gammaglobulinemia, severe combined immunodeficiency disease, thereby stopping pregnancy, preventing the birth of children, autoimmune lymphocytosis syndrome is rare, should be accurately diagnosed early It is very important to give specific treatment and provide genetic counseling (prenatal diagnosis or even intrauterine treatment) to reduce the incidence of this disease.

Pediatric autoimmune lymphocytosis syndrome complications Complications, spleen function, hypersplenism, hemolytic anemia

Lymphocyte proliferation can go to hypersplenism, spleen rupture; can be complicated by hemolytic anemia, immune thrombocytopenia, neutropenia, glomerulonephritis, multiple radiculitis, malignant tumors.

Symptoms of autoimmune lymphoproliferative syndrome in children Common symptoms Granulocyte reduction thrombocytopenia Lymph node enlargement Abnormal liver function splenomegaly

There is no gender or ethnic difference in the incidence.

1. Lymphocyte proliferative performance: 100% of ALPS cases have splenomegaly, more than 5 years old, even in the fetal period, the degree of splenomegaly varies, 74% of the sick children due to hypersplenism or Splenic rupture and splenectomy, 67% of children with mild to moderate hepatic, occasionally found abnormal liver function, about 97% of children with systemic superficial lymphadenopathy, imaging can be found in mediastinal lymphadenopathy.

2. Autoimmune diseases: Coombs-positive hemolytic anemia is the most common (75%), immune thrombocytopenia is second (54%), autoimmune neutropenia is 46%, and other kidneys are small. Glomerulitis, multiple radiculitis and skin damage (including urticaria and non-specific cutaneous vasculitis).

3. Other manifestations: Adults with malignant tumors, including Hodgkin and non-Hodgkin's lymphoma, hepatocellular carcinoma, thyroid and breast multiple adenocarcinoma, recently found a case of ALPS with autism.

Examination of pediatric autoimmune lymphocytosis syndrome

The number of CD3+ cells increased, exceeding the sum of CD4T cells and CD8 T cells, suggesting the presence of CIM-CD8-T cell subsets, and its TCR is / chain (normal people only occasionally appear, often less than 1%, and ALPS suffers) These are often higher than 5% to 20%, or even 68%. These CD4-CD8-T cells are senescent cells that have not entered apoptosis.

The T cell phenotypes are CD45RA+, CD45RO-, CD57+, most of which express DR or HLAII antigens, Th2 cytokines such as IL-4, IL-5 and IL-10 are increased, while TH1 cytokines such as IL-12, IL- 2 and IFN- decreased.

The skin delayed allergic reaction and anti-polysaccharide antigen antibody response were weakened, serum IgG, IgA and IgM were elevated, and most of them were monoclonal, mainly IgG1 antibody.

Autoantibodies are mainly directed against red blood cells and platelets. Coombs experiments are mostly positive. Other autoantibodies have anti-neutrophil antibodies, low titers of anti-smooth muscle antibodies, antiphospholipid antibodies, anti-nuclear antibodies and rheumatoid factors.

Hemoglobin can be less than 30g/L when hemolytic crisis occurs. Once spleen hyperfunction occurs, the number of platelets decreases significantly, and hemorrhagic tendency occurs. The absolute count of lymphocytes increases, generally (8-90)×109/L, or even higher. Most patients have different degrees of eosinophilia (3% to 32%), and individual patients have elevated transaminase and cholesterol.

DNA sequence analysis of the APT1 gene revealed that mutations can clearly diagnose and discover carriers of family members of the disease.

According to the clinical needs, choose chest X-ray, B-ultrasound and other examinations, you can find mediastinal lymphadenopathy, hepatosplenomegaly and tumors.

Diagnosis and diagnosis of autoimmune lymphocytosis syndrome in children

The diagnosis was confirmed according to the characteristics of clinical manifestations and the characteristics of laboratory tests.

Different from other autoimmune diseases, such as immune thrombocytopenia, neutropenia, hemolytic anemia.

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