Combined immunodeficiency disease

Introduction to combined immunodeficiency disease The disease refers to a group of diseases with clinical manifestations of antibody immunodeficiency and cellular immunodeficiency, and can be divided into severe combined immunodeficiency disease and partial combined immunodeficiency disease, and the severity of the disease varies greatly. basic knowledge The proportion of sickness: 0.00002% Susceptible people: no special people Mode of infection: non-infectious Complications: erythroderma eczema asthma urticaria hemolytic anemia lymphoma acute lymphocytic leukemia ataxia diabetes rubella cytomegalovirus infection

The cause of combined immunodeficiency disease

Severe combined immunodeficiency disease (30%):

There are autosomal recessive SCIDs, SCIDs with ADA deficiency, X-linked recessive hereditary SCIDs, and SCIDs with leukopenia. Immunodeficiency disease with thrombocytopenia and eczema is X-linked recessive inheritance, and the basic defects are unknown.

Ataxia (30%):

Telangiectasia is an autosomal recessive inheritance. Cellular immunodeficiency disease with abnormal immunoglobulin synthesis is a decrease in lymphocytes and lymphoid tissues, abnormal pleural structure, different levels of various immune proteins in serum, some increase or decrease, and some normal.

Pathogenesis

Due to congenital autosomal recessive inheritance, the basic defects of X-linked recessive inheritance lead to immunodeficiency of the antibody and cellular immunodeficiency, and related clinical diseases. The patient's thymus is small or degenerate, and the blood lymphocytes, lymph nodes and spleen lymphocytes are circulated. Significantly reduced, B cells in the B cell area of the spleen are reduced, or lymphocytes in the body do not show T, B cell markers, do not respond to phytohemagglutinin, ataxia telangiectasia is also an autosomal recessive disease, patients The thymus is small, the lymphocytes are few, the Hassall body is lacking, the cortex and medulla are unclear, the lymph nodes and spleen lymphoid follicles are insufficiency, there are Purkinje cell degeneration and cerebellar vascular malformation, and the skin epidermis papillary veins are dilated.

Combined immunodeficiency disease prevention

1. Screening and certification of immunodeficiency diseases

(1) Medical history investigation: To understand whether the mother had any rubella infection, cytomegalovirus infection, etc. during pregnancy, and whether she had taken drugs that may cause teratogenicity.

(2) Age of onset: The time when the child first developed symptoms of infection, the number of infections, such as diarrhea, purulent spots on the skin, etc.; the time of slow development, before and after the baby was born 6 months before and after birth.

(3) Family history: If there is no teratogenic factor in the immunodeficiency disease, it is often accompanied by a family history, and some are accompanied by sex chromosome inheritance. If there is a patient with this disease in the maternal line, it is helpful for diagnosis, and some are autosomal recessive.

(4) Physical examination: physical examination and X-ray examination can prove the previous infection and bronchiectasis and its sequelae. The children with immunodeficiency syndrome show dysplasia together. The continuously recorded height and weight curve may be closer and closer until Below the lower limit of the normal range, the lymph nodes or tonsils are less than normal, and some patients with cellular immunodeficiency syndrome and antibody deficiency syndrome may develop lymphadenopathy; patients with ataxia telangiectasia have telangiectasia and Ataxia manifestations, combined with immunodeficiency, may present short-limb dwarfism, Chédiak-Higashi syndrome patients with eye and skin albino.

Common infections in selective antibody deficiency syndrome are purulent and respiratory infections. The pathogens are mostly staphylococcus, streptococcus, influenza bacilli, etc., and those with cellular immunodeficiency are susceptible to fungal infections, such as Candida infection, and the prognosis of viral infections is poor. Such as measles, pneumonia, etc.

(5) Laboratory examination: 1 blood cell count: patients with immunodeficiency disease, the total number of white blood cells may decrease, the ratio of neutrophils to lymphocytes abnormally changes, the lymphocytes of normal people are 1.5 ~ 3.0 × 109 / L, children may be partial Higher, mononuclear cells isolated by lymphocyte separation solution, E-rose reaction and EAC rosette reaction to identify the ratio of T, B cells, or fluorescein-labeled antibody method for OKT test, detect T3 positive cells, determine T cell ratio, at the same time, T4 and T8 surface antigen T cells were detected by fluorescein-labeled antibody method to determine the ratio of TH to TS. The normal human TH to TS ratio was 1.2:1 to 1.4:1, 2 immunoglobulin Protein detection and immunoassay: taking serum from patients for immunoglobulin determination, mainly measuring IgG and its subclass content, IgA and IgM content, and collecting saliva to detect SIgA content, normal human IgG subclass 1, 2, 3 and 4, the total amount is 600 ~ 1600mg / 100ml, the average is 1240mg / 100ml; serum IgA content is 200 ~ 500mg / 100ml, the average is 280mg / 100ml; IgM content is 60 ~ 200mg / 100ml, the average is 120mg / 100ml, immunoassay Is detection For antibody function, the streptococcal hemolysin titer (anti-O "test) is measured with the serum of the child, because most of the infants can be infected with streptococcus type B after birth, or tetanus toxoid (or Sperm? Xl74) vaccinate the child, and check the production of anti-toxin (or X174 antibody) 3 weeks later to determine the Ig effect, especially when there is no large abnormal change in serum Ig content and species. Specific effects, 3-cell immunoassay: In addition to the aforementioned ratio of lymphocyte counts T and B, TH and TS ratio tests, the following functional tests are required: T cell transformation assay, leukocyte chemotaxis assay, phagocytic phagocytosis and Sterilization function test, B cell transformation test, various cytotoxicity tests, etc. Cellular immune function in vivo assay is a functional test that directly reflects immune cells. A delayed-type skin hypersensitivity test can be used, such as tuberculosis after vaccination with BCG. Subject (OT) test, or trichostatin, candida skin test, can also be coated with forearm method with dinitrochlorobenzene (or dinitrofluorobenzene) to sensitize subjects, 2 to 3 weeks Post-review Its skin allergic reaction, intradermal test of phytohemagglutinin, can also check its cellular immune function, 4 serum complement detection: first detect serum total complement activity, use sensitized sheep red blood cells, add different amounts of fresh serum to the subject The hemolysis curve is determined, and the total serum complement activity of the subject is calculated according to the formula.

Further, it is also possible to detect the presence or absence of each of the complement components C1 to C9, mainly to measure C3 and C1q.

2. Primary prevention measures

(1) Prevention of hereditary immunodeficiency: The genetic factors of immunodeficiency account for a large proportion, especially in severe cases. Therefore, for those with immunodeficiency, such as repeated episodes of multiple suppuration, there is no obvious infectious factor diarrhea. People, often use antibiotics to fight infections, etc., should be immunologically examined before marriage, to the immune laboratory for immune cells, serum immune factors and related cytokines, as well as in vitro and in vivo immune function tests, at the same time, to be genetically inquired Including personal history of both men and women, family history, deformity, etc., for cleft palate, cleft lip can further check the function of thymus and thymus; skin whitening should check its relationship with Wiskott-Aldrich syndrome.

(2) Prevention of teratogenic babies' immunodeficiency: In order to avoid the immunodeficiency caused by fetal teratogenicity, in addition to querying the personal history of the fetus parent, family history, deformity, etc., it is also necessary to avoid the mother's rubella virus during pregnancy. Infection with cell viruses, prevention of drugs with teratogenic tendency, prevention of harmful rays, such as gamma rays, X-ray irradiation, etc. In prenatal examination, it is necessary to pay attention to whether the fetus is deformed or not, and the deformed child can interrupt the pregnancy.

(3) Prevention of secondary immunodeficiency: strengthen physical exercise, maintain physical and mental health, prevent excessive fatigue and malnutrition, actively treat infectious diseases that may lead to immunodeficiency, and correctly use therapeutic drugs, immunosuppressants or immunomodulators; The missing immune factor is added to ensure normal immune function.

3. Secondary preventive measures for immunodeficiency diseases When suspected to be an immunodeficiency disease, a diagnosis should be made as soon as possible, and the immunization laboratory should be inspected. If the baby is required to make a record of infection and physical development, prevent it for 6 months. After severe infection.

(1) Anti-infection: Anti-infective treatment and anti-infective clean environment isolation, reducing interpersonal contact.

(2) Infusion of non-specific immune factors: infants can infuse maternal blood and normal human plasma. For severe cellular immunodeficiency, whole blood should not be imported to prevent graft-versus-host disease (GVHD).

(3) Supplementation of specific immune factors: supplementation of immunoglobulin is effective for anti-infection of humoral immunodeficiency, and immunoglobulin infusion is generally 50 mg/kg body weight per week, or 2 weeks. Note once, the dose can be doubled.

(4) Bone marrow transplantation or fetal liver cell transplantation: This method has been successful in preventing infection in patients with severe combined immunodeficiency disease. The key to its success is the accuracy of histocompatibility. Otherwise, GVHD occurs and the prognosis is poor.

(5) Fetal Thymus Gland Transplantation: Transplantation of 4 to 6 months of fetal thymus in patients with Di George syndrome can cause the child's immune function to be normal or improved within 1 to 3 weeks. This transplant still exists. The danger of GVHD.

(6) Other therapies: Treatment of certain cellular immune function defects with thymosin (sulin) has been successfully reported. It can improve the lymphocyte in vitro, many items are improved, and the serum immunoglobulin concentration is also improved. Increased, transfer factor treatment of Wiskott-Aldrich syndrome or chronic mucosa, cutaneous candidiasis, half of the recipients have clinical progress, laboratory tests have improved significantly, interleukin-2 (IL-2), with strong immunity Enhancement, IL-2 levels are reduced in a variety of immunodeficiency diseases, and some people have tried to use exogenous IL-2 to treat SCID. Pahwa et al (1989) treated 31 patients with IL-2 and was diagnosed at 6 months. SCID's baby girl, the immune function of T cells in infants is significantly enhanced, and the clinical symptoms are significantly improved. For severe combined immunodeficiency disease, there have been two reports of successful gene therapy in the United States. If this complex therapy can make offspring Genetics are normal and will be the best preventive method.

Joint immunodeficiency complications Complications, erythroderma, eczema, asthma, urticaria, hemolytic anemia, lymphoma, acute lymphocytic leukemia, ataxia, diabetes, rubella, cytomegalovirus infection

1. Severe combined immunodeficiency disease can be complicated by short-legged dwarfs, with early hair loss, erythroderma and ichthyosis.

2. Immunodeficiency disease with thrombocytopenia and eczema can be complicated by eczema. In addition, it is often accompanied by allergic diseases such as asthma and urticaria. Autoimmune diseases such as juvenile rheumatoid arthritis, vasculitis and hemolytic Anemia, children over the age of 10 can also develop malignant diseases such as lymphoma and acute lymphocytic leukemia.

3. Ataxia telangiectasia, some patients can be complicated by insulin-resistant diabetes, often complicated by lymphatic network malignant tumors and other tumors.

4. Cellular immunodeficiency disease with abnormal immunoglobulin synthesis, may be complicated by Pneumocystis carinii, rubella virus, cytomegalovirus infection, may have lymphadenopathy, chronic pulmonary fungal infection and malignant tumor.

Symptoms of combined immunodeficiency disease Common symptoms Repeated infection of herpes Normal immunoglobulin reduces diarrhea Fungal infection Rheumatoid arthritis Thrombocytopenic triad telangiectasia

1. Severe combined immunodeficiency disease begins to be infected with viruses, fungi, protozoa and bacteria within 3 months after birth, recurrent pneumonia, chronic diarrhea, oral and cutaneous Candida infection and otitis media, etc. Physical examination usually does not see superficial lymph nodes and tonsils. Chest X-ray examination does not show the shadow of the baby's thymus. If the child receives whole blood containing immunologically active lymphocytes, graft-versus-host disease will occur.

The dysplasia of reticular tissue is the most severe of SCID, which is characterized by immunodeficiency of T and B system and severe neutropenia. Most of them die within one week after birth due to streptococcal sepsis. SCID may also be associated with bone dysplasia. , resulting in short-legged gnomes, and early damage to hair, erythroderma and ichthyosis.

SCID with adenosine dehydrogenase (ADA) deficiency is autosomal recessive, and its clinical manifestations are similar to those of common SCID, but bone damage is more common, often involving the costal cartilage junction, spine, pelvis and scapula.

2. The clinical manifestations of immunodeficiency with thrombocytopenia and eczema are male, with thrombocytopenia after birth, often with bleeding as the first symptom, and platelets are significantly reduced, as low as (10 ~ 30) × 109 / L, 6 Infections occur more frequently after the month, and are aggravated with age. The pathogens are Haemophilus influenzae, pneumococcus, Candida albicans, Pneumocystis carinii, herpes virus, etc. Eczema often occurs around 1 year old. In addition, often Accommodating allergic diseases, such as asthma and urticaria, often occur in autoimmune diseases, such as juvenile rheumatoid arthritis, vasculitis, and hemolytic anemia. Children over 10 years of age can also develop malignant diseases such as lymphoma and acute lymphocytes. Leukemia.

3. Ataxia telangiectasia clinically at least 9 to 12 months of ataxia, can also be late until 4 to 6 years of age, telangiectasia usually occurs at the age of 3 to 6 years, but also early At 2 years old or as late as 8 to 9 years old, the course of the disease is progressive. As the age increases, nervous system symptoms and immunodeficiency also increase. In childhood, sinus and respiratory tract infections may occur, and puberty rarely occurs. In both sexes, most patients have mental retardation, and some patients may develop insulin-resistant diabetes, often complicated by lymphatic network malignancies and other tumors.

4. Cellular immunodeficiency disease with abnormal immunoglobulin synthesis, also known as Nezelof syndrome, clinically occurring in early infants or early childhood, mainly with repeated infections, Pneumocystis carinii, rubella virus, giant Cellular viral infections can include lymphadenopathy, chronic pulmonary fungal infections, and malignant tumors.

Joint immunodeficiency disease examination

1. Severe combined immunodeficiency disease auxiliary examination of body fluids and cellular immune function are obviously abnormal, usually: IgG, IgA and IgM are very low, but a small number of patients may have 1 or 2 Ig normal, some cases of blood and lymphoid tissue B cells decreased, In some cases, it may be normal, the cellular immune test is abnormal, the number of peripheral blood T cells is significantly reduced, and the T cell function test is also abnormal.

2. Immunodeficiency disease with thrombocytopenia and eczema, abnormal body fluids and cellular immunity, decreased IgM, elevated IgA and IgE, normal or slight decrease in IgG, different immunological tests, no reaction in skin test In vitro T cells react with PHA and concanavalin, but react poorly to specific antigens such as tetanus toxoid and mixed-reaction xenogenic cells, and also have changes in T killer cells and monocytes, thrombocytopenia, and neutropenia. , eosinophilia, may have anemia.

3. Ataxia telangiectasia, T, B cell immune function has different degrees of abnormalities, may have lymphopenia, T cell count decreased or normal, low-reactivity or normal for PHA or ConA lymphocyte transformation test, late Sexual allergy skin test was negative, 40% of patients had serum IgA deficiency, IgG4, IgG2 and IgA2 deficiency or IgE reduction, B cell count and NK cell activity were normal, EEG, EMG abnormalities, serum alpha-fetoprotein increased, Abnormal liver function, autoantibodies can be detected in serum.

4. Cell immunodeficiency disease with abnormal immunoglobulin synthesis, lymphopenia or normal, decreased T cells, different degrees of T cell function defects, decreased or absent response of lymphocytes to PHA and specific antigens, Lymphocyte response is normal or decreased, delayed skin reaction is negative, humoral immunity is also different degrees of defects, serum Ig is normal, elevated or decreased, some cases have neutropenia, eosinophilia, small thymus, surrounding lymphoid tissue Dysplasia.

Severe combined immunodeficiency disease, chest X-ray examination does not see baby thymus shadow.

Diagnosis and identification of combined immunodeficiency disease

Diagnostic criteria

1. Severe combined immunodeficiency disease can be diagnosed based on clinical manifestations such as repeated infections and laboratory-assisted examinations.

2. Immunodeficiency disease with thrombocytopenia and eczema, according to clinical manifestations and laboratory tests, such as thrombocytopenia, eczema, triad infection, IgM reduction, IgE, IgA elevation, varying degrees of cellular immune dysfunction.

3. Ataxia telangiectasia (ataxia-telangiectasia) can be diagnosed according to clinical manifestations and immunological examination.

4. Cellular immunodeficiency disease with abnormal immunoglobulin synthesis, also known as Nezelof syndrome, is mainly based on the following characteristics:

(1) It is prone to various infections.

(2) Decreased or absent T cell function.

(3) Different levels of antibody defects.

Differential diagnosis

The disease must be associated with ataxia telangiectasia (usually 3 to 4 years old), Wiskott-Aldrich syndrome (with thrombocytopenia after birth), severe combined immunodeficiency disease (complete fluid and cellular immunity), Di George Syndrome and chronic mucocutaneous candidiasis (with normal antibody response), ataxia telangiectasia, need to be differentiated from selective IgA deficiency.

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