Antibody immunodeficiency disease

Introduction to antibody immunodeficiency disease Antibody immunodeficiency disorders include a group of diseases characterized by antibody production and antibody deficiencies. This group of diseases generally have a decrease or lack of serum immunoglobulin. basic knowledge Sickness ratio: 0.0012% Susceptible people: no specific population Mode of infection: non-infectious Complications: bronchiectasis pneumonia meningitis septic arthritis hepatitis myocarditis splenomegaly thrombocytopenic purpura selective IgA deficiency

The cause of antibody immunodeficiency

(1) Causes of the disease

Humoral immunodeficiency diseases include Bruton immunoglobulin deficiency, variable immunoglobulin deficiency, selective IgA deficiency, and selective IgM deficiency.

1. Bruton immunoglobulin deficiency

Also known as congenital immunoglobulin deficiency (congenital agammaglobulinemia), congenital immunoglobulin deficiency.

2. Common variable agammaglobulinemia

Also known as idiopathic late onset immunoglobulin deficiency, mutated immunoglobulin deficiency.

3. Selective IgA deficiency

This is the cause of a group of diarrhea diarrhea. Most people with selective IgA deficiency include children, and there are autoantibodies. Autoimmune diseases are common to these people.

4. Selective IgM deficiency

It is also the cause of a variety of infections.

(two) pathogenesis

Primary immunodeficiency is a cell immunodeficiency disease, mainly thymic dysplasia, insufficient T cell function or defective B cell function due to the small number of T cells. For example, Di George syndrome is caused by embryo III, IV. Pharyngeal dysplasia leads to thymic dysplasia, hypoparathyroidism and human vascular malformation. In clinical immunological tests, the number of TH cells is low, antibody formation ability is limited, Nezelof syndrome and nucleoside phosphorylase deficiency It is an autosomal recessive hereditary disease that causes thymic hypoplasia and defective cellular immune function.

The direct manifestation of humoral immunodeficiency disease is that the total amount of immunoglobulin is reduced, or the type of immunoglobulin is incomplete, or the subclass of IgG is incomplete, and the total amount can not be significantly reduced, but a certain type of immunoglobulin is prominently reduced, Bruton Immunoglobulin deficiency is a decrease in immunoglobulin caused by sexual recessive inheritance. Other types of immunoglobulin are reduced, and some family history can also be found. In patients with immunoglobulin deficiency, some have insufficient B cell function. Some are due to T cell function effects, or the ratio of TH and TS cells is inverted.

Antibody immunodeficiency 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 inspection:

1 blood cell count: patients with immunodeficiency disease, the total number of white blood cells may be reduced, the ratio of neutrophils to lymphocytes abnormally changed, normal human lymphocytes are 1.5 ~ 3.0 × 109 / L, children may be higher, separated by lymphocytes Liquid-separated mononuclear cells, using E rosette reaction and EAC rosette reaction to identify the ratio of T, B cells, or using the fluorescein-labeled antibody method for OKT test, detecting T3 positive cells, determining the proportion of T cells, and at the same time, The T cells of T4 and T8 surface antigen were detected by a fluorescein-labeled antibody method to determine the ratio of TH to TS, and the ratio of TH to TS in a normal person was 1.2 to 1.4:1.

3 immunoglobulin detection and immunoassay: taking the patient's serum 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 The immunoassay is to detect the function of the patient's antibody. The streptococcal hemolysin titer (anti-O "test) is measured by the serum of the child, because most of the infants can be infected with streptococcus type B after birth, and tetanus can also be used. The toxoid (or phage? Xl74) is administered to the child, and the antitoxin (or ?X174 antibody) production is examined 3 weeks later to determine the Ig effect, especially when there is no large abnormal change in serum immune protein content and species. The specific effects of antibodies should be further demonstrated.

3 cell immunoassay: In addition to the aforementioned ratio of lymphocyte number T and B, TH and TS ratio examination, the following functional tests are also required: T cell transformation test, leukocyte chemotaxis test, phagocytic phagocytosis and bactericidal 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. For example, tuberculin (OT) can be used after vaccination with BCG. Test, or trichostatin, candida skin test, can also be coated with forearm method with dinitrochlorobenzene (or dinitrofluorobenzene) to sensitize the subject, and then check it after 2 to 3 weeks Skin allergic reactions, intradermal tests of phytohemagglutinin, can also be examined for cellular immune function.

4 Serum complement detection: Firstly, the serum total complement activity was detected, and the hemolytic curve was determined by sensitizing sheep red blood cells with different amounts of fresh serum, and then the total serum complement activity of the subject was calculated according to the formula.

Further, it is also possible to detect the presence or absence of each of the complement components C1 to 9, mainly measuring C3 and C1q.

2. Primary prevention measures for immunodeficiency diseases

(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. Frequently, antibiotics and anti-infectives should be administered. Before the marriage, immunological examination should be performed. The immune laboratory should be used to carry out immune cells, serum immune factors and related cytokines, as well as in vitro and in vivo immune function tests. 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 the previous personal history, family history, malformations, etc. of the fetal parents, it is necessary to avoid the mother's rubella virus during pregnancy. Infection with cytomegalovirus, prevent the use of drugs with teratogenic tendency, prevent 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 disorder, a diagnosis should be made as soon as possible, and the immunization laboratory should be inspected. If the baby is to be diagnosed with infection and physical development, prevent serious infection after 6 months.

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

(2) Infusion of non-specific immune factors: infants can be infused with 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.

Antibody immunodeficiency complications Complications Bronchiectasis pneumonia Meningitis Septic arthritis Hepatitis Myocarditis Spleen anemia Thrombocytopenic purpura Selective IgA deficiency

1. X-linked non-gamma globulinemia, complicated by bronchitis, bronchiectasis, pneumonia, otitis media, meningitis and carbuncle, etc. Some patients may develop non-suppurative arthritis, ECHO virus spread widely, and may also be concurrent Chronic myositis, subclinical hepatitis, myocarditis.

2. Common variant immunodeficiency disease, which can be complicated by splenomegaly, hemolytic anemia, thrombocytopenic purpura, thyroiditis and rheumatoid arthritis.

3. Selective IgA deficiency, complicated by rheumatoid arthritis, systemic lupus erythematosus, thyroiditis and pernicious anemia.

4. Infants with temporary hypogammaglobulinemia can be complicated by repeated infections.

Symptoms of antibody immunodeficiency disease Common symptoms Recurrent infection Recurrent infection hemolytic anemia Leukopenia Thrombocytopenia Diarrhea Swollen Lactose intolerance Pernicious anemia Gastric acid reduction

1. X-linked agammaglobulinemia

Clinical manifestations: patients are male, normal growth and development, most cases appear normal within 6 to 9 months after birth, repeated infection after 1 to 2 years old, common pathogens are staphylococcus, pneumococcus, streptococcus, bloodthirsty Influenza bacilli and meningococcal bronchitis, bronchiectasis, pneumonia, otitis media, meningitis and carbuncle, etc. Some patients may develop non-suppurative arthritis, mainly involving large joints; and easily suffer from ECHO virus encephalomyelitis ECHO virus spread widely, can cause chronic myositis, subclinical hepatitis, myocarditis and flexion and contracture of elbow and knee joints, gastrointestinal manifestations are rare.

2. Common variable immunodeficiency (CVID)

Clinical manifestations: both men and women can be ill, usually begin to have symptoms after 6 years of age, 20 to 30 years of age is significantly worse, mainly in patients with repeated infections, often chronic diarrhea, lactose intolerance, malabsorption and protein loss enteropathy Giardia infection is a common cause of diarrhea. Some patients have reduced gastric acidity, and half of them lack internal factors. In addition, there are splenomegaly and anemia and leukopenia, thrombocytopenia, and the incidence of autoimmune diseases is high, such as hemolysis. Anemia, thrombocytopenic purpura, thyroiditis and rheumatoid arthritis.

3. Selective IgA deficiency

Clinical manifestations: Most patients are asymptomatic, occasionally found during the examination, and some have obvious symptoms, mostly within 10 years of age, due to IgA deficiency, respiratory, gastrointestinal, urinary tract and other parts of the local immune function, It is prone to infection and allergic reactions. In addition, the incidence of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, thyroiditis and pernicious anemia is increased.

4. Infant transient hypogammaglobulinemia

Examination of antibody immunodeficiency disease

1. Laboratory examination of X-linked agammaglobulinemia

Serum and tissue immunoglobulins are significantly reduced, IgG<2g/L, peripheral blood lymphocytes are normal, but almost all T lymphocytes, B cells are absent or reduced, can not cause obvious antibody response by antigen stimulation, cellular immunity The function is generally perfect, the lymph node, liver, tonsil and intestinal related lymphoid germinal center are dysplastic, and the plasma cells are absent or rare.

2. Laboratory testing of common variable immunodeficiency (CVID)

Mainly for the reduction of total immunoglobulin in serum, IgG decreased, IgA, IgM lack or decrease, CD4/CD8 ratio decreased, normal response to mitogen, but reduced response to phytohemagglutinin.

3. Laboratory examination of selective IgA deficiency

Serum and secretory IgA levels are significantly reduced, a small number of patients with IgE and IgG are also reduced, peripheral blood B cell counts are normal, there are a variety of autoantibodies in the blood, such as anti-LgA antibodies, anti-thyroglobulin antibodies, anti-gastric cell antibodies, anti-smooth muscle Antibodies, anti-collagen and food antigen antibodies, anti-bovine serum albumin antibodies, lung infections may have X-ray and pulmonary dysfunction.

4. Laboratory examination of infantile transient hypogammaglobulinemia

Serum IgA, IgM can be normal, IgG is reduced, IgD and IgE are also reduced, peripheral blood lymphocyte counts are normal, T helper cells may be reduced, lymph node and intestinal biopsy are normal.

Diagnosis and identification of antibody immunodeficiency disease

Diagnostic criteria

The clinical manifestations are: male and female can be ill, the general course lasts for 6 to 18 months, the baby develops normally, some infants have no obvious symptoms, and some can have repeated infections, which behave like X-linked agammaglobulinemia, but To a lesser extent.

1. X-linked agammaglobulinemia

Mainly based on the following performance diagnosis: serum IgG, IgA and IgM concentrations below 95% of the lowest value of the normal same age group should be suspected of the disease, such as the ability to prove serum and exocrine antibody deficiency, the diagnosis of the disease Significant, the Sikh reaction can be positive.

2. Common variable immunodeficiency (CVID)

The diagnosis is mainly based on the following manifestations: the age of onset is mostly from 15 to 35 years old, repeated infections, serum immunoglobulin is reduced, antibodies can not be produced after specific immunization, and B lymphocyte counts in circulation are normal.

3. Selective IgA deficiency

Mainly based on clinical manifestations and laboratory tests, serum IgA <50mg / L can establish a diagnosis.

4. Infant transient hypogammaglobulinemia

It is mainly based on clinical performance and laboratory tests, especially regular laboratory tests (measured every 2 months).

Differential diagnosis

1. X-linked no-gammaglobulinemia, must be identified with the following diseases:

(1) Temporary hypogammaglobulinemia in infancy: its Ig deficiency is transient and antibody formation.

(2) Severe malabsorption: serum Ig in such patients can be reduced, but intestinal biopsy has a normal number of plasma cells, and there is Ig in the cells.

2. Common variant immunodeficiency disease must be differentiated from X-linked agammaglobulinemia.

3. Infants with temporary hypogammaglobulinemia must be differentiated from X-linked agammaglobulinemia. If IgG is still at a very low level after 4 years of age, the disease should be suspected.

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