Common variable immunodeficiency in children

Introduction to common variability immunodeficiency in children Common variability immunodeficiency, common variant immunodeficiency (CVID), is a common hypogammaglobulinemia, formerly known as acquired (or adult, late-onset) low gamma globulin. Blood. For a group of different causes, mainly affect the PID of antibody synthesis. basic knowledge The proportion of illness: 0.005% Susceptible people: children Mode of infection: non-infectious Complications: hemolytic anemia thrombocytopenic purpura neutropenia

Pediatric common variability immunodeficiency etiology

(1) Causes of the disease

1. Possible molecular genetic mechanisms of CVID Although most children with CVID are sporadic cases, some cases have a family history, especially in patients with selective IgA deficiency. It is speculated that CVID and selective IgA deficiency are due to The mutation or deletion of one or several genes is only unclear.

(1) The sixth pair of chromosomes: MHCIII complement gene C4A gene deficiency, and often have a special HLA or TNF- gene polymorphism; MHCII DQ site polymorphism is related to the disease, may be its candidate genome.

(2) The 9th pair of chromosomes: The PAX5 gene encodes a B cell-specific activating protein (BSAP), which affects the class switching of immunoglobulins; the inactivation of this gene can cause defects in mouse immunoglobulins, and there is no data indicating that humans are also caused. disease.

(3) CVID can occur in the 18th chromosome deletion.

2. B cell defects.

3. T cell defects Many CVIDs are closely related to T cell function defects, including T cell helper B cells or direct inhibition of B cells, 25% to 30% of cases of CD8 + T cell increase or CD4 + T Decreased cells, CD4/CD8 T cell ratio decreased, more than 1/3 of patients with elevated serum IL-4, IL-6, neopterin and soluble CD8 molecules, IL-10 levels may decline, about 40% of patients with T cells express CD40 The ligand (CD40L, gp39) is significantly down-regulated and may be related to its pathogenesis.

(two) pathogenesis

1. The mechanism of pathogenesis causing hypo-Igemia is not fully understood. Most scholars believe that the disease is a group of clinical syndromes with different etiology. There are several possibilities:

(1) Th function deficiency: The number and function of peripheral blood B cells in most CVID patients are not abnormal, but the number and function of Th are low, and it is impossible to provide auxiliary information to B cells, so that the final differentiation of B cells is blocked, and Th secretion of these patients is IL-2, IL-4, IL-6, IL-10, IFN-, B cell growth factor (BCGF) and B cell differentiation factor (BCDF) were significantly insufficient, and CD40L expression was impaired in individual patients.

(2) B cell function deficiency: the number of B cells decreases, the proliferative response is low, and it cannot differentiate into plasma cells producing Ig. In a few cases, there may be plasma cells, but it also lacks the ability to synthesize and secrete Ig, and the number and function of T cells are normal. The intrinsic defects in the cells make it impossible to secrete immunoglobulins or secrete only IgM, and cannot switch to IgG. The exact mechanism of B cell dysfunction is unclear.

(3) Ts hyperfunction: a small number of patients with Ts hyperfunction, inhibit B cell differentiation process.

(4) Anti-B cell autoantibodies: Very few patients have anti-B cell antibodies in their serum, which may be the reason for inhibiting B cell differentiation.

The genetic basis of the disease is unclear, most of which are sporadic cases, but family members often have IgA and/or IgG subtype deficiency and autoimmune diseases. CVID patients often have HLA-DR3, HLA-B8 and complotype. SCOI antigens, while family members often have HLA-DR1, HLA-B65, complotype SC2, HLA-DR7, HLA-B67, complotype SC61 and HLA-DR7, HLA-B44 and complotype FC31 hemizygotes.

The glycoside of Ig in patients with CVID cannot bind to Ig molecules, and some patients have T lymphocytes inhibiting the synthesis of Ig. The level of serum Ig deficiency is not as high as that of X-linked hypogammaglobulinemia, and the number of B lymphocytes in the blood circulation. Normal or decreased, the surrounding lymphoid tissue may have follicular structure destruction, reticular cells and cortical follicles proliferate.

2. Pathological changes The pathological changes of CVID can be divided into two types:

(1) Lymphoid hyperplasia type: more common in patients with T cell defects.

(2) Lymphatic tissue dysplasia: more common in patients with B cell defects.

After receiving antigenic stimulation, both types lack plasma cell proliferation. It is believed that these two types may also be manifested in different stages of the same disease, and the intestinal villi of the affected digestive tract are atrophied and flattened.

Pediatric common variability immunodeficiency prevention

The etiology and pathogenesis are still not fully understood, and there are no systematic preventive measures.

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 can damage the fetus. The 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. As far as possible to prevent viral infections, but also to strengthen the nutrition of pregnant women, 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 in which genetic patterns have been identified. 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 parents that they are more likely to have a disease in their next child. For immediate family members of patients with antibodies or complement deficiency, antibodies and complement should be examined. Level to determine the family's disease pattern. For some diseases that can be genetically mapped, such as chronic granulomatosis, parents, siblings and their children should be tested for localization. If a patient is found, it should be in him. The family members of her) are examined and the child's children should be carefully observed at the beginning of their 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; Blood cell immunology test can diagnose CGD, X-linked no-gammaglobulinemia, severe combined immunodeficiency disease, thereby stopping pregnancy, preventing the birth of children, the incidence of this disease is relatively high, early accurate diagnosis, early specificity It is important to treat and provide genetic counseling (prenatal diagnosis or even intrauterine treatment).

Pediatric common variability immunodeficiency complications Complications hemolytic anemia thrombocytopenic purpura neutropenia

Repeated bacterial infections, such as repeated pneumonia can lead to bronchiectasis, combined with central nervous system infection, can form non-caseal granuloma, can be chronic malabsorption syndrome, easily complicated by a variety of autoimmune diseases, hemolytic anemia, platelets Reduced purpura, pernicious anemia, neutropenia, rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis, scleroderma, chronic active hepatitis, multiple radiculitis, Crohn's disease and non-special Heterotopic chronic ulcerative colitis, etc., can be complicated by malignant tumors.

Pediatric common variability immunodeficiency symptoms Common symptoms Recurrent infection immunodeficiency malabsorption syndrome splenomegaly vitamin B12 malabsorption meningitis herpes lactose intolerance granulomatous steatorrhea

Diversity, both men and women can be sick, the age of onset can be in early childhood, but more often in school age, or even adulthood.

1. Common repeated bacterial infections such as acute, chronic sinusitis, otitis media, pharyngitis, bronchitis and pneumonia can cause bronchiectasis. The pathogens are Haemophilus influenzae, Streptococcus, Staphylococcus, Pneumococcal, etc., other pathogens. For example, mycoplasma, Candida, Pneumocystis carinii, herpes simplex and herpes zoster virus can also infect CVID patients, about 10% of patients with central nervous system infections, such as chronic suppurative meningitis and viral encephalitis, etc. The severity is less than XLA, often chronic, and the course of disease lasts for a long time, which can cause organic damage of the diseased tissue. In some cases, non-caseal granuloma can be formed, and the affected parts are lung, liver, spleen and skin.

2. Gastrointestinal symptoms include chronic malabsorption syndrome, steatorrhea, folic acid and vitamin B12 deficiency, lactose intolerance, disaccharidase deficiency, protein-losing enteropathy, etc. Intestinal-like flagellate infection is caused by intestinal tract An important cause of symptoms, nodular lymphoid hyperplasia is found in some cases. Endoscopic examination reveals multiple lymphoid follicles and germinal centers in the lamina propria of the small intestine. Gastrointestinal angiography shows coarse intestinal mucosa, uneven or polypoid imaging, and intestinal mucosal biopsy. It shows that the lamina propria cells of the mucosa are significantly reduced or even absent.

3. A small number of patients may have lymph nodes and splenomegaly, which can be differentiated from XLA. The lymph nodes of the abdomen can sometimes be misdiagnosed as lymphoma.

4. Autoimmune diseases and tumor CVID are easy to be complicated by a variety of autoimmune diseases, and the incidence of malignant tumors is also high, the incidence rate is 8.5% to 10%, including leukemia, lymphatic reticulum tumor, stomach cancer and colon cancer. .

Pediatric common variability immune defect examination

1. Immunoglobulin and antibody reaction serum immunoglobulin content is generally reduced, but generally not as low as XLA level, most CVID patients serum IgG content does not exceed 300mg / dl, individual cases can reach 500mg / dl, serum IgM And IgA levels are also very low, lack of immune response to various antigenic stimuli, serum homologous hemagglutinin titer is low, phage x174 antibody reaction shows a small amount of neutralizing antibodies, antibody class is limited to IgM, rarely to IgG conversion, 2 .B cell count The number of peripheral blood B cells in most CVID patients is approximately normal. In a few cases, B cells are reduced, B cell surface markers are normal, and peripheral blood B cells are immature.

3. T cell count and function Peripheral blood T cell count is almost normal, 1/3 of cases T cell subsets abnormal, showing increased CD8 T cells, CD4 / CD8 T cell ratio decreased (less than 1.0), these cases More often accompanied by spleen, lymphadenopathy and bronchiectasis, peripheral blood T cells through mitogen (PHA) induced proliferative response and differentiation function are low, the ability to produce cytokines is insufficient.

According to the condition, the auxiliary examination was selected. The chest film showed inflammation of the lung infection. The bronchiectasis was seen in the repeated infections. The lymph nodes and splenomegaly were observed in the B-ultrasound. The endoscopic examination revealed multiple lymphoid follicles in the lamina propria of the small intestine. Hair growth center; digestive tract angiography shows rough, uneven or polypoid images of the intestinal mucosa.

Diagnostic identification of common variability immunodeficiency in children

According to clinical features, laboratory tests and X-ray endoscopy can confirm the diagnosis.

Other PIDs should be excluded, such as XLA, high IgM syndrome, SCID and SID with low immunoglobulinemia. Infants and young children are not easily differentiated from XLA. CVID serum total Ig is generally not less than 300mg/dl, peripheral blood B. The cell count is close to normal, and the clinical symptoms are also milder than XLA, and sometimes it is difficult to distinguish it from lymphoma.

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