Selective immunoglobulin subclass G deficiency in children
Introduction
Introduction to pediatric selective immunoglobulin G subtype deficiency disease A more precise definition of a selective immunoglobulin G subtype deficiency disease should be: a patient with one or more IgG subclasses having a lower than normal age of 1.96 or less than 2 standard deviations, and a selective IgG subtype for children over 2 years of age. Class defects refer to those with IgG1 levels below 2.50 g/L, IgG2 below 0.50 g/L, and IgG3 below 0.30 g/L. If the assay used is not sensitive enough, normal infant IgG4 levels may not be detected. basic knowledge Sickness ratio: 0.000001% Susceptible people: children Mode of infection: non-infectious Complications: bronchiectasis, purulent meningitis, diarrhea
Cause
Pediatric selective immunoglobulin G subtype deficiency disease etiology
(1) Causes of the disease
IgG can be divided into four subclasses depending on its heavy chain, namely IgG1, IgG2, IgG3 and IgG4, of which IgG1 accounts for the highest proportion, IgG2 is about half of it, IgG3 is only 1/10, and IgG4 is extremely small. , IgG1, IgG3 is a T cell-dependent antibody, usually for protein antibodies, IgG2 is a non-T cell-dependent antibody, mainly for polysaccharide antigens, IgG4 is known to be closely related to type I allergic reaction, IgG subclass ratio is imbalanced or lacking, For IgG subclass deficiency, the patient's total serum IgG levels are reduced or normal, while one or more IgG subclasses are below normal levels.
The etiology of selective IgG subtype deficiency disease is not well understood and may be related to IgG heavy chain stability (CH) gene expression disorders. There are two cases:
1. Immunoglobulin CH gene deletion or mutation occurs in the corresponding IgG subclass defect, which may be accompanied by IgA and its subclass defects.
2. CH gene recombinant rearrangement disorder or heavy chain gene transcription and post-transcriptional regulation abnormality Mostly, this is related to the regulation of B cells by T cells. The decrease of interferon gamma (IFN-) produced by T cells can cause IgG2 defects. A decrease in IL-4 defects IgG1 and IgG4.
Children with simple nephrotic syndrome, nutritional disorders, long-term survival after bone marrow transplantation, acquired immunodeficiency syndrome (AIDS), some autoimmune diseases (such as SLE), refractory epilepsy and allergies (urticaria, wetness) , asthma, etc. may be associated with secondary IgG subtype defects.
(two) pathogenesis
The pathogenesis of this disease is complex, involving multiple abnormalities. In addition to genetics, there may be dysfunction of B cells themselves, and T cell dysfunction, including decreased number of CD4 cells, low proliferative function, and decreased activity of some lymphokines. Subtype deficiency is caused by partial deletion of the IgG heavy chain constant region gene of the long arm of chromosome 14, abnormality and abnormal regulation mechanism of subclass transformation. Recent studies have confirmed that IgG and its subclass conversion mechanism are still related to IL-4. Related to CD40 cells and other factors, CD40 cells play an important role in the final stage of IgG subclasses, and their loss of function can also lead to certain IgG subclass deficiency. In addition, when Th1/Th2 function in helper T cells, An imbalance in the number can also lead to IgG subclass defects.
When IgG2 is defective, infections caused by bacteria such as pneumococci, streptococci and Haemophilus influenzae type b are prone to occur; when IgG1, IgG3 anti-protein antibodies are defective, viral infection and toxoid-producing bacterial infection are apt to occur.
Prevention
Pediatric selective immunoglobulin G subtype deficiency disease 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 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.
Complication
Pediatric selective immunoglobulin G subclass deficiency disease complications Complications, bronchiectasis, purulent meningitis, diarrhea
Repeated respiratory infections can lead to bronchiectasis; recurrent purulent meningitis can lead to neurological sequelae; repeated diarrhea can lead to nutritional diseases.
Symptom
Pediatric selective immunoglobulin G subtype defect symptoms common symptoms repeated infection diarrhea meningitis immunodeficiency
Selective IgG subtype deficiency disease is one of the most common immunodeficiency diseases in childhood. The disease may have no clinical manifestations or recurrent respiratory infections. The incidence rate is 20% to 35% in children with recurrent respiratory infections. , including upper respiratory tract infection, sinusitis, otitis media, rhinitis, bronchitis, bronchiectasis, pneumonia, some patients with recurrent purulent meningitis, skin infections and diarrhea, in general, the infection is not serious, and will not endanger life.
The most common manifestation of IgG subclass defects is recurrent respiratory infections. Although the clinical manifestations of IgG subclass defects vary widely, many researchers have observed some characteristic manifestations.
1. Most patients with IgG1-deficient IgG1 deficiency are associated with other IgG subclass defects, and often have low serum IgG levels. In cases of IgG1 deficiency, some may be common variant immunodeficiency (CVID), especially with other Ig. Those with defects in the category often have a history of susceptibility to suppurative infection, and may develop into persistent, progressively exacerbated lung infections. The antibody response to diphtheria and tetanus toxins is often defective.
2. IgG2-deficient IgG2 deficiency is often accompanied by IgG4, IgA deficiency, and can also exist alone. Children often present with repeated respiratory infections. IgG2 deficiency is closely related to the defect of antibody response to polysaccharide antigen, and antibody response to diphtheria and tetanus toxin antigen Often normal, it is interesting to note that in a group of children with similar clinical manifestations, some patients have normal IgG subclass levels, but the response to polysaccharide antigen is abnormally low, that is, the IgG subclass is normal, but there is dysfunction, which It is suggested that low IgG2 levels may be a marker. These children often have defects in response to certain antigens, but not to other antigens. When IgG2 deficiency is reported, the antibody response to polysaccharide antigens is normal. This is IgG1, IgG3 compensatory. Increased, due to compensation, IgG2 subtype defect patients in addition to clinical manifestations of upper respiratory tract infections, may also be caused by Neisseria meningitidis caused by recurrent meningitis or recurrent pneumococcal infection, most patients with selective IgG2 deficiency have normal Serum immunoglobulin levels.
3. IgG3 defective anti-protein antigen antibodies, including anti-viral protein antibodies are mainly IgG1 and IgG3 subclasses, IgG3 antibodies may be the most important neutralizing virus effective antibodies, IgG3 defects mainly caused by repeated infections leading to chronic lung diseases In a Swedish study, 6580 (1864 children, 4716 adults) were collected from sera of patients with repeated infections, and 313 patients had low serum IgG levels. Of the 313 patients, 186 were IgG3 deficiency alone, 113 IgG3 is associated with IgG1 deficiency, 14 IgG3 with IgG2 deficiency, and 11 IgG3 with IgG4 deficiency.
4. The diagnosis of IgG4-deficient IgG4 deficiency is difficult to determine because most infant and child serum IgG4 cannot be detected by standard methods, and only by sensitive techniques (such as radioimmunoassay, enzyme-linked immunosorbent assay ELISA) can be unambiguously Patients with IgG4-deficiency (IgG4 concentrations <0.05 g/ml) were identified. These patients presented with severe recurrent respiratory infections, including bronchiectasis. One patient with selective IgG4-deficiency had repeated meibomian cysts and later developed pulmonary infections. Most IgG4-deficient patients have normal or elevated total IgG and other IgG subclasses, IgA, IgM, and IgE concentrations, and a small group of patients with IgG4 deficiency are associated with IgG2 and IgA deficiency. However, the significance of IgG4 deficiency is unclear because A significant proportion of normal children have low IgG4 concentrations, so it is difficult to make a single IgG4 subclass defect.
Examine
Examination of selective immunoglobulin G subtype deficiency disease in children
Laboratory tests for selective IgG sub-type deficient diseases, including determination of serum IgG, IgA, IgM as screening tests, mainly by measuring serum IgG subclass levels; conditionally, antigen-specific IgG subclass antibodies should be assayed, including anti-polysaccharides Antigen: such as anti-influenza B capsular polysaccharide, anti-streptococcal capsular polysaccharide, anti-23 pneumococcal polysaccharide antigen, anti-meningococcal polysaccharide antigen and other specific IgG subclass antibodies; anti-protein antigen: such as anti-diphtheria Specific IgG subclass antibodies such as toxins, tetanus toxoids, B. pertussis bacterial proteins, measles viruses and other viral coat protein antigens, the main problem in IgG subclass deficiency disease research is that it is difficult to establish sensitive, specific and reliable assays because There is a high degree of homology in the stable region of the IgG subclass, it is difficult to produce specific antiserum in the animal and produce a discriminating monoclonal antibody; in addition, an international standard measurement method is required, and the normal range of each laboratory is established, and the range is Should include all age groups, genders and Gm types, Chongqing Medical University Children's Hospital Immunization Laboratory with WHO67/97 standard serum and monoclonal Normal values of childhood serum IgG subclasses determined by antibody ELISA.
Serum IgG may be normal, slightly lower or elevated in IgG subclass defects, but is defective in serum IgG subclass or antigen-specific IgG subclass antibody, and 60% of anti-pneumococcal polysaccharides (PnPs) are present in children with IgG2 subtype defects Specific antibody deficiency, 73% lack of anti-meningococcal polysaccharide (MPs)-specific antibody deficiency; 24% to 29% of children with IgG1 subtype defects have anti-whitening vaccine (DTP), anti-measles vaccine (MV) Specific antibody deficiency.
Routine chest X-ray, B-ultrasound, combined with other clinical examinations to select other auxiliary examinations.
Diagnosis
Diagnosis and differential diagnosis of selective immunoglobulin G subtype deficiency in children
diagnosis
The diagnosis of selective IgG subtype deficiency disease is difficult because repeated respiratory infections are non-specific. Patients' serum IgG, IgA, and IgM are normal and can be elevated or decreased. Therefore, serum IgG subclass determination and antigen-specific antibodies Determination, the diagnosis of this disease is particularly important, the current diagnostic criteria for selective IgG subtype deficiency disease is:
1. The serum IgG subclass of patients with IgG subclass defects is below the mean value of 1.96 or 2 standard deviations of normal children of the same age.
2. The serum IgG subclass values of patients with normal IgG subclasses ranged from 1 to 1.96 standard deviations of the average children of the same age.
3. Defects in antigen-specific IgG subclass antibodies.
However, IgG4 is very low in normal infants and children, and its level may be less than 1 g/ml, so it is difficult to determine IgG4 deficiency in small infants.
Differential diagnosis
IgG1 deficiency often shows a decrease in the total amount of IgG, and it is necessary to distinguish it from common variant immunodeficiency, which often has IgA deficiency, IgG2 and IgG4 are often lacking in ataxia telangiectasia; severe combined immunodeficiency disease bone marrow transplantation Temporary immunoglobulin isotypes or subclass imbalances can occur.
