Due to the congenital abnormal differentiation of lymphoid stem cells, infants are deficient after birthT cellandB cell, sohumoral immunityandcellular immunityAll have defects.Severe combined immunodeficiency (SCID) can be divided into X-linked inheritance type, autosomal recessive inheritance type and sporadic type, belonging to the severe type of combined immunodeficiency disease.
The disease is polygenic.All patients haveT cellandB cellThe system has obvious defects and is inherited in sex linked or autosomal recessive mode (such as Swiss type non gamma globulinemia).The majority of patients are boys, 50%~60% of whom are inherited in a sex linked recessive manner, and there are also autosomal recessive inheritance and sporadic cases.Some cases may be caused by the inability of pluripotent stem cells to properly develop into B cells and T cells.Lymphoid tissue in the whole body is almost absent and cannot be synthesized by itselfimmunoglobulin，cellular immunityThe function is almost completely lacking.
clinical manifestation
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The child became ill within 1 to 2 months after birth.Lack of resistance to bacterial, fungal, viral and protozoan infections, and various infections continue.Children often suffer from skin, lung and gastrointestinal infections. Almost all children have diarrhea. Salmonella or pathogenic Escherichia coli can be seen in stool culture.Persistent cutaneous and mucosal candidiasis can occur even before the application of broad-spectrum antibiotics.The incidence of warts is increased and may be generalized.Children have no resistance to viruses with weak pathogenicity,herpes、RubellaOr varicella virus infection is very serious, and the duration of measles and rash is longer.Vaccinate some patients with cowpox orBCG vaccine, progressive cowpox rash or systemic tuberculous rash may occur.In the course of disease, there are always sinuses and respiratory tract infections. Pseudomonas aeruginosa lung abscess and pulmonary cysticercosis pneumonia are common causes of death.Often accompanied by growth and development disorders in children.
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1. Immunological examination
The functions of B cells and T cells measured in vivo and in vitro were significantly inhibited. The number of lymphocytes in general did not change much. In severe cases, the number of lymphocytes decreased significantly.6 months after birthSerum immunoglobulinIt is often lower than 0.25g/L, and the number of peripheral blood lymphocytes is often lower than 1.5 × 10/L, and there is no immune function.Gamma globulinemia is more common, but in some cases the immunoglobulin value can be normal or increased.The reactivity to antigenic stimulation is poor, so the inflammatory reaction seen in infected tissues is very light.
2. Prenatal examination
For families with affected childrenmonoclonal antibodyPrenatal detection of this disease may be carried out by classifying fluorescent activated cells in fetal blood or analyzing the level of enzymes in cultured amniotic membrane cells.
3. Carrier detection
suffer fromSex linked inheritanceThe abnormal X chromosome in T cells and B cells can be detected by the selective inactivation of the abnormal X chromosome in the mother of the boy with type A of this disease.
(1) Strengthening care and nutritionTo improve the patient's resistance and immunity.
(2) Prevention of infectionAttention should be paid to isolation to minimize contact with pathogens.For severe combined immunodeficiency disease, the children must be placed in a sterile warehouse for long-term care until the immune function is rebuilt.
(3) Avoid vaccinationFor newborns suspected of immune deficiency, live vaccines such as vaccinia and BCG should be prohibited to prevent systemic vaccinia due to vaccinia vaccination, and BCG vaccination may cause systemic spread and death.Measles and polio vaccines should also be avoided.
2. Anti infection therapy
Due to the low cellular and humoral immunity, the body is unable to kill infected viruses, bacteria, fungi and other pathogens.Therefore, in case of infection, broad-spectrum antibiotics, effective antiviral agents and antifungal drugs should be selected for treatment.Since bacteriostatic antibiotics cannot prevent the spread of pathogenic bacteria, bactericidal antibiotics should also be used for treatment.
3. Immunotherapy
(1) Replacement of humoral immune deficiency① Human serum gamma globulinGamma globulin is mainly used for substitution or compensation therapy.Most patients with congenital agammaglobulinemia die before the age of 10 years. If appropriate replacement therapy is given, such as the use of human serum gamma globulin, the children can survive normally, or even live to adulthood.Long term repeated injection will cause the formation of local injection scar, and fever, rashUrticaria、asthmaShock like reactions such as decreased blood pressure should be treated as anaphylactic shock in a timely manner.② Normal human plasmaNormal human plasma transfusion can also replace γ - globulin preparations, but for patients with severe combined immunodeficiency disease, preparations containing immunocompetent cells, such as whole blood and plasma containing white blood cells, cannot be transfused to avoid the occurrence ofGraft versus host reaction（GVHR）。③ Human blood gamma globulinTo improve the level of serum immunoglobulin.
(2) Replacement of cellular immune deficiencyIt is mainly to supplement T lymphocytes and enhance the function of T cells.① Infusion of fresh whole bloodBefore blood transfusion, the risk of serious GVHR caused by tissue matching difference should be considered.Therefore, before blood transfusion, 25~50Gy (2500~5000Rad) radiation must be used to eliminate the proliferative capacity of T cells, prevent lymphocytes in the blood from entering the newborn's body and attacking the host tissue, so as to avoid the occurrence of severe GVHR.But repeated blood transfusion is still easy to cause allergic reaction.②transfer factor（TF）It is a lymphokine released by T lymphocytes, which can transfer the specific immune information of normal people to T cells, activate the resting lymphocytes of the recipient, and thus play a role in recovering and expanding the cellular immune response.It has a rapid effect. After receiving the corresponding transfer factor, the negative skin test person can have a positive reaction 18~24 hours later, and can maintain for several months.Clinically, it can be used for immunodeficiency disease with eczema and thrombocytopenia, which can play a role in immune reconstruction to a certain extent, and can control the infection of viruses, fungi or some intracellular bacteria.The injection site should be the subcutaneous tissue close to the lymph node.③ThymosinThe polypeptide hormone extracted from bovine or porcine thymus can not only induce the differentiation and development of T cells, but also enhance the response of mature T cells to antigens or other stimuli, improve immune function and regulate immune balance.It can be used for immunodeficiency disease and severe combined immunodeficiency disease with eczema and thrombocytopenia, but it can only improve clinical symptoms.④interferon（IFN）It is a lymphokine produced when cells are infected with viruses, which can inhibit the proliferation of viruses and promoteNatural killer cells(NK) activation, so it can enhance the antiviral ability of patients with low immune function.The commonly used preparation is interferon gamma prepared from human white blood cells.The recombinant interferon prepared by genetic engineering makes the drug source more abundant.⑤Adi interleukin(Interleukin-2)It is a lymphokine produced by T helper cells, which can promote the proliferation of lymphocytes and other immune active cells, and enhance the ability of natural killer cells (NK cells) and lymphokine to activate killer cells.The experiment of virus infection in newborn animals shows that the drug has the effect of protecting the host.⑥Adenosine deaminase（ADA）In patients with severe combined immunodeficiency disease, some of them are related to the lack of ADA, while normal red blood cells contain a large amount of ADA. Therefore, infusion of fresh red blood cells after replacement and irradiation to patients can temporarily correct the immunodeficiency caused by the lack of ADA.High dose of bovine ADA conjugated polyethylene glycol (PEG-ADA) intramuscular injection once a week also has good effect.⑦bone marrow transplantationAllogeneic bone marrow transplantation can reconstruct normal cellular and humoral immune function by implanting normal hematopoietic stem cells into patients, which is the first choice for patients with this disease.The ideal donor is the identical twin, because the twin can also have the same congenital defects, it is not suitable for congenital immunodeficiency.Donors with identical human leukocyte antigen (HLA) in siblings can also be used.When bone marrow transplantation is performed for congenital immunodeficiency disease, immunosuppression preparations with different degrees should be selected according to the degree of cellular immunodeficiency to prevent rejection of the transplanted bone marrow.When implanting more than 0.5 × 10/kg bone marrow nucleated cells into patients with severe combined immunodeficiency disease, immunosuppressive preparation may not be required at all. However, for patients with incomplete cellular immunodeficiency, such as those with eczema and thrombocytopenia, stronger immunosuppressive preparation is required, such as high-dose cyclophosphamide and busulfan (Malilan).Or systemic radiation to avoid rejection.To prevent GVHR after bone marrow transplantation, cyclosporine can selectively inhibit immunocompetent cells.During and after transplantation, some protozoa such as Pneumocystis carinii and viruses such as herpesvirus were infected due to low immune function.Sulfamethoxazole/trimethoprim (compound sulfamethoxazole) and high titer specific anti herpesvirus immunoglobulin can be used for prevention and treatment.⑧ Fetal liver transplantationBecause the fetal liver of 2-6 months old contains a large number of hematopoietic stem cells, including the stem cells of lymphocytes, fetal liver transplantation can replace part of its role before there is no suitable donor for bone marrow transplantation.It is clinically applied to severe combined immunodeficiency disease.⑨Thymus transplantationThe thymosin secreted by the thymosome plays an important role in the maturation of T cells. Therefore, the fetal thymus can be implanted into patients in various ways to promote the maturation of T cells and restore cellular immune function.Thymus transplantation is also suitable for patients with severe combined immunodeficiency disease, which can improve some immune functions.⑩ Immune lymphocyteIn recent years, it has been reported that the use of immune lymphocytes for treatment has achieved temporary effects.
prognosis
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The disease mostly died within 2 years of age.The causes of death were mostly pseudomonas aeruginosa lung abscessPneumocystis jiroveci pneumonia Etc.
