OVERVIEW
Combined immunodeficiency diseases (CIDs) refer to a group of disorders with clinical manifestations of both antibody immunodeficiency and cellular immunodeficiency. They can be subdivided into severe combined immunodeficiency disorders (SCID) and partial combined immunodeficiency disorders (PCID), which vary widely in severity. It includes a group of congenital disorders such as autosomal recessive SCID, SCID with adenosine deaminase (ADA) deficiency, X-linked recessive SCID, and SCID with leukopenia, which is a severe immunodeficiency disease. It is characterized by congenital and inherited abnormalities of the B-cell and T-cell systems.
Questions you may be concerned about
What is Combined Immunodeficiency Disease
Combined immunodeficiency diseases are a group of diseases in which cellular immunodeficiency is predominantly accompanied by other cellular immunodeficiencies of varying degrees, such as humoral immunity, which are prone to recurrent infections and relatively complicated to treat.
1. Combined immunodeficiency diseases (CIDs) are a heterogeneous group of diseases characterized by defects in cellular immunity with varying degrees of defects in other cells (e.g., B-cells, NK-cells), and have been identified as being caused by at least 18 different mutations.
2. The most severe type of combined immunodeficiency disease is severe combined immunodeficiency disease (SCID), which usually presents with growth retardation, persistent diarrhea, respiratory symptoms, thrush, Pneumocystis carinii pneumonia, significant bacterial infections, and disseminated BCG infections in the first 2 to 7 months of life.
3. Severe Combined Immunodeficiency Disease is a pediatric emergency. Strict isolation, gammaglobulin replacement therapy and cotrimoxazole prophylaxis should be initiated from the time of definitive diagnosis. All live attenuated vaccines are prohibited. Blood products should be irradiated to remove proliferating cells.
The treatment of combined immunodeficiency diseases is complex. If any of the above conditions occurs, it is recommended to visit a hospital promptly for early and regular treatment.
Causes
The etiology of combined immunodeficiency diseases is either caused by congenital teratogenic factors, such as bone marrow pluripotent hematopoietic stem cell hypoplasia, or autosomal or associated chromosomal recessive inheritance, such as SCID, Wiskott-Aldrich syndrome, etc. These patients show both cellular immune function and cellular immune function. These patients show both defective cellular immune function and defective humoral immune function.
1. severe combined immunodeficiency diseases with autosomal recessive inheritance of SCID, SCID with ADA deficiency, X-linked recessive inheritance of SCID with leukopenia and other etiologies.
2. Immunodeficiency diseases with thrombocytopenia and eczema are X-linked recessive with unknown underlying defects.
3. Ataxia telangiectasia is autosomal recessive.
4. Cellular immunodeficiency disease with abnormal synthesis of immunoglobulin is characterized by a decrease in lymphocytes and lymphoid tissues, structural abnormality of the pleura, and varying levels of various types of immune proteins in the serum, with some being increased or decreased, and some being normal.
Clinical manifestations
1. Severe combined immunodeficiency disease
Clinically, most of the infections with viruses, fungi, protozoa and bacteria start within 3 months after birth, and recurrent pneumonia, chronic diarrhea, oral and skin Candida infections and otitis media occur. The child has impaired growth and development. Physical examination usually reveals superficial lymph nodes and tonsils. Infantile thymus shadows are not seen on chest X-ray. Graft-versus-host disease occurs when children are given whole blood containing immunoreactive lymphocytes. Reticular tissue hypoplasia is the most severe form of SCID. It is characterized by T and B system immunodeficiency with severe granulocyte deficiency. Most deaths occur within the first week of life as a result of streptococcal septicemia.SCID can also be associated with osteogenesis imperfecta, which results in short-limbed dwarfism with premature hair loss, erythroderma, and psoriasis.5,6 The most common form of SCID is adenosine dehydrogenase (ADH), which is the most severe form of the disease. SCID with adenosine dehydrogenase (ADA) deficiency is inherited as an autosomal recessive trait. The clinical manifestations are similar to those of common SCID, but bone damage is more frequent, often involving the costochondral junctions, vertebrae, pelvis, and scapulae.
2. Immunodeficiency disease with thrombocytopenia and eczema.
Male onset. Thrombocytopenia is present at birth and often begins with bleeding. Thrombocytopenia is significant and can be as low as (10-30) × 109/L. Infection is common after 6 months of age and worsens with age. Pathogens are Haemophilus influenzae, pneumococcus, Candida albicans, Pneumocystis carinii, and herpesvirus. Eczema often occurs around the age of 1 year, 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, often occur. malignant diseases, such as lymphoma and acute lymphoblastic leukemia, can also occur in children over 10 years old.
3. Ataxia telangiectasia
Ataxia telangiectasia occurs clinically at 9 to 12 months of age, or as late as 4 to 6 years of age. Ataxia telangiectasia usually appears at the age of 3-6 years, or as early as 2 years old or as late as 8-9 years old. The course of the disease is progressive, and neurologic symptoms and immunodeficiency worsen with age. Recurrent sinus and respiratory tract infections may occur in childhood. Secondary sexual characteristics rarely appear during puberty, and most patients have mental retardation. Insulin-resistant diabetes mellitus may occur in some patients. It is often complicated by malignant tumors of the lymphoreticular system and other tumors.
4. Cellular immunodeficiency disease with abnormal immunoglobulin synthesis
Also known as Nezelof syndrome. Clinical symptoms mostly appear in late infancy or early childhood, and there are mainly recurrent infections, which may occur in Pneumocystis carinii, rubella virus, cytomegalovirus infection. There may be lymphoid enlargement, chronic fungal infections of the lungs and malignant tumors.
Examination
1. Laboratory examination
(1) Severe Combined Immunodeficiency Disease (SCID) The humoral and cellular immune functions are clearly abnormal. Usually: IgG, IgA and IgM are very low, but a few patients may have 1 or 2 normal Ig. In some cases, blood and lymphoid B-cells are decreased, while in others they may be essentially normal. Cellular immunity tests are abnormal, and peripheral blood T-cell counts are markedly reduced; T-cell function tests are also markedly abnormal.
(2) Immunodeficiency disease with thrombocytopenia and eczema There are abnormalities in both humoral and cellular immunity; IgM is decreased, IgA and IgE are increased, and IgG is normal or mildly decreased. Cellular immunity tests may be variably abnormal. Skin tests are unreactive, in vitro T cell responses to PHA and cutin are present but very poor to specific antigens such as tetanus toxoid and mixed-reacting xenoblasts.There are also changes in T killer cell and monocyte function. Thrombocytopenia, neutropenia, eosinophilia. Anemia may be present.
(3) Ataxia telangiectasia There are varying degrees of abnormalities in T and B cell immune function. There may be lymphopenia. reduced or normal T-cell counts. Lymphocyte transformation test for PHA or ConA is hyporesponsive or normal. Skin test for delayed-onset allergic reactions is negative. 40% of patients have serum deficiency of IgA, but there are also IgG4, IgG2, and IgA2 deficiencies or reduced IgE. B-cell counts and NK-cell activity are normal. B-cell count and NK-cell activity are normal. Serum alpha-fetoprotein is elevated, liver function is abnormal, and autoantibodies can be detected in the serum.
(4) Cellular immunodeficiency disease with abnormal immunoglobulin synthesis Decreased or normal lymphocytes, decreased T-cells, varying degrees of defects in T-cell function, decreased or absent lymphocyte responses to PHA and specific antigens, normal or decreased responses to allogeneic lymphocytes, and negative delayed cutaneous reactions. Humoral immunity was also defective to varying degrees, with normal, elevated or decreased serum Ig. Some cases had neutropenia and eosinophilia. The thymus is small and the peripheral lymphoid tissue is hypoplastic.
2. Other auxiliary tests
In severe combined immunodeficiency disease, the infant’s thymus is not visualized on chest X-ray.
Diagnosis
1. Severe Combined Immunodeficiency Disease (SID) can be diagnosed on the basis of clinical manifestations such as recurrent infections and laboratory tests.
2. Immunodeficiency diseases associated with thrombocytopenia and eczema can be diagnosed on the basis of clinical manifestations and laboratory tests, such as thrombocytopenia, eczema, susceptibility to infection triad, decreased IgM, increased IgE and IgA, and different degrees of cellular immune function abnormalities.
3. Ataxia telangiectasia can be diagnosed according to clinical manifestations and immunologic examination.
4. Cellular immunodeficiency disease with abnormal immunoglobulin synthesis, also known as Nezelof syndrome. The diagnosis is mainly based on the following characteristics:
(1) susceptibility to various infections
(2) Reduced or absent T-cell function.
(3) varying degrees of antibody deficiency.
Differential Diagnosis
The disease must be differentiated from Wiskott-Aldrich syndrome (thrombocytopenia from birth), severe combined immunodeficiency disease (complete absence of humoral and cellular immunity), DiGeorge syndrome and chronic mucocutaneous candidiasis (normal antibody response).
Treatment
1. Severe combined immunodeficiency disease
To prevent the development of graft-versus-host disease, the whole blood or blood products to be transfused should be irradiated to inactivate immunoreactive cells, or frozen red blood cells should be used. Immune reconstitution with bone marrow transplantation is effective in the treatment of this disease. Fetal liver or fetal thymus can also be transplanted with limited efficacy. In ADA-deficient SCID, enzyme-supplementation therapy with the input of irradiated frozen compressed red blood cells may result in improvement. In addition, weekly intramuscular injections of high-dose polyethylene glycol for ADA (PEG-ADA) have shown good results. Other treatments are infection control and symptomatic supportive therapy.
2. Immunodeficiency disease with thrombocytopenia and eczema
Matched bone marrow transplantation is the most effective and can completely correct platelet and immunologic abnormalities. Blood or platelet transfusion can be given, and splenectomy is feasible for thrombocytopenia. Infection control and symptomatic supportive therapy.
3. Ataxia telangiectasia
Except for anti-infection and physical therapy, there is no specific treatment.
4. Cellular immunodeficiency disease with abnormal immunoglobulin synthesis
Also known as Nezelof’s syndrome, there is no specific treatment, mainly for infection control and symptomatic management.