| disease | Severe Combined Immunodeficiency (SCID) |
| alias | Severe Combined Immunodeficiency Disease, SCID |
Severe combined immunodeficiency disease (SCID), Swiss-type agammaglobulinemia, thymic lymphoid dysplasia, and reticular dysgenesis are severe immunodeficiency disorders. Their hallmark is congenital and hereditary abnormalities in the B-cell and T-cell systems. This group of diseases follows an autosomal recessive or X-linked inheritance pattern. Fifty percent of SCID cases have a positive family history. SCID associated with reticular dysgenesis is caused by defects in primitive hematopoietic stem cells; Swiss-type agammaglobulinemia results from lymphoid stem cell defects; while some forms of SCID are due to impaired T-cell differentiation and B-cell maturation dysfunction.
bubble_chart Clinical Manifestations
Most infections with viruses, fungi, protozoa, and bacteria begin within the first three months after birth, leading to recurrent pneumonia, chronic diarrhea, oral and skin Candida infections, and otitis media, among others. Affected children experience growth and developmental delays. Physical examinations typically reveal no superficial lymph nodes or tonsils. Chest radiographs show no thymic shadow in infants. If neglected, administering the smallpox vaccine or oral polio vaccine to these children can result in fatal vaccinia disease or poliomyelitis. Additionally, transfusing whole blood containing immunologically active lymphocytes into these patients may cause graft-versus-host disease.
Reticular dysgenesis is the most severe form of SCID, characterized by dual-system immune deficiency and severe granulocytopenia. Most affected infants die from streptococcal septicemia within the first week of life. SCID can also be accompanied by bone dysplasia, leading to short-limbed dwarfism, along with premature hair loss, erythroderma, and ichthyosis-like lesions.
SCID with adenosine deaminase (ADA) deficiency is inherited in an autosomal recessive pattern. Its clinical manifestations are similar to typical SCID, but bone lesions are more common, often affecting the costochondral junctions, spine, pelvis, and scapulae. ADA is a catalytic enzyme in purine catabolism; ADA deficiency can impair immune regulation through several mechanisms, leading to this condition. Measuring ADA activity in red blood cells and fetal cells can confirm the diagnosis and provide a basis for prenatal testing.bubble_chart Auxiliary Examination
SCID is a systemic immunodeficiency disease characterized by significant abnormalities in both humoral and cellular immune functions. However, laboratory tests show various changes. Typically, IgG, IgA, and IgM levels are very low, but a few patients may have normal levels of one or two Ig types. Antibody responses are almost universally absent. In some cases, B cells in the blood and lymphoid tissues are reduced, while in others they may be nearly normal. All cellular immune tests are abnormal, with a marked decrease in peripheral blood T cell counts. Memory antigen tests and intradermal phytohemagglutinin tests show very poor responses. In vitro T cell function tests are also significantly abnormal, with absent mitogen proliferation responses.
bubble_chart Treatment Measures
To prevent the occurrence of graft-versus-host disease, the whole blood or blood products intended for transfusion should be irradiated to inactivate immunocompetent cells, or frozen red blood cells should be used.
Immune reconstitution through bone marrow transplantation is the most effective treatment for this disease. Using bone marrow tissue from HLA-matched siblings yields the highest success rate; if HLA-incompatible donor marrow is used, graft-versus-host disease almost always occurs, leading to failure. Pre-treatment of donor marrow with phytohemagglutinin, monoclonal antibodies and complement, or immune toxins to remove mature T cells that cause graft-versus-host disease can significantly improve the success rate of HLA-incompatible bone marrow transplantation. Additionally, fetal liver or fetal thymus transplantation can be performed, but the efficacy is limited.
