SEVERE COMBINED IMMUNODEFICIENCY (SCID)

Severe combined immunodeficiency (SCID) is a rare genetic disease that is actually a group of inherited disorders characterized by a lack of immune response, usually occurring in infants less than six months old. SCID is the result of a combination of defects of both T-lymphocytes and B-lymphocytes. Lymphocytes are white blood cells that are made in bone marrow, and many move to the thymus gland where they become specialized immune T and B cells. In healthy individuals, T cells attack antigens while B cells make plasma cells that produce antibodies (immunoglobulins). However, this immune response in SCID patients is absent making them very susceptible to invading diseases, and thus children with untreated SCID rarely live to the age of two years.

SCID is characterized by three main features. The helper T-lymphocytes are functioning poorly or are absent, the thymus gland may be small and functioning poorly or is absent, and the stem cells in bone marrow, from which mature T- and B-lymphocytes arise, are absent or defective in their function. In all of these situations, little or no antibodies are produced. If, for example, T-lymphocytes are never fully developed, then the immune system can never function normally. Moreover, the results of these defects include the following: impairment of normal functioning T- and B-lymphocytes, negative effects on the maturation process for T-helper and T-suppressor cells, and elimination and damage of the original source of the lymphocytes.

The immune disorders characterized in SCID arise because of the inheritance of abnormal genes from one or both parents. The most common form of SCID is linked to the X chromosome inherited from the mother; this makes SCID more common among males. The second most common defect is caused by the inheritance of both parents' abnormally inactive genes governing the production of a particular enzyme that is needed for the development of immunity, called adenosine deaminase (ADA). Although many defective genes for other forms of SCID have been identified in the last few years, scientists do not fully understand all of the forms of the disease.

There are many specific clinical signs that are associated with SCID. After birth, an infant with SCID is initially protected by the temporarily active maternal immune cells; however, as the child ages, his or her immune system fails to take over as the maternal cells become inactive. Pulmonary problems such as pneumonia, non-productive coughs, inflammation around the bronchial tubes, and low alveolar oxygen levels can affect the diseased infant repetitively. Chronic diarrhea is not uncommon, and can lead to severe weight loss, malnutrition, and other gastrointestinal problem. Infants with the disease have an unusual number of bacterial, fungal, viral, or protozoal infections that are much more resistant to treatment than in healthy children. Mouth thrush and yeast infections, both fungal, appear in SCID patients and are very resistant to treatment. Additionally, chronic bacterial and fungal skin infections and several abnormalities of the blood cells can persist.

Severe combined immunodeficiency is a disease that can be successfully treated if it is identified early. The most effective treatment has been hematopoietic stem cell transplants that are best done with the bone marrow of a sister or brother; however, the parent's marrow is acceptable if the infant is less than three months old. Early treatment can also help to avoid pre-transplant chemotherapy often necessary to prevent rejection of the marrow in older children. This is especially advantageous because chemotherapy can leave the patient even more susceptible to invading bodies. When successful, treatment for SCID corrects the patient's immune system defect, and as of 2002 success rates have been shown to be nearly 80% for the bone marrow transplant.

Gene therapy is the subject of ongoing research, and shows promise as a treatment for SCID. Researchers remove T cells of SCID patients and expose those cells to the ADA gene for ten days, and then return the cells intravenously. Although it was successful in one case, this treatment of SCID is still very much in the experimental stage. Nevertheless, these and other treatments hold potential for the development of a cure for SCID.