Test for Severe Immune Deficiency

A new genetic test can rapidly identify babies born with inherited forms of severe combined immunodeficiency (SCID), an illness in which infants fail to develop a normal immune system.

SCID babies can become infected by a wide range of viruses, bacteria, and fungi that are normally controlled by a healthy immune system. When undetected and untreated, SCID typically results in death before a baby's first birthday. Earlier efforts to identify SCID by counting white blood cells in newborns proved to be unreliable and expensive. The new test can use the same dried blood sample already collected from newborns, allowing an indication of a possible immune problem immediately after birth when the babies are still protected by antibodies circulating in their blood.

This new screening tool is based on a detailed understanding of T cell maturation. T cells are one of the essential types of white blood cells that make up the immune system. Without a sufficient number of normal T cells, the immune system does not work, as happens when the AIDS virus wipes out the same population of immune cells. During normal development, an individual T cell rearranges the gene that produces the antigen receptor on the surface of the cell. This antigen receptor allows the T cell to identify an infectious agent and launch a defensive attack to kill the invader.

While re-arranging the receptor gene, the maturing T cell produces a bit of leftover genetic material that forms a ring structure within the cell. Using a quantitative laboratory technique to measure the number of these rings within a blood sample, researchers were able to differentiate normal infants from those with SCID. They detected an average of 1,000 of these genetic rings in dried blood samples from healthy babies, but found 30 or fewer in children with SCID.

The new test must be validated before widespread use. "Our false-positive rate was about 1.5%, which is too high to be practical for screening,” said Jennifer M. Puck, M.D., chief of the genetics and molecular biology branch of the U.S. National Human Genome Research Institute (NHGRI; Bethesda, MD), which developed the test.

If SCID is diagnosed in time, there are effective treatments. One form of SCID can be treated with an injectable medication. All forms can be cured through the transplantation of bone marrow if a matching donor can be identified. Also, SCID may be treated through human gene therapy, in which a normal copy of the defective gene may be inserted into the patient's own blood-forming cells. The first gene therapy experiments were carried out at the U.S. National Institutes of Health in 1990 in two young girls with SCID. The patients are still alive and well. The sooner a child is diagnosed, the sooner treatment can begin and the more likely it is to be effective.

"Too many babies are diagnosed too late,” added Dr. Puck. "Recent research shows that bone marrow transplants in the first three months of life work better than transplants at a later age. So it is critical to identify affected children immediately after birth. Since the babies lack overt clinical symptoms for some time, a molecular test is a good approach.” The development of the test by Dr. Puck and her colleagues was described in the February 2005 issue of The Journal of Allergy and Clinical Immunology.




Related Links:
U.S. National Human Genome Research Institute