Dried Blood Used to Screen Newborns for Severe Immunodeficiency

The assay employs a quantitative polymerase chain reaction (PCR) for T-cell receptor excision circles (TREC), which are copies of DNA produced only by T-cells. If the calculated TREC count is less than 30 copies/μL, it is associated with 100% sensitivity and 97% specificity for identifying SCID.

Severe combined immunodeficiency (SCID) represents a group of rare, sometimes fatal, congenital disorders characterized by little or no immune response. The defining feature of SCID, commonly known as "bubble boy" disease, is a defect in the specialized white blood cells (B- and T-lymphocytes). A review of the various methods used to diagnose SCID was published in the May 2010 issue of Pediatrics.

The review noted that a second blood spot study evaluated a two-tiered approach in which interleukin IL-7 was measured first using an enzyme-linked immunosorbent assay (ELISA), and then TRECs from those with elevated IL-7 levels, which occurs in the absence of T-cells. This study included samples from 13 children with SCID and 183 anonymized dried blood spots. For the first tier (IL-7 measurement) they calculated 96.1% specificity and 85% sensitivity (confidence interval: 55%–98%); for the second tier (TREC count) they calculated a specificity of 92.3% and a sensitivity that "approaches 100%.” If the more stringent standard of undetectable TRECs is used as a positive test result, they calculated a false-positive rate of 1.5% among children discharged from routine nurseries and 5% among children from special-care nurseries.

The study reported that on whole blood samples from infants with a median age of four months, lymphocyte counts that were less than 2.8 x 109/L had a sensitivity of 86% and a specificity of 94% for detecting SCID. From another study, they determined that among infants with a median age of 84 days, lymphocyte counts that were less than 5,000/μL had a sensitivity of only 56%, but a specificity of 100%, for detecting SCID.

Ellen A. Lipstein, M.D., M.P.H. of the MassGeneral Hospital for Children, (Boston, MA, USA), said, "The development of methods to screen for SCID by using dried blood spots, in contrast to using lymphocyte counts, which require whole blood, improves the feasibility of instituting SCID screening within current programs."

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MassGeneral Hospital for Children