NBS FOR SCID USING TREC The utility of TREC to identify SCID was first suggested by several pioneering studies which confirmed TREC level accuracy for identifying infants with SCID regardless of genetic cause (Figure 2).

Chan and Puck24 showed that, unlike filters obtained from normal newborns, which had a mean of 1,020 TRECs in two 3-mm punches, samples obtained from 23 infants with SCID had <30 TRECs. Those authors concluded that TRECs are a stable analyte that can identify T cell lymphopenia in NBS cards. A larger pilot study on 5,766 newborns and positive controls consisting of SCID patients and whole blood specimens selectively Inhibitors,research,lifescience,medical depleted of naive T cells revealed similar results.25 An important report by Morinishi et al. showed

that the TREC assay can also be used in diagnosing atypical SCID patients presenting with maternal T cell engraftment or leaky T cells, including the Omenn phenotype.26 No false-positive or -negative results were reported in Inhibitors,research,lifescience,medical that study. Three years ago, after seven successful pilot studies conducted in the USA, TREC testing was incorporated as part of the newborn screening panels in several states, including Wisconsin, Massachusetts, Inhibitors,research,lifescience,medical and California. It became the first genetic disorder of the immune system to be amenable to NBS. So far, almost one million newborns have been screened, and 14 cases of SCID, 6 cases of SCID Inhibitors,research,lifescience,medical variants, and 40 cases of non-SCID inhibitor Paclitaxel immunodeficiency were identified. These results suggest that SCID is more common than initially thought. More importantly, all SCID patients could receive appropriate therapy, and all survived. False-positive results, namely amplification failure of TREC in non-immunodeficient newborns, requiring a second

heel stick was reported in <0.08% of examined samples. This failure rate is similar to other newborn screening procedures. False-positive results were found mainly in preterm neonates weighing less than 1,500 g or due to inappropriate performance of the test. An algorithm of how to follow Inhibitors,research,lifescience,medical TREC levels in preterm infants was suggested to overcome Entinostat this limitation. Importantly, in each sample, where TREC is analyzed, a DNA detector is also measured (e.g. actin or RNaseP) to verify the accuracy of the results. Taken together, these results emphasize that screening for SCID is feasible and that SCID is not as rare as commonly believed. TREC assay can identify other T cell lymphopenia, and careful immune evaluation is needed for positive screen results. Finally, implementation of SCID screening will enable the identification of the true incidence of SCID, the causes of many other cases of T cell lymphopenia, and the incidences of SCID and other types of T cell lymphopenia among different ethnicities. Figure 2. Neonatal Screening for SCID Using TREC Content.