A Qualitative Approach for the T cell Receptor Excision Circle (TREC) Assay for the Detection of Primary Immune Deficiency Syndromes (PIDS) Demonstrates Better Sensitivity and Specificity versus Using a Quantitative Approach

Background: Newborn screening (NBS) for CF, based on an IRT-DNA-IRT protocol, was introduced in Switzerland in 2011. In the DNA panel used, only the seven most common CFTR-mutations of Switzerland were analyzed. If IRT was above the cut-off (>50ng/ml) and no mutation was detected, a second IRT measurement was requested in order to decide on further investigations. However, so far there are no norm data on IRT levels of newborns aged several weeks. We therefore aimed to calculate the percentiles for IRT in the first two months of life in relation to the age at sampling. In addition it was examined whether these data could be used to discriminate between true- and false-positive screening results. Methods: The second IRT specimens were usually collected by the family physician in the 3rd-5thweek of life and mailed to the NBS laboratory. IRT was measured with the Neonatal IRT Kit on the GSP Instrument, both from PerkinElmer (Turku, Finland). IRT analysis was done on the same day the specimen arrived in the laboratory (Monday to Saturday). Babies with an IRT >50 ng/ml were considered screening positive and then referred to one of the CF centers for a sweat test (ST). The screening negative results were used for the study and divided in four groups according to the age at sampling: 1121d, 22-28d, 29-35d and >36d. Results: So far 790 IRT results were collected and assigned to one of the four groups as follows: 383, 244, 105, and 42, respectively. Mean IRT values of the groups were 25.2, 22.4, 19.3 and 17.6 ng/ml, respectively. The 99.9 Percentile for each group was 49.8, 49.0, 37.2, and 29.6 ng/ml. Conclusions: Our results document the significant decrease of IRT levels in healthy babies during the first two months of life. When performing NBS for CF using repeated IRT measurements, the decline of IRT in relation to the age at time of sampling has to be taken into account when interpreting the IRT levels in order to avoid misinterpretation of the results. Furthermore the results show that a second IRT measurement, taken in case of sweat test failure, can help in substantiating the CF-suspicion.