To compare the IRT1 + IRT2 assay with screen-positive results from the IRTS, we evaluated 164 samples that were determined to be IRTS screen-positive by the New York NBS laboratory, consisting of a total of 19 confirmed positive cases with 2 CF mutations, 8 confirmed positive cases with 1 CF mutation, and 137 cases confirmed as non-cystic fibrosis, with no CF mutations detected.
Table 3 shows the analysis of8 single-mutation CF carrier samples that were screen-positive as established by the [greater than or equal to] 170 [micro]g/L cutoff for the IRTS assay.
Of the 137 cases that were screen-positive by the IRTS assay but had no CF mutations detected, 26 would have been screen-negative using the IRT1 +IRT2 cutoff of >97 [micro]g/L, a reduction of 19% in the false-positive rate in this selected study population.
Analysis of 3 cases of confirmed disease with an IRTS value below the 170 [micro]g/L cutoff is shown in Table 4.
Importantly, of the 11 discrepant cases that were screen-positive in the IRTS but had no mutations detected by the screening program, all were screen-negative in the IRT1 + IRT2 assay, suggesting a greater specificity for the multiplex assay.
Although this cutoff is substantially lower than that developed for the IRTS method of 170 [micro]g/L, it is nearer to the cutoff of 112 [micro]g/L reported for a monoclonal antibody-based method for total IRT (8).
In these studies, use of the sum of IRT1 + IRT2 was unable to discriminate the carrier population, with 7 of8 carriers who were screen-positive by the IRTS assay noted also to be screen-positive by the IRT1-IRT2 criteria.