Pilot regional project of neonatal screening for primary immunodeficiencies in Sverdlovsk Oblast of Russia. From screening to prophylactic medical checkup

Sverdlovsk Oblast has become one of the first Russia regions to participate in a pilot project of neonatal screening for the detection of severe forms of primary immunodeficiency (PID) in newborns yet back in 2021, prior to the nationwide rollout of the Expanded Screening Program. The purpose of this research was to evaluate preliminary the effectiveness of identifying children with severe combined immunodeficiencies as well as other life-threatening forms of lymphopenia at the stage of possible impact on the course and outcome of the disease. Materials and methods used: quantitative determination of TREC/KREC in dry blood spots was carried out in 5044 children born in the region in July-Sept. 2021. The testing was performed using the domestic “IMMUNO-BIT” kit by “ABV-TEST,” LTD (Skolkovo Innovation Center, Mozhaysky District, Moscow, Russia). Cutoffs suggested in the instructions were used: 500 copies per 105 leukocytes for TREC and 300 copies per 105 leukocytes for KREC. Results: the risk group included 157 newborns (68 girls and 89 boys) with low TREC and/or KREC values (3.1%), no children were found with a complete absence of markers. After testing the re-requested samples, 104 of them were determined to be false positive, and 53 families were invited for an immunologist’s appointment. 28 children received in-depth examination with the advisory. At the time of appointment, the condition of most of them was assessed as clinically stable, however, according to the results of laboratory and instrumental diagnostic examinations, the presence of immunological abnormalities and developmental features was demonstrated: changes in the thymus (50%), neutropenia (32%), lymphopenia and thrombocytopenia (28%), hypogammaglobulinemia (84%), congenital malformations (30%). Conclusion: for the correct understanding of the phenomenon of reduced TREC/KREC values (but not zero values) in some newborns and predicting outcomes, it is necessary to monitor the health status of these patients, which can be carried out through the formation of a dynamic observation group, which is impossible without active identification of such children through wide screening program.