Changes in the diagnosis and treatment of inborn errors of immunity with the introduction of expanded newborn screening

Abstract

Among inborn errors of immunity (IEI), severe combined immunodeficiency (SCID), which requires prompt allogeneic hematopoietic cell transplantation (HCT) after diagnosis, and B-cell deficiency (BCD), which necessitates immunoglobulin replacement therapy (IgRT), are relatively common and involve hematologists. SCID and BCD are diagnosed within months to years of birth following severe or recurrent infections and occasionally have a fatal course. However, since SCID and BCD are based on abnormalities in T and B cells, respectively, their respective neogenesis markers, T-cell receptor gene rearrangement circles (TREC) and Igκ-chain gene rearrangement circles (KREC), are low. TREC and KREC can be quantified even from small amounts of DNA extracted from dried blood spots, thereby enabling their application in newborn screening (NBS). Patients with SCID and BCD are treated with HCT and IgRT, respectively. Donor source selection and conditioning regimen choice are the key clinical decisions for HCTs. HCT for IEI requires a different approach from that used for malignant diseases. In Japan, specialized facilities for IEI are limited. Treatment necessitates regional collaboration with IEI experts. Here, we discuss the key points for diagnosing and treating IEI identified using expanded NBS.