In Saitama Prefecture, newborn screening (NBS) for severe combined immunodeficiency (SCID) was initiated as a pilot program since September 2024. Immunoglobulin kappa chain-deleting recombination excision circles (KREC) reflect newly generated B cells and enabled NBS for B cell deficiencies. However, clinical characteristics and managements of low KREC cases in Japan has not been sufficiently clarified. We investigated the clinical features of low KREC cases referred to our institution.
We retrospectively reviewed infants with low KREC levels who were referred to our hospital between April 2024 and October 2025 due to positive NBS results. Diagnoses, immunological findings, and clinical courses were analyzed.
Six cases were identified, including two cases of X-linked agammaglobulinemia (XLA), two cases of secondary immunodeficiency associated with maternal medications, one case suspected of primary immunodeficiency, and one case in which B cell levels had returned to the normal range. Both XLA patients had a positive family history, and flow cytometric analysis revealed B cell deficiency. In the two cases of secondary immunodeficiency, their mothers had received immunosuppressive medications during pregnancy. One mother was treated with azathioprine for ulcerative colitis, and the other received azathioprine and tacrolimus following kidney transplantation. In the former case, the number of B cells improved to 11.0% at 2 months. In the latter case, the number of B cells improved to 14.5% at 24 days of age. Vaccinations proceeded in both cases. The infant suspected of primary immunodeficiency showed decreased lymphocyte subsets at 17 days of age, with B cells at 1.4% and natural killer (NK) cells at 2.2%. Only inactivated vaccines were administered, and further etiological evaluation is ongoing. One infant referred as a low KREC level was found to have a B cell proportion of 6.5% at 1 month of age, which was within the normal range.
The effects of maternal immunosuppressive medications appear to be transient, and periodic FACS evaluation may help determine the appropriate timing for live vaccination. However, some infants may exhibit persistent B cell lymphopenia. Therefore, early immunological evaluation and continued postnatal monitoring using FACS are essential for appropriate clinical management.
