FOXN1 is an essential transcription factor for thymic epithelial cell differentiation and consequently, naïve T cell development. Homozygous (Hom) FOXN1 variants cause T-lymphopenia, alopecia universalis, and nail dystrophy 1. However, the phenotypic manifestations of heterozygous (Het) FOXN1 variants range from healthy to severe immunodeficiency. Herein we report the decision-making process regarding administration of live vaccines to an infant with a FOXN1-Het variant identified through newborn mass screening. A 21-day-old male neonate was suspected of having severe combined immunodeficiency (SCID) due to a low T-cell receptor excision circle (TREC) level (6.9 copies/μL [cut-off 500/μL and the CD8+ counts exceeded normal lower limits. The naïve CD4+ counts increased transiently, followed by normalization of TREC levels (Figure 1B,C). At 16 months of age the child was administered live vaccines except for Bacillus Calmette–Guérin (BCG). Following the vaccination, antibody responses were detected by enzyme-immunoassay without adverse events: anti-measles IgG, 11.3; anti-rubella IgG, 2.1; and anti-varicella zoster IgG, 2.4 (all with a normal cutoff of 500/μL after 1 year of age, and an increase in the IgG levels were helpful indicators for the administration of live vaccines. In conclusion, repetitive quantification of the TREC level not only served as a trigger for gene analysis but also helped decision-making regarding the administration of live vaccines to a patient with a FOXN1-Het variant. M.Y.-S. wrote the manuscript and Y.O. revised it and supervised the whole study process. Y.I. and T.O. treated the patient and collected the data. M.Y. organized newborn mass screening. All authors read and approved the final manuscript. I would like to thank Prof. Kohsuke Imai of the department of pediatrics, National defense medical college for his advice regarding vaccines. Informed consent for the publication of this report was obtained from the parents. The authors declare no conflicts of interest. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
Yasutomi et al. (Thu,) studied this question.