Background: Newborn screening (NBS) for inborn errors of immunity increasingly uses T-cell receptor excision circles (TREC) and, in some programs, Kappa-deleting recombination excision circles (KREC) to detect early T- and B-cell lymphopenia. While TREC-based screening is well established, the significance and management of isolated low KREC remain unclear. Objective: To evaluate the implications of two different regional post-screening algorithms for isolated low KREC and to characterize the clinical course, immunological profile, and follow-up of term newborns with transient B-cell lymphopenia. Methods: We performed a retrospective multicenter study of term newborns with isolated low KREC identified through NBS, confirmed B-cell lymphopenia, and subsequent normalization during follow-up. KREC levels, B-cell counts, and serum immunoglobulins were assessed longitudinally by RT-PCR and flow cytometry. Results: Eighteen newborns were enrolled. At the first evaluation (V1; mean age 13.5 days), all had marked peripheral B-cell lymphopenia (CD19+ ≤ 2%; mean 54 cells/μL), although repeat dried blood spot (DBS) testing already showed KREC values above the diagnostic cutoff in 78%. By the second visit (V2; mean age 50 days), B-cell percentages and absolute counts normalized in all infants, with emerging IgA and IgM production, and normal KREC on whole blood. No infectious or immunological complications were recorded over 39.5 person-years of follow-up (mean 2.3 ± 1.7 years). Conclusion: Isolated low KREC at birth may identify newborns with transient B-cell lymphopenia that resolves during early infancy. Repeat KREC testing on a second DBS before referral may represent a pragmatic triage step to reduce unnecessary immunological evaluations, while preserving early assessment for newborns with persistent abnormalities. Prospective studies are needed to refine post-screening strategies. (Figure presented.).
Transient B cell lymphopenia revealed by KRECs newborn screening: Post-screening referral strategies, clinical course, and follow-up
Enrico Drago.;Monica Traverso.;Concetta Aloi.;Alessandro Salina.;Serena Palmeri.;Michela Cassanello.;Mohamad Maghnie.;Stefano Volpi.;Silvia Ricci.
2026-01-01
Abstract
Background: Newborn screening (NBS) for inborn errors of immunity increasingly uses T-cell receptor excision circles (TREC) and, in some programs, Kappa-deleting recombination excision circles (KREC) to detect early T- and B-cell lymphopenia. While TREC-based screening is well established, the significance and management of isolated low KREC remain unclear. Objective: To evaluate the implications of two different regional post-screening algorithms for isolated low KREC and to characterize the clinical course, immunological profile, and follow-up of term newborns with transient B-cell lymphopenia. Methods: We performed a retrospective multicenter study of term newborns with isolated low KREC identified through NBS, confirmed B-cell lymphopenia, and subsequent normalization during follow-up. KREC levels, B-cell counts, and serum immunoglobulins were assessed longitudinally by RT-PCR and flow cytometry. Results: Eighteen newborns were enrolled. At the first evaluation (V1; mean age 13.5 days), all had marked peripheral B-cell lymphopenia (CD19+ ≤ 2%; mean 54 cells/μL), although repeat dried blood spot (DBS) testing already showed KREC values above the diagnostic cutoff in 78%. By the second visit (V2; mean age 50 days), B-cell percentages and absolute counts normalized in all infants, with emerging IgA and IgM production, and normal KREC on whole blood. No infectious or immunological complications were recorded over 39.5 person-years of follow-up (mean 2.3 ± 1.7 years). Conclusion: Isolated low KREC at birth may identify newborns with transient B-cell lymphopenia that resolves during early infancy. Repeat KREC testing on a second DBS before referral may represent a pragmatic triage step to reduce unnecessary immunological evaluations, while preserving early assessment for newborns with persistent abnormalities. Prospective studies are needed to refine post-screening strategies. (Figure presented.).
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
