Neonatal screening for severe primary immunodeficiency diseases using high-throughput triplex real-time PCR.

Abstract

Severe combined immunodeficiency (SCID) and X-linked agammaglobulinemia (XLA) are inborn errors of immune function that require prompt diagnosis and treatment to prevent life-threatening infections. The lack of functional T or B lymphocytes in these diseases serves as a diagnostic criterion and can be applied to neonatal screening. A robust triplex PCR method for quantitation of T-cell receptor excision circles (TRECs) and κ-deleting recombination excision circles (KRECs), using a single Guthrie card punch, was developed and validated in a cohort of 2560 anonymized newborn screening cards and in 49 original stored Guthrie cards from patients diagnosed with SCID, XLA, ataxia-telangiectasia, Nijmegen-breakage-syndrome, common variable immunodeficiency, immunoglobulin A deficiency, or X-linked hyper-IgM syndrome. Simultaneous measurement of TREC and KREC copy numbers in Guthrie card samples readily identified patients with SCID, XLA, ataxia-telangiectasia and Nijmegen-breakage-syndrome and thus facilitates effective newborn screening for severe immunodeficiency syndromes characterized by the absence of T or B cells.

• Authors: Stephan Borte, Ulrika von Döbeln, Anders Fasth, Ning Wang, Magdalena Janzi, Jacek Winiarski, Ulrich Sack, Qiang Pan-Hammarström, Michael Borte, Lennart Hammarström
• Journal: Blood (Blood) Vol. 119 Issue 11 Pg. 2552-5 (Mar 15 2012) ISSN: 1528-0020 [Electronic] United States
• PMID: 22130802 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Antigen, T-Cell

Topics

• Humans
• Infant, Newborn
• Multiplex Polymerase Chain Reaction
• Neonatal Screening
• Predictive Value of Tests
• Real-Time Polymerase Chain Reaction
• Receptors, Antigen, T-Cell (genetics)
• Severe Combined Immunodeficiency (diagnosis, genetics, immunology)