Tryptic peptide screening for primary immunodeficiency disease by LC/MS-MS.

Purpose: Early diagnosis of primary immunodeficiency disorders (PIDDs) is critical for maximizing patient survival and clinical outcomes. Consequently, there is significant interest in developing broad-based, high-throughput, screening approaches capable of utilizing small blood volumes to identify patients with PIDD.

Experimental Design: We developed a novel proteomic screening approach using tandem mass spectrometry to simultaneously identify specific signature peptides derived from the transmembrane protein cluster of differentiation 3 (CD3)ɛ and the intracellular proteins Wiskott-Aldrich syndrome protein (WASP) and Bruton's tyrosine kinase (BTK) as markers of three life-threatening PIDDs; severe combined immunodeficiency, Wiskott-Aldrich syndrome, and X-linked Agammaglobulinemia.