Abstract
The clinical outcomes of primary immunodeficiencies (PIDs) are greatly improved by accurate diagnosis early in life. However, it is not common to consider PIDs before the manifestation of severe clinical symptoms. Including PIDs in the nation-wide newborn screening programs will potentially improve survival and provide better disease management and preventive care in PID patients. This calls for the detection of disease biomarkers in blood and the use of dried blood spot samples, which is a part of routine newborn screening programs worldwide. Here, we developed a newborn screening method based on multiplex protein profiling for parallel diagnosis of 22 innate immunodeficiencies affecting the complement system and respiratory burst function in phagocytosis. The proposed method uses a small fraction of eluted blood from dried blood spots and is applicable for population-scale performance. The diagnosis method is validated through a retrospective screening of immunodeficient patient samples. This diagnostic approach can pave the way for an earlier, more comprehensive and accurate diagnosis of complement and phagocytic disorders, which ultimately lead to a healthy and active life for the PID patients.
Highlights
Primary immunodeficiencies (PIDs) are a group of inherited disorders caused by defects in different components of the immune system
Screening was performed on a sample cohort, including 37 healthy controls and 41 cases diagnosed with PID (Table 1)
The cohort included 26 newborn samples, including five PID cases of original Guthrie cards from the Newborn Screening Laboratory at Karolinska Hospital (Sweden) and 21 healthy dried blood spot (DBS) samples provided by the National Cord Blood Biobank at Karolinska University Hospital Huddinge (Sweden)
Summary
Primary immunodeficiencies (PIDs) are a group of inherited disorders caused by defects in different components of the immune system. Newborn screening programs based on the use of dried blood spot (DBS) samples have revolutionized public healthcare by detecting disorders such as phenylketonuria (PKU) during the first few days of life [2]. Further developments of this strategy introduced mass spectrometry (MS)-based screening with improved sensitivity, specificity and capacity [2]. PCR-based screening is being applied for diagnosing a subset of life-threatening PIDs, including severe combined immunodeficiency (SCID) and X-linked agammaglobulinemia (XLA), through the measurement of episomal excision products of lymphocyte receptors in DBS samples [3]. Selected countries have successfully implemented SCID-screening and several additional countries worldwide are considering to include it in their national screening programs [2]
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