Screening for C3 Deficiency in Newborns Using Microarrays

Janzi, Magdalena; Sjöberg, Ronald; Wan, Jieqing; Fischler, Björn; Döbeln, Ulrika von; Isaac, Lourdes; Nilsson, Peter; Hammarström, Lennart

doi:10.1371/journal.pone.0005321

Cited by 23 publications

(17 citation statements)

References 22 publications

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“…This may potentially include complement deficiencies (using DBS eluates as described by Janzi et al [41] for C3 deficiencies and Hamsten et al [42] for C2 deficiencies) and granulocyte defects, thus allowing coverage of a majority of the primary immunodeficiency diseases. Targeted exome sequencing or even whole genome sequencing of newborns may ultimately be considered, which could lead to identification of additional defects of immunity and a large number of other inherited, potentially fatal diseases.…”

Section: Discussionmentioning

confidence: 99%

Newborn Screening for Severe Primary Immunodeficiency Diseases in Sweden—a 2-Year Pilot TREC and KREC Screening Study

et al. 2016

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Newborn screening for severe primary immunodeficiencies (PID), characterized by T and/or B cell lymphopenia, was carried out in a pilot program in the Stockholm County, Sweden, over a 2-year period, encompassing 58,834 children. T cell receptor excision circles (TREC) and kappadeleting recombination excision circles (KREC) were measured simultaneously using a quantitative PCR-based method on DNA extracted from dried blood spots (DBS), with betaactin serving as a quality control for DNA quantity. Diagnostic cutoff levels enabling identification of newborns with milder and reversible T and/or B cell lymphopenia were also evaluated. Sixty-four children were recalled for follow-up due to low TREC and/or KREC levels, and three patients with immunodeficiency (Artemis-SCID, ATM, and an as yet unclassified T cell lymphopenia/hypogammaglobulinemia) were identified. Of the positive samples, 24 were associated with prematurity. Thirteen children born to mothers treated with immunosuppressive agents during pregnancy (azathioprine (n = 9), mercaptopurine (n = 1), azathioprine and tacrolimus (n = 3)) showed low KREC levels at birth, which spontaneously normalized. Twenty-nine newborns had no apparent cause identified for their abnormal results, but normalized with time. Children with trisomy 21 (n = 43) showed a lower median number of both TREC (104 vs. 174 copies/μL blood) and KREC (45 vs. 100 copies/3.2 mm blood spot), but only one, born prematurely, fell below the cutoff level. Two children diagnosed with DiGeorge syndrome were found to have low TREC levels, but these were still above the cutoff level.Michela Barbaro, Annika Ohlsson and Stephan Borte contributed equally to this work.Electronic supplementary material The online version of this article

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Section: Discussionmentioning

confidence: 99%

Newborn Screening for Severe Primary Immunodeficiency Diseases in Sweden—a 2-Year Pilot TREC and KREC Screening Study

et al. 2016

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“…DBS samples have been successfully used in various newborn screening tests of genetic diseases for many years. More recently, DBS have been demonstrated to be a convenient blood sample collection device for T cell receptor excision circle (TREC) analysis in SCID screening [ 20 , 38 , 39 ] and for determination of C3 deficiency [ 40 ]. Analysis of kappa-deleting recombination excision circles (KREC) using DBS samples has also been developed [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

A Novel Targeted Screening Tool for Hypogammaglobulinemia: Measurement of Serum Immunoglobulin (IgG, IgM, IgA) Levels from Dried Blood Spots (Ig-DBS Assay)

et al. 2015

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PurposeTo develop an assay to quantify serum immunoglobulin (IgG, IgM, IgA) levels using dried blood spots (DBS) obtained on collection cards to be used as a tool for targeted screening for hypogammaglobulinemia.MethodsDBS samples, along with simultaneous serum samples, were collected from 107 healthy individuals (11 months to 57 years of age). After eluting proteins from DBS, IgG, IgM, and IgA were quantified by an enzyme-linked immunosorbent assay (ELISA). The Ig-DBS assay was validated through calibration curve performance, intra- and inter-assay precision, accuracy, specificity, selectivity, and linearity. The ELISA measurements were compared with serum Ig levels obtained using a standard nephelometry assay on serum samples collected simultaneously with the DBS samples and the results of the two assays were correlated. The stability of IgG, IgM, and IgA in the DBS was tested at room temperature, 36° to 38 °C, 2 to 8 °C, and −25 to −40 °C, from 4 to 14 days.ResultsThe Ig-DBS assay demonstrated precision, accuracy, specificity, selectivity, and linearity. Using the identified correlation coefficients of 0.834 for IgG, 0.789 for IgM, and 0.918 for IgA, the standard nephelometry-based normal reference ranges for all 3 serum Ig isotypes could be used with the Ig-DBS assay in individuals ≥16 years of age. The DBS samples were stable for 14 days at room temperature in a closed polyethylene bag.ConclusionsThe Ig-DBS assay is both sensitive and accurate for quantification of serum immunoglobulins. Samples are sufficiently stable at ambient temperature to allow for convenient shipping and analysis at a centralized laboratory. This assay therefore presents a new option for screening patients ≥16 years of age for hypogammaglobulinemia in any setting.

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“…for immunodeficiency. [ 83 , 84 ] To improve sensitivity, to lower cross-reactivity and to overcome the complexity and high dynamic range of the samples, it would be beneficial to adjust sample composition. Longo et al .…”

Section: Potentials and Challenges Of Affinity-based Proteomicsmentioning

confidence: 99%

Immunocapture strategies in translational proteomics

Fredolini

Byström

et al. 2015

Expert Review of Proteomics

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Aiming at clinical studies of human diseases, antibody-assisted assays have been applied to biomarker discovery and toward a streamlined translation from patient profiling to assays supporting personalized treatments. In recent years, integrated strategies to couple and combine antibodies with mass spectrometry-based proteomic efforts have emerged, allowing for novel possibilities in basic and clinical research. Described in this review are some of the field’s current and emerging immunocapture approaches from an affinity proteomics perspective. Discussed are some of their advantages, pitfalls and opportunities for the next phase in clinical and translational proteomics.

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Screening for C3 Deficiency in Newborns Using Microarrays

Cited by 23 publications

References 22 publications

Newborn Screening for Severe Primary Immunodeficiency Diseases in Sweden—a 2-Year Pilot TREC and KREC Screening Study

Newborn Screening for Severe Primary Immunodeficiency Diseases in Sweden—a 2-Year Pilot TREC and KREC Screening Study

A Novel Targeted Screening Tool for Hypogammaglobulinemia: Measurement of Serum Immunoglobulin (IgG, IgM, IgA) Levels from Dried Blood Spots (Ig-DBS Assay)

Immunocapture strategies in translational proteomics

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