Placental Transfer of Maternally-Derived IgA Precludes the Use of Guthrie Card Eluates as a Screening Tool for Primary Immunodeficiency Diseases

Stephan Borte,Qiang Pan-Hammarström,Magdalena Janzi,Ulrika Von Döbeln,Lennart Nordvall,Lennart Hammarström,Anders Fasth,Jacek Winiarski,Clive M Gray

doi:10.1371/journal.pone.0043419

Abstract

There is a need for neonatal screening tools to improve the long-term clinical outcome of patients with primary immunodeficiency diseases (PID). Recently, a PCR-based screening method for both TRECs and KRECs using Guthrie card samples has been developed. However, the applicability of these excision circle assays is limited to patients with severe T or B cell lymphopenia (SCID, XLA and A-T), whereas the most common forms of PID are not detected. Absence of serum IgA is seen in a major fraction of patients with immunological defects. As serum IgA in newborns is considered to be of fetal origin, eluates from routinely collected dried blood spot samples might thus be suitable for identification of children with PID. To assess the applicability of such screening assays, stored Guthrie card samples were obtained from 47 patients with various forms of primary immunodeficiency diseases (SCID, XLA, A-T, HIGM and IgAD), 20 individuals with normal serum IgA levels born to IgA-deficient mothers and 51 matched healthy newborns. Surprisingly, normal serum IgA levels were found in all SCID, XLA, A-T and HIGM patients and, additionally, in all those IgAD patients born to IgA-sufficient mothers. Conversely, no serum IgA was found in any of the 16 IgAD patients born by IgA-deficient mothers. Moreover, half of the IgA-sufficient individuals born by IgA-deficient mothers also lacked IgA at birth whereas no IgA-deficient individuals were found among the controls. IgA in neonatal dried blood samples thus appears to be of both maternal and fetal origin and precludes its use as a reliable marker for neonatal screening of primary immunodeficiency diseases.

Highlights

During pregnancy, the fetus depends on maternal transfer of specific antibodies for protection against pathogens
IgA-deficiency is included in the phenotype of most antibody deficiencies, albeit to varying degrees (Table 1), and in a majority of other forms of Primary immunodeficiency diseases (PID), determination of serum IgA levels could potentially serve as a basis for screening programmes of inborn immune defects
Such a proposed screening for neonatal IgA-deficiency would result in the identification of patients with IgA deficiency (IgAD), these patients are not the primary target group for this screening as it represents a clinically mild form of PID

Summary

Introduction

The fetus depends on maternal transfer of specific antibodies for protection against pathogens. Several studies have previously demonstrated the presence of IgA in cord blood [1,10,11,12,13,14,15] and IgApositive B cells have been reported in fetal tissues [16,17] as well as in cord blood [18,19,20,21], suggesting that the IgA detected in neonatal blood is exclusively of fetal origin. Major efforts are currently undertaken to develop methods for neonatal PID screening, as early diagnosis and treatment would prevent subsequent tissue damage and premature death

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Conclusion