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Follow-up and outcome of symptomatic partial or absolute IgA deficiency in children

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Abstract

Selective IgA deficiency is defined as absolute or partial when serum IgA level is < 7 mg/dl or 2 SD below normal for age, respectively. Few data are available on partial selective IgA deficiency, as probably most children with low serum IgA are seldom referred to a specialist clinic in common pediatric practice. The aim of our study was to better define the profile of both symptomatic forms and their clinical outcome in a pediatric immunology setting. Thus, clinical and immunological data from 103 symptomatic patients with selective IgA deficiency (53 absolute and 50 partial), 4–18 years of age, were collected at diagnosis and 80 patients (44 absolute and 36 partial) were monitored for a mean period of 5 years. Also, the prevalence of TNFRSF13B mutations has been assessed in 56 patients. The most common clinical features were infections (86/103; 83%), allergy (39/103; 38%), and autoimmunity (13/103; 13%). No significative differences were observed between absolute and partial selective IgA deficiency patients. However, a significative difference in the rate of IgA normalization between partial and absolute selective IgA deficiency patients (33 vs 9%, p = 0.01) was detected. Furthermore, a lower incidence of infections was associated to a normalization reversal compared to a final absolute or partial defect status (12 vs 53 and 64% respectively, p < 0.01).

Conclusions: Regardless of a diagnosis of absolute or partial defect, monitoring of symptomatic patients with selective IgA deficiency is recommended overtime for prompt identification and treatment of associated diseases. Further, diagnostic workup protocols should be revisited in children with IgA deficiency.

What is Known:

● Selective IgA Deficiency is the most common primary immunodeficiency and is usually asymptomatic.

● Symptomatic pediatric patients with selective IgA deficiency mostly suffer with respiratory and gastrointestinal infections.

What is New:

● Symptomatic children with partial IgA defect may have similar clinical, immunological, and genetic features than symptomatic children with absolute IgA deficiency.

● Symptomatic children with partial IgA deficiency deserve accurate monitoring for associated diseases as per children with absolute IgA deficiency.

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Abbreviations

SIGAD:

Selective IgA deficiency

PID:

Primary immunodeficiency disease

TACI:

Transmembrane activator and calcium modulator and cyclophilin ligand interactor

CVID:

Common variable immunodeficiency

aSIGAD:

Absolute selective IgA deficiency

pSIGAD:

Partial selective IgA deficiency

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Acknowledgements

We thank all patients and their referring nursing and medical staff of the Italian Primary Immunodeficiency Network Centers for their participation. This work was carried out in the tutorial framework of Master in Advanced Pediatric Allergy and Immunology at University of Rome Tor Vergata.

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Authors and Affiliations

  1. Pediatric Immunopathology and Allergology Unit, University of Rome Tor Vergata, Policlinico Tor Vergata, Viale Oxford, 81, 00133, Rome, Italy

    Viviana Moschese, Loredana Chini, Simona Graziani, Mayla Sgrulletti, Gigliola Di Matteo & Silvia Di Cesare

  2. Department of Translational Medical Sciences- Section of Pediatrics, Federico II University, Naples, Italy

    Vera Gallo, Emilia Cirillo & Claudio Pignata

  3. Medical Genetics Unit, S.Orsola-Malpighi University Hospital, Bologna, Italy

    Simona Ferrari

  4. Pediatric Unit, Department of Woman, Child and Urologic Diseases, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy

    Andrea Pession & Fernando Specchia

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  1. Viviana Moschese
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  2. Loredana Chini
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Contributions

VM designed the study, analyzed and interpreted the data, wrote and critically reviewed the manuscript. LC and SG contributed to data interpretation and writing of the manuscript. CP, AP, FS critically reviewed and approved the final manuscript. MS, VG, EC contributed to the acquisition of data. SF, GDM, SDC performed all genetic and immunological analysis. VM designed the study, analyzed and interpreted the data, wrote and critically reviewed the manuscript. LC contributed to data interpretation and writing the manuscript. SG contributed to data interpretation and writing the manuscript. CP critically reviewed and approved the final manuscript. AP critically reviewed and approved the final manuscript. FS critically reviewed and approved the final manuscript. MS contributed to the acquisition of data. VG contributed to the acquisition of data. EC contributed to the acquisition of data. SF performed all genetic and immunological data. GDM performed all genetic and immunological data. SDC performed all genetic and immunological data.

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Correspondence to Viviana Moschese.

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The authors declare that they have no conflict of interest.

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Informed consent was obtained at diagnosis from all individual participants included in the study.

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The approval for the study was obtained from the institutional review board. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Communicated by Nicole Ritz

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Moschese, V., Chini, L., Graziani, S. et al. Follow-up and outcome of symptomatic partial or absolute IgA deficiency in children. Eur J Pediatr 178, 51–60 (2019). https://doi.org/10.1007/s00431-018-3248-1

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