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Increased Prevalence of Gastrointestinal Viruses and Diminished Secretory Immunoglobulin a Levels in Antibody Deficiencies

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Abstract

Purpose

Gastrointestinal disease occurs frequently in antibody deficiencies. This study aims to explore the relation between gastrointestinal infections and mucosal homeostasis in patients with antibody deficiencies.

Methods

We performed an observational study including 54 pediatric antibody deficient patients (48 % CVID, 41 % CVID-like, 11 % XLA) and 66 healthy controls. Clinical symptom scores and stool samples were collected prospectively. Stool samples were evaluated for bacteria, parasites, viruses, secretory IgA- and for calprotectin levels. Results were compared between patients and controls.

Results

24 % of antibody deficient patients versus 9 % of healthy controls tested positive for gastrointestinal viruses (p = 0.028). Fecal calprotectin levels were significantly higher in virus positive patients compared to virus negative patients (p = 0.002). However, in controls, fecal calprotectin levels were similar between virus positive and virus negative controls. Moreover, gastrointestinal virus positive patients had low serum IgA levels in 13/14 cases (94 %) versus 40/62 (62 %) patients in the virus negative patient group (p = 0.04). The virus positive patient group also displayed significantly lower secretory IgA levels in stool (median 13 ug/ml) than patients without gastrointestinal viruses detected or healthy controls (median 155 ug/ml) (p = 0.046).

Conclusion

We here report an increased prevalence of gastrointestinal viruses and gastrointestinal complaints in antibody deficient patients. Patients that tested positive for gastrointestinal viruses showed diminished serum- and secretory IgA levels, and only in patients, virus positivity was associated with signs of mucosal inflammation. These findings suggest that particularly patients with low IgA are at risk for longstanding replication of gastrointestinal viruses, which may eventually result in CVID-related enteropathy.

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Abbreviations

CVID:

Common variable immunodeficiency

GI:

Gastrointestinal

IBD:

Inflammatory bowel disease

IgA:

Immunoglobulin A

PID:

Primary immunodeficiencies

XLA:

X-linked agammaglobulinemia

RT-PCR:

Real time polymerase chain reaction

ELISA:

Enzyme-linked immunosorbent assay

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Acknowledgements

The authors would like to thank Jessica van der Aa and Géanne Krabben for assistance with participant inclusions and Karin van Veghel and Lysette Ebskamp of U-DAIR with determination of sIgA levels.

Funding

This study was supported by non-restricted educational grants from Baxter The Netherlands and GlaxoSmithKline The Netherlands.

Author information

Authors and Affiliations

  1. Department of Pediatric Immunology and Infectious Diseases/Laboratory of Translational Immunology, University Medical Center Utrecht/Wilhelmina Children’s Hospital, Lundlaan 6, Post box 85090 KC.03.063.0, 3508 AB, Utrecht, The Netherlands

    A. A. J. M. van de Ven, W. J. M. Janssen, L. S. Schulz, E. A. M. Sanders, M. Boes & J. M. van Montfrans

  2. Department of Medical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands

    S. Nierkens

  3. Department of Medical Microbiology, Virology, University Medical Center Utrecht, Utrecht, The Netherlands

    A. M. van Loon, K. Voorkamp, J. G. Kusters & A. M. J. Wensing

Authors
  1. A. A. J. M. van de Ven
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  2. W. J. M. Janssen
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  3. L. S. Schulz
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  4. A. M. van Loon
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  8. S. Nierkens
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Corresponding author

Correspondence to J. M. van Montfrans.

Additional information

A.A.J.M. van de Ven W.J.M. Janssen, A.M.J. Wensing and J.M. van Montfrans have equal contributions.

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van de Ven, A.A.J.M., Janssen, W.J.M., Schulz, L.S. et al. Increased Prevalence of Gastrointestinal Viruses and Diminished Secretory Immunoglobulin a Levels in Antibody Deficiencies. J Clin Immunol 34, 962–970 (2014). https://doi.org/10.1007/s10875-014-0087-3

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  • DOI: https://doi.org/10.1007/s10875-014-0087-3

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