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Microbial Biomarkers in Patients with Nonresponsive Celiac Disease

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Abstract

Background and Aims

In nonresponsive celiac disease (NRCD), the symptoms and duodenal damage persist despite a gluten-free diet. Celiac disease patients with persistent symptoms are found to have a dysbiotic microbiota. We thus hypothesized that increased seroreactivity to the serum gluten-sensitive microbial antibodies Saccharomyces cerevisiae (ASCA), Pseudomonas fluorescens-associated sequence (I2), and Bacteroides caccae TonB-linked outer membrane protein (OmpW) is associated with NRCD.

Methods

ASCA, I2 and OmpW were measured in 20 seronegative CD patients with persistent villous damage despite strict dietary treatment (NRCD group). Fifty-eight responsive patients served as CD controls (55 on gluten-free treatment) and 80 blood donors as non-CD controls.

Results

At least one microbial marker was positive in 80% of NRCD patients, in 97% of untreated CD and 87% of treated CD patients, and in 44% of controls. NRCD patients had the highest frequency of ASCA positivity (65% vs 52, 20, and 0%, respectively) and also significantly higher ASCA IgA (median 14.5 U/ml) and IgG (32.5 U/ml) titers than treated CD patients (7.0 U/ml, 13.0 U/ml) and non-CD controls (4.5 U/ml, 5.8 U/ml). The frequencies of I2 and OmpW were lower in NRCD than in untreated CD (65% and 45% vs 86% and 59%, respectively), and I2 titers were higher in NRCD (median absorbance 0.76) and untreated (1.0) and treated (0.83) CD than controls (0.32). OmpW was elevated in untreated (1.1) and treated (0.94) CD patients compared with controls (0.79).

Conclusions

Seropositivity and high titers of ASCA are associated with NRCD and might serve as an additional follow-up tool in CD.

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Acknowledgments

We would like to acknowledge Jonathan Braun, M.D., Ph.D, Professor and Chair, Pathology and Laboratory Medicine, UCLA David Geffen School of Medicine, UCLA Health System for his support.

Funding

This study was supported by the Academy of Finland, the Sigrid Juselius Foundation, the Päivikki and Sakari Sohlberg Foundation, the Competitive State Research Financing of the Expert Area of Tampere University Hospital, the Foundation for Pediatric Research, the Yrjö Jahnsson Foundation and State fund, Grant number Y1023G2017.

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Authors and Affiliations

  1. Tampere Center for Child Health Research, University of Tampere and Tampere University Hospital, Arvo Ylpön katu 34, 33014, Tampere, Finland

    Liisa Viitasalo, Kalle Kurppa, Merja Ashorn, Sara Ashorn, Markku Mäki & Sari Iltanen

  2. Department of Clinical Genetics and Laboratory of Genetics, HUSLAB, University of Helsinki and Helsinki University Hospital, 00029, Helsinki, Finland

    Liisa Viitasalo

  3. Research Programs Unit, Immunobiology, and Department of Medical and Clinical Genetics, University of Helsinki, P.O. Box 21, Haartmaninkatu 3, 00014, Helsinki, Finland

    Päivi Saavalainen

  4. Faculty of Social Sciences, University of Tampere, P.O. Box 100, 33014, Tampere, Finland

    Heini Huhtala

  5. Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, P.O. Box 2000, Tampere, 33521, Finland

    Tuire Ilus

  6. Celiac Disease Research Center, Faculty of Medicine and Life Sciences, University of Tampere, P.O. Box 100, 33014, Tampere, Finland

    Katri Kaukinen

  7. Department of Internal Medicine, Tampere University Hospital, P.O. Box 2000, 33521, Tampere, Finland

    Katri Kaukinen

  8. Lapland Central Hospital, P.O. Box 8041, 96101, Rovaniemi, Finland

    Sari Iltanen

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  1. Liisa Viitasalo
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  2. Kalle Kurppa
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  3. Merja Ashorn
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Corresponding author

Correspondence to Kalle Kurppa.

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Viitasalo, L., Kurppa, K., Ashorn, M. et al. Microbial Biomarkers in Patients with Nonresponsive Celiac Disease. Dig Dis Sci 63, 3434–3441 (2018). https://doi.org/10.1007/s10620-018-5285-z

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  • DOI: https://doi.org/10.1007/s10620-018-5285-z

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