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Presence of Anti-proteinase 3 Antineutrophil Cytoplasmic Antibodies (Anti-PR3 ANCA) as Serologic Markers in Inflammatory Bowel Disease

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Abstract

Anti-proteinase 3 anti-neutrophil cytoplasmic antibodies (anti-PR3 ANCA) represent an established serologic marker of active granulomatosis with polyangiitis, but their role as a serologic marker in inflammatory bowel disease (IBD) remains uncertain. This study evaluates the presence of anti-PR3 ANCA and their validity as a serologic marker to aid in the diagnosis of IBD. Retrospectively, 142 serum samples obtained at early stages of the disease were analyzed with a new chemiluminiscent assay for the measurement of anti-PR3 ANCA. The results were correlated to the diagnosis, clinical, and therapeutic data, and ANCA and anti-Saccharomyces cerevisiae antibody (ASCA) measurements available from routine clinical practice. Anti-PR3 ANCA were significantly more prevalent (p < 0.0001) and their titers significantly higher (p < 0.0001) among ulcerative colitis compared with Crohn’s disease patients. Receiver operating characteristic curve analysis performed with anti-PR3 ANCA titers to assess the diagnostic accuracy of the assay gave an area under the curve of 0.81 (95 % CI (0.76–0.89); p < 0.0001), with a cut-off titer of 11.8 chemiluminescent units displaying 52.1 % sensitivity and 97.3 % specificity for ulcerative colitis. Combining anti-PR3 ANCA positivity with IgA ASCA negativity as the diagnostic parameter demonstrated highest diagnostic utility, with a sensitivity and specificity of 47.5 % and 98.2 %, respectively. In our cohort, anti-PR3 ANCA was significantly more prevalent in ulcerative colitis than in Crohn’s disease patients, which suggests a possible role of anti-PR3 ANCA as a serologic marker to aid in the diagnosis of IBD.

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Abbreviations

ASCA:

Anti-Saccharomyces cerevisiae antibody

AUC:

Area under the curve

cANCA:

Cytoplasmic anti-neutrophil cytoplasmic antibodies

CIA:

Chemiluminescence assay

CD:

Crohn’s disease

CU:

Chemiluminescent units

GPA:

Granulomatosis with polyangitis

IBD:

Inflammatory bowel disease

IIF:

Indirect immunofluorescence assay

pANCA:

Perinuclear anti-neutrophil cytoplasmic antibodies

ROC:

Receiver operating characteristic

UC:

Ulcerative colitis

WG:

Wegener’s granulomatosis

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Acknowledgments

We acknowledge the help of Chelsea Bentow with immunoassays and Carolina Santa Cruz and Milagros Toca for their help with the sera collection and routine testing. M Teresa Arias-Loste is a Lopez-Albo fellow from the Marques de Valdecilla Foundation-IFIMAV. The guarantor of the article is Marcos López-Hoyos, Servicio Inmunología, Hospital Universitario Marqués de Valdecilla, 39008 Santander, Spain; E-mail, mlopezhoyos@humv.es

Conflict of Interest

All authors have approved the final draft submitted. Michael Mahler is employee of INOVA Diagnostics, selling autoantibody assays. The other authors have no conflict of interest.

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Authors and Affiliations

  1. Gastroenterology and Hepatology Department, Marques de Valdecilla University Hospital-IFIMAV, Santander, Spain

    Maria Teresa Arias-Loste, Irene Moraleja, Miguel Angel Mieses, Beatriz Castro, Montserrat Rivero & Javier Crespo

  2. Immunology Department, Marques de Valdecilla University Hospital-IFIMAV, Santander, Spain

    Geovana Bonilla & Marcos López-Hoyos

  3. Research and Development, INOVA Diagnostics, San Diego, CA, USA

    Michael Mahler

  4. Servicio Inmunología, Hospital Universitario Marqués de Valdecilla, 39008, Santander, Spain

    Marcos López-Hoyos

Authors
  1. Maria Teresa Arias-Loste
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  2. Geovana Bonilla
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  3. Irene Moraleja
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  4. Michael Mahler
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  5. Miguel Angel Mieses
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  6. Beatriz Castro
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  7. Montserrat Rivero
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  8. Javier Crespo
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  9. Marcos López-Hoyos
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Correspondence to Marcos López-Hoyos.

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Arias-Loste, M.T., Bonilla, G., Moraleja, I. et al. Presence of Anti-proteinase 3 Antineutrophil Cytoplasmic Antibodies (Anti-PR3 ANCA) as Serologic Markers in Inflammatory Bowel Disease. Clinic Rev Allerg Immunol 45, 109–116 (2013). https://doi.org/10.1007/s12016-012-8349-4

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  • DOI: https://doi.org/10.1007/s12016-012-8349-4

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