Segregation of pANCA antigenic recognition by DNase treatment of neutrophils: Ulcerative colitis, type 1 autoimmune hepatitis, and primary sclerosing cholangitis

Vidrich, Alda; Lee, Jonathan; James, Ellin; Cobb, L; Targan, Stephan R.

doi:10.1007/bf01541319

Cited by 102 publications

(47 citation statements)

References 29 publications

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“…These results would be interpreted as supporting a diagnosis of ulcerative colitis when they are actually more likely to be false positives due to the presence of antibodies to other specific neutrophil/nuclear antigens. A serum that was positive for dsDNA antibody was a control (it was DNase sensitive) used in the study first describing the DNase IFA methodology for detecting atypical pANCA (42).…”

Section: Discussionmentioning

confidence: 99%

Analysis of Serum Antibodies in Patients Suspected of Having Inflammatory Bowel Disease

Jaskowski

Litwin

Hill

2006

Clin Vaccine Immunol

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Inflammatory bowel disease (IBD) is the general term used for a heterogeneous group of intestinal disorders, including Crohn's disease (CD) and ulcerative colitis (UC). Serological markers such as anti-Saccharomyces cerevisiae antibodies (ASCA) and atypical perinuclear antineutrophilic cytoplasmic antibody (atypical pANCA) have proven useful in the diagnosis and differentiation of CD and UC. Immunoglobulin A (IgA) antibody directed against the outer membrane protein C (OmpC) of Escherichia coli is said by one group to have clinical utility in diagnosing IBD, specifically in ASCA-negative CD patients. Our objective in this study was to compare the results obtained from two separate laboratories offering similar IBD tests using sera from suspected IBD patients. One hundred ninety-seven sera received for IBD testing were included in the study. The agreement between the two laboratories was 93.4% for ASCA IgA, 90.9% for ASCA IgG, and 87.8% for atypical pANCA IgG. There were 25 sera with ASCA-negative/OmpC-positive results reported by one laboratory. Thirteen of these 25 (52.0%) ASCA-negative/OmpC-positive sera were also atypical pANCA positive (9 as determined by both laboratories, 3 by one, and 1 by the other). Atypical pANCA antibody is found primarily in IBD patients with UC and colon-limited CD (Crohn's colitis). We conclude that the ASCA and atypical pANCA assays showed good agreement between the two laboratories, but the data for ASCA-negative/OmpCpositive sera suggest that many (52.0%) of these patients were more likely to have had UC or Crohn's colitis based on the presence of an atypical pANCA.Crohn's disease (CD) and ulcerative colitis (UC) are the two major forms of inflammatory bowel disease (IBD). Both CD and UC are chronic, affecting children and adults (men and women almost equally), and are most common in northern Europe and North America. The onset of CD and UC is usually between the ages of 15 and 30, with a second, smaller peak of incidence between the ages of 50 and 70 (4, 23). Approximately 20% of individuals with CD have a biological relative with some form of IBD, and several reports have noted an increase in the prevalence of CD and UC in various geographic regions (2,17,24,36).Although there are many theories about the etiology of CD and UC, none have been proven. Many of the symptoms of CD and UC are similar, and diagnosis is often difficult, time-consuming, and invasive. Since CD and UC are treated differently, correct diagnosis and differentiation are medically important.Two serological markers have been found to have clinical utility in diagnosing IBD and aiding in the differentiation of CD from UC: anti-Saccharomyces cerevisiae antibody (ASCA) (immunoglobulin A [IgA] and/or IgG), using enzyme immunoassay (EIA) techniques, and antineutrophil cytoplasmic antibody (ANCA) (IgG) that demonstrates atypical perinuclear staining (pANCA), using indirect fluorescent-antibody assay (IFA) techniques. ASCA is directed against mannose sequences in the cell wall of Saccharomyces cerevisiae (26,35) and...

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Section: Discussionmentioning

confidence: 99%

Analysis of Serum Antibodies in Patients Suspected of Having Inflammatory Bowel Disease

Jaskowski

Litwin

Hill

2006

Clin Vaccine Immunol

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“…Vidrich et al (31 ) reported loss of antigenic recognition after DNA digestion of neutrophils for UC P-ANCAs but not for P-ANCAs of primary sclerosing cholangitis and autoimmune hepatitis. The P-ANCA patterns in primary sclerosing cholangitis and autoimmune hepatitis convert to a C-ANCA staining pattern after DNase treatment.…”

Section: Autoantigens Recognized By Autoantibodies To Neutrophils (Atmentioning

confidence: 99%

Serologic Markers in Inflammatory Bowel Disease

Bossuyt¹

2006

Clinical Chemistry

181

136

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Inflammatory bowel disease (IBD) is an enduring disease involving mostly young people, with symptoms of bloody diarrhea and abdominal cramps. Several antibodies have been associated with IBD, the 2 most comprehensively studied being autoantibodies to neutrophils (atypical perinuclear anti-neutrophil cytoplasmic antibodies) and anti-Saccharomyces cerevisiae antibodies. This review focuses on the value of these antibodies for diagnosing IBD, differentiating Crohn disease from ulcerative colitis, indeterminate colitis, monitoring disease, defining clinical phenotypes, predicting response to therapy, and as subclinical markers. Pancreatic antibodies and newly identified anti-microbial antibodies (anti-outer membrane porin C, anti-I2, and anti-flagellin) are also reviewed.

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“…ANCA should be tested from serum samples by indirect immunofluorescence or from normal peripheral blood neutrophils. On immunofluorescence staining, the IBD-specific ANCA displays a specific perinuclear highlighting (P-ANCA) and is DNA sensitive [13,14]. …”

Section: Best-characterized Serologic Ibd Markersmentioning

confidence: 99%

The Role of Autoantibodies in Inflammatory Bowel Disease

Herszényi

Tulassay

2012

Dig Dis

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The search for the underlying trigger of an inappropriate inflammatory reaction characteristic of inflammatory bowel diseases (IBD) has led to the discovery of several antibodies. The panel of serologic markers for IBD is rapidly expanding. Serologic markers hold the promise of helping researchers and clinicians to better understand IBD heterogeneity and natural history. The real importance of the antibodies produced against various microbial and autoantigens is still uncertain. Whether these antibodies play a primary role in the pathogenesis of IBD, or their presence is only a consequence of the inflamed mucosa is a fundamental question that remains to be clarified. The impact of the routine evaluation of these serologic markers in the everyday clinical IBD diagnostic algorithm is questionable due to their limited sensitivity. Despite their great potential, the routine use of serologic markers for diagnosis and follow-up is currently not justified. However, their correlation with disease phenotype and behavior is more established. A combination of serum markers has been shown to be of more value compared to using single markers alone. The ongoing challenge is how to best utilize these serologic markers to provide clinically relevant information in a cost-effective manner. Further prospective clinical trials are needed to determine their exact role in pathogenesis and practical clinical importance. We review the current standpoint of the clinical impact of various established and newly suggested markers in Crohn’s disease and ulcerative colitis.

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Segregation of pANCA antigenic recognition by DNase treatment of neutrophils: Ulcerative colitis, type 1 autoimmune hepatitis, and primary sclerosing cholangitis

Cited by 102 publications

References 29 publications

Analysis of Serum Antibodies in Patients Suspected of Having Inflammatory Bowel Disease

Analysis of Serum Antibodies in Patients Suspected of Having Inflammatory Bowel Disease

Serologic Markers in Inflammatory Bowel Disease

The Role of Autoantibodies in Inflammatory Bowel Disease

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