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Serological Markers in IBD: Are They Ready for Prime Time? Raymond Cross, M.D. Assistant Professor of Medicine Division of Gastroenterology and Hepatology Director, IBD Program Acting Chief, VA GI Service What are the Serological Markers in IBD? pANCA (perinuclear staining pattern)

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serological markers in ibd are they ready for prime time

Serological Markers in IBD: Are They Ready for Prime Time?

Raymond Cross, M.D.

Assistant Professor of Medicine

Division of Gastroenterology and Hepatology

Director, IBD Program

Acting Chief, VA GI Service

what are the serological markers in ibd
What are the Serological Markers in IBD?
  • pANCA (perinuclear staining pattern)
    • Loss of perinuclear pattern after DNAase
    • Differentiate from the “other pANCAs”
      • Antibody against myeloperoxidase
      • Antibody against cathepsin G, elastase, lysozyme, and lactoferrin
  • ASCA (anti-Saccharomyces cerevisiae)
    • Both IgG and IgA
    • Recognize mannose in the cell wall mannan of Saccharomyces cerevisiae
what are the serological markers in ibd 2
What are the Serological Markers in IBD-2?
  • Omp C
    • IgG only
    • Recognize outer membrane porin C protein in E. coli
  • I2
    • IgA only
    • Recognizes novel homologue of bacterial transcription-factor families from a Pseudomonas fluorescens-associated sequence
  • Cbir 1 flagellin
    • IgG
why use serological markers in clinical practice
Why Use Serological Markers in Clinical Practice?
  • Differentiate IBD from functional bowel disorders
  • Accurately diagnose Crohn’s or UC in a patient with:
    • Severe colitis
    • Indeterminate colitis
  • Predict disease course or complications in IBD
    • CD phenotype
    • Severity of disease
    • Risk of pouchitis
frequency of panca in uc patients and controls in a referral center
Frequency of pANCA in UC Patients and Controls in a Referral Center

60% sensitive

94% specific for UC

Duerr, R. H., S. R. Targan, et al. (1991). Gastroenterology100(6): 1590-6.

prevalence of asca in patients with cd and uc and controls in the different assays
Prevalence of ASCA in Patients with CD and UC and Controls in the Different Assays

Vermeire, S., S. Joossens, et al. (2001). Gastroenterology120(4): 827-33

sensitivity specificity and positive and negative predictive value of asca
Sensitivity, Specificity, and Positive and Negative Predictive Value of ASCA

*Using the Prometheus Assay

Vermeire, S., S. Joossens, et al. (2001). Gastroenterology120(4): 827-33

accuracy of serological markers in differentiating ibd from controls
Accuracy of Serological Markers in Differentiating IBD from Controls

Peeters, M., S. Joossens, et al. (2001). Am J Gastroenterol96(3): 730-4.

utility of serodiagnostics in pediatric ibd use of a two step assay
Utility of Serodiagnostics in Pediatric IBD: Use of a Two-Step Assay

Dubinsky MC, Ofman JJ, Urman M, et al. Am J Gastroenterol 2001;96(3):758-65

iga antibody to i2 in patients with cd or uc and controls
IgA Antibody to I2 in Patients with CD or UC and Controls

Sutton, C. L., J. Kim, et al. (2000). Gastroenterology119(1): 23-31.

can serological markers differentiate ibd from non ibd
Can Serological Markers Differentiate IBD from Non-IBD?
  • pANCA and ASCA are specific for and have high positive predictive value for UC and CD respectively
    • Rule in disease
  • The low sensitivity and negative predictive value preclude them as a screening test
    • Cannot rule out disease
  • Potential application in pediatric disease to avoid invasive work up
why use serological markers in clinical practice12
Why Use Serological Markers in Clinical Practice?
  • Differentiate IBD from functional bowel disorders
  • Accurately diagnose Crohn’s or UC in a patient with:
    • Severe colitis
    • Indeterminate colitis
  • Predict disease course or complications in IBD
    • CD phenotype
    • Severity of disease
    • Risk of pouchitis
criteria for indeterminate colitis
Criteria for Indeterminate Colitis
  • No evidence of small bowel involvement, fistula, or perianal disease
  • Absence of diagnostic criteria for CD or UC by microscopy
presentation of ulcerative colitis
Presentation of Ulcerative Colitis
  • Classic presentation
    • Bloody diarrhea!
    • Never or former smoker
    • Tenesmus (dry heaves of the rectum)
  • Red Flags
    • Active smoker
    • Perianal disease
    • Abdominal mass on examination
crohn s disease red flags
Crohn’s Disease Red Flags
  • Onset after stopping smoking
  • Bleeding only
  • Diverticulosis
  • Atherosclerosis
  • Prolapse
sensitivity specificity and positive and negative predictive value of asca18
Sensitivity, Specificity, and Positive and Negative Predictive Value of ASCA

*Using the Prometheus Assay

Vermeire, S., S. Joossens, et al. (2001). Gastroenterology120(4): 827-33

results of asca and panca in the study population
Results of ASCA and pANCA in the Study Population

Joossens, S., W. Reinisch, et al. (2002). Gastroenterology122(5): 1242-7

relationship between marker antibodies and cd cohort
Relationship Between Marker Antibodies and CD Cohort

Landers, C. J., O. Cohavy, et al. (2002). Gastroenterology123(3): 689-99

conclusions 2
Conclusions-2
  • pANCA and ASCA have low sensitivity in CD and UC
  • pANCA and ASCA have good specificity and PPV in CD and UC
  • In patients with indeterminate colitis, available serological markers do not accurately predict the subsequent disease course
    • Is indeterminate colitis a different form of IBD?
    • Will performance of serological markers improve with introduction of other markers?
why use serological markers in clinical practice22
Why Use Serological Markers in Clinical Practice?
  • Differentiate functional from organic disorders
  • Differentiate type of IBD
    • Implications for medical and surgical therapy
  • Predict disease course or complications in IBD
    • CD phenotype
    • Severity of disease
    • Pouchitis
antibody expression stratifies homogeneous subgroups with distinct clinical characteristics
Antibody Expression Stratifies Homogeneous Subgroups with Distinct Clinical Characteristics

Vasiliauskas, E. A., L. Y. Kam, et al. (2000). Gut47(4): 487-96

relative contribution of antibody responses and complicated small bowel disease
Relative Contribution of Antibody Responses and Complicated Small Bowel Disease

Mow, W. S., E. A. Vasiliauskas, et al. (2004). Gastroenterology126(2): 414-24

disease characteristics in patients with antibodies to multiple microbial antigens
Disease Characteristics in Patients with Antibodies to Multiple Microbial Antigens

Mow, W. S., E. A. Vasiliauskas, et al. (2004). Gastroenterology126(2): 414-24

incidence of pouchitis in panca and panca patients
Incidence of Pouchitis in pANCA+ and pANCA- Patients

Fleshner, P. R., E. A. Vasiliauskas, et al. (2001). Gut49(5): 671-7

conclusions 3
Conclusions-3
  • Antibody profiles can predict disease behavior in IBD
    • ASCA and I2 generally predict small bowel disease, fibrostenotic behavior, and need for surgery
      • Multiple antibodies associated with an even higher risk
    • pANCA predicts “UC-like” behavior
  • pANCA+ associated with risk of pouchitis after IPAA
summary
Summary
  • pANCA and ASCA are specific for UC and CD respectively
  • Neither pANCA nor ASCA are sensitive enough to exclude IBD
  • In patients with IC, available serological markers do not accurately predict the subsequent disease course
  • Antibody profiles can predict disease behavior in IBD