Tag Archives: anti-C

More on anti-glycan antibodies in Crohn’s disease

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As noted in recent blog entry (Serology in IBD), anti-glycan antibodies have some usefulness in inflammatory bowel disease.  More data on the utility of these antibodies is available in a study which examined the presence of these antibodies in both a pediatric and adult cohort (Inflamm Bowel Dis 2012; 18: 1221-31).

Anti-L, Anti-C, anti-chitobioside (ACCA), anti-laminaribioside (ALCA), anti-mannobioside and anti-Saccaromyces cervisiae (ASCA) antibodies were tested in 131 pediatric patients (59 CD, 27 UC, 45 controls) and in 728 adult patients (355 CD, 129 UC, 244 controls).  In this study, 78% of pediatric CD patients had at least one serological marker.  ASCA was most accurate for CD diagnosis; it was present in 63% of the pediatric cohort. 

Combined usage of these antibodies helped differentiate CD from UC.  While sensitivity for detecting CD was 78% with the presence of one serological marker, the presence of three (or more) markers increased the specificity to 93% (for CD compared to UC); however, the presence of this many markers occurred in only 28%. Increasing antibody levels also correlated with complicated CD behavior, CD-related surgery and ileal disease location.

Serology in IBD

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Serological antibodies against a number of antigens have shown some utility in differentiating inflammatory bowel disease (IBD) from non-IBD and in distinguishing Crohn’s disease (CD) from ulcerative colitis (UC).  A recent article evaluated 204 articles in a systematic review of these serological markers (Inflamm Bowel Dis 2012; 18: 1340-55).

The study has several useful tables and a long list of references.  In its Table 1, 10 serologies are listed with a range for prevalence in CD, UC, alternative GI conditions, and in healthy population.  Table 2 summarizes the data in terms of sensitivity, specificity, positive predictive value, negative predictive value for these antibodies in determining IBD from non-IBD.

With regard to specific antibodies, the review highlights 10 antibodies:

1. Anti-neutrophil cytoplasmic antibodies (ANCA).  Autoantibody directed against a constituent of neutrophil granules.  With IBD (especially UC), an atypical perinuclear (pANCA) staining pattern with indirect immunofluorescence and DNase-sensitive make this pattern different from ANCA due to vasculitis.

2-7. Anti-glycan antibodies –directed against cell wall microbes and reflect interaction between the immune system and glycosylated cell wall components of microbiota.

2. Anti-Saccharomyces cerevisiae (ASCA IgA and IgG) –antibodies directed against yeast cell wall.  While ASCA antibodies are commonly found in CD patients, 20-25% (or higher in some studies) of healthy relatives will test positive for these antibodies as well.  Approximately 6% of relatives of UC patients will be ASCA-positive.

3. Anti-laminaribioside carbohydrate IgG antibodies (ALCA) –antibodies directed against laminaribioside

4. Anti-chitobioside carbohydrate IgA antibodies (ACCA) –antibodies directed against chitobioside

5. Anti-mannobioside carbohydrate IgG antibodies (AMCA) –antibodies directed against mannobioside

6. Anti-L –antibodies directed against laminarin (large polysaccharide)

7. Anti-C –antibodies directed against chitin (large polysaccharide)

8. Anti-OmpC.  OmpC is a transport protein of E coli

9. Anti-I2.  I2 is a Pseudomonas-associated antigen

10. Anti-CBir1.  CBir1 is a bacterial flagellin antigen

Conclusions:

  • Serology has only limited value for the initial diagnosis of IBD.
  • Serology has ‘better value’ in differentiating CD from UC, though there is substantial variability in serologic responses in both diseases.  Probably, serology is most useful in unclassified IBD (IBD-U) in preoperative setting; serology may help predict risk of developing complications among patients undergoing pouch surgery.
  • Serology is useful in predicting a complicated disease course. The presence and magnitude of these antibodies are strong predictors of disease progression.

Additional references:

  • Pediatrics. 2010 Jun ;125 (6):1230-6.  Shortcomings of the inflammatory bowel disease Serology 7 panel. 
  • -Clin Gastro & Hep 2008; 6: 1105. Increased immune reactivity/markers associated with aggressive disease.
  • -IBD 2006; 12:1122. Expression of I2 antibodies (against a bacterial antigen of psedomonas fluorescens) was highly associated with clinical response to diversion. 15/16 with I2-pos had clinical response; 2/11 I2-neg had clinical response.
  • -IBD 2008; 14: S4 abstract 0010. Practical experience with IBD serology (n=90) much less accurate than reported by Prometheus: overall accuracy of 63% (vs 92%), 66% sensitivity (vs 93%), 59% specificity (vs 95%), 75% PPV (vs 96%), and 49% NPV (vs 90%). In this population, 34% of known IBD were incorrectly predicted. Of 32 who did not have any evidence of IBD after clinical investigation, 40% (13) were seropositive.
  • -Clin Gastro & Hep 2008; 6: 1105. Increased immune reactivity/markers associated with aggressive disease.
  • -IBD 2008; 14; 129. Serologic markers not very useful clinically.
  • -Pediatrics 2007; 119: e193. IBD serology performed poorly in comparison to combination of Hgb/ESR with regard to sensitivity (60% vs. 83%), specificity (92% vs. 96%), positive predictive value (60% vs. 79%) for IBD in children, n=227. Also one third of all positive serology in patients w/o IBD. The positive predictive value in patients w/o rectal bleeding was 35% vs 60% for routine tests.
  • -Gastroenterol 2006; 131: 366. antibodies against laminaribioside, chitobioside, and mannan have predictive value in detecting Crohn’s disease.
  • -Gastroenterol 2006; 130: 1078. Unaffected relatives positive for either OmpC or ASCA in 20% in large cohor (n=619 unaffected relatives. OmpC present in up to 44% of CD pts, up to 24% of UC pts, and 6% of controls.