Review for 10.1186/s12876-014-0190-1 (2014)

Reviewer's report
Title:Anti-Outer membrane protein C and anti-glycoprotein 2 antibodies in
inflammatory bowel disease and their association with complicated forms of
Crohn's disease
Version:1Date:18 February 2014
Reviewer: Antonio Di Sabatino
Reviewer's report:
Aim of Kohoutova et al. in this study is to assess relationship between serum
anti-OmpC IgA, anti-GP2 IgG and anti-GP2 IgA antibodies with IBD and their
association with complicated forms of Crohn’s disease. This manuscript shows
that serum anti-OmpC IgA antibodies are higher in IBD patients compared to
controls, whereas serum anti-GP2 IgG and anti-GP2 IgA antibodies are
increased only in Crohn’s disease patients compared to controls. Moreover,
Kohoutova et al. demonstrate that in Crohn’s disease anti-OmpC IgA are higher
in B2 and in B2+B3 phenotypes than in B1, whereas anti-GP2 IgA are higher in
B2+B3 and B3 phenotypes compared to B1. The paper also describes a
significant difference in anti-OmpC IgA between Crohn’s disease patients with or
without surgery and a significant difference in anti-GP2 IgA between Crohn’s
disease patients with or without extraintestinal manifestations. On this basis,
Kohoutova et al. depict an association between anti-OmpC IgA and IBD, an
association between anti-GP2 (IgA and IgG) and Crohn’s disease and higher
levels of anti-OmpC IgA and anti-GP2 IgA in complicated forms of Crohn’s
disease. The topic is interesting but the manuscript should be improved
addressing the following issues.
Major criticisms:
1. In the results the Authors state there is a significant difference in anti-GP2 IgA
between Crohn’s disease patients with or without extraintestinal manifestations,
p=0.05. How did they find significant difference if p=0.05 rather than p<0.05? It
does not seem plausible to be typing mistake, since they repeat “p=0.05” both in
abstract (page 2, line 29) and in results (page 6, line 7). Please clarify it.
2. Please add sensitivity, specificity, negative and positive predictive values of
serum anti-OmpC IgA, anti-GP2 IgG and anti-GP2 IgA antibodies in all groups.
Could you add them both in Table 1 and in “Results” sections?
3. From page 5, line 30 to page 6, line 4: on the basis of values of Crohn’s
disease patients with surgery, they look to be approximately the sum of B2
patients with B3 patients, as I expect. Therefore, if I am right, please remove this
analysis, as it is already described in Table 2.
4. Page 6, line 8-11: Since anti-GP2 IgA are higher in Crohn’s disease patients
with immunosuppressive therapy, please specify if these patients are responder
or not. If there are both subgroups (responder and not responder) please split
them and, accordingly, compare them with the group of Crohn’s disease patients
without any treatment or treated with 5-aminosalicylates only. Moreover, please
compare the other antibodies (anti-OmpC IgA and anti-GP2 IgG) between these
three groups of Crohn’s disease patients.
5. Page 20, line 20-22: you cannot declare that anti-OmpC and anti-GP2
antibodies are useful to identify Crohn’s disease patients, who are more likely to
develop complicated forms of disease. In order to be state it, you should have a
follow-up of Crohn’s disease patients from diagnosis to complication
development in association with measurement of these antibodies, which – on
the other hand - are increased once patients already have the complication (B2
and/or B3 phenotypes).
Minor criticisms:
1. In the methods of abstract please delete number of men, women and age for
each group recruited in the study, since this information is reported in the
“Methods” section afterwards.
2. In the methods of abstract please write which antibodies are tested in patients’
sera.
3. The introduction is very short, only 178 words. Please expand it with major
comments on papers cited (in particular from Reference 8 to 16) and with some
observations regarding anti-OmpC and anti-GP2 antibodies, their target and what
it is known about these antibodies in IBD.
4. In the “Methods” section please type a title of any method used in the study,
for instance “Patients”, “ELISA”, “Statistical analysis” and so on.
5. In the “Methods” section please add duration disease and what treatments the
patients are on at the time of blood withdrawal.
6. Please calculate whether in UC patients there is a correlation between
anti-OmpC IgA and anti-GP2 IgA values in UC patients, between and anti-GP2
IgG and anti- OmpC IgA values, between anti-GP2 IgG and anti-GP2 IgA as well
as you did in CD patients (Page 5, line 1-3).
7. What are the extraintestinal manifestations of Crohn’s disease patients
enrolled in this study? Please specify them in “Methods” section.
8. Page 6, line 7: Please compare the other antibodies (anti-OmpC IgA and
anti-GP2 IgG) between Crohn’s disease patients with or without extraintestinal
manifestations.
9. Page 7, line 15-16: please remove this statement, since Crohn’s disease
patients with surgery look to be approximately the sum of B2 patients with B3
patients.
10. Page 8, line 11-12: please specify that even if the anti-GP2 IgA antibodies
are higher in Crohn’s disease patients with extraintestinal manifestations, there is
not significant difference.
11. Graph 1 legend: please associate asterisk with p<0.001, as described in
“Results” sections.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests