Reviewer's report
Title:Transcript levels of different cytokines and chemokines correlate with
clinical and endoscopic activity in ulcerative colitis
Version: 1Date:28 January 2008
Reviewer: Giuliano Ramadori
Reviewer's report:
The authors studied the correlation of mRNA-transcript levels of the chemokines
Interleukin-8, IP-10, MRP-14 and MIP-2ï#¡ and the clinical activity index (CAI) or
the endoscopic activity index (EAI) in patients with ulcerative colitis.
They found a significant correlation, concluding that real time PCR quantification
of both chemokines and cytokines might be helpful in grading inflammation of
intestinal mucosa in patients who have ulcerative colitis, suggesting such a
measurement as objective tool to evaluate therapeutic approaches in clinical
trials.
Although the reported chemokines have been reported to be elevated in patients
of ulcerative colitis earlier, the novelty of the present paper is the correlation of
quantitative PCR-results with clinical and endoscopical activity indices.
It is a potentially interesting paper, however there are some points of criticism.
Criticism
Major points:
1) The authors state in the background chapter that there are so far no data
concerning the correlation between transcript levels of selected pro-inflammatory
cytokines in mucosal biopsies and disease activity indices. This point is not
correct. Raddatz et al. did a comprehensive study showing a positive correlation
between interleukin-6 mRNA transcript levels and the colitis activity index in
patients with pancolitis (Raddatz et al., European Journal of Gastroenterology
and Hepatology, 2005). This study should be mentioned and discussed.
2) The authors state that 49 biopsies from 27 different patients were examined
and that if patients were included twice, biopsies were taken at two different time
points.
Have samples been taken from different localisations within one patient, e.g.
comparing inflamed and non inflamed mucosa at one time point?
3) It should also be mentioned if patients had a pancolitis, a left sided colitis or
proctitis.
4) Is there any information about the intra-assay variability or the variability of
mRNA-expression in samples taken from two different inflamed regions within
the same patients ?
5) If the study included patients with both â## pancolitis and distal colitis â## is
there any difference with regard to clinical activity? Eventually a sub group
analysis should be performed.
6) There is no information about the premedication of the patients. If there was
any premedication it might have had an influence of mRNA-expression. Where
all the patients treatment naÃ¯ve?
7) The authors state in the results that a clinical and endoscopic improvement led
to decreased chemokine levels.
It becomes not entirely clear if this is mend for each individual patient or for the
whole collective. This point should be clarified. It may be helpful to correlate
delta-mRNA to delta CAI.
Minor points:
1) In some figures a positive correlation is hardly detectable visually because the
Y-axis is too compressed. Maybe it would be better to omit some outliners (CAE
versus MRP -14) or eventually to decompress the axis.
2) The CXC nomenclature of chemokines should be used instead or at least
mentioned in parenthesis.
What next?: Unable to decide on acceptance or rejection until the authors have
responded to the major compulsory revisions
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Reviewer's report
Title:Transcript levels of different cytokines and chemokines correlate with
clinical and endoscopic activity in ulcerative colitis
Version: 1Date:28 January 2008
Reviewer: Giuliano Ramadori
Reviewer's report:
The authors studied the correlation of mRNA-transcript levels of the chemokines
Interleukin-8, IP-10, MRP-14 and MIP-2ï#¡ and the clinical activity index (CAI) or
the endoscopic activity index (EAI) in patients with ulcerative colitis.
They found a significant correlation, concluding that real time PCR quantification
of both chemokines and cytokines might be helpful in grading inflammation of
intestinal mucosa in patients who have ulcerative colitis, suggesting such a
measurement as objective tool to evaluate therapeutic approaches in clinical
trials.
Although the reported chemokines have been reported to be elevated in patients
of ulcerative colitis earlier, the novelty of the present paper is the correlation of
quantitative PCR-results with clinical and endoscopical activity indices.
It is a potentially interesting paper, however there are some points of criticism.
Criticism
Major points:
1) The authors state in the background chapter that there are so far no data
concerning the correlation between transcript levels of selected pro-inflammatory
cytokines in mucosal biopsies and disease activity indices. This point is not
correct. Raddatz et al. did a comprehensive study showing a positive correlation
between interleukin-6 mRNA transcript levels and the colitis activity index in
patients with pancolitis (Raddatz et al., European Journal of Gastroenterology
and Hepatology, 2005). This study should be mentioned and discussed.
2) The authors state that 49 biopsies from 27 different patients were examined
and that if patients were included twice, biopsies were taken at two different time
points.
Have samples been taken from different localisations within one patient, e.g.
comparing inflamed and non inflamed mucosa at one time point?
3) It should also be mentioned if patients had a pancolitis, a left sided colitis or
proctitis.
4) Is there any information about the intra-assay variability or the variability of
mRNA-expression in samples taken from two different inflamed regions within
the same patients ?
5) If the study included patients with both â## pancolitis and distal colitis â## is
there any difference with regard to clinical activity? Eventually a sub group
analysis should be performed.
6) There is no information about the premedication of the patients. If there was
any premedication it might have had an influence of mRNA-expression. Where
all the patients treatment naÃ¯ve?
7) The authors state in the results that a clinical and endoscopic improvement led
to decreased chemokine levels.
It becomes not entirely clear if this is mend for each individual patient or for the
whole collective. This point should be clarified. It may be helpful to correlate
delta-mRNA to delta CAI.
Minor points:
1) In some figures a positive correlation is hardly detectable visually because the
Y-axis is too compressed. Maybe it would be better to omit some outliners (CAE
versus MRP -14) or eventually to decompress the axis.
2) The CXC nomenclature of chemokines should be used instead or at least
mentioned in parenthesis.
What next?: Unable to decide on acceptance or rejection until the authors have
responded to the major compulsory revisions
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Please review this paper.
user
Reviewer's report
Title:Transcript levels of different cytokines and chemokines correlate with
clinical and endoscopic activity in ulcerative colitis
Version: 1Date:28 January 2008
Reviewer: Giuliano Ramadori
Reviewer's report:
The authors studied the correlation of mRNA-transcript levels of the chemokines
Interleukin-8, IP-10, MRP-14 and MIP-2ï#¡ and the clinical activity index (CAI) or
the endoscopic activity index (EAI) in patients with ulcerative colitis.
They found a significant correlation, concluding that real time PCR quantification
of both chemokines and cytokines might be helpful in grading inflammation of
intestinal mucosa in patients who have ulcerative colitis, suggesting such a
measurement as objective tool to evaluate therapeutic approaches in clinical
trials.
Although the reported chemokines have been reported to be elevated in patients
of ulcerative colitis earlier, the novelty of the present paper is the correlation of
quantitative PCR-results with clinical and endoscopical activity indices.
It is a potentially interesting paper, however there are some points of criticism.
Criticism
Major points:
1) The authors state in the background chapter that there are so far no data
concerning the correlation between transcript levels of selected pro-inflammatory
cytokines in mucosal biopsies and disease activity indices. This point is not
correct. Raddatz et al. did a comprehensive study showing a positive correlation
between interleukin-6 mRNA transcript levels and the colitis activity index in
patients with pancolitis (Raddatz et al., European Journal of Gastroenterology
and Hepatology, 2005). This study should be mentioned and discussed.
2) The authors state that 49 biopsies from 27 different patients were examined
and that if patients were included twice, biopsies were taken at two different time
points.
Have samples been taken from different localisations within one patient, e.g.
comparing inflamed and non inflamed mucosa at one time point?
3) It should also be mentioned if patients had a pancolitis, a left sided colitis or
proctitis.
4) Is there any information about the intra-assay variability or the variability of
mRNA-expression in samples taken from two different inflamed regions within
the same patients ?
5) If the study included patients with both â## pancolitis and distal colitis â## is
there any difference with regard to clinical activity? Eventually a sub group
analysis should be performed.
6) There is no information about the premedication of the patients. If there was
any premedication it might have had an influence of mRNA-expression. Where
all the patients treatment naÃ¯ve?
7) The authors state in the results that a clinical and endoscopic improvement led
to decreased chemokine levels.
It becomes not entirely clear if this is mend for each individual patient or for the
whole collective. This point should be clarified. It may be helpful to correlate
delta-mRNA to delta CAI.
Minor points:
1) In some figures a positive correlation is hardly detectable visually because the
Y-axis is too compressed. Maybe it would be better to omit some outliners (CAE
versus MRP -14) or eventually to decompress the axis.
2) The CXC nomenclature of chemokines should be used instead or at least
mentioned in parenthesis.
What next?: Unable to decide on acceptance or rejection until the authors have
responded to the major compulsory revisions
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
assistant