Review for 10.1186/1471-230X-13-14 (2013)

Reviewer's report
Title:The impact of MFG-E8 in chronic pancreatitis: potential for future
immunotherapy?
Version: 1Date:29 August 2012
Reviewer: Thomas Griesbacher
Reviewer's report:
The manuscript describes correlations of expression of MFG-E8 with pain and
fibrosis in pancreatic tissue from patients with chronic pancreatitis. The data
clearl are very interesting. There are a few (minor) points which should be
observed, however:
1) Statistical analysis: In the case of comparison of more than 2 groups the
authors appear to have used the Mann-Whitney U-test as post-test (after the
Kruskal-Wallis test). However, the Mann-Whitney U-test is only valid for pairwise
comparisons. In case of the data shown in Fig. 4 one group (pain 0) is used twice
for comparisons, which violates the assumptions of the Mann-Whitney U-test and
results of the procedure therefore might be incorrect. In this particular instance a
(non-parametric) post-test for multiple comparisons (with a control) should be
used in order to achieve correct conclusions.
2) Thourghout the manuscript (abstract, results, discussion...) the authors state
that MFG-E8 expression correlated with the severity of pain and the severity of
fibrosis. This is not really correct. In the case of pain, MFG-E8 only correlated
with the presence of pain, but not with its severity as expression evels were very
similar in patients with mild pain and in those with moderate-to-severe pain. This
must be stated more clearly and sicussion should be more cautious. Similarly, in
the case of correlation with fibrosis, it should be noted that MFG-E8 was only
elevated in the severe fibrosis goup, while being similar to control levels in the
mild fibrosis group; it might be argued that the use of the term 'correlation' might
also be not entirely adequate in this case.
3) Data shown in Fig.3A (MFG-E8 & fractalkine): There is a discrepancy between
the text in the Results section and the figure with respect to the significance level.
In the text the probability value p for the correlation is given as <0.01, while in the
figure it is indicated as <0.02. Looking at the individual data points given in the
figure, the possibility of a bell-shaped relationship remains so that the 'correlation'
should again be discueed cautiously.
4) Apart from describing a positive relationship between expression of MFG-E8
and pain/fibrosis, the authors discuss that MFG-E8 might be causally involved in
the induction of pain and fibrosis. Although this is of course a valid hypothesis
that would fit the data, the authors shoud at least briefly discuss two other,
alternative principal possibilities: A) MFG-E8 expression could be elicited by the
same (unknown) common factor or event that also leads to the induction of pain
and fibrosis. Even if MFG-E8 would neither cause pain or fibrosis, the same
correlation between MFGE8 and pai/fibrosis would result. B) MFG-E8 might even
be hypothesised to be a protective (analgetic, antifibrotic) factor that could be
released by the tissue in order to limit pain and fibrosis; in such a case it still
would be very conceivable that in situations of severe pain and/or severe fibrosis
more of 'protective' factors could be released; the result would be the same
observation as in the current study: a positive relationship between MFG-E8 and
pain/fibrosis.
(If case B was a bit confusing now, here an analog example: patients with
severely painful conditions likely have a greater endogenous release of
endorphins than patients with only mild pain while there will be no or only minimal
endorphin release in persons wihout pain: endorphin release in this case
correlates positively with pain, but clearly we know that endorphins are not
algesic...)
The authors should discuss what published data would make their hypothesis
more likely than the other possibilities of explanation.
5) Figure legends should not repeat the explanation of the results (this is done
already in the Resuts section), but should explain what is shown (e.g.
"relationship of ... and ... in tissue samples of ...; data are expressed as... etc.",
number of experiments...)
6) Table 1 might be deleted as its contents can easily (and are already anyway)
described in the Results section.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests