Reviewer's report
Title:The impact of MFG-E8 in chronic pancreatitis: potential for future
immunotherapy?
Version: 1Date:28 August 2012
Reviewer: Patrick Yachimski
Reviewer's report:
The authors investigate expression of MFG-E8 in chronic pancreatitis, previously
uninvestigated in this realm. The principal findings are that MFG-E8 is
overexpressed in chronic pancreatitis relative to "healthy" controls, and that
MFG-E8 may correlate with severity of pain in CP. The experimental assays are
appropriate and the findings are of relevance and interest. I would offer the
following comments.
1) The introduction needs to be more succinct and streamlined--there is an
extensive discussion of MFG-E8 expression in extrapancreatic tissue and rat
sepsis models, which are not entirely relevant to the introduction. The
introduction would be more powerful if the authors quickly stated the rationale for
MFG-E8 expression in a pancreatic model.
2) It would be appropriate to include some additional clinical data from the
subjects with chronic pancreatitis, in part to address the role of possible systemic
confounders influencing MFG-E8 expression. Of particular interest would be the
tobacco use/smoking history of the enrolled subjects. Smoking is an independent
risk factor for development of chronic pancreatitis, and may have direct impact on
both the composition of secretions and development of pancreatic fibrosis. Might
smoking influence MFG-E8 expression?
3) It is probably not appropriate to include patients with autoimmune pancreatitis
in the chronic pancreatitis cohort. While, arguably, autoimmune pancreatitis may
progress to a burnt-out stage resembling fibrotic chronic pancreatitis, the
pathogenesis and histopathology of autoimmine pancreatitis is sufficiently distinct
from chronic pancreatitis of other etiologies to suggest that this is a different
disease entity (not even, in fact, pancreatitis, but merely the pancreatic
manifestation of a systemic IgG4-mediated disorder).
4) What was the nature of the surgical resections performed--ie Whipple, Frey,
etc.
5) Regarding the correlation between MFG-E8 expression and fractalkine
expression, the text states that the P value for this relationship is <0.01 and
Figure 3A states that the P value is <0.02. Which is correct? In either case, a r
value of 0.34 is a relatively modest correlation, independent of statistical
significance.
6) The assay of MFG-E8 expression in pancreatic stellate cells is the most
important experiment in the manuscript. PSCs are central to the pathogenesis of
fibrosis in chronic pancreatitis, and it is of critical importance for us to elucidate
and understand the stimuli which transform these cells from a quiescent state to
a myofibroblast phenotype, and vice versa. This experiment should be
emphasized more prominently in the manuscript. Some attention to PSCs is
included in the discussion, however the authors might want to include some
discussion of PSCs in the introduction, as well.
7) The authors' conclusion that the "MFG-E8 [is] a promising candidate as a
novel therapeutic target in future treatment of painful chronic pancreatitis" seems
a bit strong--perhaps a reasonable hypothesis for promising future investigation,
but not fully supported on the basis of these data.
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:
No competing interests.
Reviewer's report
Title:The impact of MFG-E8 in chronic pancreatitis: potential for future
immunotherapy?
Version: 1Date:28 August 2012
Reviewer: Patrick Yachimski
Reviewer's report:
The authors investigate expression of MFG-E8 in chronic pancreatitis, previously
uninvestigated in this realm. The principal findings are that MFG-E8 is
overexpressed in chronic pancreatitis relative to "healthy" controls, and that
MFG-E8 may correlate with severity of pain in CP. The experimental assays are
appropriate and the findings are of relevance and interest. I would offer the
following comments.
1) The introduction needs to be more succinct and streamlined--there is an
extensive discussion of MFG-E8 expression in extrapancreatic tissue and rat
sepsis models, which are not entirely relevant to the introduction. The
introduction would be more powerful if the authors quickly stated the rationale for
MFG-E8 expression in a pancreatic model.
2) It would be appropriate to include some additional clinical data from the
subjects with chronic pancreatitis, in part to address the role of possible systemic
confounders influencing MFG-E8 expression. Of particular interest would be the
tobacco use/smoking history of the enrolled subjects. Smoking is an independent
risk factor for development of chronic pancreatitis, and may have direct impact on
both the composition of secretions and development of pancreatic fibrosis. Might
smoking influence MFG-E8 expression?
3) It is probably not appropriate to include patients with autoimmune pancreatitis
in the chronic pancreatitis cohort. While, arguably, autoimmune pancreatitis may
progress to a burnt-out stage resembling fibrotic chronic pancreatitis, the
pathogenesis and histopathology of autoimmine pancreatitis is sufficiently distinct
from chronic pancreatitis of other etiologies to suggest that this is a different
disease entity (not even, in fact, pancreatitis, but merely the pancreatic
manifestation of a systemic IgG4-mediated disorder).
4) What was the nature of the surgical resections performed--ie Whipple, Frey,
etc.
5) Regarding the correlation between MFG-E8 expression and fractalkine
expression, the text states that the P value for this relationship is <0.01 and
Figure 3A states that the P value is <0.02. Which is correct? In either case, a r
value of 0.34 is a relatively modest correlation, independent of statistical
significance.
6) The assay of MFG-E8 expression in pancreatic stellate cells is the most
important experiment in the manuscript. PSCs are central to the pathogenesis of
fibrosis in chronic pancreatitis, and it is of critical importance for us to elucidate
and understand the stimuli which transform these cells from a quiescent state to
a myofibroblast phenotype, and vice versa. This experiment should be
emphasized more prominently in the manuscript. Some attention to PSCs is
included in the discussion, however the authors might want to include some
discussion of PSCs in the introduction, as well.
7) The authors' conclusion that the "MFG-E8 [is] a promising candidate as a
novel therapeutic target in future treatment of painful chronic pancreatitis" seems
a bit strong--perhaps a reasonable hypothesis for promising future investigation,
but not fully supported on the basis of these data.
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:
No competing interests.
Please review this paper.
user
Reviewer's report
Title:The impact of MFG-E8 in chronic pancreatitis: potential for future
immunotherapy?
Version: 1Date:28 August 2012
Reviewer: Patrick Yachimski
Reviewer's report:
The authors investigate expression of MFG-E8 in chronic pancreatitis, previously
uninvestigated in this realm. The principal findings are that MFG-E8 is
overexpressed in chronic pancreatitis relative to "healthy" controls, and that
MFG-E8 may correlate with severity of pain in CP. The experimental assays are
appropriate and the findings are of relevance and interest. I would offer the
following comments.
1) The introduction needs to be more succinct and streamlined--there is an
extensive discussion of MFG-E8 expression in extrapancreatic tissue and rat
sepsis models, which are not entirely relevant to the introduction. The
introduction would be more powerful if the authors quickly stated the rationale for
MFG-E8 expression in a pancreatic model.
2) It would be appropriate to include some additional clinical data from the
subjects with chronic pancreatitis, in part to address the role of possible systemic
confounders influencing MFG-E8 expression. Of particular interest would be the
tobacco use/smoking history of the enrolled subjects. Smoking is an independent
risk factor for development of chronic pancreatitis, and may have direct impact on
both the composition of secretions and development of pancreatic fibrosis. Might
smoking influence MFG-E8 expression?
3) It is probably not appropriate to include patients with autoimmune pancreatitis
in the chronic pancreatitis cohort. While, arguably, autoimmune pancreatitis may
progress to a burnt-out stage resembling fibrotic chronic pancreatitis, the
pathogenesis and histopathology of autoimmine pancreatitis is sufficiently distinct
from chronic pancreatitis of other etiologies to suggest that this is a different
disease entity (not even, in fact, pancreatitis, but merely the pancreatic
manifestation of a systemic IgG4-mediated disorder).
4) What was the nature of the surgical resections performed--ie Whipple, Frey,
etc.
5) Regarding the correlation between MFG-E8 expression and fractalkine
expression, the text states that the P value for this relationship is <0.01 and
Figure 3A states that the P value is <0.02. Which is correct? In either case, a r
value of 0.34 is a relatively modest correlation, independent of statistical
significance.
6) The assay of MFG-E8 expression in pancreatic stellate cells is the most
important experiment in the manuscript. PSCs are central to the pathogenesis of
fibrosis in chronic pancreatitis, and it is of critical importance for us to elucidate
and understand the stimuli which transform these cells from a quiescent state to
a myofibroblast phenotype, and vice versa. This experiment should be
emphasized more prominently in the manuscript. Some attention to PSCs is
included in the discussion, however the authors might want to include some
discussion of PSCs in the introduction, as well.
7) The authors' conclusion that the "MFG-E8 [is] a promising candidate as a
novel therapeutic target in future treatment of painful chronic pancreatitis" seems
a bit strong--perhaps a reasonable hypothesis for promising future investigation,
but not fully supported on the basis of these data.
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:
No competing interests.
assistant