Review for 10.1186/1471-230X-14-26 (2014)

Reviewer's report
Title:Effect of gluten free diet on immune response to gliadin in patients with
non-celiac gluten sensitivity
Version:1Date:3 December 2013
Reviewer: Armin Alaedini
Reviewer's report:
This study evaluates antibody reactivity to gliadin in patients with “non-celiac
gluten sensitivity” in response to gluten withdrawal and examines the potential
correlation with clinical symptoms. The results appear to indicate a strong
correlation between gluten intake and the anti-gliadin antibodies in NCGS
patients, as well a correlation between the antibodies and symptoms. While
being a highly interesting and timely study, some issues need to be addressed
before publication.
1) Abstract and Background: The text of the Background makes the assumption
that the so-called “non-celiac gluten sensitivity” or “NCGS” is a gluten-dependent
condition. For example: “This is an emerging syndrome evoked by gluten
ingestion in patients ….” However, there is no evidence in this paper or others to
indicate that gluten proteins in wheat are actually responsible for the associated
symptoms. In Discussion section the authors say “A link between gluten and
symptoms has been clearly proved in NCGS patients” citing a paper by Carroccio
et al. I would suggest removing the sentence. The cited paper used “wheat
capsules” to challenge patients, not purified gluten. Similarly, the conclusions
from the cited Biesiekierski paper have been at least partly invalidated by a
follow-up study from the same authors. I would suggest addressing this fact in
Background and mentioning the possibility of non-gluten proteins in wheat as
potential contributors in NCGS.
2) Methods: Because the measurement of anti-gliadin antibodies is a central
aspect of this study, the article would greatly benefit from including a detailed
description of the methodology for the assay. This should include a discussion of
how the assay was normalized when testing patients before and 6 months after
the gluten-free diet.
3) Methods: It is not clear how the investigators scored the patient symptoms
from 0 to 3. The algorithm for this should be presented in detail.
4) Results: “In the CD group the persistence of AGA IgG after 6 months of GFD
did not show any correlation either with the compliance to the diet or the clinical
response following the gluten-free regimen.” This is in contrast to what one would
expect, as well as to what has been previously published for CD. Basically, the
authors are concluding that the anti-giadin antibody response in CD patients is
NOT dependent on gluten intake. As such, the paper should present at least a
brief overview of what has been previously published with regard to correlation
between AGA and gluten intake in CD, and to compare their results with those.
5) Discussion: “Probably, this short-time gluten exposure in NCGS patients was
not enough to evoke the reactivation of the innate immunity to produce AGA in
response to gliadin.” This sentence implies that AGA is produced as part of
innate immunity. However, there is no evidence to indicate that. Antibody
production is an adaptive immune response, even if it might involve innate
immunity.
6) Figure 1. It is not clear if the y-axis represents single patients. If so, it should
be labeled clearly, so that it is possible to see the drop in antibody level for each
single patient. For example, it needs to be clarified if the AGA titer drop from 100
to 10 for the first y-axis dots belong to the same patient.
7) In the format presented, the data are not convincing with regard to the
conclusion that there is a major difference in antibody response between NCGS
and CD patients. The authors have only presented the NCGS IgG data in Figure
1. The CD data appear to be omitted. Please include both IgG and IgA data for
NCGS and CD patients. What should be important is not so much whether the
antibody level goes from an arbitrary positive to an arbitrary negative, but instead
the extent of the decline in antibodies when comparing NCGS and CD cohorts.
The paper should include a statistical analysis to compare the extent of antibody
drop between NCGS and CD patients.
Level of interest: An article of importance in its field
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.