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of August 2012
The authors would like to thank the reviewers for their specific and helpful comments.
Please find enclosed the edited manuscript in word format (file name: tack et al 2012.doc)
Title: Serum parameters in the spectrum of coeliac disease: beyond standard antibody testing
Author: G.J.Tack
, R.L.J. van Wanrooij
, B. M. E. Von Blomberg
, H.Amini
, V.M.H. Coupe
, P.
, C. J. J. Mulder
M.W.J. Schreurs
Manuscript no: 1116128447734235
The manuscript has been improved according to the suggestions of the reviewer:
Major points
1. As suggested by the reviewer, we changed the title in ´serum´ parameters as this would
underline the evaluation of new parameters as opposed to the traditional serological parameters
used in celiac disease.
2. To provide more insight in the variation and clinical relevance of the serum levels determined,
we displayed the cut-off values of each ELISA-kit in the corresponding graph (dotted line in Figure 1).
Furthermore, the group of CD patients with biopsy proven remission, as previously included in our
study, can be considered a representative control group. Regarding the subject of age-dependency
the reviewer addresses a relevant point as a minimal increase of the levels of serum cytokines has
been reported in men but not woman (Young et al. Clinical and Experimental immunology 1999). In
accordance with current literature, in our study the group with uncomplicated CD is indeed
somewhat younger than the complicated CD group, but based on the relative small differences in
age in aforementioned minimal increase we argue this is not of clinical relevance. Nevertheless, in
case these parameters would be applied to various age groups, including both children and elderly,
this would be a point of concern. Yet, our patients of interest represent a homogenic group
regarding age, as they are almost without exception between 40-60 years of age.
We added the following sentence in the discussion: ‘Care must be taken in case our
findings are extrapolated to other age groups, as it can not be excluded that normal values vary
over age’
3. The reviewer raised the question whether complicated CD represents merely a higher level of
inflammation compared to CD, and possibly other inflammatory conditions. As we focus on ‘the
spectrum of coeliac disease’, inclusion of other comparison groups is beyond the scope of this study.
However, in the discussion we did place the various CD entities more in perspective with other
gastrointestinal diseases, with a specific focus on Crohn’s disease. By doing so, we hope to provide
more insight in our data that indeed suggests that complicated CD merely represents a more
extended inflammation state. In accordance with the suggestion of the reviewers we attempted to
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