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Referee comments: Referee 1

Posted by PLOS_ONE_Group on 24 Apr 2008 at 13:34 GMT

Referee 1's review:

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N.B. These are the comments made by the referee when reviewing an earlier version of this paper. Prior to publication the manuscript has been revised in light of these comments and to address other editorial requirements.
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This is a well written manuscript that reports exciting data concerning the inverse relationship between serum levels of anti P. gingivalis HtpG antibodies and periodontal disease severity/outcome. This group has previously reported somewhat preliminary data describing this relationship in certain periodontal diseases patients. The present manuscript describes a systematic and in-depth analysis of this relationship in a variety of disease conditions/stages and with appropriate enrollment numbers and matched control patients. The conclusions derived in this manuscript are consistent with the data and are of significant interest to periodontal disease researchers specifically as well as those studying other diseases in which inflammation is an important component of disease. It is possible that certain similarities exist among a group of diseases and that the results/conclusions reported here may have application to other diseases. More specific comments are as follows:

1. With regard to the PLoS One editorial criteria, I have no concerns that this manuscript is consistent with all seven of the criteria.

2. For preparation of the his-tagged HtpG protein, the method of determining the purity should be provided.

3. Under the heading, "Antibodies to P. gingivalis HtpG peptide p18", there is no data regarding the AP patients in either Table 3 or 4. Furthermore, Table 5 is not mentioned in the results section. Should the AP statement refer to Table 5?

4. The discussion is interesting and significant and I have no reservations about any statements made here. Of note, it could also be important to understand the conservation/variation in the p18 peptide among P. gingivalis isolates, as part of future studies. Are their more "virulent", less virulent" or more "protective, less protective" strains?