Review for 10.1186/1471-230X-13-50 (2013)

Reviewer's report
Title:Autoantibodies Directed Against a Novel Cytoplasmic Compartment (Rods
and Rings) in Hepatitis C Virus Infection
Version: 1Date:26 November 2012
Reviewer: Carlo Selmi
Reviewer's report:
In this manuscript, the authors focus on the study of anti-rods and rings (anti-RR)
antibodies in patients with chronic HCV infection. In particular the authors
describe the pattern and its association with HCV treatment by interferon/ribavirin
that is responsible for the induction of this new specificity. They show images at
electron microscopy with cytoplasmic structures that may be the anti-RR
antigenic targets, but these data are not confirmed by further analysis. After
performing protein arrays, they identify new potential targets that may be reacting
with anti-RR sera. This study follows a recently published report and is of great
interest but some concerns arise.
MAJOR POINTS
1- The population studied in this manuscript includes a high number of HCV
patients (n= 315) but only 14 had been previously treated with interferon/ribavirin,
this is quite difficult to understand.
• Are the other patients receiving different therapies? Are they untreated? What is
the reason for the low number of patients treated with interferon/ribavirin even if
this therapy is considered as “cornerstone in the management of HCV infection”
(Introduction, page 4)?
• The association anti-RR and prior HCV treatment is the only significant finding
obtained in the clinical analysis, but it is based only on 14 patients. This is a
limitation of the study, as mentioned in the last paragraph of the Discussion, but it
should be more stressed.
2- Considering the weakness of the clinical associations of anti-RR antibodies, I
would focus the results description and discussion on the new targets identified
by protein arrays. I think Table 2 needs a longer description, to explain the role
that these targets physiologically play and what their possible link with anti-RR
antibodies is (only the influence on purine biosynthesis? Other mechanisms?).
3- The results on electron microscopy structures are intriguing, but showing
cytoplasmic structures that are present in anti-RR positive cells without
confirmation by further experiments is quite weak. This needs further study and
explanation.
MINOR POINTS
• The title is very generic and it does not tell what the main novelty of this study
on anti-RR antibodies is.
• Some words are not used homogeneously, as for HEp-2 cells that sometimes
are used with hyphen (i.e. page 6) and sometimes not (i.e. pages 2 and 4). Other
words are misspelled, as interferon (INF instead of IFN in page 9-Study
Population) and Triton X (misspelled as Trion X in page 7). I would suggest a
revision of the language used in the manuscript.
• References:
- a new paper on anti-RR antibodies was published by Carcamo WC et al in J
Clin Immunol in October 2012 and it should be added to the manuscript and
references list;
- reference 33 should be updated.
• Figures: it is not clear what to look at precisely, arrows may be helpful to direct
the reader’s attention. This could be used to indicate examples of rods and rings
in Figure 1, and what are the cytoplasmic bodies described in Figure 2.
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.