PONE-D-20-23955

TST conversions and an increase in systemic interferon-gamma after MTX introduction in psoriasis patients: An interventional study associated with a cohort.

PLOS ONE

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Reviewer #2: Partly

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Reviewer #2: Yes

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Reviewer #1: Immunosuppression is an important cause of the reactivation of LTBI. Although there are no highly specific diagnostic tests for the diagnosis of LTBI, the use of TST and IGRA are surrogate markers. This study provides prospective data to interpret TST/IGRA conversion in patients with psoriasis who are taking MTX. However, the small sample size makes the data difficult to interpret. Given that participants were BCG vaccinated, the significance of TST changes, while IGRA remains unchanged is hard to interpret. Perhaps the results are a result of boosting (although the repeat test is at 90 days)? I appreciate that the authors have acknowledged several of the limitations of the TST however the sample size is very small, making it difficult to interpret further. I can see that there is a sample size calculation, perhaps a bio-statistician is better placed to comment if conclusions can be made based on the calculation and sample size (not sure if this has already been completed?). It does however, seem the authors have addressed some of the concerns of the previous reviewers.

Although reassuring that no one developed TB in the three-month period, it is a very short follow up period.

- Mix of past and present tense e.g. line 172 (there were no exclusions…), line 241, 317

- Line 206 change to “they were advised to attend the consultation….”

- Line 212 remove “they presented”

- Line 234: should missing data be considered zero or not applicable, as this may artificially increase the number of negative test results (or where these tests not considered negative)?

- Line 276: can this be worded more clearly?

- Line 312: ?”report a discordance between…”

- Line 360/1 – sentence structure needs to be changed

- Sometimes the discussion is a little difficult to follow, one final proofread with a focus on structure may help.

Reviewer #2: In the "Discussion" session, the authors did not mention the possibility of "Boosting effect" occurrence. Even though the TST repetition was performed 12 weeks after the first exam, "Boosting effect" could had happened.

Reference: Cauthen GM, Snider DE Jr, Onorato IM. Boosting of tuberculin sensitivity among Southeast Asian refugees. Am J Respir Crit Care Med. 1994;149(6):1597-1600. doi:10.1164/ajrccm.149.6.8004319

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TST  conversions and systemic interferon-gamma increase after methotrexate introduction in psoriasis patients

PONE-D-20-23955R1

Dear Dr. Medeiros,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Remco PH Peters, MD, PhD, DLSHTM

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Please respond to Reviewer 3's suggestions:

Reviewer 3:

A single arm, self-controlled study was conducted to determine if the results of the tuberculin skin test (TST) or interferon-gamma release assay in psoriasis patients change after 12 weeks of methotrexate treatment. Clinical and inflammatory markers were also investigated. The proportion of positive TST cases significantly increased at post-treatment. Additionally, serum IFN-γ increased at post-treatment.

Minor revisions:

1-  Line 132: Indicate the statistical testing method which achieves 80% power.

2-  Line 212: Indicate the specific type of Wilcoxon test, as there are at least two.

3- Indicate if any adverse events were observed during the course of the study.

Reviewers' comments: