Inflammation and Psoriasis: A Comprehensive Review
, Meda Sandra Orăsan 2, Oana-Alina Hoteiuc 1, Maria-Cristina Olănescu-Vaida-Voevod 1 and Teodora Mocan 1,3,*Round 1
Reviewer 1 Report
Comments and Suggestions for Authors
The review article by Qu et al., is an exhaustive and detailed summary of psoriasis covering all aspects of the disease with respect to the cause, diagnosis, treatment and molecular basis. The manuscript has been divided into six subsections mostly with appropriate contents. The review starts with section 1, describing the link between different genetic background and psoriasis followed by detailing the intrinsic and extrinsic triggers that are associated with Psoriasis and the clinical presentation. Section 2 summarizes the psoriasis diagnostic methods which includes both invasive (histopathology, serum/tissue biomarkers) and non-invasive methods in a detailed manner, in the context of how these methods could be used for both prognosis and diagnosis with specific examples. Section 3 describes the molecular pathophysiology of psoriasis, in which the different molecular pathways and mechanisms involved in psoriasis genesis to progression has been elucidated succinctly. Section 4 is definitely important since it deals with the co-morbidities of Psoriasis and elucidates the causal/consequential link between different comorbidities (IBD, CVD, Metabolic syndrome, Obesity and other inflammatory diseases) and Psoriasis. Section 5 provides details on the up-to-date therapeutic strategies involving biological (Antibodies), non-biological (small molecules) and nanotechnological approaches for Psoriasis treatment. Lastly section 6 deliberates the limitations on the current diagnosis and treatment strategies and briefly mentions the role of AI and personalized medicine in Psoriasis therapy. This is an exhaustive review on Psoriasis covering all the aspects of the disease. Probably due to this exhaustive nature of information, some discordance is noted in some sections. However, overall, this review could be a one-stop read for the readers to know everything about Psoriasis. Some major concerns are presented which need to be addressed before it is accepted for publication.
Major comments:
1. The authors can consider a broader title rather than the current title “ Inflammation and psoriasis. From physiopathology to innovative therapies” since the manuscript covers wider range of topics including diagnostic methods & comorbidities.
2. In multiple places, the abbreviations are not expanded at first use (ERAP I, PCR-SSP, mDC, PRR, MACE, FDG-PET/CT, CAC, HR, ATS, ACS, BSA, PGA, COPD, TAC, LBNPs & MTX) This needs to be done to improve the comprehensibility of the review.
3. The first section is titled as definition but this also includes subsections detailing the epidemiology, genetic background, triggers and clinical presentation. Hence this section can be renamed as introduction instead of definition.
4. Non-uniformity in terms of describing the tables. In some sections the tables are left for the authors to comprehend (for ex. Table 1, 2, 5 &6) whereas in other cases a proper summary of the table is provided (for ex. Table 3 & 4). Further, it would be better to discuss how these biomarkers described in Table 2 are linked to psoriasis pathogenesis (whether these biomarkers have a causal role or consequence of psoriasis?).
5. The authors should seriously reconsider sentence construction in several places. Manuscript is filled with grammatical mistakes and sentences that are not comprehensible (a few ex: line nos 50-51, 79-80, 93-96). Especially section 1 requires particular attention. Best option is to proof read the entire article by native English speaker.
6. What is HLA-Cw6? It has been introduced abruptly without any detailed information about this allele.
7. Line 77: “HLA-negative patients” This can’t be right. If the particular allele is absent then the allele name (HLA-???) needs to be clearly mentioned. Similarly “high PASI 90 response” does not sound right. It could be “high PASI 90 score”
8. It would also be better to discuss the conflicting reports/observations in this review with respect to the molecular players in psoriasis. For instance, Ref 55 in table 2 states that serotonin is increased in psoriasis lesional skin while in Ref 31, table 1, states that proinflammatory cytokines often high in psoriasis inhibits serotonin production.
9. Line 357: “IL-17A and IL17F are 50% homolog”. They could either be homologous or share 50% similarity/identity not “50% homolog”.
10. Use uniform gene symbols: IL8 and CXCL8 are the same. Use either one of them not both in different places.
11. What is OR in Figure 2? Is it odds ratio? If yes this needs to be mentioned in legends.
Comments on the Quality of English Language
Section 1 (Definition), in particular requires extensive langauge editing. Sentense construction needs special attention.
Author Response
We appreciate you taking the time to read through and comment on our manuscript. We value your efforts and recommendations, which have assisted us in raising the quality of our work. Your suggestions have been carefully evaluated, and the appropriate changes have been implemented in response. We sincerely hope that you will find our revised manuscript adequate, and we eagerly await your feedback.
Point-by-point response to Comments and Suggestions for Authors
1.The authors can consider a broader title rather than the current title “Inflammation and psoriasis. From physiopathology to innovative therapies” since the manuscript covers a wider range of topics including diagnostic methods & comorbidities.
Response 1: Thank you for pointing this out. We agree with this comment. Therefore, we changed the title into “Inflammation and psoriasis: a comprehensive review.”
- In multiple places, the abbreviations are not expanded at first use (ERAP I, PCR-SSP, mDC, PRR, MACE, FDG-PET/CT, CAC, HR, ATS, ACS, BSA, PGA, COPD, TAC, LBNPs & MTX) This needs to be done to improve the comprehensibility of the review.
Response 2: Agree. We have, accordingly, added the abbreviation expansions.
- The first section is titled as definition, but this also includes subsections detailing the epidemiology, genetic background, triggers and clinical presentation. Hence this section can be renamed as introduction instead of definition.
Response 3: We agree with this comment. Therefore, we modified section 1 title into Introduction
- Non-uniformity in terms of describing the tables. In some sections the tables are left for the authors to comprehend (for ex. Table 1, 2, 5 &6) whereas in other cases a proper summary of the table is provided (for ex. Table 3 & 4). Further, it would be better to discuss how these biomarkers described in Table 2 are linked to psoriasis pathogenesis (whether these biomarkers have a causal role or consequence of psoriasis?).
Response 4: We introduced a proper summary of Table 1,2,5 and 6 and a succinct paragraph explaining how biomarkers described in Table 2 are linked to psoriasis pathogenesis in 2.1. section.
- The authors should seriously reconsider sentence construction in several places. Manuscript is filled with grammatical mistakes and sentences that are not comprehensible (a few ex: line nos 50-51, 79-80, 93-96). Especially section 1 requires particular attention. Best option is to proof read the entire article by native English speaker.
Response 5: Thank you for your observation. We have, accordingly reconstructed the mentioned sentences and had our manuscript revised and corrected by a professional English translato. The updated text is highlighted in the resubmitted manuscript.
- What is HLA-Cw6? It has been introduced abruptly without any detailed information about this allele.
Response 6: HLA-Cw6 is the same as HLA-C*06:02. The information about this allele cand be found in line 62: “HLA-C*06:02 (PSORS 1) is the most likely allele linked to susceptibility, disease severity, comorbidities, phenotypic features (early-onset, guttate form) and variability in treatment response”
- Line 77: “HLA-negative patients” This can’t be right. If the particular allele is absent, then the allele name (HLA-???) needs to be clearly mentioned. Similarly, “high PASI 90 response” does not sound right. It could be “high PASI 90 score.”
Response 7: We agree with this comments. Indeed, the HLA-Cw6 alelle is absent. We modified the manuscript accordingly.
- It would also be better to discuss the conflicting reports/observations in this review with respect to the molecular players in psoriasis. For instance, Ref 55 in table 2 states that serotonin is increased in psoriasis lesional skin while in Ref 31, table 1, states that proinflammatory cytokines often high in psoriasis inhibits serotonin production.
Response 8: We agree with your observation and this aspect has been clarified in the new manuscript version. Ref 31 in Table 1 must be replaced because it explains how psoriasis may lead to depression rather than explaining how psychological stress contributes to psoriasis onset. In this manner, Ref 55 in Table 2 could stay in place and the conflicting observations could be eliminated. In the new version of manuscript Ref 31 in Table 1 is Ref 37, while Ref 55 in Table 2 has become Ref 63.
- Line 357: “IL-17A and IL17F are 50% homolog”. They could either be homologous or share 50% similarity/identity not “50% homolog”.
Response 9: We have corrected this error accordingly.
- Use uniform gene symbols: IL8 and CXCL8 are the same. Use either one of them, not both in different places.
Response 10: We modified the manuscript following your suggestion.
- What is OR in Figure 2? Is it odds ratio? If yes this needs to be mentioned in legends.
Response 11: We mentioned that OR in Figure 2 stands for odds ratio.
Response to Comments on the Quality of English Language
We regret there were problems with the English. The paper has been carefully revised and corrected by a professional English translator as to improve the grammar and readability.
Reviewer 2 Report
Comments and Suggestions for Authors1. The paper presents a lot of information about the genetic aspects and various studies related to psoriasis. However, it lacks critical analysis and discussion of the findings. After presenting the information, engage in a discussion about the implications of these findings. For instance, what do the genetic studies suggest about potential targeted therapies? Are there any controversies or gaps in the research that need addressing? Engaging critically with the information will elevate the depth of the review.
2. Consider comparing the genetic findings in psoriasis with other autoimmune diseases. Highlight similarities and differences in genetic susceptibility between psoriasis and conditions like rheumatoid arthritis, lupus, or Crohn's disease. This comparative analysis can provide a broader perspective on autoimmune mechanisms and potentially lead to insights about common pathways or therapeutic targets shared among these diseases.
3. Include a section on epigenetic modifications in psoriasis. Explore how DNA methylation, histone modifications, and non-coding RNAs regulate gene expression in psoriatic lesions. Discuss the impact of epigenetic changes on the activation or suppression of psoriasis-related genes. Address recent studies investigating epigenetic therapies and their potential in modulating gene expression patterns in psoriasis. This section could provide insights into the dynamic regulation of the psoriasis genome beyond genetic variations.
4. Delve into functional genomics studies that elucidate the biological functions of psoriasis-associated genes. Highlight experiments such as gene knockdowns, knockout animal models, or CRISPR/Cas9-based gene editing used to validate the functional relevance of specific genetic variants. Discuss the implications of these experiments on our understanding of psoriasis biology and potential therapeutic targets. Evaluate the challenges and advancements in experimental validation techniques, emphasizing recent breakthroughs in the field.
Comments on the Quality of English LanguageMinor editing of English language required
Author Response
We appreciate you taking the time to read through and comment on our manuscript. We value your efforts and recommendations, which have assisted us in raising the quality of our work. Your suggestions have been carefully evaluated, and the appropriate changes have been implemented in response. We sincerely hope that you will find our revised manuscript adequate, and we eagerly await your feedback.
Point-by-point response to Comments and Suggestions for Authors
- The paper presents a lot of information about the genetic aspects and various studies related to psoriasis. However, it lacks critical analysis and discussion of the findings. After presenting the information, engage in a discussion about the implications of these findings. For instance, what do the genetic studies suggest about potential targeted therapies? Are there any controversies or gaps in the research that need addressing? Engaging critically with the information will elevate the depth of the review.
Response 1: We agree with the reviewer that further elaborating on this point would be helpful. However, we believe that we highlighted in section 1.2 - Genetic background what are the implications of these findings, concretely how these genes influence response to treatment or the clinical presentation of a patient with psoriasis.
- Consider comparing the genetic findings in psoriasis with other autoimmune diseases. Highlight similarities and differences in genetic susceptibility between psoriasis and conditions like rheumatoid arthritis, lupus, or Crohn's disease. This comparative analysis can provide a broader perspective on autoimmune mechanisms and potentially lead to insights about common pathways or therapeutic targets shared among these diseases.
Response 2: Thank you for your suggestions. We value your input and have given your proposal a special section: 4.4. Other comorbidities. Autoimmune skin disorders linked to psoriasis, that briefly describes the intriguing links between psoriasis and other autoimmune diseases such as vitiligo, bullous pemphigoid and hidradenitis suppurativa .
- Include a section on epigenetic modifications in psoriasis. Explore how DNA methylation, histone modifications, and non-coding RNAs regulate gene expression in psoriatic lesions. Discuss the impact of epigenetic changes on the activation or suppression of psoriasis-related genes. Address recent studies investigating epigenetic therapies and their potential in modulating gene expression patterns in psoriasis. This section could provide insights into the dynamic regulation of the psoriasis genome beyond genetic variations.
Response 3: We have revised the text to address your suggestion as epigenetic modifications indeed highlight the dynamic regulation of the psoriasis genome. The corresponding paragraph has been included in Section 1, Subsection 1.2., of the resubmitted manuscript.
- Delve into functional genomics studies that elucidate the biological functions of psoriasis-associated genes. Highlight experiments such as gene knockdowns, knockout animal models, or CRISPR/Cas9-based gene editing used to validate the functional relevance of specific genetic variants. Discuss the implications of these experiments on our understanding of psoriasis biology and potential therapeutic targets. Evaluate the challenges and advancements in experimental validation techniques, emphasizing recent breakthroughs in the field.
Response 4: We have, accordingly updated the manuscript upon CRISPR/Cas-9 genome editing. The corresponding paragraph has been added to Section 1, Subsection 1.2., of the resubmitted manuscript.
Response to Comments on the Quality of English Language
We regret there were problems with the English. The paper has been carefully revised and corrected by a professional English translator as to improve the grammar and readability.
Round 2
Reviewer 1 Report
Comments and Suggestions for AuthorsAuthors have addressed my concerns.
Reviewer 2 Report
Comments and Suggestions for AuthorsI have no comments
Comments on the Quality of English LanguageMinor editing of English language required
