Kappa Free Light Chains in Multiple Sclerosis as a Marker of Intrathecal Humoral Response: A Sex-Disaggregated Study

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The article by Candeloro et al. focuses on the potential use of KFLCs as a better biomarker for diagnosing MS in CFS samples. The strength of this study is that the authors include the sex-related differences. However, in the present form, the manuscript has several flaws that do not allow it to be accepted for publication.

- The abstract must indicate what KFLCs are and the association with MS before mentioned that has been used as biomarkers. The relevance of the study must mentioned. Abovoid the wrong use of capitalization (Lines 20, 55, 59).

Line 71: use MS.

- This study has an essential bias since it is a monocentric approach. This point is relevant because it is not possible to generalize their findings. Another critical flaw is the sample size since fewer males than females exist. It is known that females are most susceptible to MS, but the authors include sex-related differences. However, the size of the number does not allow for the visualization of the variability of the results, limiting the study.

- The inclusion criteria must be described extensively, and healthy control must be included.

- Since this study uses different thresholds for KFCL indices, the authors must justify which is most relevant in the clinic.

- Regarding comparing OCB analysis with KFCL, it is important to establish that this diagnosis technique has limitations due to the dependence on the operator.

- There are confidence intervals that, in some comparisons, overlap, reducing the statistical significance of the differences. The authors must explore the low specificity in females in more detail since they are more susceptible to MS.

- The exact threshold must be adequately supported by statistical evidence.

- The authors must clarify how only the use of KFCL analysis will allow them to distinguish between other neuroinflammatory diseases

 

Comments on the Quality of English Language

The quality is deficient and must be extensively corrected.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The authors of the manuscript describe an original clinical study aimed at solving the urgent task of finding new diagnostic markers of multiple sclerosis based on the detection of free kappa light chains in the cerebrospinal fluid. 

The manuscript is written in an understandable and correct form. All the main aspects of the study were taken into account and described. The rationale for the presented research is made in a clear and understandable form with an indication of current trends. The results shown by the authors can make a significant contribution to the development of diagnostic algorithms for laboratory testing for multiple sclerosis and assistance to neurologists. Therefore, the conducted research will be relevant for publication in the journal Diagnostics.

However, I would recommend that the authors prepare a graphic abstract for the manuscript and replace some of the tables with illustrations with graphs. This will increase the visibility of the manuscript.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

The article is scientifically sound and addresses an important topic. However, improving the structure, language, and clarity, along with providing more detailed explanations and visual representations, will significantly enhance its readability and impact.

In Abstract

Line 20: Kappa Free Light Chains (KFLCs) seem to be a promising new biomarker, in the diagnostic framing of multiple sclerosis (MS) based on the analysis of cerebrospinal fluid (CSF).

The sentence is long and complex. The phrase "diagnostic framing" is redundant.

Suggested Revision:

Kappa Free Light Chains (KFLCs) are emerging as a promising biomarker for diagnosing multiple sclerosis (MS) through cerebrospinal fluid (CSF) analysis.

Line 32: Our study confirms the potential of KFLCs but shows how their specificity may vary between the two sexes, suggesting that sex-adjusted thresholds should be established and that KFLCs should be interpreted with caution in patients with suspected MS.

The sentence is repetitive and could be more concise.

The phrase "interpreted with caution" is generic and expected.

Suggested Revision:

The study highlights the potential of KFLCs as a biomarker for MS but emphasizes the need for sex-specific thresholds to improve diagnostic accuracy. 

Introduction

Line 44: In this context, CSF examination can replace distribution in time.

The sentence is unclear, and the phrase "replace distribution in time" is ambiguous.

Suggested Revision:

In this context, CSF examination plays a crucial role in diagnosing MS when clinical and MRI findings are inconclusive.

Materials and Methods

Line 113: Serum and CSF concentrations of albumin, IgG, and KFLC were measured by turbidimetry using the Optilite® instrument.

Lacks information about the sensitivity and precision of the measurements.

 

Tables:

The tables (e.g., Table 1 and Table 2) contain too much information, which can overwhelm the reader.

General Issues and Recommendations

Language and Clarity:

Many sentences are long and complex, making the text difficult to read.

The limitations section is insufficiently detailed.

 

Recommendation: Provide more information on the study's limitations, such as the lack of a healthy control group and the small sample size.

 

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The authors made some improvements to the manuscript. Still, some points to correct.

- Line 105: Mention all neurological disorders included. It is important.

- Figures 1 and 2: Each graph must include A, B, and C. Also in legends.

 

 

Comments on the Quality of English Language

The English could be improved to more clearly express the research.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf