Please summarize the main findings of the study: The study investigated SNPs of some cytokine genes in a sample of patients with anti-NMDAR encephalitis. No significant variations were observed between patients and control. The IL-1β rs16944 SNP was an exception and G allele frequency was significantly decreased in patients.

Please highlight the limitations and strengths: The main limitation of this study is the lacking of proper statistical analysis. First, the p-value was not corrected due to multiple comparisons. Second, the authors estimated odds ratio (OR) and 95% CI, but their data were not given in Table 1. Whatever the methods used, regression analysis must be applied in estimating the OR and 95% CI and under different genetic models (recessive, dominant, over-dominant and co-dominant).

Please comment on the methods, results and data interpretation. If there are any objective errors, or if the conclusions are not supported, you should detail your concerns: • Methods: No detailed information about the genotyping methods was given; otherwise, a reference(s) can be mentioned. • Results and conclusions: They are not well-elaborated and clearer and concise presentations are required; for instance, the authors used the word “absence” in describing the decreased frequency of G allele. Actually, it was a decreased frequency of allele rather than absence.

With interest the manuscript entitled “” was reviewed. The subject was novel; however, a major revision is required before publication. • As a general note, the cytokine genes have to be abbreviated as they appear in scientific literature; TNFA, IL1B, IL4, IL6, IL10 and IL17A. Alleles also must be written in italic font. • Abstract: 1. It was written: we enrolled 107 patients with anti-NMDAR encephalitis as well as 202 inpatient controls; what did the author mean with inpatient controls. If we inspect the matter in the methods; we found that controls were consenting volunteers, having no first-degree relative with autoimmune diseases. So, please clear this point. 2. It was written: Genotyping determination of all 309 patients was conducted for the IL-1β rs16944, IL-4 rs2243250, IL-4 rs2070874, IL-6 rs1800796, IL-10 rs1800872 and IL-17 rs2275913 genes. Actually, they are gene SNPs or variants rather than genes. Of course, the gene abbreviation has to be considered as early given. 3. In line 14: Delete “the frequencies of” and add “SNPs” after IL17 in line 15. 4. The conclusions have to be revised, and must be limited by the main findings of study. For instance, in which basis you concluded that patients with anti-NMDAR encephalitis exhibit a distinct immunological profile. Further, it was stated: we found that patients carrying certain cytokine-related SNPs may be at risk of more severe outcomes associated with this condition. The presented results in the manuscript did not support such conclusion. 5. In line 19, it was stated: absence of G allele in IL-1β rs16944 may increase susceptibility to anti-NMDAR. If you examine your results you find that this allele showed a decreased frequency in patients; so, it is a protective allele rather than a susceptibility allele. Please, give this point a thought. • Introduction 1. In line 9: TNFα, IL17A and CXCL13; they must be written like tumor necrosis factor-α (TNF-α), interleukin-17A (IL-17A) and CXCL13. 2. In line 12: change IL17A to IL-17A. 3. In line 13: change Interleukin 10 (IL-10) and interleukin 4 (IL-4) to IL-4 and IL-10. 4. In lines 22-23: change IL-1β, IL-4, TNF-α and IL-10 TNFA, IL1B, IL4 and IL10. 5. In lines 25-26: Nevertheless, recent studies found that some polymorphisms do not affect susceptibility in anti-NMDAR encephalitis; The statement requires supporting references. • Methods 1. SNPs Genotyping: No detailed information about the genotyping methods was given; otherwise, a reference(s) can be mentioned. 2. Statistical analysis: The study lacks a proper statistical analysis. First, the p-value was not corrected due to multiple comparisons. Second, the authors estimated odds ratio (OR) and 95% CI, but their data were not given in Table 1. Whatever the methods used, regression analysis must be applied in estimating the OR and 95% CI and under different genetic models (recessive, dominant, over-dominant and co-dominant). • Results 1. Participants: Normally, we do not start a sentence with an absolute number like “8” in line 6; it is better to be Eight. 2. The results have to be clear and concise. For instance; A) these two patient groups; you have to clarify the status of control. B) In addition, we compared the frequencies of A, G, and T alleles between the control and anti-NMDAR encephalitis groups; It is a confusing statement as you presented three alleles, and you have six SNPs, D) As early given, there was no absence of allele, and instead, there was a decreased frequency, and the allele is suggested to be protective. • Discussion: 1. It is OK, but in line 19 (page 5), it was stated: Our study was concentratd on the gene polymorphisms of cytokines and chemokines. First correct concentratd to concentrated. Second, none of the six investigated cytokines was a chemokine. 2. In line 22: clear and concise conclusion has to be given and must be limited by the main findings of study.