Author's response to reviews Title:Influence of KIR genes and their HLA ligands in the pathogenesis of leprosy in a hyperendemic population of Rondonopolis, Southern Brazil Authors: Luciana R Jarduli ([email protected]) Hugo V Alves ([email protected]) Fabiana C Souza ([email protected]) Elaine V C Marcos ([email protected]) Ana C Pereira ([email protected]) Ida M F Dias-Baptista ([email protected]) Vinícius M Fava ([email protected]) Marcelo T Mira ([email protected]) Milton O Moraes ([email protected]) Marcos C L Virmond ([email protected]) Jeane E L Visentainer ([email protected]) Version:4Date:14 July 2014 Author's response to reviews: see over COVERING LETTER BMC Infectious Diseases – BioMed Central Editor‐in‐Chief Professor Philippa Harris Floor 6, 236 Gray's Inn Road London, WC1X 8HB United Kingdom Telephone: 20‐3192‐2009 Fax:20‐3192‐2010 Email:[email protected] Subject: Resubmission of manuscript (original paper) 14th July, 2014 Dear Editor Dr Philippa Harris: We would like to resubmit the following manuscript for possible publication: Influence of KIR genes and their HLA ligands in the pathogenesis of Leprosy in a hyperendemic population of Rondonópolis, Southern Brazil. Luciana Ribeiro Jarduli; Hugo Vicentin Alves; Fabiana Covolo de Souza; Elaine Valim Camarinha Marcos; Ana Carla Pereira; Ida Maria Foschiani Dias‐Baptista; Vinícius Medeiros Fava; Marcelo Távora Mira; Milton Ozório de Moraes; Marcos da Cunha Lopes Virmond; Jeane Eliete Laguila Visentainer Address reprint requests to: Jeane Eliete Laguila Visentainer Universidade Estadual de Maringá ‐ Departamento de Ciências Básicas da Saúde. Bloco T‐20, sala 111. Av. Colombo, 5790. Zona 07. Maringá, PR, Brazil – CEP 87020‐900 Phone number: (+55 44) 3011‐5392 E‐mail: [email protected] Point‐by‐point response to the concerns: Firstly, we would like to thank to editor and reviewers for their comments and suggestions in this second step. We affirm that the manuscript has been revised according to editor and reviewer comments and to journal style. Reviewer: William Berrington Reviewer's report: Major compulsory Revisions 1) Please address multiple comparisons (at least in table 2). How to adjust for the additional studies may be more statistically difficult (for example looking at gene‐gene interactions). By my count there are at least 15 KIR gene analyzed and P values should be adjusted to determine if significance still remains. This should be added to the discussion or results section. This has nothing to do with multiple logistic regression, which was performed in later analyses. R: Thank you for your observation. We performed these corrections in Table 2, Methods and Results section, according your suggestion. There are 14 KIR genes, and then the Bonferroni correction was performed multiplying the P value by 14. (Page 5, lines 17‐18; Page 6, lines 1 and 2; Page 7, Lines 13‐15). 2) Since HLA is on different genome than KIR genes, Hardy‐weinberg equilibrium cannot be conferred between the two gene groups. Not sure what the authors are referring to on page 7 line 5 with "homogeneous distribution of the haplotypes of the KIR gene". If data on the heterogeneity of the KIR gene was not obtained, then HW equilibrium cannot be done. Since there is no data on the heterozygosity of the KIR domain, the HW distribution q^2+2qr+r^2 cannot be done, it is a simple limitation of the technique and should be stated in the discussion. R: Thanks for the observation and major comments in this point. We agree with your observation and we decided rewrite this section just with the information about the HLA genes and then, avoid the comments about haplotypes of the KIR gene: “When only the HLA ligands of the KIR gene were evaluated, they were in equilibrium of Hardy‐Weinberg, however no significant differences in their frequencies were found between groups.'' (Page 7, line 12‐14). Sincerely, _________________________________ Correspondent author Jeane Eliete Laguila Visentainer, Ph.D. State University of Maringá, PR, Brazil Health Sciences Center Immunogenetics Laboratory Phone: (+ 55 44) 3011‐5392 Email: [email protected]