Ethics approval and consent to participate
Included subjects donated peripheral blood and induced sputum samples following oral and written informed consent. Ethical approval for Sweden was obtained from the Regional Ethics Review Board in Linköping, (2016/237-31) and for Peru from the Institutional Committee on Research Ethics of the Cayetano Heredia National Hospital for the inclusion of patients (082-018) and by Universidad Peruana Cayetano Heredia Institutional Review Board for the inclusion of healthy subjects (101773). The study protocol included questionnaires on respiratory and overall health, the evaluation of IGRA status and sputum samples for DNA extraction. The subjects’ samples and questionnaires were not linked to any personal information at any stage of the study. The sputum sample collections were performed in accordance with guidelines from the Department of Respiratory Medicine at Linköping University Hospital. In Sweden, the IGRA samples (QuantiFERON-TB Gold) were collected and analysed by medical personnel according to the guidelines at the Department of Clinical Microbiology at Linköping University Hospital. In Peru, the IGRA samples (T-SPOT.TB) was taken and analysed by medical students under supervision.
Consent for publication
Availability of data and materials
The datasets generated and/or analysed during the current study are not publicly available due to intellectual property restrictions but are available from the corresponding author on reasonable request.
The authors declare that they have no competing interests.
This study was funded through generous grants from Forskningsrådet Sydöstra Sverige (FORSS-932096), the Swedish Research Council (2015-02593, 2018-02961 and 2018-04246), the Swedish Heart Lung Foundation (20150709 and 20180613) and CONCYTEC - PROCIENCIA (106-2018-FONDECYT). The DNA methylome data were generated at the Bioinformatics and Expression Analysis Core Facility at the Department of Biosciences and Nutrition, which is supported by the Board of Research at the Karolinska Institute, Stockholm. The computations were enabled by resources provided by the Swedish National Infrastructure for Computing (SNIC) at Linköping University campus partially funded by the Swedish Research Council through grant agreement (2018-05973). We further want to acknowledge the support with a travel grant from the World Infection Fund.
M.L, N.I, C.U-G, M.M-A and J.P designed and conceptualized the study. I.P and N.I performed the laboratory work and the related analyses. J.D, S.S and M.L designed and performed the bioinformatic analyses of the data. J.D and S.S wrote the scripts for analysis and created figures. I.P, N.I, J.D, S.S, and M.L wrote the manuscript. J.D and M.L are co-authors of a patent application “Biomarker for detection of mycobacterial infection and exposure” filed on February 2nd with the Swedish Patent Registry (100692).
We direct our gratitude to the staff at Linköping University Hospital and the Vrinnevi Hospital in Norrköping for assistance in sample collection and all the subjects for donating samples. We especially thank Hilma Hård af Segerstad, Helena Rylander, Elsa Reuterswärd and Emma Marttala for establishing the study logistics and starting up inclusions. We are also grateful for the valuable help provided by Ronald Cadillo Hernandez, Rodrigo Cachay Figueroa and the medical personnel at the Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia. We would like to acknowledge the Bioinformatics Core Facility, Faculty of Medicine and Health Sciences and Clinical Genomics Linköping, Science for Life Laboratory, Department of Biomedical and Clinical Sciences, Linköping University, for assistance with bioinformatics analyses.