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Leukocytes methylome of individuals from leprosy endemic area

ABSTRACT: Inflammaging is the name given to this chronic and asymptomatic inflammatory state generated by the aging process and by chronic and infectious diseases. Chronic diseases can alter the epigenetic profile of tissues leading to an increased epigenetic aging and some of the differentially methylated genes can be used to characterize the disease and as disease biomarkers. Leprosy is an infection caused by Mycobacterium leprae and can be lifelong, exposing the individual to a low-grade inflammation environment. In this study, we evaluated the inflammatory profile in 35 individuals from a leprosy endemic area from Brazil by cytokine analysis with a luminex assay. In adition, we investigated the leucocytes genome-wide DNA methylation profile using the Infinium MethylationEPIC BeadChip array. A total number of 31 CpGs were significantly methylated, between cases and controls, which belonged to 8 genes potentially peripherally perturbed in the pathogenesis of the disease. Affected individuals from endemic area were epigenetically aged in relation to control samples and interesting control samples from endemic area were aged in relation to unaffected control samples from non-endemic area. In conclusion, leprosy showed a deregulated methylation profile in comparison with control samples. The epigenetic analysis provided valuable clues for further investigations in understanding peripherical blood leprosy alterations and the use of these genes as biomarkers.

ORGANISM(S): Homo sapiens

PROVIDER: GSE197331 | GEO | 2023/02/21

REPOSITORIES: GEO

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Project description:Leptospirosis is the most widespread zoonotic disease in the world. The lack of an adequate laboratory test is a major barrier for the diagnosis, especially during the early stages of illness, when antibiotic therapy is most effective. Therefore, there is a critical need for an efficient diagnostic test for this life threatening disease. In order to identify new targets that could be used as diagnostic makers for leptopirosis, we constructed a protein microarray chip comprising 61% of Leptospira interrogans proteome and investigated the IgG response against leptospiral antigens from 274 individuals, including 80 acute-, 80 convalescent-phase patients and 114 healthy control subjects from regions with endemic, high endemic and no endemic transmission of leptospirosis. A nitrocellulose line blot assay was performed to validate the accuracy of the protein microarray results. We found 16 antigens that can discriminate between acute cases and healthy individuals from a region with high endemic transmission of leptospirosis, and 18 antigens that distinguish convalescent cases. Some of the antigens identified in this study, such as LipL32, the non-identical domains of the Lig proteins, GroEL and Loa22 are already known to be recognized by sera from human patients, thus serving as a proof-of-concept for the serodiagnostic antigen discovery approach. Several novel antigens were identified, including the hypothetical protein LIC10215 which showed good sensitivity and specificity rates for both acute- and convalescent-phase patients. Our study is the first large-scale evaluation of immunodominant antigens associated with naturally acquired leptospiral infection and novel as well as known serodiagnostic leptospiral antigens that are recognized by antibodies in the sera of leptospirosis cases were identified. The novel antigens identified here may have potential use in both the development of new tests and the improvement of currently available assays for diagnosing this neglected tropical disease. Further research is needed to assess the accuracy of these antigens in more appropriate diagnostic platforms. Antibody profiling was peformed on sera from infected and non-infected subjects to investigate the IgG response against leptospiral antigens. These samples comprised 80 acute-, 80 convalescent-phase patients and 114 healthy control subjects, including 29 subjects from United States (non-endemic area), 35 blood donors from Salvador/Brazil (endemic area) and 50 healthy individuals from region with high endemicity of leptospirosis.

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Leukocytes methylome of individuals from leprosy endemic area

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