Algorithm Design for a Cytokine Release Assay of Antigen-Specific In Vitro Stimuli of Circulating Leukocytes to Classify Leprosy Patients and Household Contacts.

Autor: Marçal PHF; Universidade Vale do Rio Doce-Univale, Governador Valadares, Minas Gerais, Brazil., de Souza MLM; Programa Multicêntrio de Bioquímica e Biologia Molecular-Núcleo de Pesquisa em Hansenologia, Universidade Federal de Juiz de Fora, Instituto de Ciências da Vida, Governador Valadares, Minas Gerais, Brazil., Gama RS; Universidade Vale do Rio Doce-Univale, Governador Valadares, Minas Gerais, Brazil., de Oliveira LBP; Universidade Vale do Rio Doce-Univale, Governador Valadares, Minas Gerais, Brazil., Gomes MS; Laboratório de Bioinformática e Análises Moleculares, Universidade Federal de Uberlândia, Institute of Genetics and Biochemistry/Faculty of Computer Science, Patos de Minas, Minas Gerais, Brazil., do Amaral LR; Laboratório de Bioinformática e Análises Moleculares, Universidade Federal de Uberlândia, Institute of Genetics and Biochemistry/Faculty of Computer Science, Patos de Minas, Minas Gerais, Brazil., Pinheiro RO; Laboratório de Hanseníase, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil., Sarno EN; Laboratório de Hanseníase, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil., Moraes MO; Laboratório de Hanseníase, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil., Fairley JK; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA., Martins-Filho OA; Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil., de Oliveira Fraga LA; Programa Multicêntrio de Bioquímica e Biologia Molecular-Núcleo de Pesquisa em Hansenologia, Universidade Federal de Juiz de Fora, Instituto de Ciências da Vida, Governador Valadares, Minas Gerais, Brazil.
Jazyk: angličtina
Zdroj: Open forum infectious diseases [Open Forum Infect Dis] 2022 Jan 30; Vol. 9 (3), pp. ofac036. Date of Electronic Publication: 2022 Jan 30 (Print Publication: 2022).
DOI: 10.1093/ofid/ofac036
Abstrakt: Background: Immunological biomarkers have often been used as a complementary approach to support clinical diagnosis in several infectious diseases. The lack of commercially available laboratory tests for conclusive early diagnosis of leprosy has motivated the search for novel methods for accurate diagnosis. In the present study, we describe an integrated analysis of a cytokine release assay using a machine learning approach to create a decision tree algorithm. This algorithm was used to classify leprosy clinical forms and monitor household contacts.
Methods: A model of Mycobacterium leprae antigen-specific in vitro assay with subsequent cytokine measurements by enzyme-linked immunosorbent assay was employed to measure the levels of tumor necrosis factor (TNF), interferon-γ, interleukin 4, and interleukin 10 (IL-10) in culture supernatants of peripheral blood mononuclear cells from patients with leprosy, healthy controls, and household contacts. Receiver operating characteristic curve analysis was carried out to define each cytokine's global accuracy and performance indices to identify clinical subgroups.
Results: Data demonstrated that TNF (control culture [CC]: AUC = 0.72; antigen-stimulated culture [Ml]: AUC = 0.80) and IL-10 (CC: AUC = 0.77; Ml: AUC = 0.71) were the most accurate biomarkers to classify subgroups of household contacts and patients with leprosy, respectively. Decision tree classifier algorithms for TNF analysis categorized subgroups of household contacts according to the operational classification with moderate accuracy (CC: 79% [48/61]; Ml: 84% [51/61]). Additionally, IL-10 analysis categorized leprosy patients' subgroups with moderate accuracy (CC: 73% [22/30] and Ml: 70% [21/30]).
Conclusions: Together, our findings demonstrated that a cytokine release assay is a promising method to complement clinical diagnosis, ultimately contributing to effective control of the disease.
(© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
Databáze: MEDLINE
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