Author | Marçal, Pedro Henrique Ferreira | |
Author | Souza, Márcio Luís Moreira de | |
Author | Gama, Rafael Silva | |
Author | Oliveira, Lorena Bruna Pereira de | |
Author | Gomes, Matheus de Souza | |
Author | Amaral, Laurence Rodrigues do | |
Author | Pinheiro, Roberta Olmo | |
Author | Sarno, Euzenir Nunes | |
Author | Moraes, Milton Ozório | |
Author | Fairley, Jessica K. | |
Author | Martins Filho, Olindo Assis | |
Author | Fraga, Lucia Alves de Oliveira | |
Access date | 2022-08-14T16:56:25Z | |
Available date | 2022-08-14T16:56:25Z | |
Document date | 2022 | |
Citation | MARÇAL, Pedro Henrique Ferreira et al. Algorithm Design for a Cytokine Release Assay of Antigen-Specific In Vitro Stimuli of Circulating Leukocytes to Classify Leprosy Patients and Household Contacts. Open Forum Infectious Diseases, v. 9, n. 3, p. 1 - 9, Jan. 2022. | pt_BR |
ISSN | 2328-8957 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/54630 | |
Language | eng | pt_BR |
Publisher | Oxford University Press | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Projeto de algoritmo | pt_BR |
Subject in Portuguese | Ensaio de citocinas | pt_BR |
Subject in Portuguese | Diagnóstico diferencial | pt_BR |
Subject in Portuguese | Contatos domésticos | pt_BR |
Subject in Portuguese | Hanseníase | pt_BR |
Title | Algorithm Design for a Cytokine Release Assay of Antigen-Specific In Vitro Stimuli of Circulating Leukocytes to Classify Leprosy Patients and Household Contact | pt_BR |
Type | Article | pt_BR |
DOI | 10.1093/ofid/ofac036 | |
Abstract | 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 enzymelinked
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. | pt_BR |
Affilliation | Universidade Vale do Rio Doce–Univale. Governador Valadares, MG, Brasil. | pt_BR |
Affilliation | Universidade Federal de Juiz de Fora. Instituto de Ciências da Vida. Programa Multicêntrio de Bioquímica e Biologia Molecular-Núcleo de Pesquisa em Hansenologia. Juiz de Fora, MG, Brasil. | pt_BR |
Affilliation | Universidade Vale do Rio Doce–Univale. Governador Valadares, MG, Brasil. | pt_BR |
Affilliation | Universidade Vale do Rio Doce–Univale. Governador Valadares, MG, Brasil. | pt_BR |
Affilliation | Universidade Federal de Uberlândia. Laboratório de Bioinformática e Análises Moleculares. Faculdade de Ciência da Computação. Instituto de Genética e Bioquímica. Patos de Minas, MG, Brasil. | pt_BR |
Affilliation | Universidade Federal de Uberlândia. Laboratório de Bioinformática e Análises Moleculares. Faculdade de Ciência da Computação. Instituto de Genética e Bioquímica. Patos de Minas, MG, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine. Atlanta, Georgia, USA. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil. | pt_BR |
Affilliation | Universidade Federal de Juiz de Fora. Instituto de Ciências da Vida. Programa Multicêntrio de Bioquímica e Biologia Molecular-Núcleo de Pesquisa em Hansenologia. Juiz de Fora, MG, Brasil. | pt_BR |
Subject | Algorithm design | pt_BR |
Subject | Cytokine assay | pt_BR |
Subject | Differential diagnosis | pt_BR |
Subject | Household contacts | pt_BR |
Subject | Leprosy | pt_BR |