TY - JOUR
T1 - Identifying promising peptide targets for leprosy serological tests
T2 - From prediction to ELISA
AU - Parreiras de Jesus, Augusto César
AU - Fraga, Vanêssa Gomes
AU - Pimenta-Carvalho, Samuel Alexandre
AU - Guimarães, Tania Mara Pinto Dabés
AU - Araújo, Marcio Sobreira Silva
AU - de Carvalho, Jairo Campos
AU - Santos, Marcio Bezerra
AU - Araújo, Marcelo Grossi
AU - Pascoal-Xavier, Marcelo Antonio
AU - Lyon, Sandra
AU - Ferreira, Sebastião Rodrigo
AU - Arreguin-Campos, Rocio
AU - Eersels, Kasper
AU - van Grinsven, Bart
AU - Cleij, Thomas
AU - Bueno, Lilian Lacerda
AU - Bartholomeu, Daniella Castanheira
AU - Menezes, Cristiane Alves da Silva
AU - Grossi de Oliveira, Ana Laura
AU - Fujiwara, Ricardo Toshio
N1 - Funding Information:
We would like to thank the following institutions for all the support: P\u00F3s-Gradua\u00E7\u00E3o em Ci\u00EAncias da Sa\u00FAde: Infectologia e Medicina Tropical/UFMG; Hospital Universit\u00E1rio \u2013 Universidade Federal de Sergipe (HU/UFS); Instituto Ren\u00E9 Rachou - Funda\u00E7\u00E3o Oswaldo Cruz (Fiocruz Minas); and Hospital Eduardo de Menezes (FHEMIG).
Funding Information:
This work was supported by Funda\u00E7\u00E3o de Amparo \u00E0 Pesquisa do Estado de Minas Gerais (FAPEMIG \u2212 PPSUS \u2013 Edital APQ \u2013 4035/17; FAPEMIG BPD-00394\u201322). ACPJ is supported by Coordena\u00E7\u00E3o de Aperfei\u00E7oamento de Pessoal de N\u00EDvel Superior (CAPES) and ALGO is supported by Conselho Nacional de Pesquisa (CNPq). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2025
PY - 2025/3/1
Y1 - 2025/3/1
N2 - Leprosy remains a significant health concern, particularly in India, Brazil, and Indonesia. Early diagnosis is essential to prevent complications, highlighting the need for improved diagnostic tools. This study aimed to identify novel Mycobacterium leprae antigens and assess their effectiveness against human sera through immunotools for antibody response evaluation. Using bioinformatics, we predicted B-cell epitopes in M. leprae, which were chemically synthesized and tested via dot blotting with sera from leprosy patients, tuberculosis patients, and healthy controls. Promising peptides underwent further analysis through ELISA using 465 serum samples from leprosy patients, household contacts, and healthy controls across Brazil. The samples were also tested against known antigens HSA-NDO, LID-1, and NDO-LID. A total of 102 epitope sequences were generated, of which eight (PEP1 to PEP8) demonstrated the ability to differentiate between individuals with and without exposure to M. leprae. The results of the ELISA test exhibited statistically significant differences in absorbance responses between the experimental groups for the novel synthetic peptides (p < 0.05). PEP3, PEP4, and PEP5 demonstrated the most favorable outcomes, with values of the area under the receiver operating characteristic curve (AUC) of 0.9759, 0.9796 and 0.9551 respectively in the comparison of healthy controls with household contacts, and 0.8257, 0.7945, and 0.7961 comparing the same controls with patients. Furthermore, the synthetic peptides demonstrated superior sensitivity, specificity, and AUC compared to HSA-NDO, LID-1, and NDO-LID. The identified peptides showed significant responses in samples from patients and household contacts (HHC), indicating their potential for tracing exposure to M. leprae bacilli. These novel synthetic peptides could enhance the sensitivity of rapid diagnostic tests for leprosy, facilitating early detection of the infection. This could help prevent disease progression and interrupt transmission.
AB - Leprosy remains a significant health concern, particularly in India, Brazil, and Indonesia. Early diagnosis is essential to prevent complications, highlighting the need for improved diagnostic tools. This study aimed to identify novel Mycobacterium leprae antigens and assess their effectiveness against human sera through immunotools for antibody response evaluation. Using bioinformatics, we predicted B-cell epitopes in M. leprae, which were chemically synthesized and tested via dot blotting with sera from leprosy patients, tuberculosis patients, and healthy controls. Promising peptides underwent further analysis through ELISA using 465 serum samples from leprosy patients, household contacts, and healthy controls across Brazil. The samples were also tested against known antigens HSA-NDO, LID-1, and NDO-LID. A total of 102 epitope sequences were generated, of which eight (PEP1 to PEP8) demonstrated the ability to differentiate between individuals with and without exposure to M. leprae. The results of the ELISA test exhibited statistically significant differences in absorbance responses between the experimental groups for the novel synthetic peptides (p < 0.05). PEP3, PEP4, and PEP5 demonstrated the most favorable outcomes, with values of the area under the receiver operating characteristic curve (AUC) of 0.9759, 0.9796 and 0.9551 respectively in the comparison of healthy controls with household contacts, and 0.8257, 0.7945, and 0.7961 comparing the same controls with patients. Furthermore, the synthetic peptides demonstrated superior sensitivity, specificity, and AUC compared to HSA-NDO, LID-1, and NDO-LID. The identified peptides showed significant responses in samples from patients and household contacts (HHC), indicating their potential for tracing exposure to M. leprae bacilli. These novel synthetic peptides could enhance the sensitivity of rapid diagnostic tests for leprosy, facilitating early detection of the infection. This could help prevent disease progression and interrupt transmission.
KW - Bioinformatics
KW - Diagnostics
KW - Leprosy
KW - Peptides
KW - Serology
U2 - 10.1016/j.jgeb.2025.100475
DO - 10.1016/j.jgeb.2025.100475
M3 - Article
SN - 1687-157X
VL - 23
JO - Journal of Genetic Engineering and Biotechnology
JF - Journal of Genetic Engineering and Biotechnology
IS - 1
M1 - 100475
ER -