PPE59 antibodies in tuberculous patients and potential use for diagnosis when assayed with other rapid biomarkers.
Humans
Enzyme-Linked Immunosorbent Assay
Antibodies, Bacterial
/ blood
Antigens, Bacterial
/ immunology
Immunoglobulin G
/ blood
Immunoglobulin M
/ blood
Male
Female
Biomarkers
/ blood
Adult
Immunoglobulin A
/ blood
Sensitivity and Specificity
Middle Aged
Mycobacterium tuberculosis
/ immunology
Tuberculosis
/ diagnosis
Young Adult
Tuberculosis, Pulmonary
/ diagnosis
Sputum
/ microbiology
Brazil
Bacterial Proteins
/ immunology
Aged
Adolescent
Cohort Studies
Journal
Memorias do Instituto Oswaldo Cruz
ISSN: 1678-8060
Titre abrégé: Mem Inst Oswaldo Cruz
Pays: Brazil
ID NLM: 7502619
Informations de publication
Date de publication:
2024
2024
Historique:
received:
06
10
2023
accepted:
26
06
2024
medline:
18
9
2024
pubmed:
18
9
2024
entrez:
18
9
2024
Statut:
epublish
Résumé
PPE 59, which is absent from bacillus Calmette Guérin (BCG) strains, seems to induce a humoral immune response in patients with tuberculosis (TB). Additional studies are needed to better evaluate this protein in immune response to tuberculosis. To evaluate the response of antibodies to PPE59 in TB individuals, its combination with IgG response to other, previously tested mycobacterial antigens (Ag) and with sputum smear microbiology (SM) results. We have cloned and expressed the rv3429 gene that encodes PPE59, then IgG, IgM, and IgA against PPE59 antigens measured by enzyme-linked immunosorbent assay (ELISA) in 212 sera samples obtained from the following subject cohorts: TB residents from Italy (79) and in Brazil (52); and an all-Brazilian cohort of 55 patients with other respiratory disorders; 10 patients infected with non-tuberculous mycobacteria, and 16 asymptomatic subjects. Drawing on results from a previous study(17) of serum samples from Brazilian subjects tested for IgG by ELISA against mycobacterial antigens ESAT-6, 16kDa, MT10.3, MPT-64 and 38kDa, the results were analysed in combination with those of the PPE59 and SM tests. Keeping the specificity rate at 97%, the overall PPE59 IgA sensitivity was 42.7%, while IgG and IgM showed lower performance (p < 0.0001). Combining PPE59 IgA/16kDa IgG results increased sensitivity to 71%, and even higher rates when the results were combined with SM results (86.5%, p = 0.001), at 88.9% specificity. Positive IgA was associated with pulmonary image alterations of high TB probability (p < 0.05). Tests with TB patients found a moderate frequency of positivity for PPE59 IgA. However, the higher level of sensitivity attained in combination with PPE59 IgA/16kDa IgG/SM results unheard of before, although imperfect, suggests that this may be a potential additional tool for rapid detection of TB in low-resource areas.
Sections du résumé
BACKGROUND
BACKGROUND
PPE 59, which is absent from bacillus Calmette Guérin (BCG) strains, seems to induce a humoral immune response in patients with tuberculosis (TB). Additional studies are needed to better evaluate this protein in immune response to tuberculosis.
OBJECTIVES
OBJECTIVE
To evaluate the response of antibodies to PPE59 in TB individuals, its combination with IgG response to other, previously tested mycobacterial antigens (Ag) and with sputum smear microbiology (SM) results.
METHODS
METHODS
We have cloned and expressed the rv3429 gene that encodes PPE59, then IgG, IgM, and IgA against PPE59 antigens measured by enzyme-linked immunosorbent assay (ELISA) in 212 sera samples obtained from the following subject cohorts: TB residents from Italy (79) and in Brazil (52); and an all-Brazilian cohort of 55 patients with other respiratory disorders; 10 patients infected with non-tuberculous mycobacteria, and 16 asymptomatic subjects. Drawing on results from a previous study(17) of serum samples from Brazilian subjects tested for IgG by ELISA against mycobacterial antigens ESAT-6, 16kDa, MT10.3, MPT-64 and 38kDa, the results were analysed in combination with those of the PPE59 and SM tests.
FINDINGS
RESULTS
Keeping the specificity rate at 97%, the overall PPE59 IgA sensitivity was 42.7%, while IgG and IgM showed lower performance (p < 0.0001). Combining PPE59 IgA/16kDa IgG results increased sensitivity to 71%, and even higher rates when the results were combined with SM results (86.5%, p = 0.001), at 88.9% specificity. Positive IgA was associated with pulmonary image alterations of high TB probability (p < 0.05).
MAIN CONCLUSIONS
CONCLUSIONS
Tests with TB patients found a moderate frequency of positivity for PPE59 IgA. However, the higher level of sensitivity attained in combination with PPE59 IgA/16kDa IgG/SM results unheard of before, although imperfect, suggests that this may be a potential additional tool for rapid detection of TB in low-resource areas.
Identifiants
pubmed: 39292107
pii: S0074-02762024000101124
doi: 10.1590/0074-02760230183
pii:
doi:
Substances chimiques
Antibodies, Bacterial
0
Antigens, Bacterial
0
Immunoglobulin G
0
Immunoglobulin M
0
Biomarkers
0
Immunoglobulin A
0
Bacterial Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM