Diagnostic value of antibody responses to multiple antigens from Mycobacterium tuberculosis in active and latent tuberculosis

Tuberculosis remains a major public health problem. Conventional tests are inadequate to distinguish between active tuberculosis (ATB) and latent tuberculosis infection (LTBI). We measured antibody responses to Mycobacterium tuberculosis antigens (Mycobacterium tuberculosis chorismate mutase (TBCM), antigen 85B (Ag85B), early secreted antigen-6 (ESAT-6), and culture filtrate protein-10 (CFP-10) in ATB, LTBI, and non-infected (NI) individuals. Serum immunoglobulin G (IgG) and immunoglobulin A (IgA) levels were measured and the QuantiFERON-TB Gold In-Tube assay was used to diagnose LTBI. IgG levels against TBCM were significantly higher in LTBI than NI subjects. IgG and IgA levels against Ag85B and IgG levels against CFP-10 were significantly higher in ATB, followed by LTBI, and then NI. When the ATB group was subdivided, IgG levels against Ag85B and CFP-10 were significantly higher in each subgroup compared with those in LTBI and NI groups. Positive correlation trends between interferon-gamma and IgG levels against Ag85B, TBCM, and CFP-10 and IgA levels against Ag85B in LTBI and NI subjects were observed. Age- and sex-adjusted models showed that IgG against TBCM and CFP-10 was independently related to LTBI diagnosis, and IgG against Ag85B was independently related to the diagnosis of ATB and could distinguish between LTBI and ATB. Overall, IgG antibody responses to TBCM, Ag85B, and CFP-10 can discriminate among ATB, LTBI, and NI groups.

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Patterns of T and B cell responses to Mycobacterium tuberculosis membrane-associated antigens and their relationship with disease activity in rheumatoid arthritis patients with latent tuberculosis infection

PLoS ONE ◽

10.1371/journal.pone.0255639 ◽

2021 ◽

Vol 16 (8) ◽

pp. e0255639

Author(s):

Shashi Kant Kumar ◽

Suvrat Arya ◽

Ankita Singh ◽

Ramnath Misra ◽

Amita Aggarwal ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Mycobacterium Tuberculosis ◽

T Cell ◽

Latent Tuberculosis Infection ◽

Latent Tuberculosis ◽

T Cell Responses ◽

Antibody Responses ◽

Time Points ◽

Cell Responses

This study was aimed at exploring whether latent tuberculosis infection (LTBI) contributes to the pathogenesis of immune-mediated inflammatory diseases in a TB endemic setting. We screened 198 rheumatoid arthritis (RA) patients with tuberculin skin test (TST) and studied 61 (median DAS28-ESR = 6.3) who were positive. Whole blood T cell proliferative responses to Mycobacterium tuberculosis (Mtb) membrane (MtM) antigens, including the latency-induced protein alpha crystallin (Acr), were determined by flow cytometry using Ki67 expression as the marker for nuclear proliferation. Serum antibody levels were determined by ELISA. Follow-up investigations (at 3–6, 9–12 and 15–18 months after baseline) were performed in 41 patients who were classified empirically as ‘high’ (HR-T/HR-B) or ‘low’ (LR-T/LR-B) responders based on their dynamic T cell or antibody responses. Significant correlations were seen between baseline T cell responses to MtM and Acr, and between IgG, IgA and IgM antibody responses to MtM. However, no correlation was seen between T and B cell responses. At all time points during the follow-up, T cell responses to both antigens (except for MtM at one point) were significantly higher in HR-T (n = 25) than LR-T (n = 16) patients. Levels of IgA and IgM (but not IgG) antibodies to MtM were also significantly higher in HR-B (n = 13) than LR-B (n = 28) at all time points. Importantly, HR-T patients exhibited significantly higher baseline and follow-up DAS28 scores than LR-T. Ten (of 61) patients had a history of TB and developed RA 6 years (median) after contracting TB. Three new TB cases (1 from TST-positive and 2 from TST-negative groups) emerged during the follow-up. Our results suggest that persistently elevated T cell responses to Mtb antigens may contribute to disease activity in RA.

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Cytokine Biosignature of Active and Latent Mycobacterium Tuberculosis Infection in Children

Pathogens ◽

10.3390/pathogens10050517 ◽

2021 ◽

Vol 10 (5) ◽

pp. 517

Author(s):

Magdalena Druszczynska ◽

Michal Seweryn ◽

Sebastian Wawrocki ◽

Magdalena Kowalewska-Pietrzak ◽

Anna Pankowska ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Inflammatory Mediators ◽

Latent Tuberculosis ◽

Serum Levels ◽

Diagnostic Tools ◽

Mycobacterium Tuberculosis Infection ◽

Only Children ◽

Latent Tb ◽

Ifn Γ ◽

Multiplex Bead

None of the currently used diagnostic tools are efficient enough in diagnosing Mycobacterium tuberculosis (M.tb) infection in children. The study was aimed to identify cytokine biosignatures characterizing active and latent tuberculosis (TB) in children. Using a multiplex bead-based technology, we analyzed the levels of 53 Th17-related cytokines and inflammatory mediators in sera from 216 BCG-vaccinated children diagnosed with active TB (TB) or latent TB (LTBI) as well as uninfected controls (HC). Children with active TB, compared to HC children, showed reduced serum levels of IL-17A, MMP-2, OPN, PTX-3, and markedly elevated concentrations of APRIL/TNFSF13. IL-21, sCD40L, MMP-2, and IL-8 were significantly differentially expressed in the comparisons between groups: (1) HC versus TB and LTBI (jointly), and (2) TB versus LTBI. The panel consisting of APRIL/TNFSF13, sCD30/TNFRSF8, IFN-α2, IFN-γ, IL-2, sIL-6Rα, IL-8, IL-11, IL-29/IFN-λ1, LIGHT/TNFSF14, MMP-1, MMP-2, MMP-3, osteocalcin, osteopontin, TSLP, and TWEAK/TNFSF12 possessed a discriminatory potential for the differentiation between TB and LTBI children. Serum-based host biosignatures carry the potential to aid the diagnosis of childhood M.tb infections. The proposed panels of markers allow distinguishing not only children infected with M.tb from uninfected individuals but also children with active TB from those with latent TB.

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Cytokine and Chemokine mRNA Expressions after Mycobacterium tuberculosis-Specific Antigen Stimulation in Whole Blood from Hemodialysis Patients with Latent Tuberculosis Infection

Diagnostics ◽

10.3390/diagnostics11040595 ◽

2021 ◽

Vol 11 (4) ◽

pp. 595

Author(s):

Ji Young Park ◽

Sung-Bae Park ◽

Heechul Park ◽

Jungho Kim ◽

Ye Na Kim ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Mrna Expression ◽

Whole Blood ◽

Latent Tuberculosis Infection ◽

Latent Tuberculosis ◽

Expression Level ◽

Mrna Expression Level ◽

Healthy Individuals ◽

Relative Mrna Expression ◽

Mrna Expression Levels

There have been few reports on the kinetics of hemodialyzed (HD) patients’ immune responses in latent tuberculosis infection (LTBI). Therefore, in the present study, messenger ribonucleic acid (mRNA) expression levels of nine immune markers were analyzed to discriminate between HD patients with LTBI and healthy individuals. Nine cytokines and chemokines were screened through relative mRNA expression levels in whole blood samples after stimulation with Mycobacterium tuberculosis (MTB)-specific antigens from HD patients with LTBI (HD/LTBI), HD patients without LTBI, and healthy individuals, and results were compared with the QuantiFERON-TB Gold In-Tube (QFT-GIT) test. We confirmed that the C-C motif chemokine 11 (CCL11) mRNA expression level of the HD/LTBI group was significantly higher than the other two groups. Especially, the CCL11 mRNA expression level of the >0.7 IU/mL group in the QFT-GIT test was significantly higher than the <0.2 IU/mL group in the QFT-GIT test and the 0.2–0.7 IU/mL group in the QFT-GIT test (p = 0.0043). The present study reveals that the relative mRNA expression of CCL11 was statistically different in LTBI based on the current cut-off value (i.e., ≥0.35 IU/mL) and in the >0.7 IU/mL group. These results suggest that CCL11 mRNA expression might be an alternative biomarker for LTBI diagnosis in HD patients.

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Impaired Degranulation and Proliferative Capacity of Mycobacterium tuberculosis–Specific CD8+ T Cells in HIV-Infected Individuals With Latent Tuberculosis

The Journal of Infectious Diseases ◽

10.1093/infdis/jiu505 ◽

2014 ◽

Vol 211 (4) ◽

pp. 635-640 ◽

Cited By ~ 16

Author(s):

Ameeta S. Kalokhe ◽

Toidi Adekambi ◽

Chris C. Ibegbu ◽

Susan M. Ray ◽

Cheryl L. Day ◽

...

Keyword(s):

T Cells ◽

Mycobacterium Tuberculosis ◽

Cd8 T Cells ◽

Latent Tuberculosis ◽

Proliferative Capacity

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The diagnostic value of polymerase chain reaction for Mycobacterium tuberculosis to distinguish intestinal tuberculosis from crohn's disease: A meta-analysis

Saudi Journal of Gastroenterology ◽

10.4103/1319-3767.199135 ◽

2017 ◽

Vol 23 (1) ◽

pp. 3 ◽

Cited By ~ 8

Author(s):

Baoying Fei ◽

Ting Jin ◽

Yu Zhang ◽

Xujun He

Keyword(s):

Polymerase Chain Reaction ◽

Mycobacterium Tuberculosis ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Meta Analysis ◽

Intestinal Tuberculosis ◽

Diagnostic Value ◽

Chain Reaction ◽

Polymerase Chain

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Perbedaan Antara Jumlah Sel T Subset Gamma-Delta di Darah Tepi pada Penderita Tuberkulosis dan Orang dengan Latent Tuberculosis Infection

Jurnal Biosains Pascasarjana ◽

10.20473/jbp.v18i2.2016.162-171 ◽

2016 ◽

Vol 18 (2) ◽

pp. 162

Author(s):

Ryzky Widi Atmaja ◽

Jusak Nugraha

Keyword(s):

Mycobacterium Tuberculosis ◽

Heat Shock ◽

Heat Shock Protein ◽

Latent Tuberculosis Infection ◽

Latent Tuberculosis ◽

Tuberculosis Infection ◽

Gamma Delta

Abstrak Latar Belakang. Imunitas memiliki peranan penting untuk melindungi host dari bacilli Mycobacterium tuberculosis (M.tb), bakteri Obligat intraseluler yang menyebabkan Tuberkulosis (TB) dan latent tuberculosis infection (LTBI). Sel T subset gamma-delta (T-γδ) adalah sel-sel potensial tersembunyi yang bermain peran di imunitas innate dan adaptive pada TB. Tetapi, hingga kini perananya di LTBI masih menjadi misteri. Bahan dan Metode. Penelitian dilakukan dengan melibatkan 10 penderita TB serta 10 orang dengan LTBI. Mereka didapatkan dari Rumah Sakit Paru Surabaya melalui suatu persetujuan kelaikan etik dari Universitas Airlangga. Sampel-sampel tersebut akan dihitung jumlah sel T-γδ menggunakan F A C S C a l i b u r. Hasil. Jumlah sel T-γδ meningkat pada TB (10,7%) dan LTBI (15, 4%). Jumlah dari kedua kelompok tersebut melebihi rerata normal di darah tepi (1% - 5%). Kesimpulan. Penigkatan jumlah sel T-γδ pada TB disebabkan melimpahnya kadar IL-12 yang dilepas oleh makrofag selama infeksi. Sementara, peningkatan jumlah sel T-γδ pada LTBI diasumsikan karena banyaknya heat shock protein (HSPs) yang dilepas oleh M.tb di bawah kondisi stres. ...Kata kunci: tuberkulosis, latent tuberculosis infection, Mycobacterium tuberclosis, sel T subset gamma-d e l t a.

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