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Abstract
Discussion Forum (0)
Abstract number: 3463

Session Type: 1-hour Mini Oral Flash

Session Title: 1-hour Mini Oral Flash

Authors(s): S. Halkur Shankar (1), P. Kaur (2), D.K. Mitra (2), A. Ray (1), K. Madan (3), M. Soneja (1), R.M. Pandey (4), A. Biswas (1)

Authors Affiliations(s): (1) Department of Medicine, All India Institute of Medical Sciences, India, (2) Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, India, (3) Department of Pulmonary Medicine, Critical Care, and Sleep Disorders, All India Institute of Medical Sciences, India, (4) Department of Biostatistics, All India Institute of Medical Sciences, India

Background:

The pathogenesis of cavitation in pulmonary tuberculosis (PTB) is poorly understood. There are currently no studies on T cell exhaustion in this process. We aimed to study T cell exhaustion marker expression levels in cavitary PTB and compare it with non-cavitary disease. We also aimed to compare the expression levels in active PTB with latent tuberculosis infection (LTBI).

Methods:

We conducted a cross-sectional study including 21 PTB patients and 6 individuals with LTBI. Microbiologically proven PTB within 7 days of anti-tubercular therapy initiation were included in the study. Patients were radiologically divided into cavitary (N = 11) and non-cavitary (N = 10) disease based on chest imaging. Peripheral blood CD4+ T cells were studied by multicolor flow cytometry. The expression levels of Programmed cell death protein 1 (PD-1), Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), and T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) were determined. These were compared between cavitary and non-cavitary disease, and between active PTB and LTBI. 

Results:

The age (Median age = 29 years) and sex distribution was similar between the three groups. The following results are described in Table 1 and Figure 1. PD-1 expression levels were higher on CD4+ T cells (14.10% vs 7.48%) in non-cavitary PTB when compared to cavitary PTB. This difference, however, did not reach statistical significance. The difference in CTLA-4 (0.96% vs 0.96%) and TIM-3 (2.34% vs 1.89%) were not significant between the non-cavitary and cavitary group. PD-1 (8.45% vs 1.31%, p < 0.0001), CTLA-4 (0.96% vs 0.37%, p = 0.006), and TIM-3 (1.89% vs 0.58%, p = 0.01) expression levels on CD4+ T cells were significantly higher in active PTB when compared to LTBI.

Conclusions:

We conclude that PD-1, CTLA-4, and TIM-3 have a significantly higher expression on CD4+ T cells in patients with active PTB when compared to LTBI. We propose that cavitary lesions in PTB occur due to a florid inflammatory reaction. The higher expression of PD-1 in patients with non-cavitary tuberculosis may temper the immune response, preventing progression to cavitation. Thus, PD-1 may be used to identify progression to cavitary lesions in PTB.

Keyword(s): Pulmonary tuberculosis, Immune exhaustion, Cavitary lesion

Abstract number: 3463

Session Type: 1-hour Mini Oral Flash

Session Title: 1-hour Mini Oral Flash

Authors(s): S. Halkur Shankar (1), P. Kaur (2), D.K. Mitra (2), A. Ray (1), K. Madan (3), M. Soneja (1), R.M. Pandey (4), A. Biswas (1)

Authors Affiliations(s): (1) Department of Medicine, All India Institute of Medical Sciences, India, (2) Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, India, (3) Department of Pulmonary Medicine, Critical Care, and Sleep Disorders, All India Institute of Medical Sciences, India, (4) Department of Biostatistics, All India Institute of Medical Sciences, India

Background:

The pathogenesis of cavitation in pulmonary tuberculosis (PTB) is poorly understood. There are currently no studies on T cell exhaustion in this process. We aimed to study T cell exhaustion marker expression levels in cavitary PTB and compare it with non-cavitary disease. We also aimed to compare the expression levels in active PTB with latent tuberculosis infection (LTBI).

Methods:

We conducted a cross-sectional study including 21 PTB patients and 6 individuals with LTBI. Microbiologically proven PTB within 7 days of anti-tubercular therapy initiation were included in the study. Patients were radiologically divided into cavitary (N = 11) and non-cavitary (N = 10) disease based on chest imaging. Peripheral blood CD4+ T cells were studied by multicolor flow cytometry. The expression levels of Programmed cell death protein 1 (PD-1), Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), and T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) were determined. These were compared between cavitary and non-cavitary disease, and between active PTB and LTBI. 

Results:

The age (Median age = 29 years) and sex distribution was similar between the three groups. The following results are described in Table 1 and Figure 1. PD-1 expression levels were higher on CD4+ T cells (14.10% vs 7.48%) in non-cavitary PTB when compared to cavitary PTB. This difference, however, did not reach statistical significance. The difference in CTLA-4 (0.96% vs 0.96%) and TIM-3 (2.34% vs 1.89%) were not significant between the non-cavitary and cavitary group. PD-1 (8.45% vs 1.31%, p < 0.0001), CTLA-4 (0.96% vs 0.37%, p = 0.006), and TIM-3 (1.89% vs 0.58%, p = 0.01) expression levels on CD4+ T cells were significantly higher in active PTB when compared to LTBI.

Conclusions:

We conclude that PD-1, CTLA-4, and TIM-3 have a significantly higher expression on CD4+ T cells in patients with active PTB when compared to LTBI. We propose that cavitary lesions in PTB occur due to a florid inflammatory reaction. The higher expression of PD-1 in patients with non-cavitary tuberculosis may temper the immune response, preventing progression to cavitation. Thus, PD-1 may be used to identify progression to cavitary lesions in PTB.

Keyword(s): Pulmonary tuberculosis, Immune exhaustion, Cavitary lesion

Higher expression of PD-1 on CD4+ T cells in pulmonary tuberculosis: implication in cavitary and non-cavitary lesions
Sujay Halkur Shankar
Sujay Halkur Shankar
ESCMID eAcademy. Halkur Shankar S. 07/09/2021; 332705; 3463
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Sujay Halkur Shankar
Abstract
Discussion Forum (0)
Abstract number: 3463

Session Type: 1-hour Mini Oral Flash

Session Title: 1-hour Mini Oral Flash

Authors(s): S. Halkur Shankar (1), P. Kaur (2), D.K. Mitra (2), A. Ray (1), K. Madan (3), M. Soneja (1), R.M. Pandey (4), A. Biswas (1)

Authors Affiliations(s): (1) Department of Medicine, All India Institute of Medical Sciences, India, (2) Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, India, (3) Department of Pulmonary Medicine, Critical Care, and Sleep Disorders, All India Institute of Medical Sciences, India, (4) Department of Biostatistics, All India Institute of Medical Sciences, India

Background:

The pathogenesis of cavitation in pulmonary tuberculosis (PTB) is poorly understood. There are currently no studies on T cell exhaustion in this process. We aimed to study T cell exhaustion marker expression levels in cavitary PTB and compare it with non-cavitary disease. We also aimed to compare the expression levels in active PTB with latent tuberculosis infection (LTBI).

Methods:

We conducted a cross-sectional study including 21 PTB patients and 6 individuals with LTBI. Microbiologically proven PTB within 7 days of anti-tubercular therapy initiation were included in the study. Patients were radiologically divided into cavitary (N = 11) and non-cavitary (N = 10) disease based on chest imaging. Peripheral blood CD4+ T cells were studied by multicolor flow cytometry. The expression levels of Programmed cell death protein 1 (PD-1), Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), and T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) were determined. These were compared between cavitary and non-cavitary disease, and between active PTB and LTBI. 

Results:

The age (Median age = 29 years) and sex distribution was similar between the three groups. The following results are described in Table 1 and Figure 1. PD-1 expression levels were higher on CD4+ T cells (14.10% vs 7.48%) in non-cavitary PTB when compared to cavitary PTB. This difference, however, did not reach statistical significance. The difference in CTLA-4 (0.96% vs 0.96%) and TIM-3 (2.34% vs 1.89%) were not significant between the non-cavitary and cavitary group. PD-1 (8.45% vs 1.31%, p < 0.0001), CTLA-4 (0.96% vs 0.37%, p = 0.006), and TIM-3 (1.89% vs 0.58%, p = 0.01) expression levels on CD4+ T cells were significantly higher in active PTB when compared to LTBI.

Conclusions:

We conclude that PD-1, CTLA-4, and TIM-3 have a significantly higher expression on CD4+ T cells in patients with active PTB when compared to LTBI. We propose that cavitary lesions in PTB occur due to a florid inflammatory reaction. The higher expression of PD-1 in patients with non-cavitary tuberculosis may temper the immune response, preventing progression to cavitation. Thus, PD-1 may be used to identify progression to cavitary lesions in PTB.

Keyword(s): Pulmonary tuberculosis, Immune exhaustion, Cavitary lesion

Abstract number: 3463

Session Type: 1-hour Mini Oral Flash

Session Title: 1-hour Mini Oral Flash

Authors(s): S. Halkur Shankar (1), P. Kaur (2), D.K. Mitra (2), A. Ray (1), K. Madan (3), M. Soneja (1), R.M. Pandey (4), A. Biswas (1)

Authors Affiliations(s): (1) Department of Medicine, All India Institute of Medical Sciences, India, (2) Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, India, (3) Department of Pulmonary Medicine, Critical Care, and Sleep Disorders, All India Institute of Medical Sciences, India, (4) Department of Biostatistics, All India Institute of Medical Sciences, India

Background:

The pathogenesis of cavitation in pulmonary tuberculosis (PTB) is poorly understood. There are currently no studies on T cell exhaustion in this process. We aimed to study T cell exhaustion marker expression levels in cavitary PTB and compare it with non-cavitary disease. We also aimed to compare the expression levels in active PTB with latent tuberculosis infection (LTBI).

Methods:

We conducted a cross-sectional study including 21 PTB patients and 6 individuals with LTBI. Microbiologically proven PTB within 7 days of anti-tubercular therapy initiation were included in the study. Patients were radiologically divided into cavitary (N = 11) and non-cavitary (N = 10) disease based on chest imaging. Peripheral blood CD4+ T cells were studied by multicolor flow cytometry. The expression levels of Programmed cell death protein 1 (PD-1), Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), and T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) were determined. These were compared between cavitary and non-cavitary disease, and between active PTB and LTBI. 

Results:

The age (Median age = 29 years) and sex distribution was similar between the three groups. The following results are described in Table 1 and Figure 1. PD-1 expression levels were higher on CD4+ T cells (14.10% vs 7.48%) in non-cavitary PTB when compared to cavitary PTB. This difference, however, did not reach statistical significance. The difference in CTLA-4 (0.96% vs 0.96%) and TIM-3 (2.34% vs 1.89%) were not significant between the non-cavitary and cavitary group. PD-1 (8.45% vs 1.31%, p < 0.0001), CTLA-4 (0.96% vs 0.37%, p = 0.006), and TIM-3 (1.89% vs 0.58%, p = 0.01) expression levels on CD4+ T cells were significantly higher in active PTB when compared to LTBI.

Conclusions:

We conclude that PD-1, CTLA-4, and TIM-3 have a significantly higher expression on CD4+ T cells in patients with active PTB when compared to LTBI. We propose that cavitary lesions in PTB occur due to a florid inflammatory reaction. The higher expression of PD-1 in patients with non-cavitary tuberculosis may temper the immune response, preventing progression to cavitation. Thus, PD-1 may be used to identify progression to cavitary lesions in PTB.

Keyword(s): Pulmonary tuberculosis, Immune exhaustion, Cavitary lesion

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