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T Cell Surface Expression of Programmed Death-1 (PD-1) as Biomarkers for Chemotherapeutic Response Among Tuberculosis Patients FREE TO VIEW

Amar Singh*, PhD; Dipendra Mitra, PhD; Aparajita Dey, MD; Anant Mohan, MD; Surendra Sharma, PhD
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All India Institute Of Medical Sciences, New Delhi, India

Chest. 2012;142(4_MeetingAbstracts):146A. doi:10.1378/chest.1389878
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PRESENTED ON: Sunday, October 21, 2012 at 01:15 PM - 02:45 PM

PURPOSE: Identifying predictive biomarkers for efficacy of chemotherapeutic regimens for tuberculosis is important. Chemotherapeutic efficacies are mostly predicted by assays using sputum or serum. We intended for predictive biomarker in the peripheral (PBL) of tuberculosis patients to illustrate the response of anti-tubercular treatment (ATT). Over expression of the programmed death-1 (PD-1) molecules is hallmark of exhaust T cells, imposing negative impact on T cells activation and function during chronic viral and bacterial infections and associated with its downregulation on a wide range of cells during anti viral therapy. Therefore, we examined the dynamics of PD-1 expression among pulmonary tuberculosis (PTB) patients undergoing ATT.

METHODS: We performed follow-up (Baseline, 3 months, 6 month and 12 months) study among 20 PTB patients undergoing anti-tubercular treatment and enumerated the frequencies of PD-1 expressing CD3+ T cells along with Mycobacterium tuberculosis (Mtb.) specific CD4+ T cells response in PBL, assessed by flow cytometry.

RESULTS: We observed treatment induced reduction in bacillary load tandem with reduction in frequencies of CD3+ T cells bearing exhaustion markers PD-1. This was inversely correlated with Mtb. specific IFN-γ function of CD4+T cells during follow-up.

CONCLUSIONS: High proportion of T cells expressing exhaustion markers PD-1 which is tightly correlated with therapeutic efficacy, therefore PD-1 positive T cells may serve as biomarker for disease activity and clearance.

CLINICAL IMPLICATIONS: Screening of PD-1 positive T cells in the PBL could be useful biomarker to monitor treatment outcomes during therapy and vaccine trial for tuberculosis patients.

DISCLOSURE: The following authors have nothing to disclose: Amar Singh, Dipendra Mitra, Aparajita Dey, Anant Mohan, Surendra Sharma

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All India Institute Of Medical Sciences, New Delhi, India




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