Program Cell Death Receptor 1 in Mycobacterium Avium Complex Lung Disease

The Pathogenic Role and Diagnostic Implication of Program Cell Death Receptor 1 Expressed on T Cells in Mycobacterium Avium Complex Lung Disease

1. To understand the components of PBMC in MAC-LD patients, including T cells, B cells, nature killer cells, and monocyte.
2. To confirm the phenomenon of reduced PBMC response in MAC-LD patients
3. To study the proportion of apoptosis and PD-1 expression in T cells among MAC-LD patients, MAC colonizers, patients with tuberculosis, and healthy controls.
4. To study the apoptosis and PD-1/PD-L1 expression in T cells/macrophage from bronchial lavage among MAC-LD patients, MAC colonizers, patients with tuberculosis,
5. To examine the PD-1 gene polymorphism and the correlation with MAC-LD.

Study Overview

• Status: Completed
• Conditions: Mycobacterium Avium
• Intervention / Treatment: Other: Blood examination

Detailed Description

Background: Nontuberculous mycobacteria Lung disease (NTM-LD) becomes an important clinical concern, because its incidence has increased over the last decade. Mycobacterium avium complex (MAC) is the most common responsible species for NTM-LD in Taiwan. The clinical relevance of MAC in sputum is, however, only 35~42% because it exists in the environment ubiquitously. According to the guideline of the American Thoracic Society, the diagnosis of MAC-LD is based on clinical, radiographic, and mycobacteriology criteria which require two or more positive sputum cultures for MAC. The major limitation of mycobacterial culture is the long turn-around-time, usually 2-4 weeks. In addition, both mycobacterial culture and nucleic acid amplification test cannot discriminate true MAC infection and colonization because airway colonization of MAC is not uncommon. Therefore, diagnosis of MAC-LD remains a big challenge in clinical practice, and rapid and accurate diagnostic test should be developed.

Beyond the contemporary diagnostic criteria, the host immune response in NTM disease has recently been proposed to help diagnosis. Inflammatory markers may represent host response and discriminate MAC infection from colonization. But inflammatory markers can be influenced by infection other than MAC infection. By contrast, lymphocyte response to antigen stimulation may be more specific in diagnosis. In our preliminary results, in-vitro response of peripheral blood mononuclear cell (PBMC) is lower in MAC-LD than healthy controls. The underlying mechanism responsible for the reduced PBMC response in MAC-LD is not fully understood. In previous studies conducted in tuberculosis patients, interaction between programmed cell death ligand-1 (PD-L1) from dendritic cells and programmed cell death-1 (PD-1) in T cells leads to apoptosis or anergy of T lymphocyte and thus suppresses cellular immunity. Therefore, it is possible that similar alteration in immune response also occurs in patients with MAC-LD and correlates with the PBMC response as well as disease severity.

• Study Type: Observational
• Enrollment (Actual): 112

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patient with Mycobacterium avium complex lung disease

Description

Inclusion Criteria:

• Age ≥ 20 years
• MAC lung disease: Diagnosis is based on the guidelines by American Thoracic Society. In brief, there should be pulmonary symptoms, comparable findings in chest image and appropriate exclusion other possible causes as well as meeting the microbiology criteria.
• MAC pulmonary colonizers: Those without fulfilling the diagnostic criteria but having at least one set of positive sputum for MAC are defined.
• Healthy controls:
• Active tuberculosis group: patients with pulmonary tuberculosis diagnosed by positive respiratory culture

Exclusion Criteria:

• Patients who have acquired immunodeficiency syndrome

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
MAC-LD; patients with MAC-LD Do Blood examination	Other: Blood examination; blood sampling
Control; controls without NTM or tuberculosis infection Do Blood examination	Other: Blood examination; blood sampling
Tuberculosis infection; patients with tuberculosis infection which diagnosis by culture or typical pathology Do Blood examination	Other: Blood examination; blood sampling
MAC colonization; patients with MAC pulmonary colonization by American Thoracic Society guideline Do Blood examination	Other: Blood examination; blood sampling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent of disease progression	2 year

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Chin-Chung Shu, MD, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: May 18, 2016
• First Submitted That Met QC Criteria: May 19, 2016
• First Posted (Estimate): May 20, 2016

Study Record Updates

• Last Update Posted (Estimate): December 15, 2016
• Last Update Submitted That Met QC Criteria: December 13, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections, Nontuberculous; Lung Diseases; Mycobacterium Infections; Mycobacterium avium-intracellulare Infection
• Other Study ID Numbers: 201407079RIND

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided