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Antigen-specific cytokine profiles for pulmonary Mycobacterium avium complex disease stage diagnosis
Yoshiro Yamashita1,2, Ikkoh Yasuda1,3, Takeshi Tanaka4
1Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Nagasaki, Japan.
Insights
Diagnosing pulmonary Mycobacterium avium complex (MAC) disease stages is challenging. This study reveals distinct cytokine profiles in CD4+T and CD19+B cells that can help identify clinical stages of MAC.
Area of Science:
- Immunology
- Infectious Diseases
- Respiratory Medicine
Background:
- Pulmonary Mycobacterium avium complex (MAC) disease diagnosis is hindered by the inability to accurately determine clinical staging.
- Current diagnostic methods lack effective biomarkers for assessing disease progression and treatment response.
Purpose of the Study:
- To characterize cytokine profiles of CD4+T and CD19+B cells recognizing Mycobacterium avium antigens across different clinical stages of MAC.
- To explore the potential of cell-mediated immunity as a diagnostic tool for MAC staging.
Main Methods:
- Recruited 47 MAC patients (before-, on-, and after-treatment) and 17 healthy controls.
- Cultured peripheral blood mononuclear cells with specific Mycobacterium avium antigens.
- Analyzed cytokine profiles (IFN-γ, TNF-α, IL-2, IL-10, IL-17) of CD4+ and CD19+ cells via flow cytometry.
Main Results:
- Th1 cytokines (IFN-γ, TNF-α) were significantly elevated in on- and after-treatment groups compared to before-treatment and controls.
- IL-2 presence correlated with post-treatment stages, suggesting a role in memory function.
- Non-Th1 cytokines (IL-10, IL-17) showed higher responses in the before-treatment group.
Conclusions:
- Distinct cytokine profiles characterize each clinical stage of pulmonary MAC.
- Cytokine analysis of CD4+T and CD19+B cells offers potential for staging MAC patients.
Introduction:
Controlling pulmonary Mycobacterium avium complex (MAC) disease is difficult because there is no way to know the clinical stage accurately. There have been few attempts to use cell-mediated immunity for diagnosing the stage. The objective of this study was to characterize cytokine profiles of CD4+T and CD19+B cells that recognize various Mycobacterium avium-associated antigens in different clinical stages of MAC.
Methods:
A total of 47 MAC patients at different stages based on clinical information (14 before-treatment, 16 on-treatment, and 17 after-treatment) and 17 healthy controls were recruited. Peripheral blood mononuclear cells were cultured with specific antigens (MAV0968, 1160, 1276, and 4925), and the cytokine profiles (IFN-γ, TNF-α, IL-2, IL-10, IL-13, and IL-17) of CD4+/CD3+ and CD19+ cells were analyzed by flow cytometry.
Results:
The response of Th1 cytokines such as IFN-γ and TNF-α against various antigens was significantly higher in both the on-treatment and after-treatment groups than in the before-treatment group and control (P < 0.01-0.0001 and P < 0.05-0.0001). An analysis of polyfunctional T cells suggested that the presence of IL-2 is closely related to the stage after the start of treatment (P = 0.0309-P < 0.0001) and is involved in memory function. Non-Th1 cytokines, such as IL-10 and IL-17, showed significantly higher responses in the before-treatment group (P < 0.0001 and P < 0.01-0.0001). These responses were not observed with purified protein derivative (PPD). CD19+B cells showed a response similar to that of CD4+T cells.
Conclusion:
There is a characteristic cytokine profile at each clinical stage of MAC.
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