AUTHOR=Yamashita Yoshiro , Yasuda Ikkoh , Tanaka Takeshi , Ikeda Toru , Terada Mayumi , Takaki Masahiro , Tsuchihashi Yoshiko , Asoh Norichika , Ohara Yukiko , Enany Shymaa , Kobayashi Haruka , Matsumoto Sohkichi , Morimoto Konosuke 

TITLE=Antigen-specific cytokine profiles for pulmonary Mycobacterium avium complex disease stage diagnosis

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1222428

DOI=10.3389/fimmu.2023.1222428

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>Controlling pulmonary <italic>Mycobacterium avium</italic> 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 <italic>Mycobacterium avium</italic>-associated antigens in different clinical stages of MAC.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>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 &lt; 0.01–0.0001 and P &lt; 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 &lt; 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 &lt; 0.0001 and P &lt; 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.</p></sec><sec><title>Conclusion</title><p>There is a characteristic cytokine profile at each clinical stage of MAC.</p></sec>