Frontiers in Immunology (Jul 2023)

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

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

DOI
https://doi.org/10.3389/fimmu.2023.1222428
Journal volume & issue
Vol. 14

Abstract

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IntroductionControlling 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.MethodsA 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.ResultsThe 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.ConclusionThere is a characteristic cytokine profile at each clinical stage of MAC.

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