Kazutaka Yoshizawa1, Ami Aoki1, Kenjiro Shima1, Yoshinari Tanabe1, Toshiyuki Koya1, Takashi Hasegawa1, Toshiaki Kikuchi1, Takuro Sakagami2,3. 1. Department of Respiratory Medicine and Infectious Disease, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-dori, Niigata, Japan. 2. Department of Respiratory Medicine and Infectious Disease, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-dori, Niigata, Japan. stakuro@kumamoto-u.ac.jp. 3. Department of Respiratory Medicine, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjyo, Chuo-ku, Kumamoto, Japan. stakuro@kumamoto-u.ac.jp.
Abstract
PURPOSE: In the past decade, the relationship between naturally occurring interferon-γ-neutralizing autoantibodies (IFNγ-Ab) and disseminated non-tuberculous mycobacteria (NTM) infection has been established. Furthermore, immune suppressive therapy aimed at the suppression of antibody production has shown efficacy as a supportive treatment. However, the nature of antibody behavior and antibody titer during the course of this disease, as well as the pathophysiological significance of IFNγ-Ab, has not yet been fully elucidated. METHODS: Thirteen Japanese subjects suffering from disseminated NTM (dNTM) infection with IFNγ-Ab were evaluated. The fluctuation of IFNγ-Ab titer and the neutralizing capacity against IFN-γ during the course of the disease were retrospectively analyzed. IFNγ-Ab titers in the sera were quantified using an enzyme-linked immunosorbent assay; neutralizing capacity was evaluated via flow cytometry. RESULTS: Serum antibody titers were not constant during the treatment period and varied over the course of the disease. The antibody titer decreased when the disease was improved by anti-mycobacterial treatment (p < 0.01) and increased as the disease progressed (p < 0.05). Even after the antibody titer decreased, the neutralizing capacity against IFN-γ was maintained by individual sera. CONCLUSIONS: Despite the improvement in the pathological condition via treatment, the patients' sera maintained neutralizing capacity against IFN-γ. Antibody titer fluctuated over the course of the disease and exhibited potential as a biomarker for judgment of the disease state.
PURPOSE: In the past decade, the relationship between naturally occurring interferon-γ-neutralizing autoantibodies (IFNγ-Ab) and disseminated non-tuberculous mycobacteria (NTM) infection has been established. Furthermore, immune suppressive therapy aimed at the suppression of antibody production has shown efficacy as a supportive treatment. However, the nature of antibody behavior and antibody titer during the course of this disease, as well as the pathophysiological significance of IFNγ-Ab, has not yet been fully elucidated. METHODS: Thirteen Japanese subjects suffering from disseminated NTM (dNTM) infection with IFNγ-Ab were evaluated. The fluctuation of IFNγ-Ab titer and the neutralizing capacity against IFN-γ during the course of the disease were retrospectively analyzed. IFNγ-Ab titers in the sera were quantified using an enzyme-linked immunosorbent assay; neutralizing capacity was evaluated via flow cytometry. RESULTS: Serum antibody titers were not constant during the treatment period and varied over the course of the disease. The antibody titer decreased when the disease was improved by anti-mycobacterial treatment (p < 0.01) and increased as the disease progressed (p < 0.05). Even after the antibody titer decreased, the neutralizing capacity against IFN-γ was maintained by individual sera. CONCLUSIONS: Despite the improvement in the pathological condition via treatment, the patients' sera maintained neutralizing capacity against IFN-γ. Antibody titer fluctuated over the course of the disease and exhibited potential as a biomarker for judgment of the disease state.
Authors: Sarah K Browne; Rifat Zaman; Elizabeth P Sampaio; Kamonwan Jutivorakool; Lindsey B Rosen; Li Ding; Minjal J Pancholi; Lauren M Yang; Debra Long Priel; Gulbu Uzel; Alexandra F Freeman; Carlton E Hayes; Roger Baxter; Stuart H Cohen; Steven M Holland Journal: Blood Date: 2012-03-08 Impact factor: 22.113
Authors: Sarah K Browne; Peter D Burbelo; Ploenchan Chetchotisakd; Yupin Suputtamongkol; Sasisopin Kiertiburanakul; Pamela A Shaw; Jennifer L Kirk; Kamonwan Jutivorakool; Rifat Zaman; Li Ding; Amy P Hsu; Smita Y Patel; Kenneth N Olivier; Viraphong Lulitanond; Piroon Mootsikapun; Siriluck Anunnatsiri; Nasikarn Angkasekwinai; Boonmee Sathapatayavongs; Po-Ren Hsueh; Chi-Chang Shieh; Margaret R Brown; Wanna Thongnoppakhun; Reginald Claypool; Elizabeth P Sampaio; Charin Thepthai; Duangdao Waywa; Camilla Dacombe; Yona Reizes; Adrian M Zelazny; Paul Saleeb; Lindsey B Rosen; Allen Mo; Michael Iadarola; Steven M Holland Journal: N Engl J Med Date: 2012-08-23 Impact factor: 91.245