Toshinori Takada1, Kazumasa Ohashi2, Masachika Hayashi3, Katsuaki Asakawa3, Takuro Sakagami3, Toshiaki Kikuchi3, Shinji Sato4. 1. Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Minami-uonuma, Japan; Division of Respiratory Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan. Electronic address: ttakada@med.niigata-u.ac.jp. 2. Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Minami-uonuma, Japan. 3. Division of Respiratory Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan. 4. Division of Rheumatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan.
Abstract
BACKGROUND: Anti-MDA-5 antibody is closely associated with interstitial lung disease (ILD) in amyopathic dermatomyositis (ADM). Patients with ADM with anti-MDA-5 antibody sometimes develop fatal ILD in spite of intensive immunosuppressive therapy. However, an initial decrease after treatment in anti-MDA-5 antibody titers may not be predictive of subsequent better survival of the disease. METHODS: To clarify immunoregulatory features of deadly ILD in ADM with the anti-MDA-5 antibody, we retrospectively examined clinical records of consecutive patients with anti-MDA-5 antibody positive ADM-ILD with preserved serum since 2000. Serum cytokine/growth factor (GF) protein concentration was measured using a cytokine panel analysis. We compared concentrations of each cytokine/GF between survivors and non-survivors and further examined changes in cytokines/GF levels during treatment in some patients. RESULTS: Twenty-six patients were enrolled in the study. Nine out of 26 patients did not respond to intensive immunosuppressive therapy and died due to respiratory failure. We compared cytokine/GF concentrations and found that serum IL-15 before treatment was significantly elevated in non-survivors than in survivors (p < 0.05). 11 out of 17 responders and 6 of 9 dead patients had preserved serum taken more than one time. We then calculated rates of change per day (slopes) in each cytokine/GF concentration. Comparison of slopes of cytokine/GF protein over the treatment duration showed that the slopes in non-survivors were significantly increased in IL-10 and IL-15 (p < 0.01). CONCLUSIONS: IL-15, as well as IL-10, may play a key role in the progression of the patients with ADM-ILD with anti-MDA-5 antibody positive.
BACKGROUND: Anti-MDA-5 antibody is closely associated with interstitial lung disease (ILD) in amyopathic dermatomyositis (ADM). Patients with ADM with anti-MDA-5 antibody sometimes develop fatal ILD in spite of intensive immunosuppressive therapy. However, an initial decrease after treatment in anti-MDA-5 antibody titers may not be predictive of subsequent better survival of the disease. METHODS: To clarify immunoregulatory features of deadly ILD in ADM with the anti-MDA-5 antibody, we retrospectively examined clinical records of consecutive patients with anti-MDA-5 antibody positive ADM-ILD with preserved serum since 2000. Serum cytokine/growth factor (GF) protein concentration was measured using a cytokine panel analysis. We compared concentrations of each cytokine/GF between survivors and non-survivors and further examined changes in cytokines/GF levels during treatment in some patients. RESULTS: Twenty-six patients were enrolled in the study. Nine out of 26 patients did not respond to intensive immunosuppressive therapy and died due to respiratory failure. We compared cytokine/GF concentrations and found that serum IL-15 before treatment was significantly elevated in non-survivors than in survivors (p < 0.05). 11 out of 17 responders and 6 of 9 dead patients had preserved serum taken more than one time. We then calculated rates of change per day (slopes) in each cytokine/GF concentration. Comparison of slopes of cytokine/GF protein over the treatment duration showed that the slopes in non-survivors were significantly increased in IL-10 and IL-15 (p < 0.01). CONCLUSIONS:IL-15, as well as IL-10, may play a key role in the progression of the patients with ADM-ILD with anti-MDA-5 antibody positive.