Role of IL-15 in interstitial lung diseases in amyopathic dermatomyositis with anti-MDA-5 antibody
Role of IL-15 in interstitial lung diseases in amyopathic dermatomyositis with anti-MDA-5 antibody
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IL-15在抗MDA-5抗体无肌病性皮肌炎间质性肺疾病中的作用
DOI：
10.1016/j.rmed.2018.06.012
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发表时间：
2018
影响因子：
4.3
通讯作者：
Sato Shinji
中科院分区：
文献类型：
--
作者：
Takada Toshinori;Ohashi Kazumasa;Hayashi Masachika;Asakawa Katsuaki;Sakagami Takuro;Kikuchi Toshiaki;Sato Shinji
背景抗MDA-5抗体与无肌病性皮肌炎（ADM）患者间质性肺病（ILD）密切相关。抗MDA-5抗体阳性的ADM患者尽管接受了强化免疫抑制治疗，但有时仍会发生致死性ILD。然而，在抗MDA-5抗体滴度治疗后的初始下降可能不能预测随后更好的生存率的diseases.MethodsTo澄清免疫调节功能的ADM与抗MDA-5抗体的致命ILD，我们回顾性研究了自2000年以来的抗MDA-5抗体阳性ADM-ILD保存血清连续患者的临床记录。使用细胞因子组分析测量血清细胞因子/生长因子（GF）蛋白浓度。我们比较了幸存者和非幸存者之间的每种细胞因子/GF的浓度，并进一步研究在治疗过程中的细胞因子/GF水平的变化在一些patients.ResultsTwenty-six例患者参加了这项研究。26例患者中有9例对强化免疫抑制治疗无反应，死于呼吸衰竭。我们比较了细胞因子/GF浓度，发现治疗前血清IL-15在非幸存者中比在幸存者中显著升高（p < 0.05）。17例应答者中有11例和9例死亡患者中有6例保存血清多次采集。然后，我们计算了每种细胞因子/GF浓度的每日变化率（斜率）。结论IL-15和IL-10在抗MDA-5抗体阳性的ADM-ILD患者病情进展中可能起重要作用。
BackgroundAnti-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.MethodsTo 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.ResultsTwenty-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).ConclusionsIL-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.