CD4+CXCR4+ T cells as a novel prognostic biomarker in patients with idiopathic inflammatory myopathy-associated interstitial lung disease. (1st December 2018)

• Record Type: Journal Article
• Authors: Wang, Kaiwen; Zhao, Jiangfeng; Chen, Zhiwei; Li, Ting; Tan, Xiaoming; Zheng, Yu; Gu, Liyang; Guo, Li; Sun, Fangfang; Wang, Haiting; Li, Jiajie; Wang, Xiaodong; Riemekasten, Gabriela; Ye, Shuang
• Is Part Of: Rheumatology. Volume 58:Number 3(2019)
• Page Start: 511
• Page End: 521
• Publication Date: 2018-12-01
• Subjects: idiopathic inflammatory myopathy -- amyopathic dermatomyositis -- CD4+CXCR4+ -- T cells -- interleukin 21 -- interstitial lung disease; Rheumatism -- Periodicals; Rheumatology -- Periodicals; 616.723005
• DOI: 10.1093/rheumatology/key341
• Languages: English
• ISSNs: 1462-0324

Abstract

Abstract: Backgroud: There is an unmet need for the development of new biomarkers for idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD). Methods: Peripheral CD4 + CXCR4 + T cells, stromal cell-derived factor-1 and Krebs von den Lungen-6 were measured in patients with IIM-ILD ( n = 85) and controls. The relation to pulmonary functions, high-resolution CT scores, specific clinical phenotypes and survival was analysed. Cytokine-expression profiling of these CD4 + CXCR4 + T cells and their co-culture with pulmonary fibroblasts were conducted. Results: The peripheral percentages of CD4 + CXCR4 + T cells were significantly elevated in IIM-ILD patients, and correlated with high-resolution CT score ( r = 0.7136, P < 0.0001) and pulmonary function impairments, such as percentage of forced volume vital capacity ( r = −0.4734, P = 0.0005). They were associated with anti-melanoma differentiation-associated gene 5 autoantibodies and the amyopathic DM phenotype. In IIM-ILD, peripheral percentages of CD4 + CXCR4 + T cells ⩾30% revealed a 6-month mortality as high as 47%. These CD4 + CXCR4 + T cells express high levels of IL-21 and IL-6. In vitro blockade of IL-21 signalling by neutralization of IL-21 or Janus kinase inhibitor could abolished the fibroblast proliferation. Conclusion: Overall, peripheral CD4 + CXCR4 + T cells appear to be a potentially valuable novel biomarker associated with the severity and prognosis of IIM-ILD. They promote pulmonary fibroblast proliferation via IL-21, which may herald future targeted treatments for this severe disease.