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Abstract：
OBJECTIVE: To explore whether cytokines could be potential biomarkers to predict the occurrence of the progressive fibrosis (PF) phenotype among patients with interstitial pneumonia with autoimmune features (IPAF).
METHODS: This study prospectively collected 51 IPAF and 15 idiopathic pulmonary fibrosis (IPF) patients who were diagnosed at the First Affiliated Hospital of Guangzhou Medical University from July 2020 to June 2021. All IPAF patients were followed up for 1 year to assess the development of PF phenotype. Paired bronchoalveolar lavage fluid (BALF) and serum samples were collected at enrolment and analysed for differences in 39 cytokines expression. Principal component analysis (PCA) and cluster analysis were conducted to identify a subgroup of IPAF patients at high risk for developing the PF phenotype. Finally, cytokine differences were compared between subgroups to identify potential biomarkers for PF-IPAF occurrence.
RESULTS: According to the PCA analysis, 81.25% of PF-IPAF patients share overlapped BALF cytokine profiles with IPF. Cluster analysis indicated that IPAF patients in subtype 2 had a higher risk of developing the PF phenotype within 1 year (P = 0.048), characterized by higher levels of CCL2 and CXCL12, and lower lymphocyte proportion (LYM%) in BALF. Elevated levels of BALF CCL2 (>299.16 pg/ml) or CXCL12 (>660.115 pg/ml) were associated with a significantly higher risk of developing PF phenotype within the 1-year follow-up period (P = 0.009, 0.001, respectively).
CONCLUSIONS: PF-IPAF phenotype exhibits similar inflammatory cytokine profiles to IPF. Cytokine CCL2 and CXCL12, and LYM% in BALF serve as potential biomarkers for predicting the PF phenotype in IPAF patients.
BACKGROUND: Register: Qian Han, Website: http://www.chictr.org.cn/showproj.aspx?proj=61619, Registration number: ChiCTR2000040998.
METHODS: This study prospectively collected 51 IPAF and 15 idiopathic pulmonary fibrosis (IPF) patients who were diagnosed at the First Affiliated Hospital of Guangzhou Medical University from July 2020 to June 2021. All IPAF patients were followed up for 1 year to assess the development of PF phenotype. Paired bronchoalveolar lavage fluid (BALF) and serum samples were collected at enrolment and analysed for differences in 39 cytokines expression. Principal component analysis (PCA) and cluster analysis were conducted to identify a subgroup of IPAF patients at high risk for developing the PF phenotype. Finally, cytokine differences were compared between subgroups to identify potential biomarkers for PF-IPAF occurrence.
RESULTS: According to the PCA analysis, 81.25% of PF-IPAF patients share overlapped BALF cytokine profiles with IPF. Cluster analysis indicated that IPAF patients in subtype 2 had a higher risk of developing the PF phenotype within 1 year (P = 0.048), characterized by higher levels of CCL2 and CXCL12, and lower lymphocyte proportion (LYM%) in BALF. Elevated levels of BALF CCL2 (>299.16 pg/ml) or CXCL12 (>660.115 pg/ml) were associated with a significantly higher risk of developing PF phenotype within the 1-year follow-up period (P = 0.009, 0.001, respectively).
CONCLUSIONS: PF-IPAF phenotype exhibits similar inflammatory cytokine profiles to IPF. Cytokine CCL2 and CXCL12, and LYM% in BALF serve as potential biomarkers for predicting the PF phenotype in IPAF patients.
BACKGROUND: Register: Qian Han, Website: http://www.chictr.org.cn/showproj.aspx?proj=61619, Registration number: ChiCTR2000040998.
摘要：
目的：探讨细胞因子是否可以作为预测具有自身免疫特征的间质性肺炎（IPAF）患者进行性纤维化（PF）表型发生的潜在生物标志物。
方法：本研究前瞻性收集2020年7月至2021年6月在广州医科大学附属第一医院确诊的51例IPAF和15例特发性肺纤维化患者。所有IPAF患者均随访1年以评估PF表型的发展。在登记时收集配对的支气管肺泡灌洗液(BALF)和血清样品,并分析39种细胞因子表达的差异。进行主成分分析（PCA）和聚类分析，以确定IPAF患者的高风险亚组，以发展PF表型。最后,比较亚组之间的细胞因子差异,以确定PF-IPAF发生的潜在生物标志物.
结果：根据PCA分析，81.25%的PF-IPAF患者与IPF共享重叠的BALF细胞因子谱。聚类分析显示2型IPAF患者在1年内发生PF表型的风险较高(P=0.048)。BALF中CCL2，CXCL12水平较高，淋巴细胞比例（LYM%）较低。BALFCCL2水平升高（>299.16pg。/ml）或CXCL12（>600.115pg。/ml）与一年随访期内发生PF表型的风险显着相关（P=0.009，0.001）。
结论：PF-IPAF表型表现出与IPF相似的炎性细胞因子谱。BALF中细胞因子CCL2、CXCL12和LYM%作为预测IPAF患者PF表型的潜在生物标志物。
背景：注册：钱涵，网站：http://www.chictr.org.cn/showproj.aspx?proj=61619,注册号:ChiCTR2000040998。
方法：本研究前瞻性收集2020年7月至2021年6月在广州医科大学附属第一医院确诊的51例IPAF和15例特发性肺纤维化患者。所有IPAF患者均随访1年以评估PF表型的发展。在登记时收集配对的支气管肺泡灌洗液(BALF)和血清样品,并分析39种细胞因子表达的差异。进行主成分分析（PCA）和聚类分析，以确定IPAF患者的高风险亚组，以发展PF表型。最后,比较亚组之间的细胞因子差异,以确定PF-IPAF发生的潜在生物标志物.
结果：根据PCA分析，81.25%的PF-IPAF患者与IPF共享重叠的BALF细胞因子谱。聚类分析显示2型IPAF患者在1年内发生PF表型的风险较高(P=0.048)。BALF中CCL2，CXCL12水平较高，淋巴细胞比例（LYM%）较低。BALFCCL2水平升高（>299.16pg。/ml）或CXCL12（>600.115pg。/ml）与一年随访期内发生PF表型的风险显着相关（P=0.009，0.001）。
结论：PF-IPAF表型表现出与IPF相似的炎性细胞因子谱。BALF中细胞因子CCL2、CXCL12和LYM%作为预测IPAF患者PF表型的潜在生物标志物。
背景：注册：钱涵，网站：http://www.chictr.org.cn/showproj.aspx?proj=61619,注册号:ChiCTR2000040998。
