Greif Lenarčič Dana, Bidovec Stojković Urska, Kristanc Pia, Kopač Peter, Malovrh Mateja Marc, Kern Izidor, Osolnik Katarina, Korošec Peter
University Clinic of Respiratory and Allergic Diseases, 4204 Golnik, Slovenia.
Medical Faculty, University of Ljubljana, 1000 Ljubljana, Slovenia.
Int J Mol Sci. 2025 Jul 16;26(14):6831. doi: 10.3390/ijms26146831.
Diagnosing and prognosing immune-mediated airway diseases, like hypersensitivity pneumonitis (HP) and sarcoidosis, is complicated due to their overlapping symptoms and the lack of definitive biomarkers. Hence, we wanted to compare bronchoalveolar lavage (BAL) cytokine and chemokine profiles from 92 patients with different immune-mediated and inflammatory airway diseases, namely, HP, sarcoidosis, non-allergic asthma, amiodarone lung, and EGPA. We also compared pulmonary function parameters, BAL's cellularity, and lymphocyte immunophenotypes. We found significant differences across all measured lung functions (VC, VC%, FEV1, FEV1%, and Tiff%) and in the number of macrophages, lymphocytes, neutrophils, and eosinophils. Furthermore, we showed significant differences in CD4, CD8, and CD4/8 across all included ILDs and OLDs; however, no significant differences were found in CD3, CD19, NK, or NKT. We identified nine biomarkers (IL-1β, IL-6, IL-8, IL-13, VEGF, angiogenin, C4a, RANTES, and MCP-1) that significantly differ in the BAL of patients with HP and sarcoidosis and showed that RANTES and IL-6 are associated with fibrotic outcome. We have demonstrated that interstitial and obstructive lung diseases differ in cytokine and cellular lung imprint, which may, in the future, enable the determination of the disease subtype and thus the identification of targets for the treatment of individuals or subgroups within diseases.
诊断和预测免疫介导的气道疾病，如过敏性肺炎（HP）和结节病，由于其症状重叠且缺乏明确的生物标志物而变得复杂。因此，我们想比较92例患有不同免疫介导和炎性气道疾病（即HP、结节病、非过敏性哮喘、胺碘酮肺和嗜酸性肉芽肿性多血管炎）患者的支气管肺泡灌洗（BAL）细胞因子和趋化因子谱。我们还比较了肺功能参数、BAL的细胞成分和淋巴细胞免疫表型。我们发现所有测量的肺功能（肺活量、肺活量百分比、第1秒用力呼气容积、第1秒用力呼气容积百分比和 Tiff 指数）以及巨噬细胞、淋巴细胞、中性粒细胞和嗜酸性粒细胞数量均存在显著差异。此外，我们发现所有纳入的间质性肺疾病（ILDs）和阻塞性肺疾病（OLDs）在CD4、CD8和CD4/8方面存在显著差异；然而，在CD3、CD19、自然杀伤细胞（NK）或自然杀伤T细胞（NKT）方面未发现显著差异。我们确定了9种生物标志物（白细胞介素-1β、白细胞介素-6、白细胞介素-8、白细胞介素-13、血管内皮生长因子、血管生成素、C4a、调节活化正常T细胞表达和分泌的趋化因子（RANTES）和单核细胞趋化蛋白-1），它们在HP和结节病患者的BAL中存在显著差异，并表明RANTES和白细胞介素-6与纤维化结局相关。我们已经证明，间质性和阻塞性肺疾病在细胞因子和细胞肺印记方面存在差异，这在未来可能有助于确定疾病亚型，从而识别疾病中个体或亚组的治疗靶点。
