Division of Rheumatology, Jeju National University School of Medicine, Jeju National University Hospital, Jeju, Republic of Korea.
Division of Rheumatology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.
Clin Rheumatol. 2021 Jun;40(6):2447-2456. doi: 10.1007/s10067-021-05659-x. Epub 2021 Mar 22.
Connective tissue disease (CTD) might occur during the course of idiopathic pulmonary fibrosis (IPF). Clinical factors associated with CTD development in IPF patients have still not been identified. We investigated which antibodies have a significant association with the development of CTD during the clinical course of IPF.
We retrospectively reviewed the records of 527 patients with a first diagnosis of IPF between January 2007 and March 2014 and investigated the time to CTD development after IPF diagnosis in these patients.
CTD developed in 15 patients at a median of 2.1 years (range 1.2-4.8) after IPF diagnosis. All patients had anti-neutrophil cytoplasmic antibodies (ANCA) or autoantibodies that met the serology criteria for interstitial pneumonia with autoimmune features (IPAF). Survival duration for IPF patients with progression to CTD was 5.3 (3.8, 6.7) years, which was significantly longer than for IPF patients without progression to CTD [2.9 (1.7, 4.8), p = 0.001]. Independent risk factors for CTD development in IPF patients included female gender [adjusted hazard ratio (HR) 5.319, p = 0.0082], titer of rheumatoid factor (RF; adjusted HR, 1.006; p = 0.022), titer of anti-citrullinated protein antibody (ACPA; adjusted HR, 1.009; p = 0.0011), and titer of myeloperoxidase (MPO)-ANCA (adjusted HR, 1.02; p < 0.0001).
Progression to CTD is uncommon in IPF patients. However, a significant number of IPF patients with high titers of RF, ACPA, or MPO-ANCA progressed to CTD. RF, ACPA, and MPO-ANCA might be significantly associated with CTD development in IPF patients. Key Points • A significant number of IPF patients with high titers of RF, ACPA, or MPO-ANCA progressed to CTD. • IPF/UIP with high titers of RF, ACPA, or MPO-ANCA might be the initial clinical manifestation of CTD. • RF, ACPA, and MPO-ANCA may be significantly associated with the development of pulmonary fibrosis in patients with CTD.
结缔组织病（CTD）可能发生在特发性肺纤维化（IPF）过程中。与 IPF 患者 CTD 发展相关的临床因素仍未确定。我们研究了哪些抗体与 IPF 患者临床病程中的 CTD 发展有显著关联。
我们回顾性分析了 2007 年 1 月至 2014 年 3 月间首次诊断为 IPF 的 527 例患者的记录，并调查了这些患者在 IPF 诊断后发生 CTD 的时间。
在 IPF 诊断后中位数为 2.1 年（范围 1.2-4.8）时，15 例患者发生 CTD。所有患者均有抗中性粒细胞胞质抗体（ANCA）或自身抗体，符合自身免疫特征性间质性肺炎（IPAF）的血清学标准。进展为 CTD 的 IPF 患者的生存时间为 5.3（3.8，6.7）年，明显长于未进展为 CTD 的 IPF 患者[2.9（1.7，4.8），p=0.001]。IPF 患者发生 CTD 的独立危险因素包括女性[校正风险比（HR）5.319，p=0.0082]、类风湿因子（RF）滴度[校正 HR，1.006；p=0.022]、抗瓜氨酸化蛋白抗体（ACPA）滴度[校正 HR，1.009；p=0.0011]和髓过氧化物酶（MPO）-ANCA 滴度[校正 HR，1.02；p<0.0001]。
进展为 CTD 在 IPF 患者中并不常见。然而，相当数量的 IPF 患者 RF、ACPA 或 MPO-ANCA 滴度较高进展为 CTD。RF、ACPA 和 MPO-ANCA 可能与 IPF 患者的 CTD 发展显著相关。
关键点
• 相当数量的 RF、ACPA 或 MPO-ANCA 滴度较高的 IPF 患者进展为 CTD。
• RF、ACPA 或 MPO-ANCA 滴度较高的 IPF/UIP 可能是 CTD 的初始临床表现。
• RF、ACPA 和 MPO-ANCA 可能与 CTD 患者的肺纤维化发展显著相关。
