Assistance Publique-Hôpitaux de Paris, DHU FIRE (Fibrosis, Inflammation and Remodeling), Hôpital Bichat, Service de Pneumologie A, 75018 Paris, France.
Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Service de Pneumologie et Transplantation, 75018 Paris, France; INSERM UMR 1152, Labex Inflamex, Paris, France; Université Paris Diderot, Paris, France.
Respir Med. 2018 Feb;135:15-21. doi: 10.1016/j.rmed.2017.12.011. Epub 2018 Jan 2.
Autoantibodies against lung epithelial antigens are often detected in patients with Idiopathic Pulmonary Fibrosis (IPF). Anti-Parietal Cell Antibodies (APCA) target the H+/K+ATPase (proton pump). APCA prevalence and lung H+/K+ATPase expression was never studied in IPF patients.
We retrospectively collected clinical, lung function and imaging data from APCA positive patients (APCA+IPF) and compared them with APCA negative IPF patients matched on the date of diagnostic assessment. H+/K+ATPase expression was assessed with immunohistochemistry and PCR.
Among 138 IPF patients diagnosed between 2007 and 2014 and tested for APCA, 19 (13.7%) APCA+ patients were identified. APCA+IPF patients were 16 men and 3 women, mean age 71 years. The median titer of APCA was 1:160. A pernicious anemia was present in 5 patients and preceded the fibrosis in 3 cases. With a mean follow up of 31 months, 2 patients had an exacerbation and 7 patients died. As compared with 19 APCA- IPF patients, APCA+IPF patients had a less severe disease with better DLCO (57% vs 43% predicted), preserved PaO (85 ± 8 mmHg vs 74 ± 11 mmHg), a lower rate of honeycombing on HRCT (58% vs 89%), but they experienced an accelerated decline of FVC (difference 61.4 ml/year; p = .0002). The H+/K+ATPase was strongly expressed by hyperplastic alveolar epithelial cells in the fibrotic lung.
Anti-parietal cell autoimmunity is detected in some IPF patients and is associated with an accelerated decline of lung function. Anti-parietal cell autoimmunity may promote lung fibrosis progression.
特发性肺纤维化（IPF）患者常检测到针对肺上皮抗原的自身抗体。壁细胞抗体（APCA）针对 H+/K+ATPase（质子泵）。从未在 IPF 患者中研究过 APCA 的患病率和肺 H+/K+ATPase 表达。
我们回顾性地收集了 APCA 阳性患者（APCA+IPF）的临床、肺功能和影像学数据，并将其与在诊断评估日期上相匹配的 APCA 阴性 IPF 患者进行了比较。使用免疫组织化学和 PCR 评估 H+/K+ATPase 的表达。
在 2007 年至 2014 年间诊断为 138 例 IPF 并检测 APCA 的患者中，发现 19 例（13.7%）APCA+患者。APCA+IPF 患者中有 16 名男性和 3 名女性，平均年龄为 71 岁。APCA 的中位滴度为 1:160。5 例患者存在恶性贫血，其中 3 例先于纤维化。在平均 31 个月的随访中，2 例患者发生加重，7 例患者死亡。与 19 例 APCA-IPF 患者相比，APCA+IPF 患者的疾病较轻，DLCO 更好（57% vs 43%预计值），PaO 保持不变（85±8mmHg vs 74±11mmHg），HRCT 上蜂窝状结构的发生率较低（58% vs 89%），但 FVC 下降速度较快（差异 61.4ml/年；p=0.0002）。纤维化肺中的增生肺泡上皮细胞强烈表达 H+/K+ATPase。
一些 IPF 患者检测到抗壁细胞自身免疫，与肺功能加速下降相关。抗壁细胞自身免疫可能促进肺纤维化的进展。
