Wallace W A, Roberts S N, Caldwell H, Thornton E, Greening A P, Lamb D, Howie S E
Department of Pathology, Edinburgh University Medical School, UK.
Thorax. 1994 Mar;49(3):218-24. doi: 10.1136/thx.49.3.218.
It has been hypothesised that cryptogenic fibrosing alveolitis has an immunological pathogenesis mediated by T lymphocytes. It is, however, recognised that patients may show dysregulation of the humoral immune system and that the presence of large numbers of B lymphocytes in open lung biopsies may be associated with a poor prognosis. Evidence of a role for the humoral immune system in the pathogenesis of cryptogenic fibrosing alveolitis has been suggested, but attempts to demonstrate circulating immunoglobulin to antigen within the lung have been inconclusive.
Plasma samples from 22 patients with cryptogenic fibrosing alveolitis, 22 patients with sarcoidosis, and 17 healthy controls were screened by SDS-PAGE and Western blotting for the presence of autoantibodies to lung proteins derived from cryptogenic fibrosing alveolitis, sarcoid and control lung tissue, as well as four normal non-pulmonary tissues. Possible site(s) of target protein(s) within the lung tissue were identified by immunohistochemical examination using IgG purified from the plasma of six patients and two controls.
Eighteen of the plasma samples from patients with cryptogenic fibrosing alveolitis had reactive IgG to lung protein(s) in the 70-90 kDa molecular weight range compared with five of 18 plasma samples from patients with sarcoidosis and one of 17 controls. Plasma from patients with cryptogenic fibrosing alveolitis recognised antigen(s) of the same molecular weight in control and sarcoid lung tissue, but not non-pulmonary tissues, with a similar frequency. Immunohistochemical staining of cryptogenic fibrosing alveolitis biopsy material using IgG purified from plasma samples from patients with cryptogenic fibrosing alveolitis, but not control samples, revealed fine linear positivity in the lung parenchyma in a pattern suggestive of reaction with alveolar lining cells. The pattern was cytoplasmic/membranous and not nuclear.
Patients with cryptogenic fibrosing alveolitis have a high frequency of plasma IgG autoantibodies to protein(s) within lung tissue associated with alveolar lining cells. This is believed to be the site where immunological injury occurs in cryptogenic fibrosing alveolitis, but the significance of these antibodies to the aetiology and pathogenesis is as yet unclear.
有假说认为隐源性纤维性肺泡炎具有由T淋巴细胞介导的免疫发病机制。然而，人们认识到患者可能存在体液免疫系统失调，并且开放性肺活检中大量B淋巴细胞的存在可能与预后不良有关。体液免疫系统在隐源性纤维性肺泡炎发病机制中所起作用的证据已被提出，但试图证明循环免疫球蛋白与肺内抗原的关系尚未得出明确结论。
通过SDS - PAGE和蛋白质印迹法，对22例隐源性纤维性肺泡炎患者、22例结节病患者和17名健康对照者的血浆样本进行筛查，以检测针对源自隐源性纤维性肺泡炎、结节病和对照肺组织以及四种正常非肺组织的肺蛋白的自身抗体。使用从6例患者和2例对照者血浆中纯化的IgG，通过免疫组织化学检查确定肺组织内靶蛋白的可能位点。
与18例结节病患者血浆样本中的5例以及17名对照者中的1例相比，22例隐源性纤维性肺泡炎患者的血浆样本中有18例对分子量在70 - 90 kDa范围内的肺蛋白具有反应性IgG。隐源性纤维性肺泡炎患者的血浆在对照肺组织和结节病肺组织中识别出相同分子量的抗原，但在非肺组织中未识别出，频率相似。使用从隐源性纤维性肺泡炎患者血浆样本中纯化的IgG（而非对照样本）对隐源性纤维性肺泡炎活检材料进行免疫组织化学染色，显示肺实质内有细微的线性阳性，其模式提示与肺泡衬里细胞发生反应。该模式为细胞质/膜性，而非核性。
隐源性纤维性肺泡炎患者血浆中针对与肺泡衬里细胞相关的肺组织蛋白的IgG自身抗体频率较高。这被认为是隐源性纤维性肺泡炎发生免疫损伤的部位，但这些抗体对病因和发病机制的意义尚不清楚。
