1 SciLifeLab, School of Biotechnology, KTH-Royal Institute of Technology, Stockholm, Sweden.
Am J Respir Crit Care Med. 2015 Mar 1;191(5):574-83. doi: 10.1164/rccm.201407-1341OC.
There is a need to further characterize the antibody repertoire in relation to sarcoidosis and potentially related autoantigens.
We investigated bronchoalveolar lavage (BAL) and serum samples from patients with sarcoidosis and healthy and diseased control subjects to discover sarcoidosis-associated autoantigens.
Antigen microarrays built on 3,072 protein fragments were used to screen for IgG reactivity in 73 BAL samples from subjects with sarcoidosis, subjects with asthma, and healthy subjects. A set of 131 targets were selected for subsequent verification on suspension bead arrays using 272 additional BAL samples and 141 paired sera. Reactivity to four antigens was furthermore analyzed in 22 unprocessed BAL samples from patients with fibrosis and 269 plasma samples from patients diagnosed with myositis.
Reactivity toward zinc finger protein 688 and mitochondrial ribosomal protein L43 were discovered with higher frequencies in patients with sarcoidosis, for mitochondrial ribosomal protein L43 especially in patients with non-Löfgren syndrome. Increased reactivity toward nuclear receptor coactivator 2 was also observed in patients with non-Löfgren syndrome as compared with patients with Löfgren syndrome. The antigen representing adenosine diphosphate-ribosylation factor GTPase activating protein 1 revealed high reactivity frequency in all sample groups but with significantly higher level of IgG reactivities in patients with sarcoidosis.
Autoantigen reactivity was present in most BAL and serum samples analyzed, and the results revealed high interindividual heterogeneity, with most of the reactivities observed in single individuals only. Four proteins are here proposed as sarcoidosis-associated autoimmune targets and of interest for further validation in independent cohorts.
需要进一步研究与结节病相关的潜在自身抗原的抗体库。
我们研究了结节病患者、健康对照者和疾病对照者的支气管肺泡灌洗液（BAL）和血清样本，以发现与结节病相关的自身抗原。
使用基于 3072 个蛋白质片段的抗原微阵列筛选 73 例结节病患者、哮喘患者和健康对照者的 BAL 样本中的 IgG 反应性。选择了 131 个靶标，用于在 272 个额外的 BAL 样本和 141 对血清样本上的悬浮珠阵列上进行后续验证。此外，在 22 例纤维化患者的未经处理的 BAL 样本和 269 例肌炎患者的血浆样本中分析了对 4 种抗原的反应性。
锌指蛋白 688 和线粒体核糖体蛋白 L43 的反应性在结节病患者中出现频率更高，特别是在非 Löfgren 综合征患者中，线粒体核糖体蛋白 L43 的反应性更高。与 Löfgren 综合征患者相比，非 Löfgren 综合征患者的核受体共激活因子 2 的反应性也增加了。代表二磷酸腺苷-核糖基化因子 GTP 酶激活蛋白 1 的抗原在所有分析的样本组中均具有高反应频率，但在结节病患者中 IgG 反应性水平显著更高。
在分析的大多数 BAL 和血清样本中均存在自身抗原反应性，结果显示个体间异质性很高，大多数反应性仅在单个个体中观察到。这里提出了 4 种蛋白质作为与结节病相关的自身免疫靶标，值得在独立队列中进一步验证。
