Kaster Collin, Yang Sufang, Adamus Grazyna
Ocular Immunology Laboratory, Casey Eye Institute, Oregon Health and Science University, Portland, OR 97239, USA.
Int J Mol Sci. 2025 Mar 13;26(6):2569. doi: 10.3390/ijms26062569.
Autoantibodies have been implicated in the pathogenesis of autoimmune diseases, including autoimmune retinopathies. Our study aimed to identify retinal autoantigens recognized by serum autoantibodies (AAbs) in patients with visual disturbance. We evaluated 2453 serum samples for anti-retinal AAbs from patients with or without cancer and complaints of visual loss. Anti-TULP1 AAbs were more prevalent in the subset of women with breast cancer and vision loss. Epitope mapping was determined by ELISA using peptides covering the conservative carboxy terminal of TULP1, revealing major lineal epitopes within the sequences 334-341 and 480-488. We found no significant difference in the main epitope recognition between sera from patients with or without breast cancer. Although we show a correlation of anti-TULP1 AAbs with breast cancer, we found no TULP1 protein expression in breast cells, making this association unclear. In the retina, anti-TULP1 AAbs can disrupt the transport of proteins to outer segments and be involved in the degeneration of photoreceptors in a similar fashion to the degeneration induced by gene mutation. Nevertheless, the strong association of detectable anti-TULP1 AAbs in breast cancer patients with vision problems indicates its potential as a biomarker for cancer-associated autoimmune retinopathy.
自身抗体与包括自身免疫性视网膜病在内的自身免疫性疾病的发病机制有关。我们的研究旨在鉴定视觉障碍患者血清自身抗体（AAbs）所识别的视网膜自身抗原。我们评估了2453份来自有或无癌症且有视力丧失主诉患者的血清样本中的抗视网膜AAbs。抗TULP1 AAbs在患有乳腺癌且视力丧失的女性亚组中更为普遍。通过使用覆盖TULP1保守羧基末端的肽进行ELISA确定表位图谱，揭示了序列334 - 341和480 - 488内的主要线性表位。我们发现乳腺癌患者和非乳腺癌患者血清之间在主要表位识别上没有显著差异。尽管我们显示抗TULP1 AAbs与乳腺癌相关，但我们在乳腺细胞中未发现TULP1蛋白表达，使得这种关联尚不清楚。在视网膜中，抗TULP1 AAbs可破坏蛋白质向视锥外节的转运，并以与基因突变诱导的变性类似的方式参与光感受器的变性。然而，乳腺癌患者中可检测到的抗TULP1 AAbs与视力问题的强关联表明其作为癌症相关自身免疫性视网膜病生物标志物的潜力。
