Chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplant reflects a complex immune response resulting in chronic damage to multiple tissues. Previous studies indicated that donor B cells and the antibodies they produce play an important role in the development of cGVHD. To understand the pathogenic role of antibodies in cGVHD, we focused our studies on posttransplant production of immunoglobulin G antibodies targeting cell surface antigens expressed in multiple cGVHD affected tissues, due to their potential functional impact on living cells in vivo. Using plate-bound cell membrane proteins as targets, we detected a significantly higher level of antibodies reactive with these membrane antigens in patients who developed cGVHD, compared with those who did not and healthy donors. Plasma-reactive antibody levels increased significantly prior to the clinical diagnosis of cGVHD and were reduced following cGVHD therapies including prednisone, interleukin-2, or extracorporeal photophoresis. Using cell-based immunoprecipitation with plasma from cGVHD patients and mass spectrometry, we identified 43 membrane proteins targeted by these antibodies. The presence of antibodies in cGVHD patients' plasma that specifically target 6 of these proteins was validated. Antibodies reactive with these 6 antigens were more frequently detected in patients with cGVHD compared with patients without cGVHD and healthy donors. These results indicate that antibodies that target membrane antigens of living cells frequently develop in cGVHD patients and further support a role for B cells and antibodies in the development of cGVHD.

中文翻译：

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针对慢性移植物抗宿主病患者表面膜抗原的抗体

异基因造血干细胞移植后的慢性移植物抗宿主病 (cGVHD) 反映了复杂的免疫反应，导致多种组织的慢性损伤。先前的研究表明，供体 B 细胞及其产生的抗体在 cGVHD 的发展中起着重要作用。为了了解抗体在 cGVHD 中的致病作用，我们的研究重点是移植后免疫球蛋白 G 抗体的产生，这些抗体针对在多个 cGVHD 受影响组织中表达的细胞表面抗原，因为它们对体内活细胞的潜在功能影响。使用与板结合的细胞膜蛋白作为靶标，我们在发生 cGVHD 的患者中检测到与这些膜抗原反应的抗体水平显着高于未发生 cGVHD 的患者和健康供体。血浆反应性抗体水平在 cGVHD 临床诊断之前显着增加，并在 cGVHD 治疗（包括泼尼松、白细胞介素 2 或体外光泳）后降低。使用来自 cGVHD 患者的血浆的基于细胞的免疫沉淀和质谱法，我们确定了这些抗体靶向的 43 种膜蛋白。验证了 cGVHD 患者血浆中特异性靶向这些蛋白质中的 6 种的抗体的存在。与没有 cGVHD 的患者和健康供体相比，在 cGVHD 患者中更频繁地检测到与这 6 种抗原反应的抗体。这些结果表明，靶向活细胞膜抗原的抗体经常在 cGVHD 患者中发展，并进一步支持 B 细胞和抗体在 cGVHD 发展中的作用。