Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Stanford Institute for Immunity Transplantation and Infection, Stanford, California, USA.
Ann Rheum Dis. 2023 May;82(5):670-680. doi: 10.1136/ard-2021-221926. Epub 2023 Jan 18.
Results from the SCOT (Scleroderma: Cyclophosphamide Or Transplantation) clinical trial demonstrated significant benefits of haematopoietic stem cell transplant (HSCT) versus cyclophosphamide (CTX) in patients with systemic sclerosis. The objective of this study was to test the hypothesis that transplantation stabilises the autoantibody repertoire in patients with favourable clinical outcomes.
We used a bead-based array containing 221 protein antigens to profile serum IgG autoantibodies in participants of the SCOT trial.
Comparison of autoantibody profiles at month 26 (n=23 HSCT; n=22 CTX) revealed antibodies against two viral antigens and six self-proteins (SSB/La, CX3CL1, glycyl-tRNA synthetase (EJ), parietal cell antigen, bactericidal permeability-increasing protein and epidermal growth factor receptor (EGFR)) that were significantly different between treatment groups. Linear mixed model analysis identified temporal increases in antibody levels for hepatitis B surface antigen, CCL3 and EGFR in HSCT-treated patients. Eight of 32 HSCT-treated participants and one of 31 CTX-treated participants had temporally varying serum antibody profiles for one or more of 14 antigens. Baseline autoantibody levels against 20 unique antigens, including 9 secreted proteins (interleukins, IL-18, IL-22, IL-23 and IL-27), interferon-α2A, stem cell factor, transforming growth factor-β, macrophage colony-stimulating factor and macrophage migration inhibitory factor were significantly higher in patients who survived event-free to month 54.
Our results suggest that HSCT favourably alters the autoantibody repertoire, which remains virtually unchanged in CTX-treated patients. Although antibodies recognising secreted proteins are generally thought to be pathogenic, our results suggest a subset could potentially modulate HSCT in scleroderma.
SCOT（硬皮病：环磷酰胺或移植）临床试验的结果表明，造血干细胞移植（HSCT）与环磷酰胺（CTX）相比，在系统性硬化症患者中具有显著优势。本研究的目的是检验以下假设，即移植可稳定具有良好临床结局患者的自身抗体谱。
我们使用包含 221 种蛋白抗原的珠基阵列来分析 SCOT 试验参与者的血清 IgG 自身抗体谱。
比较 26 个月时（n=23 例 HSCT；n=22 例 CTX）的自身抗体谱，发现两组之间存在针对两种病毒抗原和六种自身蛋白（SSB/La、CX3CL1、甘氨酰-tRNA 合成酶（EJ）、壁细胞抗原、杀菌通透性增加蛋白和表皮生长因子受体（EGFR））的抗体存在显著差异。线性混合模型分析确定了 HSCT 治疗组患者乙型肝炎表面抗原、CCL3 和 EGFR 抗体水平的时间性增加。在 32 例 HSCT 治疗组参与者中有 8 例和在 31 例 CTX 治疗组参与者中有 1 例在 14 种抗原中的一种或多种上具有时间变化的血清抗体谱。在无事件生存至 54 个月的患者中，基线时针对 20 种独特抗原（包括 9 种分泌蛋白（白细胞介素、IL-18、IL-22、IL-23 和 IL-27）、干扰素-α2A、干细胞因子、转化生长因子-β、巨噬细胞集落刺激因子和巨噬细胞移动抑制因子）的自身抗体水平显著升高。
我们的结果表明，HSCT 可有利地改变自身抗体谱，而 CTX 治疗组患者的自身抗体谱几乎没有变化。尽管通常认为识别分泌蛋白的抗体具有致病性，但我们的结果表明，在硬皮病中，这些抗体中的一部分可能具有调节 HSCT 的潜力。
