The immune system undergoes a myriad of changes with age. While it is known that antibody-secreting plasma and long-lived memory B cells change with age, it remains unclear how the binding profile of the circulating antibody repertoire is impacted. To understand humoral immunity changes with respect to age, we characterized serum antibody binding to high density peptide microarrays in a diverse cohort of 1675 donors. We discovered thousands of peptides that bind antibodies in age-dependent fashion, many of which contain di-serine motifs. Peptide binding profiles were aggregated into an “immune age” by a machine learning regression model that was highly correlated with chronological age. Applying this regression model to previously-unobserved donors, we found that a donor’s predicted immune age is longitudinally consistent over years, suggesting it could be a robust long-term biomarker of humoral immune ageing. Finally, we assayed serum from donors with autoimmune disease and found a significant association between “accelerated immune ageing” and autoimmune disease activity. The circulating antibody repertoire has increased binding to thousands of di-serine peptide containing peptides in older donors, which can be represented as an immune age. Increased immune age is associated with autoimmune disease, acute inflammatory disease severity, and may be a broadly relevant biomarker of immune function in health, disease, and therapeutic intervention.

中文翻译：

---

循环人类抗体库中与年龄相关的变化在自身免疫中上调

随着年龄的增长，免疫系统会发生无数变化。虽然已知分泌抗体的血浆和长寿命记忆 B 细胞会随着年龄的增长而变化，但仍不清楚循环抗体库的结合特征如何受到影响。为了了解体液免疫随年龄的变化，我们在 1675 名供体的不同队列中描述了与高密度肽微阵列结合的血清抗体。我们发现了数千种以年龄依赖性方式结合抗体的肽，其中许多含有二丝氨酸基序。通过与实际年龄高度相关的机器学习回归模型将肽结合谱聚合成“免疫年龄”。将此回归模型应用于以前未观察到的供体，我们发现供体的预测免疫年龄多年来纵向一致，表明它可能是体液免疫老化的一个强有力的长期生物标志物。最后，我们检测了患有自身免疫性疾病的供体的血清，发现“加速免疫老化”与自身免疫性疾病活动之间存在显着关联。循环抗体库增加了与老年供体中数千种含有二丝氨酸肽的肽的结合，这可以表示为免疫年龄。免疫年龄增加与自身免疫性疾病、急性炎症性疾病的严重程度相关，并且可能是健康、疾病和治疗干预中免疫功能的广泛相关生物标志物。循环抗体库增加了与老年供体中数千种含有二丝氨酸肽的肽的结合，这可以表示为免疫年龄。免疫年龄增加与自身免疫性疾病、急性炎症性疾病的严重程度相关，并且可能是健康、疾病和治疗干预中免疫功能的广泛相关生物标志物。循环抗体库增加了与老年供体中数千种含有二丝氨酸肽的肽的结合，这可以表示为免疫年龄。免疫年龄增加与自身免疫性疾病、急性炎症性疾病的严重程度相关，并且可能是健康、疾病和治疗干预中免疫功能的广泛相关生物标志物。