Institute of Medical Technology, Peking University Health Science Center, Beijing, China.
Department of Clinical Laboratory, Peking University Third Hospital, Beijing, China.
Autoimmunity. 2024 Dec;57(1):2360490. doi: 10.1080/08916934.2024.2360490. Epub 2024 Jun 5.
The heterogeneity of the T cell receptor (TCR) repertoire critically influences the autoimmune response in obstetric antiphospholipid syndrome (OAPS) and is intimately associated with the prophylaxis of autoimmune disorders. Investigating the TCR diversity patterns in patients with OAPS is thus of paramount clinical importance. This investigation procured peripheral blood specimens from 31 individuals with OAPS, 21 patients diagnosed with systemic lupus erythematosus (SLE), and 22 healthy controls (HC), proceeding with TCR repertoire sequencing. Concurrently, adverse pregnancy outcomes in the OAPS cohort were monitored and documented over an 18-month timeframe. We paid particular attention to disparities in V/J gene utilisation and the prevalence of shared clonotypes amongst OAPS patients and the comparative groups. When juxtaposed with observations from healthy controls and SLE patients, immune repertoire sequencing disclosed irregular T- and B-cell profiles and a contraction of diversity within the OAPS group. Marked variances were found in the genomic rearrangements of the V gene, J gene, and V/J combinations. Utilising a specialised TCRβ repertoire, we crafted a predictive model for OAPS classification with robust discriminative capability (AUC = 0.852). Our research unveils alterations in the TCR repertoire among OAPS patients for the first time, positing potential covert autoimmune underpinnings. These findings nominate the TCR repertoire as a prospective peripheral blood biomarker for the clinical diagnosis of OAPS and may offer valuable insights for advancing the understanding of OAPS immunologic mechanisms and prognostic outcomes.
T 细胞受体（TCR）库的异质性对产科抗磷脂综合征（OAPS）中的自身免疫反应具有重要影响，并且与自身免疫疾病的预防密切相关。因此，研究 OAPS 患者的 TCR 多样性模式具有至关重要的临床意义。本研究从 31 名 OAPS 患者、21 名系统性红斑狼疮（SLE）患者和 22 名健康对照者（HC）中采集外周血标本，进行 TCR 库测序。同时，在 18 个月的时间内监测和记录 OAPS 队列中的不良妊娠结局。我们特别关注 OAPS 患者与对照组之间 V/J 基因利用和共享克隆型的差异。与健康对照者和 SLE 患者的观察结果相比，免疫受体库测序揭示了 OAPS 组中 T 细胞和 B 细胞谱的不规则和多样性的收缩。V 基因、J 基因和 V/J 组合的基因重排存在明显差异。利用专门的 TCRβ 库，我们构建了一个用于 OAPS 分类的预测模型，具有强大的判别能力（AUC = 0.852）。我们的研究首次揭示了 OAPS 患者 TCR 库的改变，提出了潜在的隐匿性自身免疫基础。这些发现将 TCR 库指定为 OAPS 临床诊断的潜在外周血生物标志物，并可能为深入了解 OAPS 的免疫机制和预后结果提供有价值的见解。
