The MITRE Corporation, McLean, Virginia.
Hospital for Special Surgery, New York, New York.
Arthritis Rheumatol. 2023 Dec;75(12):2137-2147. doi: 10.1002/art.42653. Epub 2023 Nov 15.
We sought to develop computer vision methods to quantify aggregates of cells in synovial tissue and compare these with clinical and gene expression parameters.
We assembled a computer vision pipeline to quantify five features encompassing synovial cell density and aggregates and compared these with pathologist scores, disease classification, autoantibody status, and RNA expression in a cohort of 156 patients with rheumatoid arthritis (RA) and 149 patients with osteoarthritis (OA).
All five features were associated with pathologist scores of synovial lymphocytic inflammation (P < 0.0001). Three features that related to the cells per unit of tissue were significantly increased in patients with both seronegative and seropositive RA compared with those with OA; on the other hand, aggregate features (number and diameter) were significantly increased in seropositive, but not seronegative, RA compared with OA. Aggregate diameter was associated with the gene expression of immunoglobulin heavy-chain genes in the synovial tissue. Compared with blood, synovial immunoglobulin isotypes were skewed from IGHM and IGHD to IGHG3 and IGHG1. Further, patients with RA with high levels of lymphocytic infiltrates in the synovium demonstrated parallel skewing in their blood with a relative decrease in IGHGM (P < 0.002) and IGHD (P < 0.03) and an increase in class-switched immunoglobulin genes IGHG3 (P < 0.03) and IGHG1 (P < 0.002).
High-resolution automated identification and quantification of synovial immune cell aggregates uncovered skewing in the synovium from naïve IGHD and IGHM to memory IGHG3 and IGHG1 and revealed that this process is reflected in the blood of patients with high inflammatory synovium.
我们旨在开发计算机视觉方法来量化滑膜组织中的细胞聚集体，并将其与临床和基因表达参数进行比较。
我们组装了一个计算机视觉管道来量化五个特征，包括滑膜细胞密度和聚集体，并将其与 156 例类风湿关节炎（RA）和 149 例骨关节炎（OA）患者的病理评分、疾病分类、自身抗体状态和 RNA 表达进行比较。
所有五个特征都与滑膜淋巴细胞炎症的病理评分相关（P < 0.0001）。与 OA 患者相比，三种与单位组织细胞相关的特征在血清阴性和阳性 RA 患者中均显著增加；另一方面，在血清阳性 RA 患者中，聚集体特征（数量和直径）明显增加，但在血清阴性 RA 患者中则没有。聚集体直径与滑膜组织中免疫球蛋白重链基因的表达相关。与血液相比，滑膜免疫球蛋白同型从 IGHM 和 IGHD 偏向于 IGHG3 和 IGHG1。此外，滑膜中淋巴细胞浸润水平较高的 RA 患者，其血液中也出现了类似的偏向性，IGHGM（P < 0.002）和 IGHD（P < 0.03）相对减少，而 IGHG3（P < 0.03）和 IGHG1（P < 0.002）的类转换免疫球蛋白基因增加。
高分辨率自动识别和量化滑膜免疫细胞聚集体揭示了滑膜中从幼稚 IGHD 和 IGHM 向记忆 IGHG3 和 IGHG1 的偏向性，并且表明该过程反映在高炎症滑膜患者的血液中。
