OBJECTIVE To define the relationship of synovial B cells to clinical phenotypes at different stages of disease evolution and drug exposure in rheumatoid arthritis (RA). METHODS Synovial biopsy specimens and demographic and clinical data were collected from 2 RA cohorts (n = 329), one of patients with untreated early RA (n = 165) and one of patients with established RA with an inadequate response to tumor necrosis factor inhibitors (TNFi-IR; n = 164). Synovial tissue was subjected to hematoxylin and eosin and immunohistochemical staining and semiquantitative assessment for the degree of synovitis (on a scale of 0-9) and of CD20+ B cell infiltrate (on a scale of 0-4). B cell scores were validated by digital image analysis and B cell lineage-specific transcript analysis (RNA-Seq) in the early RA (n = 91) and TNFi-IR (n = 127) cohorts. Semiquantitative CD20 scores were used to classify patients as B cell rich (≥2) or B cell poor (<2). RESULTS Semiquantitative B cell scores correlated with digital image analysis quantitative measurements and B cell lineage-specific transcripts. B cell-rich synovitis was present in 35% of patients in the early RA cohort and 47.7% of patients in the TNFi-IR cohort (P = 0.025). B cell-rich patients showed higher levels of disease activity and seropositivity for rheumatoid factor and anti-citrullinated protein antibody in early RA but not in established RA, while significantly higher histologic synovitis scores in B cell-rich patients were demonstrated in both cohorts. CONCLUSION We describe a robust semiquantitative histologic B cell score that closely replicates the quantification of B cells by digital or molecular analyses. Our findings indicate an ongoing B cell-rich synovitis, which does not seem to be captured by standard clinimetric assessment, in a larger proportion of patients with established RA than early RA.

中文翻译：

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B 细胞滑膜炎和类风湿性关节炎的临床表型：与疾病阶段和药物暴露的关系。

目的 明确滑膜 B 细胞与类风湿性关节炎 (RA) 疾病演变和药物暴露不同阶段临床表型的关系。方法 从 2 个 RA 队列（n = 329）中收集滑膜活检标本以及人口统计和临床数据，其中一名未经治疗的早期 RA 患者（n = 165）和一名对肿瘤坏死因子抑制剂反应不足的已确诊 RA 患者（n = 165）。 TNFi-IR；n = 164)。对滑膜组织进行苏木精和伊红染色以及免疫组织化学染色，并对滑膜炎的程度（0-9的等级）和CD20+B细胞浸润​​的程度（0-4的等级）进行半定量评估。在早期 RA (n = 91) 和 TNFi-IR (n = 127) 队列中，通过数字图像分析和 B 细胞谱系特异性转录本分析 (RNA-Seq) 验证 B 细胞评分。半定量 CD20 评分用于将患者分类为 B 细胞丰富 (≥2) 或 B 细胞缺乏 (<2)。结果半定量 B 细胞评分与数字图像分析定量测量和 B 细胞谱系特异性转录本相关。早期 RA 队列中 35% 的患者存在富含 B 细胞的滑膜炎，而 TNFi-IR 队列中 47.7% 的患者存在富含 B 细胞的滑膜炎 (P = 0.025)。富含 B 细胞的患者在早期 RA 中表现出较高水平的疾病活动性以及类风湿因子和抗瓜氨酸蛋白抗体血清阳性，但在已确诊的 RA 中则不然，而在两个队列中，富含 B 细胞的患者的组织学滑膜炎评分均显着较高。结论 我们描述了一种稳健的半定量组织学 B 细胞评分，它通过数字或分子分析精确复制了 B 细胞的定量结果。我们的研究结果表明，与早期 RA 相比，确诊 RA 患者中存在持续的富含 B 细胞的滑膜炎，标准临床评估似乎无法捕获这种滑膜炎。