Clinical Rheumatology, Kumamoto Shinto General Hospital, Kumamoto, Japan.
Clin Exp Rheumatol. 2014 Jul-Aug;32(4):501-8. Epub 2014 Jun 23.
To examine the efficacy and safety of abatacept (ABT) in patients with amyloid A (AA) amyloidosis secondary to rheumatoid arthritis (RA), and to speculate about the immunologic association of ABT with AA amyloid deposit regression.
We administered ABT to 70- and 65-year-old Japanese women with RA and AA amyloidosis. We quantified serum cytokine concentrations and analysed regulatory T lymphocytes (Treg cells) via flow cytometry. We also studied AA amyloid deposits via histopathology and immunohistochemistry.
ABT improved rheumatoid inflammation and AA amyloidosis, one case showing clinical remission and the other demonstrating incomplete recovery of nephrosis but stable kidney function. Serum levels of interleukin-6 and tumour necrosis factor α decreased to baseline in the first 6 months of treatment, but serum interleukin-2 concentrations did not change. CD4+CD25++FoxP3+ Treg cells gated on T lymphocytes and CD4+ T lymphocytes decreased to baseline in the first 3 treatment months. One case showed complete regression of AA amyloid fibrils in serial upper gastrointestinal biopsies, but the other case still had AA amyloid deposits despite ABT-induced normalised rheumatoid inflammation, with polymorphonuclear leukocytes and macrophages infiltrating tissues containing AA amyloid.
ABT demonstrated efficacy and safety in AA amyloidosis secondary to RA and affected Treg cells and inflammatory cytokines. Because the gradual decrease in Treg cells population coincided with AA amyloid deposit regression during ABT therapy, AA amyloid fibril turnover in these patients may involve an immunologic mechanism. Phagocytes seemed to have an important role in AA amyloid fibril regression, which suggests an immunologic interaction.
观察阿巴西普（ABT）治疗类风湿关节炎（RA）继发淀粉样变性 A（AA）的疗效和安全性，并推测 ABT 与 AA 淀粉样沉积物消退的免疫相关性。
我们对两名患有 RA 和 AA 淀粉样变性的 70 岁和 65 岁日本女性患者使用 ABT 进行治疗。我们通过流式细胞术定量检测血清细胞因子浓度并分析调节性 T 淋巴细胞（Treg 细胞）。我们还通过组织病理学和免疫组织化学研究 AA 淀粉样沉积物。
ABT 改善了类风湿炎症和 AA 淀粉样变性，其中 1 例患者出现临床缓解，另 1 例患者肾病不完全恢复但肾功能稳定。治疗的前 6 个月，血清白细胞介素-6 和肿瘤坏死因子-α水平降至基线，但血清白细胞介素-2 浓度没有变化。T 淋巴细胞和 CD4+T 淋巴细胞上 CD4+CD25++FoxP3+Treg 细胞在治疗的前 3 个月降至基线。1 例患者在上消化道连续活检中观察到 AA 淀粉样纤维完全消退，但另 1 例患者尽管接受 ABT 治疗后类风湿炎症得到正常化，但仍存在 AA 淀粉样沉积物，组织中存在浸润的多形核白细胞和巨噬细胞。
ABT 在 RA 继发 AA 淀粉样变性中显示出疗效和安全性，并且影响 Treg 细胞和炎症细胞因子。由于 Treg 细胞群的逐渐减少与 ABT 治疗期间 AA 淀粉样沉积物的消退相吻合，这些患者的 AA 淀粉样纤维的周转可能涉及免疫机制。吞噬细胞在 AA 淀粉样纤维的消退中似乎具有重要作用，这表明存在免疫相互作用。
