IVIG ameliorate inflammation in collagen‐induced arthritis: projection for IVIG therapy in rheumatoid arthritis,Clinical & Experimental Immunology

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IVIG ameliorate inflammation in collagen‐induced arthritis: projection for IVIG therapy in rheumatoid arthritis
Clinical & Experimental Immunology ( IF 3.4 ) Pub Date : 2020-10-06 , DOI: 10.1111/cei.13532
G Halpert ₁ , I Katz ₁ , O Shovman ₁ , S Tarasov _{2,

3} , K K Ganina ₂ , N Petrova _{2,

3} , M Tocut ₄ , A Volkov ₅ , I Barshack ₅ , M Blank ₁ , H Amital _{1,

6}

Affiliation

Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease that leads to joint destruction and disability. Despite a significant progress in administration of biological agents for RA patients, there is still a need for improved therapy. Intravenous immunoglobulins (IVIG), a pooled polyspecific immunoglobulin (Ig)G extracted from 5000 to 20 000 healthy subjects, showed beneficial therapeutic effect in patients with immune deficiency, sepsis and autoimmune diseases. The current study aimed to investigate the beneficial effect of treatment with IVIG in established collagen‐induced arthritis in DBA/1j mice. Murine arthritis was induced in DBA/1j mice. Treatment with IVIG began when the disease was established. The clinical score was followed twice a week until day 48. The mice were bled for plasma and the paws were hematoxylin and eosin (H&E)‐stained. Cytokine profile in the plasma was analyzed by Luminex technology and titers of circulating anti‐collagen antibodies in the plasma was tested by enzyme‐linked immunosorbent assay. Our results show that treatment with IVIG in murine significantly reduced the clinical arthritis score (P < 0·001). Moreover, mode of action showed that IVIG significantly reduced circulating levels of inflammatory cytokines [interferon (IFN)‐γ, interleukin (IL)‐1β, IL‐17, IL‐6, tumor necrosis factor (TNF)‐α, P < 0·001], inhibiting anti‐collagen antibodies (P < 0·001) in the plasma of collagen‐induced arthritis mice. Importantly, histopathological examination revealed that IVIG treatment prevented the migration of inflammatory immune cells into the cartilage and synovium, reduced the extent of joint damage and preserved joint architecture. Our results proved for the first time the valuable anti‐inflammatory treatment of IVIG in experimental RA. We propose IVIG therapy for a subgroup of patients with rheumatologically related diseases.

中文翻译：

IVIG 改善胶原诱导性关节炎的炎症：IVIG 治疗类风湿性关节炎的预测

类风湿性关节炎（RA）是一种全身性炎症性自身免疫性疾病，可导致关节破坏和残疾。尽管在对 RA 患者使用生物制剂方面取得了重大进展，但仍然需要改进的治疗方法。静脉注射免疫球蛋白 (IVIG) 是从 5000 至 20000 名健康受试者中提取的混合多特异性免疫球蛋白 (Ig)G，对免疫缺陷、脓毒症和自身免疫性疾病患者显示出有益的治疗效果。目前的研究旨在调查 IVIG 治疗对 DBA/1j 小鼠已建立的胶原诱导关节炎的有益效果。在 DBA/1j 小鼠中诱导小鼠关节炎。当疾病确诊时，开始使用 IVIG 治疗。临床评分每周跟踪两次，直至第 48 天。对小鼠抽血提取血浆，并对爪子进行苏木精和伊红 (H&E) 染色。通过 Luminex 技术分析血浆中的细胞因子谱，并通过酶联免疫吸附测定法测试血浆中循环抗胶原抗体的滴度。我们的结果表明，用 IVIG 治疗小鼠可显着降低临床关节炎评分 ( P < 0·001)。此外，作用方式表明 IVIG 显着降低炎症细胞因子的循环水平[干扰素 (IFN)-γ、白细胞介素 (IL)-1β、IL-17、IL-6、肿瘤坏死因子 (TNF)-α， P < 0 ·001]，抑制胶原诱导关节炎小鼠血浆中的抗胶原抗体（ P < 0·001）。重要的是，组织病理学检查表明 IVIG 治疗可阻止炎症免疫细胞迁移到软骨和滑膜中，减少关节损伤的程度并保留关节结构。我们的结果首次证明 IVIG 在实验性 RA 中具有有价值的抗炎治疗作用。我们建议对患有风湿病相关疾病的亚组患者进行 IVIG 治疗。

更新日期：2020-10-06

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