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Effects of infliximab on lung and circulating natural killer cells, CD56+ T cells and B cells in sarcoidosis
BMJ Open Respiratory Research ( IF 4.1 ) Pub Date : 2021-07-01 , DOI: 10.1136/bmjresp-2021-000933
Susanna Kullberg 1, 2 , Natalia V Rivera 2 , Johan Grunewald 2, 3 , Anders Eklund 2, 3
Affiliation  

Background Tumour necrosis factor α (TNF-α) is pivotal in sarcoid granuloma formation, and inhibitors of TNF-α offer an attractive third-line treatment option in sarcoidosis. The sarcoid inflammation is characterised by an exaggerated T helper 1 response, and evidence indicates a contribution of dysregulated and/or deficient NK (natural killer) cells, CD56+ T cells and B cells. Objectives Insight into how TNF-α inhibitors influence these cells may provide more information on inflammatory mechanisms in sarcoidosis and improve understanding of such treatment. We therefore evaluated treatment effects of the TNF-α inhibitor infliximab on lung and peripheral blood (PB) NK, CD56+ T cells and B cells. Methods Fifteen patients were assessed with PB samples, spirometry and CT scan, and 11 of them also underwent bronchoalveolar lavage (BAL) close to start of infliximab treatment. These investigations were repeated after 6 months of treatment. Results Twelve out of 15 patients disclosed a clinical improvement at follow-up. Median percentage of BAL fluid (BALF) CD56+ T cells increased while a decrease was seen in PB (p<0.05 and 0.005, respectively). No significant changes were observed for NK cells. There was a trend towards increased median percentage of PB B cells (p=0.07), and a negative correlation was observed between PB and BALF B cells after treatment (p<0.05). Conclusion In conclusion, 6 months of infliximab treatment in patients with sarcoidosis, of whom the majority benefited from the treatment, influenced immune cells in the lung and circulation differently, highlighting the importance of investigating several compartments concomitantly when evaluating treatment effects on the inflammatory activity. All data relevant to the study are included in the article or uploaded as supplemental information. Data are available on reasonable request from the corresponding author.

中文翻译:

英夫利昔单抗对结节病患者肺和循环自然杀伤细胞、CD56+ T 细胞和 B 细胞的影响

背景 肿瘤坏死因子 α (TNF-α) 在结节性肉芽肿形成中起关键作用,而 TNF-α 抑制剂为结节病提供了有吸引力的三线治疗选择。肉瘤炎症的特征在于过度的 T 辅助 1 反应,并且证据表明失调和/或缺乏 NK(自然杀伤)细胞、CD56+ T 细胞和 B 细胞的贡献。目标 了解 TNF-α 抑制剂如何影响这些细胞可能会提供更多关于结节病炎症机制的信息,并提高对此类治疗的理解。因此,我们评估了 TNF-α 抑制剂英夫利昔单抗对肺和外周血 (PB) NK、CD56+ T 细胞和 B 细胞的治疗效果。方法 对 15 名患者进行 PB 样本、肺活量测定和 CT 扫描评估,其中 11 人还在英夫利昔单抗治疗开始前接受了支气管肺泡灌洗 (BAL)。在治疗 6 个月后重复这些调查。结果 15 名患者中有 12 名在随访时出现临床改善。BAL 液 (BALF) CD56+ T 细胞的中位百分比增加,而 PB 则减少(分别为 p<0.05 和 0.005)。NK细胞未观察到显着变化。PB B细胞的中位百分比有增加的趋势(p=0.07),治疗后PB和BALF B细胞之间呈负相关(p<0.05)。结 强调在评估治疗对炎症活动的影响时同时研究几个隔室的重要性。所有与研究相关的数据都包含在文章中或作为补充信息上传。数据可根据通讯作者的合理要求提供。
更新日期:2021-07-07
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