Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Red de Apoyo a La Investigación, Universidad Nacional Autónoma de México E Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Clin Rheumatol. 2024 Jan;43(1):501-509. doi: 10.1007/s10067-023-06810-6. Epub 2023 Nov 15.
To address the relationship between systemic lupus erythematosus (SLE) disease activity and the functional parameters of the innate immunity.
We evaluated a cohort of 26 adult SLE patients and 10 sex and age-paired healthy donors. When the patients had a disease flare (baseline) and when they achieve clinical response (follow-up), we assessed the systemic lupus erythematosus disease activity index 2 K (SLEDAI 2 K) and the following parameters with flow cytometry and confocal microscopy: monocyte subsets, their expression of TLR2, phagocytic monocytes and neutrophils using the pHrodo Red E. coli BioParticles, the respiratory burst with 123-dihydrorhodamine in neutrophils, and the spontaneous and lipopolysaccharide (LPS)-induced production of neutrophil extracellular traps (NETs). We used the Wilcoxon test to compare the paired medians with interquartile range (IQR) and the Mann-Whitney U test for independent medians. To assess the effect of prednisone and SLEDAI 2 K on the mentioned parameters, we applied a generalized mixed linear model.
Twenty-three patients (88.4%) were women. The SLEDAI 2 K was higher at baseline 8 (6-14) in comparison to that at follow-up (6 (4-8), P = 0.028). At baseline, SLE patients had a decreased percentage of intermediate monocytes, a higher expression of TLR2 in total monocytes, increased phagocytosis in monocytes and neutrophils, a decreased respiratory burst intensity, and an increased production of NETs. In the mix model, the SLEDAI 2 K was the main factor influencing these functional innate immune parameters.
Disease activity regulates the innate immune function in SLE which may contribute to the clinical features and infection predisposition. Key points • This is the first cohort study addressing the effect of disease activity and prednisone use on the innate immune function of lupus patients. • Our results show that the disease activity is a key regulator of the respiratory burst, phagocytosis, and the production of neutrophil extracellular traps. • Also, we observed a differential proportion of monocyte subsets according to SLE disease activity. • We consider that our manuscript contributes to the evidence addressing the intrinsic immune abnormalities of patients with SLE regardless of the use of immunosuppressants and set the bases for new research work considering the disease activity as an element to decide the prescription and duration of antibiotic prophylaxis in SLE patients, which is of interest to all rheumatologists.
探讨系统性红斑狼疮（SLE）疾病活动与固有免疫功能参数之间的关系。
我们评估了 26 例成年 SLE 患者和 10 名性别和年龄匹配的健康供体的队列。当患者出现疾病发作（基线）和达到临床缓解（随访）时，我们使用流式细胞术和共聚焦显微镜评估系统性红斑狼疮疾病活动指数 2K（SLEDAI 2K）和以下参数：单核细胞亚群、其 TLR2 表达、吞噬性单核细胞和中性粒细胞使用 pHrodo Red E. coli BioParticles，中性粒细胞中的 123-二氢罗丹明呼吸爆发，以及中性粒细胞胞外诱捕网（NETs）的自发性和脂多糖（LPS）诱导产生。我们使用 Wilcoxon 检验比较配对中位数和四分位距（IQR），使用 Mann-Whitney U 检验比较独立中位数。为了评估泼尼松和 SLEDAI 2K 对上述参数的影响，我们应用了广义混合线性模型。
23 例患者（88.4%）为女性。与随访时（6（4-8）相比，基线时 SLEDAI 2K 更高（8（6-14），P=0.028）。基线时，SLE 患者中间性单核细胞比例降低，总单核细胞 TLR2 表达增加，单核细胞和中性粒细胞吞噬作用增加，呼吸爆发强度降低，NETs 产生增加。在混合模型中，SLEDAI 2K 是影响这些固有免疫功能参数的主要因素。
疾病活动调节 SLE 固有免疫功能，可能有助于临床特征和感染易感性。关键点：• 这是第一项研究疾病活动和泼尼松使用对狼疮患者固有免疫功能影响的队列研究。• 我们的结果表明，疾病活动是呼吸爆发、吞噬作用和中性粒细胞胞外诱捕网产生的关键调节因素。• 此外，我们根据 SLE 疾病活动观察到单核细胞亚群的比例不同。• 我们认为，我们的论文有助于提供证据，证明无论是否使用免疫抑制剂，SLE 患者的固有免疫异常，为考虑将疾病活动作为决定 SLE 患者抗生素预防处方和持续时间的因素的新研究工作奠定基础，这对所有风湿病学家都有意义。
