系统性红斑狼疮中的干燥综合征：一种以全身炎症状态为特征的亚型。
Sjögren Syndrome in Systemic Lupus Erythematosus: A Subset Characterized by a Systemic Inflammatory State.
机构信息
From the Department of Medicine Solna, Division of Rheumatology, Karolinska Institutet, Stockholm; Karolinska University Hospital, Stockholm; Karolinska Institutet/AstraZeneca Integrated Cardio Metabolic Centre (KI-AZ ICMC), Stockholm; Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet, Stockholm; Center for Clinical Research, Uppsala University, Sörmland; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala; Cardiovascular, Renal and Metabolism, Innovative Medicines and Early Development (IMED) Biotech Unit, AstraZeneca, Huddinge, Sweden.
G. Ruacho, DMD, Department of Medicine Solna, Division of Rheumatology, Karolinska Institutet, and Center for Clinical Research, Uppsala University; M. Kvarnström, MD, PhD, Department of Medicine Solna, Division of Rheumatology, Karolinska Institutet, and Karolinska University Hospital; A. Zickert, MD, PhD, Department of Medicine Solna, Division of Rheumatology, Karolinska Institutet, and Karolinska University Hospital; V. Oke, MD, PhD, Department of Medicine Solna, Division of Rheumatology, Karolinska Institutet, and Karolinska University Hospital; J. Rönnelid, MD, PhD, Department of Immunology, Genetics and Pathology, Uppsala University; S. Eketjäll, PhD, Cardiovascular, Renal and Metabolism, IMED Biotech Unit, AstraZeneca, and KI-AZ ICMC; K. Elvin, MD, PhD, Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet and Karolinska University Hospital; I. Gunnarsson, MD, PhD, Department of Medicine Solna, Division of Rheumatology, Karolinska Institutet, and Karolinska University Hospital; E. Svenungsson, MD, PhD, Department of Medicine Solna, Division of Rheumatology, Karolinska Institutet, and Karolinska University Hospital.
出版信息
J Rheumatol. 2020 Jun 1;47(6):865-875. doi: 10.3899/jrheum.190250. Epub 2019 Sep 15.
OBJECTIVE
An often-neglected subset of patients with systemic lupus erythematosus (SLE) is those with secondary Sjögren syndrome (SLE-sSS). Further, primary SS overlaps and can be difficult to delineate from SLE. To shed light on the SLE-sSS subset, we investigated a large and well-characterized SLE cohort, comparing patients with SLE-sSS and SLE patients without SS (SLE-nonsSS) and controls.
METHODS
We included 504 consecutive patients with SLE, fulfilling the 1982 revised American College of Rheumatology criteria, and 319 controls from the general population, matched for age and sex to the first 319 patients. SLE-sSS was defined according to the American-European Consensus Criteria (AECC). A thorough clinical examination, including subjective and objective quantifications of sicca symptoms, was performed in all participants. Autoantibodies and 20 selected cytokines were measured by luminex and multiplex analysis, respectively.
RESULTS
SLE-sSS, as defined by AECC, occurred in 23% of the patients with SLE. In comparison to SLE-nonsSS, the SLE-sSS group was older and more frequently female. Leukopenia and peripheral neuropathy were more frequent and nephritis less frequent. Circulating levels of 6/20 investigated proinflammatory cytokines [tumor necrosis factor-α, interleukin (IL) 6, monocyte chemoattractant protein 4, macrophage inflammatory protein 1β, IL-12/IL-23p40, and interferon γ-induced protein 10], total IgG, anti-SSA/Ro52, anti-SSA/Ro60, anti-SSB/La antibodies, and rheumatoid factor (IgM and IgA) were higher in the SLE-sSS group (p < 0.05 for all comparisons).
CONCLUSION
The frequency of SLE-sSS increased with age and affected roughly one-quarter of all patients with SLE. Despite less internal organ involvement, a systemic inflammatory state with high levels of proinflammatory cytokines is present in the SLE-sSS subgroup. This is a novel observation that may affect future understanding and treatment of the SLE-sSS subset.
目的
系统性红斑狼疮（SLE）患者中常被忽视的一个亚组是继发干燥综合征（SLE-sSS）患者。此外，原发性干燥综合征与 SLE 重叠，且难以与 SLE 相区分。为了阐明 SLE-sSS 亚组，我们研究了一个大型且特征明确的 SLE 队列，比较了 SLE-sSS 患者和无 SS 的 SLE 患者（SLE-nonsSS）以及对照组。
方法
我们纳入了 504 例符合 1982 年修订版美国风湿病学会标准的连续 SLE 患者和 319 例来自普通人群的对照，按年龄和性别与前 319 例患者匹配。根据美国-欧洲共识标准（AECC）定义 SLE-sSS。所有参与者均进行了详细的临床检查，包括主观和客观的干燥症状量化。通过 Luminex 和多重分析分别测量自身抗体和 20 种选定的细胞因子。
结果
根据 AECC 定义，SLE-sSS 发生在 23%的 SLE 患者中。与 SLE-nonsSS 相比，SLE-sSS 组年龄更大，女性更多。白细胞减少症和周围神经病更常见，肾炎更少见。循环中 6/20 种炎症细胞因子 [肿瘤坏死因子-α、白细胞介素（IL）6、单核细胞趋化蛋白 4、巨噬细胞炎性蛋白 1β、IL-12/IL-23p40 和干扰素 γ诱导蛋白 10]、总 IgG、抗 SSA/Ro52、抗 SSA/Ro60、抗 SSB/La 抗体和类风湿因子（IgM 和 IgA）在 SLE-sSS 组中水平更高（所有比较 p<0.05）。
结论
SLE-sSS 的频率随年龄增加而增加，约影响所有 SLE 患者的四分之一。尽管内脏器官受累较少，但 SLE-sSS 亚组存在全身性炎症状态和高水平的促炎细胞因子。这是一个新的观察结果，可能会影响对 SLE-sSS 亚组的未来理解和治疗。
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