Munroe Melissa E, Vista Evan S, Merrill Joan T, Guthridge Joel M, Roberts Virginia C, James Judith A
Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK, 73104, USA.
Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK, 73104, USA; St. Luke's Medical Center, Taguig, 1112, Philippines.
J Autoimmun. 2017 Mar;78:70-78. doi: 10.1016/j.jaut.2016.12.005. Epub 2017 Feb 2.
Immune dysregulation in systemic lupus erythematosus (SLE) contributes to increased disease activity. African-American (AA) SLE patients have an increased prevalence of complications from disease flares and end-organ damage that leads to increased morbidity and early mortality. We previously reported alterations in inflammatory and regulatory immune mediator levels prior to disease flare in European American (EA) SLE patients. In the current study, we assessed baseline and follow-up plasma levels of 52 soluble mediators, including innate, adaptive, chemokine, and TNF superfamily members, in AA SLE patients who developed SELENA-SLEDAI defined flare 6 or 12 weeks after baseline assessment. These patients were compared to themselves during a comparable, clinically stable period (SNF, n = 18), or to demographically matched SLE patients without impending disease flare (NF, n = 13 per group). We observed significant (q < 0.05) alterations in 34 soluble mediators at baseline, with increased levels of both innate (IL-1α and type I interferons [IFN]) and adaptive cytokines (Th1-, Th2-, and Th17-type), as well as IFN-associated chemokines and soluble TNF superfamily members weeks before clinical disease flare. In contrast, stable SLE patients exhibited increased levels of the regulatory mediators IL-10 (q ≤ 0.0045) and TGF-β (q ≤ 0.0004). Because heterogeneous immune pathways were altered prior to clinical disease flare, we developed a soluble mediator score that encapsulates all mediators tested. This score is the sum of all log transformed, standardized soluble mediator levels assessed at baseline (pre-flare), weighted by their Spearman correlation coefficients for association with the SELENA-SLEDAI score at time of concurrent flare. While baseline SELENA-SLEDAI scores were similar between flare vs. NF (p = 0.7214) and SNF (p = 0.5387), the SMS was significantly higher in pre-flare SLE patients (Flare vs NF or SNF, p < 0.0001). By capturing alterations in the balance between inflammatory and regulatory mediators associated with SLE pathogenesis, the soluble mediator score approximates the immune status of SLE patients and provides a robust, predictive gauge of impending disease flare.
系统性红斑狼疮（SLE）中的免疫失调会导致疾病活动增加。非裔美国（AA）SLE患者因疾病发作和终末器官损伤而出现并发症的患病率增加，这会导致发病率上升和早期死亡。我们之前报道了欧美（EA）SLE患者在疾病发作前炎症和调节性免疫介质水平的变化。在本研究中，我们评估了在基线评估后6或12周出现SELENA-SLEDAI定义的发作的AA SLE患者的52种可溶性介质的基线和随访血浆水平，这些介质包括先天免疫、适应性免疫、趋化因子和TNF超家族成员。将这些患者在可比的临床稳定期（SNF，n = 18）的自身情况进行比较，或与在人口统计学上匹配的无即将发作疾病的SLE患者（NF，每组n = 13）进行比较。我们观察到在基线时34种可溶性介质有显著（q < 0.05）变化，在临床疾病发作前数周，先天免疫细胞因子（IL-1α和I型干扰素[IFN]）、适应性细胞因子（Th1、Th2和Th17型）以及IFN相关趋化因子和可溶性TNF超家族成员的水平均升高。相比之下，病情稳定的SLE患者的调节性介质IL-10（q≤0.0045）和TGF-β（q≤0.0004）水平升高。由于在临床疾病发作前多种免疫途径发生了改变，我们制定了一个可溶性介质评分，该评分涵盖了所有检测的介质。这个评分是在基线（发作前）评估的所有经对数转换、标准化的可溶性介质水平的总和，并根据它们与同期发作时SELENA-SLEDAI评分的Spearman相关系数进行加权。虽然发作组与NF组（p = 0.7214）和SNF组（p = 0.5387）之间的基线SELENA-SLEDAI评分相似，但发作前SLE患者的SMS显著更高（发作组与NF组或SNF组相比，p < 0.0001）。通过捕捉与SLE发病机制相关的炎症和调节性介质之间平衡的变化，可溶性介质评分近似于SLE患者的免疫状态，并为即将发作的疾病提供了一个可靠的预测指标。
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