Type III Interferons in Systemic Lupus Erythematosus Association Between Interferon λ3, Disease Activity, and Anti-Ro/SSA Antibodies
Type III Interferons in Systemic Lupus Erythematosus Association Between Interferon λ3, Disease Activity, and Anti-Ro/SSA Antibodies
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DOI：
10.1097/rhu.0000000000000581
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发表时间：
2017-10-01
影响因子：
3.4
通讯作者：
Bojalil, Rafael
中科院分区：
文献类型：
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作者：
Amezcua-Guerra, Luis M.;Marquez-Velasco, Ricardo;Bojalil, Rafael
目的：本研究旨在探讨系统性红斑狼疮（SLE）患者血清Ⅲ型（λ）干扰素（IFN-λ）与疾病活动性的关系。方法：检测93例SLE患者和67例健康人血清IFN-λ 1、IFN-λ 2和IFN-λ 3水平。结果：SLE患者和对照组IFN-λ 1水平中位数分别为0 pg/mL（范围0-510 pg/mL）和0 pg/mL（0-171 pg/mL; P = 0.814）。IFN-λ 2的这些数值分别为0 pg/mL（0-28 pg/mL）和0 pg/mL（0-43 pg/mL; P = 0.659），IFN-λ 3的数值分别为83 pg/mL（0-965 pg/mL）和42 pg/mL（0-520 pg/mL; P = 0.002）。根据系统性红斑狼疮疾病活动指数分类，静止期IFN-λ 3水平为44 pg/mL（0-158 pg/mL），轻度为117 pg/mL（0-344 pg/mL），中度为79 pg/mL（0-965 pg/mL），重度为78 pg/mL（0-329 pg/mL），在血清或皮肤受累患者中发现最高水平。与此一致，IFN-λ 3水平与C3（λ = -0.44; 95%置信区间，-0.62至-0.20; P = 0.0003）和C4（λ = -0.40; 95%置信区间，-0.59至-0.15; P = 0.0001）补体蛋白呈负相关。此外，在抗Ro/SSA抗体阳性的患者中，IFN-λ 3水平高于该抗体阴性的患者（122 pg/mL [0-965 pg/mL] vs. 0 pg/mL [0-165 pg/mL]; P = 0.001）。接受糖皮质激素的患者IFN-λ 3的浓度也较高（104 pg/mL [0-965 pg/mL] vs. 30 pg/mL [0-165 pg/mL]; P = 0.009），并观察到剂量相关效应。这种关联可能与抗Ro/SSA抗体有关。
Objective: The aim of this study was to assess associations between serum type III (lambda) interferons (IFN-lambda) and disease activity in systemic lupus erythematosus (SLE).Methods: Serum levels of IFN-lambda 1, IFN-lambda 2, and IFN-lambda 3 were measured in 93 SLE patients and 67 healthy individuals. The associations with overall disease activity, organ-specific damage, and SLE-related antibodies were assessed.Results: Median IFN-lambda 1 levels were 0 pg/mL (range, 0-510 pg/mL) and 0 pg/mL (0-171 pg/mL; P = 0.814) in SLE patients and control subjects, respectively. These figures were 0 pg/mL (0-28 pg/mL) and 0 pg/mL (0-43 pg/mL; P = 0.659) for IFN-lambda 2, as well as 83 pg/mL (0-965 pg/mL) and 42 pg/mL (0-520 pg/mL; P = 0.002) for IFN-lambda 3, respectively. According to the Systemic Lupus Erythematosus Disease Activity Index categories, IFN-lambda 3 levels were 44 pg/mL (0-158 pg/mL) in quiescent, 117 pg/mL (0-344 pg/mL) in mild, 79 pg/mL (0-965 pg/mL) in moderate, and 78 pg/mL (0-329 pg/mL) in severe disease, with the highest levels found in patients with serosal or cutaneous involvement. In line with this, IFN-lambda 3 levels were inversely correlated with C3 (lambda = -0.44; 95% confidence interval, -0.62 to -0.20; P = 0.0003) and C4 (lambda = -0.40; 95% confidence interval, -0.59 to -0.15; P = 0.0001) complement proteins. In addition, higher IFN-lambda 3 levels were found in patients positive for anti-Ro/SSA antibodies than in those negative for that antibody (122 pg/mL [0-965 pg/mL] vs. 0 pg/mL [0-165 pg/mL]; P = 0.001). The concentration of IFN-lambda 3 also was higher in patients receiving glucocorticoids (104 pg/mL [0-965 pg/mL] vs. 30 pg/mL [0-165 pg/mL]; P = 0.009), and a dose-related effect was observed.Conclusions: Interferon lambda 3, a subtype of type III IFNs, is associated with the extent of lupus activity, in particular with active serosal and cutaneous disease. This association could be mechanistically related to anti-Ro/SSA antibodies.