Decreased serum thrombospondin-1 and elevation of its autoantibody are associated with multiple exacerbated clinical manifestations in systemic lupus erythematosus
Decreased serum thrombospondin-1 and elevation of its autoantibody are associated with multiple exacerbated clinical manifestations in systemic lupus erythematosus
复制标题
血清血小板反应蛋白-1降低及其自身抗体升高与系统性红斑狼疮多种临床表现加重相关
DOI：
10.1007/s10067-018-4188-x
复制
发表时间：
2018-10-01
影响因子：
3.4
通讯作者：
Sun, Xiaolin
中科院分区：
文献类型：
--
作者：
Meng, Yang;Zhang, Meng;Sun, Xiaolin
在许多临床前肿瘤模型和类风湿性关节炎中研究了血小板反应蛋白-1（TSP-1）的病理学作用。然而，TSP-1和抗血小板反应蛋白-1自身抗体（ATSA）在系统性红斑狼疮（SLE）中的作用尚未明确。本研究旨在探讨TSP-1和ATSA在SLE患者中的临床相关性和功能意义。采用ELISA法检测138例SLE患者和60例健康对照者血清TSP-1和ATSA水平。通过标准实验室技术测量血细胞计数、类风湿因子（RF）、免疫球蛋白、红细胞沉降率（ESR）、补体和SLE相关自身抗体。系统性红斑狼疮疾病活动指数（SLEDAI）评估疾病活动性。SLE患者TSP-1浓度显著低于健康对照组。在浆膜炎、C3降低、RF阳性、白细胞减少和血小板减少患者中观察到TSP-1的显著差异。TSP-1水平与白细胞数、血小板数呈正相关，与抗dsDNA抗体、IgG、ESR、SLEDAI呈负相关。SLE患者ATSA阳性率为58.7%（81/138），显著高于健康对照组（7/60）（P< 0.05）。活动期SLE患者ATSA阳性率（67.1%）明显高于非活动期SLE患者（47.1%，p < 0.05）。ATSA与抗rRNP抗体、IgG、总蛋白、C4呈正相关。本研究首次揭示了TSP-1及其自身抗体在SLE中相反的临床意义。TSP-1可能在SLE自身免疫中发挥抗炎和免疫调节作用。ATSA在疾病活动性患者中更频繁地增加，并且与更严重的临床表现相关，这暗示其对TSP-1的拮抗作用及其参与SLE的发病机制。
The pathological effects of thrombospondin-1 (TSP-1) have been studied in many preclinical tumor models and rheumatoid arthritis. However, the role of TSP-1 and anti-thrombospondin-1 autoantibodies (ATSA) in systemic lupus erythematosus (SLE) has not been specifically defined. In this study, we investigated the clinical relevance and functional significance of TSP-1 and ATSA in SLE patients. Serum levels of TSP-1 and ATSA were measured by ELISA in 138 adult SLE patients and 60 healthy controls. Blood cell counts, rheumatoid factor (RF), immunoglobulins, erythrocyte sedimentation rate (ESR), complements, and SLE-related autoantibodies were measured by standard laboratory techniques. Disease activity was assessed by systemic lupus erythematosus disease activity index (SLEDAI). TSP-1 concentrations were significantly lower in SLE patients compared with those in healthy controls. A significant difference of TSP-1 was observed in the patients with serositis, C3 decrease, RF positive, leukocytopenia, and thrombocytopenia. The levels of TSP-1 showed a positive correlation with the number of leukocyte and thrombocyte, while a negative correlation with anti-dsDNA antibody, IgG, ESR, and SLEDAI. ATSA was observed in 58.7% (81/138) of SLE patients, which was significantly higher than that in healthy controls (7/60,p< 0.05). Patients with active SLE showed higher ATSA positivity (67.1%) than those with inactive disease (47.1%,p< 0.05). ATSA was positively correlated with anti-rRNP antibody, IgG, total protein, and C4. This study revealed the opposite clinical relevance of TSP-1 and its autoantibody in SLE for the first time. TSP-1 may play an anti-inflammatory and immunoregulatory role in SLE autoimmunity. ATSA increased more frequently in disease-active patients and was associated with more severe clinical manifestations, which implicated its antagonistic role on TSP-1 and its involvement in the pathogenesis of SLE.