Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection/Rheumatology, Linköping University, Campus US, 581 85, Linköping, Sweden.
Department of Nephrology in Linköping, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
Arthritis Res Ther. 2022 Jun 11;24(1):139. doi: 10.1186/s13075-022-02831-9.
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a large production of autoantibodies and deficient clearance of cellular waste. The disease typically oscillates between episodes of elevated disease activity and quiescent disease. C-reactive protein (CRP) is a pentameric acute-phase protein usually reflecting inflammation and tissue damage. However, despite increased inflammation and elevated interleukin-6, the levels of CRP typically remain low or only slightly raised in SLE. Under certain conditions, pentameric CRP (pCRP) can dissociate into its monomeric isoform (mCRP), which mainly has been ascribed pro-inflammatory properties. The present study aims to investigate the potential relationship between pCRP and mCRP, respectively, with disease activity and clinical features of SLE.
The levels of pCRP and mCRP were measured, by turbidimetry (high-sensitive) and sandwich enzyme-linked immunosorbent assay (ELISA) respectively, in serum samples from 160 patients with SLE and 30 patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Twenty-two of the SLE cases were selected for analysis at two time-points; quiescent disease and active disease. The two CRP isoforms were evaluated in relation to disease activity and clinical features in the two diseases.
Levels of pCRP and mCRP were significantly lower in SLE than AAV (p < 0.001) and the ratio of mCRP/pCRP was higher in SLE compared to AAV. The mCRP/pCRP ratio was higher for patients in remission and able to significantly separate between active/quiescent disease in paired, but not in non-paired, samples from patients with SLE. Significant correlations were observed with SLICC/ACR damage index for pCRP levels as well as inversely with the mCRP/pCRP ratio. Lower mCRP levels associated with malar rash.
As the interrelationship between the two isoforms appear to (a) discriminate between quiescent and active SLE and (b) differ between SLE and AAV, our data indicates that the two CRP isoforms could exert contrasting immunological effects and/or reflect different milieus. Given the biological effects of mCRP, it is possible that altered levels may indicate increased opsonization of immune complexes and apoptotic debris, and thereby prevent their deposition outside the reticuloendothelial system and manifestations such as lupus nephritis and lupus-related skin disease.
系统性红斑狼疮(SLE)是一种自身免疫性疾病,其特征是大量产生自身抗体和细胞废物清除不足。该疾病通常在疾病活动期和静止期之间波动。C 反应蛋白(CRP)是一种五聚体急性期蛋白,通常反映炎症和组织损伤。然而,尽管炎症增加和白细胞介素-6 水平升高,SLE 患者的 CRP 水平通常较低或仅略有升高。在某些情况下,五聚体 CRP(pCRP)可解离为其单体形式(mCRP),后者主要具有促炎特性。本研究旨在分别探讨 pCRP 和 mCRP 与 SLE 疾病活动度和临床特征的潜在关系。
通过比浊法(高敏)和夹心酶联免疫吸附测定(ELISA)分别测量 160 例 SLE 患者和 30 例抗中性粒细胞胞浆抗体相关性血管炎(AAV)患者血清样本中的 pCRP 和 mCRP 水平。选择 22 例 SLE 病例在两个时间点进行分析;静止期疾病和活动期疾病。在两种疾病中评估两种 CRP 同工型与疾病活动度和临床特征的关系。
SLE 患者的 pCRP 和 mCRP 水平明显低于 AAV(p<0.001),且 SLE 患者的 mCRP/pCRP 比值高于 AAV。在缓解期患者和能够显著区分 SLE 患者配对而非非配对样本活动期/静止期的患者中,mCRP/pCRP 比值较高。pCRP 水平与 SLICC/ACR 损伤指数显著相关,而 mCRP/pCRP 比值与 SLICC/ACR 损伤指数呈负相关。mCRP 水平较低与蝶形皮疹有关。
由于两种同工型之间的相互关系似乎(a)可区分静止期和活动期 SLE,(b)在 SLE 和 AAV 之间不同,我们的数据表明,两种 CRP 同工型可能发挥相反的免疫作用和/或反映不同的环境。鉴于 mCRP 的生物学效应,改变的水平可能表明免疫复合物和凋亡碎片的调理作用增加,从而防止它们在网状内皮系统外沉积和出现狼疮肾炎和狼疮相关皮肤病等表现。