Grenmyr Elsa, Zervides Kristoffer, Najibi Seyed Morteza, Gullstrand Birgitta, Welinder Charlotte, Nystedt Jessika, Nilsson Petra C, Sundgren Pia C, Kahn Robin, Jönsen Andreas, Bengtsson Anders A
Rheumatology, Department of Clinical Sciences, Lund University and Skåne University Hospital, Lund, Sweden.
Rheumatology and Neurology, Department of Clinical Sciences, Lund University and Skåne University Hospital, Lund, Sweden.
ACR Open Rheumatol. 2025 Sep;7(9):e70089. doi: 10.1002/acr2.70089.
To explore the cerebrospinal fluid (CSF) proteome in systemic lupus erythematosus (SLE) and the associations between the CSF proteomic patterns and clinical manifestations.
CSF samples from 29 female outpatients with SLE were analyzed with label-free liquid chromatography tandem mass spectrometry. Inclusion and CSF collection were conducted irrespective of clinical manifestations and disease duration. Proteomic data were used for sample clustering and analyzed for clinical variance. Proteins were clustered using Weighted Gene Co-expression Correlation Network Analysis. Modules were biologically characterized and analyzed for correlation to the clinical dataset.
Three patient clusters were identified. Cluster 1 was characterized by the highest frequency of nephritis, depression, and cognitive dysfunction. Cluster 2 showed the highest frequency of alopecia and Sjogren disease antigen A-antibodies (anti-SSA) and a low frequency of cognitive impairment. Cluster 3 had a higher frequency of autonomic neuropathy and headache. Six protein modules were identified (module 1 [M1]-M6). Modules were characterized by nervous tissue proteins (M1), central nervous system (CNS) lipoproteins (M2), macrophage proteins (M3), plasma proteins (M4), Ig (M5), and intracellular metabolic proteins (M6). M1 and M2 proteins were most abundant in cluster 1 and correlated with nephritis, depression, and cognitive impairment. Increased abundance of M4 and M5 proteins were most distinct in cluster 2 and inversely correlated to cognitive impairment and brain atrophy.
Patients clustered by their CSF proteomic pattern had different disease phenotypes. Nephritis and neuronal damage defined the group with higher levels of neuronal proteins in CSF, which may suggest shared pathogenetic pathways in SLE affecting the kidney and CNS.
探讨系统性红斑狼疮（SLE）患者的脑脊液（CSF）蛋白质组，以及CSF蛋白质组模式与临床表现之间的关联。
采用无标记液相色谱串联质谱法分析29例SLE女性门诊患者的CSF样本。纳入研究及采集CSF样本时不考虑临床表现和疾病病程。蛋白质组学数据用于样本聚类分析，并分析临床差异。使用加权基因共表达网络分析对蛋白质进行聚类。对模块进行生物学特征分析，并分析其与临床数据集的相关性。
识别出三个患者聚类。聚类1的特征是肾炎、抑郁和认知功能障碍的发生率最高。聚类2显示脱发和抗干燥综合征A抗原抗体（抗SSA）的发生率最高，而认知障碍的发生率较低。聚类3自主神经病变和头痛的发生率较高。识别出六个蛋白质模块（模块1 [M1]-M6）。这些模块的特征分别为神经组织蛋白（M1）、中枢神经系统（CNS）脂蛋白（M2）、巨噬细胞蛋白（M3）、血浆蛋白（M4）、免疫球蛋白（M5）和细胞内代谢蛋白（M6）。M1和M2蛋白在聚类1中最为丰富，与肾炎、抑郁和认知障碍相关。M4和M5蛋白丰度增加在聚类2中最为明显，且与认知障碍和脑萎缩呈负相关。
根据CSF蛋白质组模式聚类的患者具有不同的疾病表型。肾炎和神经元损伤确定了CSF中神经元蛋白水平较高的组，这可能提示SLE中影响肾脏和中枢神经系统的共同致病途径。
