Dataset Information

Data-driven Clustering of the Cerebrospinal Fluid Proteome Reflects Disease Phenotypes of Systemic Lupus Erythematosus

ABSTRACT: In this study, we employed a hypothesis-free and data-driven analytical approach to investigate the CSF proteome in 29 patients with SLE. Herein, our aim was to explore the CSF proteome with data-independent acquisition mass spectrometry (DIA-MS) and cluster SLE patients based on their CSF proteomic patterns. In addition, we aimed to investigate the relationship between protein patterns and a comprehensive clinical dataset including demographic variables, medical history, clinical rheumatologic and neurologic disease manifestations, neurocognitive functionality, cerebral MRI and laboratory measurements.The proteomic data was used for sample clustering and clusters were analyzed for clinical dataset variance. Proteins were clustered in modules using Weighted Gene Co-expression Correlation Network Analysis (WGCNA) and 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 SSA-antibodies, and a low frequency of cognitive impairment. Cluster 3 had a higher frequency of autonomic neuropathy and lupus headache. Six protein modules were identified (M1-M6). The modules were characterized by nervous tissue proteins (M1), CNS lipoproteins (M2), macrophage proteins (M3), plasma proteins (M4), immunoglobulins (M5), and intracellular metabolic proteins (M6). Module 1 and M2 proteins were most abundant in patient cluster 1 and correlated with nephritis, depression and cognitive impairment. Increased abundance of M4 and M5 proteins were most distinct in patient cluster 2 and inversely correlated to cognitive impairment and brain atrophy. We conclude that 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cerebrospinal Fluid

DISEASE(S): Systemic Lupus Erythematosus

SUBMITTER: ELSA GRENMYR

LAB HEAD: Elsa Grenmyr

PROVIDER: PXD053422 | Pride | 2026-02-09

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	2021-10-28_CW_ELSA_CSF_16253_EV1109_60SPD_200ng_diaPASEF_S3-A1_1_3197.htrms	Other
	2021-10-28_CW_ELSA_CSF_16270_EV1109_60SPD_200ng_diaPASEF_S3-B1_1_3198.htrms	Other
	2021-10-28_CW_ELSA_CSF_16288_EV1109_60SPD_200ng_diaPASEF_S3-C1_1_3199.htrms	Other
	2021-10-28_CW_ELSA_CSF_16297_EV1109_60SPD_200ng_diaPASEF_S3-D1_1_3200.htrms	Other
	2021-10-28_CW_ELSA_CSF_16385_EV1109_60SPD_200ng_diaPASEF_S3-E1_1_3201.htrms	Other

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Publications

Data-Driven Cluster Analysis of Cerebrospinal Fluid Proteome and Associations with Clinical Phenotypes in Systemic Lupus Erythematosus.

Grenmyr Elsa E Zervides Kristoffer K Najibi Seyed Morteza SM Gullstrand Birgitta B Welinder Charlotte C Nystedt Jessika J Nilsson Petra C PC Sundgren Pia C PC Kahn Robin R Jönsen Andreas A Bengtsson Anders A AA

ACR open rheumatology 20250901 9

<h4>Objective</h4>To explore the cerebrospinal fluid (CSF) proteome in systemic lupus erythematosus (SLE) and the associations between the CSF proteomic patterns and clinical manifestations.<h4>Methods</h4>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 fo ...[more]

PMID: 40874685

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