Cerebrospinal fluid MMP-2 and TIMP-2 reflect blood–cerebrospinal fluid barrier dysfunction in Guillain–Barré syndrome and CIDP

Background This study aimed to investigate patterns of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in Guillain–Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP). It also examined how these patterns relate to dysfunction of the blood–cerebrospinal fluid barrier (BCB). Methods This prospective observational study enrolled 86 participants: 33 patients with GBS, 34 with CIDP, and 19 with Alzheimer’s disease (AD) as controls. Enzyme-linked immunosorbent assay (ELISA) quantified MMP-2, MMP-9, TIMP-1, and TIMP-2 levels in blood and cerebrospinal fluid (CSF). Analyses included group comparisons, multivariable logistic regression, ROC curve analysis, and multivariable linear regression to assess classification value and association with CSF protein (CSF-Pro). Results Compared to controls, patients with immune-mediated peripheral neuropathies had lower blood MMP-2 and TIMP-2 levels and higher blood MMP-9 levels. CSF MMP-2 and TIMP-2 levels were higher in CIDP than in GBS. Multivariable logistic regression showed CSF MMP-2 was associated with disease classification. ROC analysis revealed CSF MMP-2 moderately distinguished CIDP from GBS (AUC = 0.700). Multivariable linear regression showed CSF TIMP-2 was independently and negatively associated with CSF-Pro levels. Conclusion The MMP-2/TIMP-2 axis may contribute to BCB dysfunction in immune-mediated peripheral neuropathies. CSF MMP-2 levels are associated with disease classification, while elevated CSF TIMP-2 levels may alleviate barrier damage. These biomarkers may serve as potential reference indicators for assessing barrier dysfunction and could provide a basis for differentiating GBS from CIDP.