Serum Levels of Biomarkers of Immune Activation and Associations With Neurological Impairment in Relapsing-Remitting Multiple Sclerosis Patients During Remission

Abstract

Introduction: Although much is known about cytokines and adhesion molecules during an active course of multiple sclerosis (MS), there is limited information about their serum levels during remission. Objective: This study aimed to (1) compare peripheral levels of tumor necrosis factor-α (TNF-α), soluble interleukin-2 receptor α (sIL-2Rα), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble E-selectin (sE-selectin) in MS patients during clinical remission with those of healthy controls and (2) explore possible relationships between the levels of these cytokines and adhesion molecules and neurological impairment. Methods: Initially, 92 patients with relapsing-remitting multiple sclerosis (RRMS) who were in clinical remission and 30 healthy controls were recruited for this study. The severity of neurological impairment was assessed with the Expanded Disability Status Scale (EDSS). Serum concentrations of TNF-α, sIL-2Rα, sICAM-1, and sE-selectin were determined using the sandwich enzyme-linked immunosorbent (ELISA) technique and compared between patients and controls. In a subset of RRMS patients ( n = 67), the levels of these cytokines and adhesion molecules were compared between subgroups of patients based on scores on the EDSS subscales, which measure disability level for specific neurological functions. Results: The MS patients’ TNF-α, sICAM-1, and sE-selectin levels were markedly lower than those of the controls, while their sIL-2Rα level was higher. The serum sICAM-1 concentration was positively associated with EDSS total score (ρ = .291, p = .017) as well as with the EDSS pyramidal (ρ = .267, p = .029) and cerebellar subscores (ρ = .303, p = .013). In the patients with cerebellar deficits and severe brain stem dysfunction, sICAM-1 levels were upregulated. Conclusion: Although a decreased sICAM-1 concentration was observed in RRMS patients in remission as compared to healthy controls, sICAM-1 seemed to reflect neurological impairment and clinical disability. These data suggest that increasing serum sICAM-1 levels may be associated with progression of cerebellar or brain stem perturbations. However, further studies are required to confirm these findings in a larger population of RRMS patients.