engleski

Decreased level of sRAGE in the cerebrospinal fluid of patients with multiple sclerosis at clinical onset

Background/aim. Multiple sclerosis (MS) is the most common autoimmune demyelinating disease of the central nervous system (CNS). Some studies suggested that high mobility group box 1 (HMGB1) has a role in amplifying neuroinflammatory processes in MS. Our study aimed to assess changes in HMGB1 and its receptor for advanced glycation end products (RAGE) in peripheral blood (PB) and cerebrospinal fluid (CSF) of MS patients. Methods. PB and CSF were collected from healthy controls (Ctrl ; n=16, age range 26-60) and MS patients (n=22, age range 20-48) after the informed consent. Control patients were routinely undergoing epidural anesthesia prior to lower extremity surgery, allowing obtainment of CSF. Soluble RAGE (sRAGE) and HMGB1 were measured in CSF and plasma by ELISA. Gene expression (as RNA relative quantity) in PB mononuclear cells (PBMC) was detected by qPCR for RAGE, HMGB1 and several proinflammatory cytokines. Results are expressed as median (range). Results. ELISA showed lower CSF sRAGE in MS (2.68 (0-13.45) pg/mL in MS vs. 9.08 (3.35-16.15) pg/mL in Ctrl, p=0.02). Gene expression in PBMC revealed no difference between group for IL- 1β, TNF-α, IL-6 and RAGE, only IL-1α was increased (1.55 (0.83- 309.48) in MS vs. 1.02 (0.22-3.75) in Ctrl ; p=0.05), whereas HBGB1 was decreased in MS (1.95 (0.53-3.14) in MS vs. 2.54 (0.79-5.41) in Ctrl ; p=0.04). Conslusions. Lower level of decoy sRAGE in CSF may allow enhanced HMGB1 proinflammatory effects within CNS. IL-1α is possible upstream mediator of HMGB1 release, whereas downregulated HMGB1 expression in PBMC may represent the compensatory mechanism to reduce inflammatory process.

multiple sclerosis ; CSF ; RAGE ; HMGB

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