Multiple skleroz hastaliğinda serum ve bos'da neuregulin-1 ve sTREM-2-2'nin biyobelirteç olarak değeri

Introduction: Multiple sclerosis (MS) is an autoimmune disease that typically emerges at a young age, causing disability through inflammation and degeneration. Early diagnosis and treatment are crucial in determining prognosis. Therefore, in recent years, there has been an increase in studies investigating biomarkers to aid in the diagnosis of MS, predict prognosis, and evaluate the effectiveness of treatment. To date, the most reliable and consistent data have been obtained from cerebrospinal fluid (CSF) oligoclonal bands (OCB), the IgG index, and neurofilament light chain (NfL) studies. However, these biomarkers are not specific to MS. Furthermore, the invasiveness of lumbar puncture limits its repeatability and use in follow-up. As a result, efforts have focused on finding safe, specific, and novel biomarkers that can be detected in serum. Aim: The aim of this study was to investigate sTREM-2 and NRG-1, newly researched biomarkers with limited data in MS, in the CSF and serum of MS patients and compare these with NfL and GFAP. Materıals and Methods: This study included 60 patients newly diagnosed with relapsing-remitting multiple sclerosis (RRMS), with no prior treatment and who had undergone lumbar puncture for CSF collection. The control group for CSF consisted of 48 individuals who underwent lumbar puncture with a preliminary diagnosis of idiopathic intracranial hypertension. The serum control group consisted of 30 healthy individuals. Serum and CSF samples from MS patients and the CSF control group were obtained retrospectively from samples stored at -20°C, while serum samples from the control group were collected prospectively. The samples were analyzed using the ELISA method. The washing procedures for ELISA were performed using an automatic washing device in the biochemistry laboratory (BioTek ELx50 BioTek Instruments Inc. Highland Park, Winooski, VT, USA). Absorbance readings were performed using the ELISA reader (BioTek Epoch, BioTek Instruments Inc. Highland Park, Winooski, VT, USA). Results: The CSF sTREM-2 level was significantly higher in MS patients compared to the control group (p = 0.006). ROC analysis revealed that values above 0.09 ng/ml in MS patients showed 69% sensitivity and 70% specificity. The serum sTREM-2 level was also significantly higher in the MS group compared to the control group (p = 0.049), with a cutoff value of 0.24 ng/ml, which demonstrated 59% sensitivity and 58% specificity. The NRG-1 level was significantly lower in MS patients compared to the control group (p < 0.001). A cutoff value of 6985.66 pg/ml for serum NRG-1 demonstrated 73% sensitivity and specificity in distinguishing MS patients. However, the CSF NRG-1 level did not differ significantly between MS patients and controls. Both CSF and serum NfL levels were significantly higher in the MS group compared to the control group (p < 0.001). The cutoff value for CSF NfL was 288.52 pg/ml, with 81% sensitivity and specificity, while the cutoff value for serum NfL was 4.81 pg/ml, showing 80% sensitivity and 81% specificity. No significant difference was observed in GFAP levels between MS patients and controls, either in serum or CSF. There was a positive correlation between the levels of NfL, NRG-1, and sTREM-2 in both CSF and serum (p < 0.001, p = 0.016, p = 0.016, respectively), but no correlation was found between the biomarkers themselves. When the relationship between the biomarkers and clinical and MRI parameters was assessed, no significant correlation was found between NRG-1 serum levels, sTREM-2 levels in both serum and CSF, and any clinical or radiological parameters. A significant relationship was found only between the CSF NRG-1 level and the MSFC 9-Hole Peg score (r = 0.404, p = 0.041) and the number of errors on the SDMT scale (r = 0.549, p = 0.004). Additionally, a reverse correlation was observed between CSF NfL levels and BMVLT (p = 0.032), while a positive correlation was found between serum NfL levels and contrast-enhancing lesions (p = 0.022). Although no difference was observed in GFAP levels between the groups, significant correlations were found between CSF GFAP levels and the CVLT score, EDSS scores at 3-6 months and 1 year (p = 0.028, p = 0.017), depression score (p = 0.003), and fatigue score (p = 0.025). Serum GFAP levels were significantly correlated with the age of MS onset (p = 0.042). Conclusion: In this study, we found that sTREM-2 levels were higher in both CSF and serum of MS patients compared to controls, while NRG-1 levels were lower in serum but not significantly different in CSF compared to controls. Both biomarkers showed positive correlations between CSF and serum levels but no correlation with each other. This study contributes limited data on both biomarkers, particularly NRG-1, and shows promise. It is also the first study to examine NRG-1 levels in the CSF of healthy MS patients. However, these results need to be confirmed with additional studies and data.