Investigation of prognostic biomarkers in clinically isolated syndrome

Background: Multiple sclerosis is a chronic inflammatory disease with different clinical subtypes. The disease usually begins with an attack that can be explained by a single white matter lesion in about 85% of cases. This isolated attack is called clinically isolated syndrome [1]. It is very important to predict whether the patient presenting with such an attack will transform to MS or not, and if so, the prognosis. In addition to clinical features, magnetic resonance imaging and blood and cerebrospinal fluid examination are known to be useful in the first attack. In studies conducted in recent years, neurofilament light chain in both serum and CSF has been found to be higher in CIS patients transforming into MS. Similarly, YKL-40 (chitinase-3-like-1) protein, a member of the chitinase-like protein family, was also found to be higher in patients with conversion to MS. It has been reported that HOXB3, a member of the human transcription factor family and playing a role in lymphocyte maturation, can also be elevated in patients who convert to MS. In our study, we aimed to investigate the prognostic value of potential biomarkers NFL, YKL-40 and HOX-B3 in predicting KIS-MS transformation. Material and Methods: It was aimed to include 30 patients who applied to the Neurology Clinic of Diyarbakır Dicle University Medical Faculty Hospital and were diagnosed with CIS in the study and to determine the conversion rates to MS by following at least 3 years. The healthy control group of 20 participants was also included in the study with similar demographic characteristics to the patients. After the first attack, venous blood samples were taken from the patients between 2015- 2017; and YKL-40, NFL and HOX-B3 levels in the serum of venous blood samples previously collected from the patients were analyzed between 2019-2020 by ELISA method. Statistical Package Program for Social Sciences (SPSS) version 25.0 was used to analyze the data, and P value was accepted as 0.05 for the level of statistical significance. GraphPad Prism program was used for graphics. Results: Thirty patients (20 female and 10 male) followed up with CIS and 20 healthy controls (SK group) with similar demographic characteristics such as age and ix gender were included in the study. 12 of 30 CIS patients continued to be followed up as CIS (CIS-CIS group). 18 patients showed conversion to MS (CIS-MS group). The mean age of the patients included in the study was 35 years in the CIS-CIS group, 27 years in the CIS-MS group and 37 years in the SC group, and there was no significant difference between the age of groups. In our study, oligoclonal band (OCB) could be determined in 6 of 12 patients in the CIS-CIS group and all of them were found as negative. OCB could be determined in 13 of 18 patients in the CIS-MS group and all of them were reported as positive. In our study, the mean NFL levels were 60.9 in the CIS-CIS group and 65.6 in the CIS-MS group, and the difference was not significant. The mean YKL-40 level of the CIS-CIS group was 537.8, and 1162.2 in the CIS-MS group. Serum YKL-40 levels were significantly higher in the CIS-MS group. The mean value of serum HOX-B3 levels was 5.3 in the CIS-CIS group and 3.3 in the CIS-MS group. Serum HOX-B3 levels were significantly lower in the CIS-MS group. Finally, a significant correlation was found between the number of lesions on MRI T2/FLAIR imaging, serum YKL-40 and serum HOX-B3 levels in CIS-MS patients. EDSS score and age showed a significant relationship with only HOX-B3 level among three parameters. Significance was not found in terms of other parameters examined. Discussion and Conclusion: We determined that especially serum YKL-40 and HOX-B3 levels can successfully predict CIS-MS transformation. The relationship between serum HOX-B3 level and KIS-MS transformation is quite strong. Although a significant relationship was determined with serum YKL-40 levels in addition to HOX-B3 in our study, it was concluded that serum NFL levels were not sufficiently successful in predicting CIS-MS transformation. In future studies, larger data about the prognostic value of these parameters in KIS-MS transformation will be available. Keywords: Multiple Sclerosis, Clinically Isolated Syndrome, NFL, YKL-40, HOXB3