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Abstract Multiple sclerosis (MS) is a progressive autoimmune disease and affects young adults (20 – 40 years), being two to three times more common in women than men. The prevalence of MS in Egypt is found to be 1.41% of other neurological diseases. The etiology of MS is unknown. It is a complex of multifactorial disorder, in which environmental factors interact with genetically susceptible individuals. It is characterized by chronic inflammation and demyelination of the CNS. Inflammation of the CNS is a major driver of MS pathology. Differential immune responses including the adaptive and the innate immune system, are observed at various stages of MS and drive disease development and progression. There are other mediators/pathways that contribute to MS pathology. The most important pathway is the activation of inflammasomes, which are multiprotein complexes involved in the innate immune cells (e.g. macrophages). where NLRP3 inflammasome is the most extensively studied and the most common one. The activated NLRP3 inflammasome induces maturation of procaspase-1 to become caspase-1, secretion of pro-inflammatory cytokines such as IL-1β, IL-18 and cause inflammatory cell death termed pyroptosis. The activation of the NLRP3 inflammasome by a variety of DAMPs and PAMPs that lead to release of NLRP3 and adaptor protein ASC from macrophages and amplify the inflammatory response. Moreover, BCL-6 has been reported to have an important role in macrophages functions and act as an inhibitor of macrophage-mediated inflammatory responses. Some authors found that BCL-6 binds to NLRP3 promoter and negatively regulates the NLRP3 expression in some inflammatory diseases. However, little is known about the role of BCL-6 in MS and whether it shows a relation with inflammasome adaptor ASC. Therefore, The present study was carried to investigate the role of inflammasome adaptor protein ASC and the transcription factor BCL-6 in Egyptian MS patients. In addition, both parameters were correlated to each other and with the clinical features of the disease. This study included 45 individuals; divided into two groups. group one comprised 30 RRMS patients (based on the Revised McDonald MS criteria for classification 2017). There were 18 patients who had received treatment while 12 patients did not receive treatment. The second group involved 15 healthy volunteers, matched in age and sex as a control group. All individuals were examined for (CBC, urea, creatinine, ALT and AST). Also, inflammasome protein (ASC) and BCL-6 levels were measured using culture supernatant after culturing of PBMCs by ELISA. Collagenic profile was done to exclude other inflammatory diseases that may mimic MS. CSF oligoclonal bands (OCBs) and IgG index in selected cases were examined for MS patients only. Concerning laboratory findings, the present study revealed no statistically significant differences between MS patients and control group regarding Hgb level, platelet count and differential leukocytic count (lymphocytes, neutrophils, basophils, eosinophils and monocytes). Also, this study showed no significant difference between cases and control group as regards both liver enzymes (ALT and AST) and renal function (serum creatinine and blood urea). Summary, Conclusion and Recommendation 62 Regarding the CSF OCBs, the CSF OCBs have been described in 17 MS patients, the immunological bands were found in 58.8% of MS patients (positive), compared to 41.2% in patients who did not (negative). In addition, there was a statistical positive association between CSF OCBs, IgG in CSF and IgG index (p<0.05). The present study showed a significant increase in the mean of ASC protein relative to a non-significant increase in BCL-6 concentration in patients compared to healthy individuals. Our findings revealed that there was a significant negative correlation between ASC protein concentration and serum IgG in patients, while there was a significant positive correlation between ASC protein and IgG index. Finally, statistical analysis of these results revealed that, there was a significant negative correlation between adaptor protein ASC and transcription factor BCL-6 concentration. Thus, we can conclude from this study that ASC protein and BCL-6 could be utilized as novel biomarkers for diagnosis and predictors of inflammatory disease severity. Also, these results may describe a mechanism controlling the neuroinflammation in MS patients. 6.2 Conclusion According to our study findings, we can conclude the following: - This study has confirmed that there was a positive correlation between CSF OCBs, CSF IgG and IgG index in MS patients. - There was a significant increase in the adaptor protein ASC level in MS patients compared to the control individuals where this upregulation was associated with the presence of white lesions in the brain and spinal cord MRI. - The adaptor protein ASC concentration was negatively correlated with both serum IgG and CSF albumin but positively correlated with IgG index in patients’ CSF. - The BCL-6 level was slightly increased in MS patients compared to the healthy control, but there was statistically significant difference between the two studied groups. - BCL-6 concentration was significantly associated with CSF OCBs and positively correlated with serum IgG and serum or CSF albumin in MS patients. - This study showed that there was a statistically negative correlation between the adaptor protein ASC and BCL-6 concentration in Egyptian RRMS patients. |