الفهرس 
TitleOnly 14 pages are availabe for public view
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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
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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.