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Advanced Neurology Multiple sclerosis: Immunopathogenesis

diagnostic markers used in the screening for MS . NfL are been known that aging is the most important risk factor for
[52]
important components of the axon cytoskeleton. During the occurrence of neurodegenerative diseases and a likely
neuroaxonal injury, these molecules are released into cause of progression of MS . A recent study showed that
[60]
the interstitial fluid, then into the CSF, and then into the a shorter leukocyte telomere length, which is a biological
serum. While other clinical parameters remain stable, NfL aging biomarker, was associated with more severe clinical
measurements in serum may indicate future or ongoing disability and loss of brain volume in MS patients, who
disease activity. NfL is regularly associated with new or maintained higher EDSS and lower brain volume at baseline
enlarging T2 lesions, current inflammation, and future brain for more than 10 years . MRI studies have shown that the
[61]
atrophy in progressive MS, and is also a promising marker brain volume of MS patients decreases by approximately
of response to treatment with immunosuppressive disease- 0.5% to 1.3% per year, which is outside the physiological
[62]
modifying therapies. It can be said that the increase in range .
NfL concentration reflects neurodegeneration and disease Growth-associated protein 43 (GAP-43) is highly
activity in the years that follow [5,53-55] . Interestingly, serum expressed during axon growth and there is no such expression
samples from asymptomatic individuals have shown that an during MS progression. In this study, it was found that CSF
increase in NfL concentration was observed as early as 6 years GAP-43 levels significantly decreased during the progression
before the diagnosis of MS . EBV-infected individuals who of MS compared with the healthy control group (P = 0.004)
[56]
later developed MS tended to have elevated levels of NfL and with RRMS individuals (P ≤ 0.001). The concentration
after the initial infection, but before MS development . of GAP-43 was higher in RRMS subjects who had signs of
[16]
Therefore, to avoid neurodegeneration, early initiation active inflammatory disease than in subjects in remission
with effective neuroprotective drugs proves beneficial in (P = 0.042) . Despite the benefits in serological testing, the
[63]
retarding the progression of PMS . Serum NfL is believed application of GAP-43 in routine MS clinical assessment may
[5]
to be a plausible biomarker of neurodegeneration, and its result in unnecessary diagnostic hold-up, excessive testing
measurement is high accurate, sensitive, and reproducible. and increased costs. During the study, 150 patients had
However, standardization of sample processing and undergone 823 serologic tests, and only 40 individuals were
analysis is needed before it can be used as one of the PMS MS-positive and thus required further testing .
[64]
markers [55,57] . κFLC offers logistical advantages, such as
diagnostic speed, lower cost, and no requirement of paired There is growing interest in the role of the gut microbiome
serum samples, and performs similarly to CSF oligoclonal and its impact on the immune system, particularly in
bands. Although further research concerning the influence autoimmune diseases. Recent studies have compared the
of blood- and saliva-derived κFLC and steroid therapy on gut microbiota of MS patients and healthy controls. In
κFLC levels are needed, Kaisey et al. brought up in their MS patients, a large amount of Akkermansia muciniphila
review osteopontin (OPN), a glycoprotein which functions and Methanobrevibacter bacteria was found. These two
as an extracellular matrix protein and a cytokine . OPN types of bacteria were consistent with the expression of
[52]
is associated with immune cell migration, and recent genes affecting the adaptive immune system [65,66] . In vitro,
[67]
research has found a notable increase of serum OPN in A. muciniphila increased Th1 lymphocyte differentiation .
persons with MS in comparison to healthy control group . In addition, the prevalence of Butyricicoccus was found to
[58]
[68]
The authors deemed chitinase-3-like protein 1 as a non- be lower in PMS patients compared to RRMS patients .
specific biomarker of neurovegetative disease. Utilizing Despite the abundant ongoing research on biomarkers
extracellular vesicles in diagnostics is a challenge because and their importance in mechanisms of MS pathogenesis,
of their origins, subtypes, and content, and thus, further disease progression, and severity, biomarker use in
research is warranted to devise strategies for differentiating clinical practice is still limited. These novel biological
patients with MS from those without MS and to predict the markers remain a subject of research and, in our opinion,
conversion of clinically isolated syndrome (CIS) to MS . clinicians should continue testing with the most important
[52]
Another serum and CSF biomarker – glial fibrillary acidic biomarkers, such as oligoclonal bands, neurofilaments, and
protein (GFAP) – is associated with astrocyte activation. immunoglobulin G in CSF, in the effort to detect MS. We
In addition, the glycoprotein chitinase 3-like 1 (CHI3L1) remain hopeful that carrying out more clinical studies with
synthesized by astrocytes and microglia, sCD163, which is a other biomarkers in the future may lead to discoveries of
marker for microglia and macrophages, and chemoattractant more biomarkers applicable in routine clinical practice for
CXCL13, was detected in MS patients. NfL levels were MS screening, diagnosis, prognosis, and treatment.
associated with brain volume loss, while CHI3L1 levels Figure 1 illustrates the mechanism of MS development,
correlated with spinal atrophy. However, the clinical utility taking into account environment factors, infectious factors,
of these biomarkers remains unconfirmed [54,59] . It has long and genetic factors.

Volume 2 Issue 3 (2023) 5 https://doi.org/10.36922/an.1319