Bioms-eu » Biomarkers

Antimyelin antibodies

No associations were found between antimyelin antibodies with progression to clinically
definite MS or a diagnosis of MS as outlined by the McDonald criteria.

B-cell activating factor (BAFF)

TNF superamily member and plays a role in the survival and maturation of B cells. BAFF has
been found to be elevated in the serum of SLE and Sjogren’s patients.

Clusterin and Chromogranin A

Elevated in the CSF of MS patients. Clusterin regulates complement activation and is
involved in apoptosis, whilst chromogranin A has been found in GM along the meneigeal
border and may play a role in the maintenance of neuronal integrity.

Vitamin D

Children with lower levels of vitamin D seem to be at a greater risk of being diagnosed with
MS. Vitamin D has been shown to regulate the immune system

Apolipoprotein E (Apo-E)

Apo-E ε4 allele is assocated with MS and may predispose carriers to faster disease
progression.

Ferritin

Ferritin is an acute phase reactant and increased levels have been found in MS patients.
Serum ferritin levels have been associated with male gender and relapsing-progressive MS.

Genomics

Genome-wide association study using SNP arrays in MS patients and healthy controls lead to
a number of canidate genes that conferred susceptibility for the disease. The use of high-
density genotyping technologies in association studies may prove to be a powerful tool to
uncover the genetic component of complex disorders such as MS.
Broad screening for biomarkers associated with the clinical response to IFN-b lead to a
number of SNPs and differentially expressed genes that are related to and predicitive of the
responder status. The use of genomics and gene expression platforms at the level of the
entire genome offers unique opportunities for biomarker research. Cross-validation of genomic
data by information from gene expression profiling strengthens the search for
candidate biomarkers.

24S-Hydroxycholesterol

Crucial for maintaining lipid neuronal membranes. Higher CSF 24-OH-chol levels were
demonstrated in patients with GAD-enhancing lesions indicating release from damaged cells
during inflammation.

Interferon-beta

Out of the total population of binding antibodies (BAb) induced by IFNβ, neutralizing
antibodies (NAb) reduce or abolish in vitro IFNβ-bioactivity

c-Jun

c-Jun has been found on microglia and oligodendrocytes in chronic active MS lesions,
comapared to silent lesions and OND/non-neurological controls. Inductions of c-Jun has
been shown to correlate with apoptosis.

Granzyme K

Granzyme K plays plays a role in immunoregulation of adaptive immunity. Gene silencing of
granzyme K inhibited the ability of natural killer (NK)-92 cells to kill activated syngeneic T cells.

Kallikreins

KLK-1 and KLK-6 may serve as biomarkers of progressive MS; highest levels are found in
secondary progressive MS.

Lactate
CSF Lactate levels have been found to reduced in MS compared to controls and may be
related to altererd astrocytic metabolism during disease. This has diagnostic potential in MR
spectroscopy.

Mannan-binding Lectin
In one study, the mean serum concentration of MBL did not differ from healthy controls.
The value of MBL was neither influenced by the number of days from onset to venous
puncture nor to the disease severity judged by MRI and CSF findings.

N-acetylaspartate

CSF NAA levels decrease during the MS disease course. Decreased CSF NAA levels likely are a
reflection of axonal loss in various neurological diseases.
Neurofilaments
Cannabinoid-receptor 1 null mice are susceptible to neurofilament damage and caspase 3
activation.

Osteopontin
Osteopontin is a pro-inflammatory cytokine and elevated levels have been demonstrated
during relapses in RRMS. It has been also found to be highly expressed in MS lesions.

Proteasome autoantibodies
Proteasome autoantibodies to human proteasomes predict multiple sclerosis in
monosymptomatic optic neuritis.
Proteomic Profiles
A clear differences has been shown in the proteome profile of patients with RRMS and CIS as
compared to normal controls.

CCL5/RANTES
RANTES (regulated upon activation, normal T-cell expressed and secreted), a CC chemokine,
enhances inflammatory response. Inteferon-beta-1b treatment reduces RANTES production

S100B
S100B is a biochemical of neurodegeneration. CSF and serum levels of S100B are increased
in MS patients.

TNF-a
Tumour necrosis factor is pro-inflammatory cytokine and is involved in the pathophysiology
of MS

Uric Acid

Uric acid is a natural antioxidant. A few studies reported decreased serum and/or CSF uric
acid levels in MS patients.

VEGF-A
VEGF-A (vascular endothelial growth factor-A) expression is reduced CSF cells in MS patients
compared to controls and SPMS cases have reduced VEGF-A mRNA expression in PBMC
compared to RRMS and controls.

YKL-40
YKL-40 (chitinase 3-like protein) is expressed in inflammatory conditions and has been found
to be increased in lentiviral encephalitis and MS.

Zinc
Zinc levels in erythroctes have been found to be elevated in MS patients, however serum
levels have been found to be low