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Volume10, Issue 12 (Suppl)
J Proteomics Bioinform, an open access journal
ISSN: 0974-276X
Page 116
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World Biomarkers & Pharma Biotech 2017
December 07-09, 2017
December 07-09, 2017 | Madrid, Spain
&
20
th
International Conference on
PHARMACEUTICAL BIOTECHNOLOGY
9
th
WORLD BIOMARKERS CONGRESS
JOINT EVENT ON
J Proteomics Bioinform 2017, 10:12(Suppl)
DOI: 10.4172/0974-276X-C1-110
Antibodies with functionality as a new generation of translational tools to monitor, predict and prevent
demyelination
Sergey Suchkov
1-3
, Noel Rose
4
, Aleks Gabibov
5
and
Harry Schroeder
6
1
I M Sechenov First Moscow State Medical University, Russia
2
A I Evdokimov Moscow State Medical & Dental University, Russia
3
EPMA, Brussels, EU
4
Johns Hopkins Medical Institutions, Baltimore, USA
5
Russian Academy of Sciences, Russia
6
UAB at Birmingham, USA
A
bs against myelin basic protein/MBP endowing with proteolytic activity (Ab-proteases with functionality) is of great value to
monitor demyelination to illustrate the evolution of multiple sclerosis (MS). Anti-MBP autoAbs from MS patients and mice
with EAE exhibited specific proteolytic cleavage of MBP which, in turn, markedly differed between: (i) MS patients and healthy
controls; (ii) different clinical MS courses; (iii) EDSS scales of demyelination to correlate with the disability of MS patients to predict
the transformation prior to changes of the clinical course. Ab-mediated proteolysis of MBP was shown to be sequence-specific whilst
demonstrating five sites of preferential proteolysis to be located within the immunodominant regions of MBP and to fall inside into 5
sequences fixed. Some of the latter (with the highest encephalitogenic properties) were proved to act as a specific inducer of EAE and
to be attacked by the MBP-targeted Ab-proteases in MS patients with the most severe (progradient) clinical courses. The other ones
whilst being less immunogenic happened to be EAE inducers very rare but were shown to be attacked by Ab-proteases in MS patients
with moderate (remission-type) clinical courses. The activity of Ab-proteases was first registered at the subclinical stages 1-2 years
prior to the clinical illness. About 24% of the direct MS-related relatives were seropositive for low-active Ab-proteases fromwhich 22%
of the seropositive relatives established were being monitored for 2 years whilst demonstrating a stable growth of the Ab-associated
proteolytic activity. Moreover, some of the low-active Ab-proteases in persons at MS-related risks (at subclinical stages of MS), and
primary clinical and MRT manifestations observed were coincided with the activity to have its mid-level reached. Registration in the
evolution of highly immunogenic Ab-proteases would illustrate either risks of transformation of subclinical stages into clinical ones,
or risks of exacerbations to develop. The activity of Ab-proteases in combination with the sequence-specificity would confirm a high
subclinical and predictive (translational) value of the tools as applicable for personalized monitoring protocols. Ab-proteases can be
programmed and re-programmed to suit the needs of the body metabolism or could be designed for the development of principally
new catalysts with no natural counterparts. Further studies on targeted Ab-mediated proteolysis may provide a translational tool for
predicting demyelination and thus the disability of the MS patients.
ssuchkov57@gmail.com