Title : Antibodies with functionality as a new generation of translational tools designed to monitor autoimmune myocarditis at clinical and subclinical stages
Abstract:
Catalytic Abs (catAbs) are multivalent immunoglobulins (Igs) with a capacity to hydrolyze the antigenic (Ag) substrate. In this sense, proteolytic Abs (Ab-proteases) represent Abs to provide proteolytic effects. Autoimmune myocarditis (AIM) can be defined as the autoimmune inflammatory process affecting the muscular tissues of the heart (myocardium). And then is being transformed in a stepwise manner into dilated cardiomyopathy (DCM). New targeted therapies for autoimmune and inflammatory diseases (including AIM) would require greater understanding of a patient or a person-at-risk to get the therapy personalized for either of those subsets, for specific biomarkers and the targets. In this sense, the identification and implementation of diagnostic, predictive and prognostic biomarkers remain the Holy Grail of platforms, algorithms and protocols which are the crucial for Personalized & Precision Medicine (PPM). The primary damage in AIM progression and evolution which is mediated by anti-CM autoAbs to trigger a release of separate and pathogenically valuable cardiac-associated epitopes into the bloodstream. A subset of patients with AIM and of their symptom-free relatives has circulating heart-reactive autoAbs. Moreover, some of these autoAbs may also have a functional role in patients, as suggested by in vitro data as well as by preliminary clinical observations, though further work is in progress to clarify this important issue. And along with canonical Abs, some of the families proven to occur are Abs possessing with catalytic (proteolytic) activity (catAbs or abzymes) and thus to belong to Abs with a feature of functionality! The unique clinical case is a family of Ab-proteases detectable in AIM to cleave CM. Of great interest is the evolution of Ab-associated proteolytic activity at different stages of the disease progression. The activity of Ab-proteases was first registered at the subclinical stages 4-12 months prior to the clinical illness. And the activity of the Ab-proteases revealed significant correlation with scales of autoaggression and the disability of the patients with AIM as well. So, the activity of Ab-proteases and its dynamics tested would confirm a high subclinical and predictive value of the tools as applicable for monitoring protocols. The translational potential of this knowledge is in the rational design of new diagnostic tools and new targeted therapeutics based on principles of artificial biocatalysts and Biodesign. And thus Ab-proteases can be programmed and re-programmed to suit the needs of the body metabolism or could be designed for the development of new catalysts with no natural counterparts. Further studies on Ab-mediated CM degradation and other targeted Ab-mediated proteolysis may provide biomarkers of newer generations or even new biomaker families and thus supplementary tools to diagnose, to monitor, to control and to treat and rehabilitate AIM patients at clinical stages and to prevent the disorder at subclinical stages in persons-at-risks to secure the efficacy of regenerative manipulations and for assessing the disease progression and predicting disability of the AIM patients and persons-at-risks.
Audience Take Away
- To learn more about Ab-mediated catalysis (proteolysis) as the biological phenomenon of the next-step generation and its impact in daily practice of cardiac practitioner
- The presentation would get the audiences armed with new approaches to monitor both clinical and subclinical stages of AIM in precise scenarios
- In this translational research faculty could use the latter for setting up translational pipelines on one hand and to teach the students and postgraduate physicians on the other one
- The findings will solve a problem of predictive diagnostics, preventive and rehabilitative measures to be applied for monitoring the AIM patients, the persons-at-risks and to prevent transformation of subclinical stages of AIM into clinical ones
