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. Abs against Cardiac Myosin (CM) with proteolytic activity exhibiting targeted cleavage of CM molecule are of great value to monitor stages of autoimmune inflammation in patients with autoimmune myocarditis (AIM) and persons-at-risk.
AIM is just one of the chronic organ-specific autoimmune diseases resulting in a destruction of cardiac tissue by different tools, including highly aggressive and destructive autoAbs. 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! Such Ab-proteases have been found in a series of autoimmune disorders, including multiple sclerosis, autoimmune thyroiditis, etc.
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 registered at the subclinical stages 4-12 months prior to the clinical illness. 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.
So, further studies on Ab-mediated CM degradation and other targeted Ab-mediated proteolysis may provide biomarkers of newer generations to monitor and to treat 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.
