Polyreactive monoclonal autoantibodies in multiple sclerosis: functional selection from phage display library and characterization by deep sequencing analysis.

Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease
of the central nervous system that primarily affects young and
middle-aged people. It is widely accepted that B lymphocyte activation
is required for MS progression. Despite the fact that the exact
triggering mechanisms of MS remain enigmatic, one may suggest that MS
can be induced by viral or bacterial infection in combination with
specific genetic and environmental factors. Using deep sequencing and
functional selection methodologies we characterized clones of poly- and
cross-reactive antibodies that are capable of simultaneous recognition
of viral proteins and autoantigens. The latter, in turn, possibly may
trigger MS progression through molecular mimicry. It was identified that
two cross-reactive antigens are probably recognized by light or heavy
chains individually. According to the high structural homology between
selected autoantibodies and a number of various antiviral IgGs, we
suggest that a wide range of pathogens, instead of a single virus, be
regarded as possible triggers of MS.