Alpha-enolase (Eno) is an ubiquitary glycolytic
enzyme playing multiple functions that go well beyond its principal metabolic role of energy supplier during glycolysis. Eno is localized in the cytoplasm, but also expressed on the cell membrane, where it binds
plasminogen allowing its activation. Its shorter form, in the nucleus, acts as
transcription factor. In inflammatory conditions, Eno undergoes post-translational modifications, such as citrullination, oxidation and phosphorylation. Eno is also an
autoantigen in different disorders. In fact,
autoantibodies to Eno have been detected in
rheumatoid arthritis,
lupus nephritis, primary
glomerulonephritis,
cancer,
infections and other disorders, and in many cases they represent specific markers to be utilized in clinical practice. Anti-Eno
antibodies in the different clinical conditions are not equal: they differ in isotype and often recognize different
epitopes on the
enzyme.
IgG1 and
IgG3 are prevalent in
Rheumatoid Arthritis,
IgG2 in
Lupus nephritis and
IgG4 in primary autoimmune glomerulopathy. This review analyzes the characteristics of anti-Eno
autoantibodies in autoimmune disorders and
cancer, describing their fine specificity and isotype restriction. The post-translational modifications that are target of
autoantibodies are also discussed, as they represent the basis for elucidating the molecular mechanisms responsible for
epitope generation. Despite an impressive amount of experimental work on anti-Eno
antibodies, it is still necessary to validate the use of anti-Eno
antibodies as
biomarkers of selected diseases and extend the knowledge on the mechanisms of anti-Eno
autoantibody production. Strategies that downmodulate the immune response to Eno may represent in the future novel approaches in the treatment of autoimmune disorders.