The Role of Posttranslational Protein Modifications in Rheumatological Diseases: Focus on Rheumatoid Arthritis
Table 1
Summary of some posttranslational modifications in rheumatoid arthritis.
PTM
Effect(s)
Reference
Glycosylation: PTM that consists in the addiction of glucides on an atom of nitrogen (N-glycosylation) or oxygen (O-glycosylation) of the lateral chain of the amino acids that forms a protein.
Epitopes presentation: -Protein glycosylation interacts with the processes of antigen presentation. -These interactions regard both antigen processing pathways in APCs and TCR-MHC II complex formation.
Haurum et al., 1999 [6] Jefferis et al., 1995 [22]
Igs properties: -Fc fragment of immunoglobulins has an important site of N-glycosylation, the asparagine 297 (Asn297). -It has been shown that IgG can have both proinflammatory and anti-inflammatory activity, depending on which Fc receptor they preferentially bind to: those different affinities for receptors are strictly dependent on the composition of the saccharine lateral chain linked to Asn297.
Citrullination: PTM consisting in the switch of the imine nitrogen of an arginine to an atom of oxygen, linked to the backbone structure as a ketone. It is mediated by a family of enzymes called PAD (or PADI).
-It is associated with histone modification, genomic regulation and NET formation. -PAD activation can be an intracellular or extracellular event, due to various conditions. -This activation can lead to the creation of altered self-epitopes and ACPA formation.
Yamada et al., 2005 [49] Khandpur et al., 2013 [60]
Carbamylation: Nonenzymatic PTM that consists in the addiction of a cyanate group on proteins.
-Loss of the native proteic structure. This event can lead to a break of tolerance and finally results in the formation of anti-CarP autoantibodies.