Sialic acid acetylesterase (SIAE) removes acetyl moieties from the carbon 9 and 4 hydroxyl groups of sialic acid and recently a debate has been opened on its association to autoimmunity.
The function of rare genotypes encoding defective variants of sialic acid acetylesterase (SIAE) in some autoimmune diseases, including rheumatoid arthritis (RA), is ambiguous.
Sialic acid acetylesterase (SIAE) plays a crucial role in regulating the threshold of autoantibody production of B-cells and the defective variants of SIAE are associated with an increased risk of various autoimmune diseases such as type 1 diabetes (T1DM).
We fine mapped two primary biliary cirrhosis (PBC) risk loci, CLEC16A (C-type lectin domain family 16 member A)-suppressor of cytokine signaling 1 (SOCS1) and Spi-B protein (SPIB) and sequenced a locus, sialic acid acetylesterase (SIAE), proposed to harbor autoimmunity-associated mutations.
We conclude that further studies are needed before the proposed strong effect of defective SIAE variants on susceptibility to autoimmunity can be universally accepted.
Functionally defective SIAE rare and polymorphic variants represent a strong genetic link to susceptibility in relatively common human autoimmune disorders.