Finally, there is also a body of evidence suggesting that chronic exposure to PICs changes the relative abundance of the two GR isoforms, with an increase in the dominant negative beta isoform and a decrease in the alpha isoform leading to a marked decrease in GR efficiency, which may be the major mechanism underpinning GC resistance in chronic inflammatory conditions such as RA [110, 235]. This evidence concerns the gene NR3C1 and rheumatoid arthritis.