Redox-Mediated Carbamylation As a Hapten Model Applied to the Origin of Antibodies to Modified Proteins in Rheumatoid Arthritis

Citrullination of a phage-displayed human peptidome library reveals the fine specificities of rheumatoid arthritis-associated autoantibodies

“…First, peptides may not contain the necessary conformational requirements for binding to ACPAs, thus contributing to false negative results. However, ACPAs are thought to behave to some extent like anti-hapten antibodies such that citrulline is recognized as the primary point of contact [45], while the surrounding amino acids underlie each ACPA's substrate binding profile. This model is supported by a significant monoclonal cross-reactivity among citrullinated substrates [46], and the fact that non-physiologic anti-cyclic citrullinated peptide (CCP) assays perform with high clinical accuracy.…”

High expression level of homocitrulline is correlated with seborrheic keratosis and skin aging

“… 6 This reaction usually occurs with lysine ε-amino groups, forming N(6)-Carbamoyl-L-Lysine (CBL): the common name for this compound is Homocitrulline (HCit), which is the most characteristic carbamyl reaction product. 7 Previous studies have reported that protein carbamylation reaction occurs in patients with chronic diseases, such as chronic kidney disease, atherosclerosis, and rheumatoid arthritis, 8 , 9 , 10 but only a few studies have reported the relationship between protein carbamylation reaction and skin aging. Gorisse et al 11 found that the contents of HCit in total skin extract increased significantly with the age of subjects.…”

“…Previous studies have reported that protein carbamylation reaction is involved in pathological processes of chronic diseases, such as chronic kidney disease, atherosclerosis, and rheumatoid arthritis. 8 , 9 , 10 On the other hand, very few studies have investigated the role of protein carbamylation reaction in the skin aging process. Gorisse et al 11 quantitatively analyzed the contents of HCit in total skin extract, and they isolated type Ⅰ collagen proteins from human, cow, and mouse skin tissues.…”

Redox Pathogenesis in Rheumatic Diseases

“…The PADI locus on chromosome 1 is also an independent risk factor for RA. 98 The expression of PAD4 on the surface of monocytes and proinflammatory molecules present in the synovium of patients with RA suggests that inflammation attracts NETs, as well as cells expressing PAD4. Moreover, anti–citrullinated protein antibodies (ACPAs) are cross‐reactive to carbamylated and acetylated peptides.…”

“…This function is likely linked to the ability of PAD4 to act as an epigenetic modifier via its citrullinating activity. The PADI locus on chromosome 1 is also an independent risk factor for RA 98 . The expression of PAD4 on the surface of monocytes and proinflammatory molecules present in the synovium of patients with RA suggests that inflammation attracts NETs, as well as cells expressing PAD4.…”