ABSTRACT
Both the innate and adaptive arms of the immune system are involved in RA pathogenesis, and both humoral and cellular immune mechanisms are believed to be culprits in the disease (McInnes and Schett 2011). The early humoral response in RA patients is characterized by the presence of
Department of Internal Medicine, Division of Rheumatology, University of Michigan School of Medicine , 5514 MSRB-1, 1150 West Medical Center Drive, SPC 5680, Ann Arbor, MI 481095680 USA. aEmail:lblanco@umich.edu bEmail:songlin@umich.edu cEmail: jholo@umich.edu *Corresponding author
auto antibodies against the Fc portion of IgG antibodies (called rheumatoid factor) and/or against post-translationally modifi ed proteins containing citrulline residues (Bax et al. 2011, McInnes and Schett 2011). The presence of antibodies against citrullinated proteins is a strong marker of RA, and therefore their detection is important for RA diagnosis (Verpoort et al. 2007). Citrullinated proteins are generated by posttranslational modifi cation of arginine residues, by removing the amino group of arginine by the action of peptidylargininedeiminase (PAD) enzymes (György et al. 2006). This modifi cation produces proteins that are more hydrophobic because they lack positively charged residues. Citrullination of proteins might affect their function, interaction with other molecules, and folding (Kilsgård et al. 2011). Contributing to the complexity of RA diagnostic and pathology, antibodies against citrullinated proteins are present in the majority of RA patients, but some patients still develop RA without these auto antibodies (Griffi ths 2008, Bax et al. 2011).
