Abstract
Advent of biologic agents drastically changed the outcome of rheumatoid arthritis (RA) treatment. However, with its high cost and relatively high incidence of opportunistic infection, application of biologics has to be very cautious. In this sense, selection of RA patients of poor joint prognosis is important. Factors of poor joint prognosis in RA patients have been determined in many reports. American college of rheumatology (ACR) and European league against rheumatism (EULAR) recommendations adopted anti-CCP antibodies and rheumatoid factors as the most important biomarkers to predict poor prognosis. High disease activity such as high ESR and CRP is also the important prognostic factors. The major genetic factor of poor prognosis is HLA-DR. HLA-DR shared epitope in 70-74 amino acid position of DRβ chain (QRRAA, QKRAA, RRRAA) is of poor prognosis and DERAA in the same position of DRβ chain is of good prognosis. DERAA is reported to be more dominant than anti-CCP antibodies, i.e. RA patients with anti-CCP(+) DERAA(+) are less bone-destructive than those with anti-CCP(+) DERAA(-). Other than HLA, polymorphisms in PADI4, DKK1, IL15, CD40, MMP9, IL2RA, GRZB, IL4R, and SPAG16 are the candidate genes to predict poor prognosis, but proving their association is difficult mainly due to the heterogeneity of treatment and RA subsets such as CCP positivity in the cohorts.
