Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation in the joints involving the synovial tissue and ultimately leading to the destruction of cartilage and bone. The aetio-pathogenic processes leading to the development of the disease are not fully understood.
We and others have shown that antibodies against citrullinated proteins/peptides (ACPA), detectable as anti-CCP2 antibodies of the IgG, IgA and IgM isotype, precede the development of RA by several years. Increased levels of pro-inflammatory cytokines and chemokines suggest ongoing inflammation years before onset of symptoms in some individuals who subsequently develop RA.
The fluorescence intensity of antibodies against citrullinated peptides, fibrinogen (Fib)ß36–52, Fibß74, CEP-1, citC1III, and filaggrin were significantly increased in pre-disease individuals compared with controls. Antibodies against Fibß36-52, CEP-1 and filaggrin increased gradually reaching the highest levels of all antibodies before symptom onset. The levels of the earliest detectable antibodies (Fibα591 and vimentin (Vim)60-75) increased only slightly before onset of symptoms, although more after onset of disease. A cluster of antibodies, citC1III, Fibα573 and Fibß74 increased only slightly before onset of symptoms but prominently after disease onset. The odds ratio for development of RA with a combination of CEP-1 and Fibß36-52 antibodies (<3.35 years pre-dating) was 38.8 (CI 95%14.5-103.5) compared with having either.
Besides these antibodies the development was also predicted by presence of HLA-shared epitope and smoking independently. The combinaions of HLA-shared spitope, smoking and any of the three most frequently occuring antibodies and anti-CCP were highly associated with disease develoment compared with not having any of these factors. Disease development was also associed with socio-economic and life stile factors e.g. lower education and manual work increased the risk. There were no impact on disease development by cost or alcholhol intake.
Presence of antibodies against citrullinated peptides (Fibß36-52, fillagrin, CEP-1, CCP) was associated with smoking habits, HLA-shared epitope, particularly 0401 and PTPN22 independently for each factor and without demonstrable interactions
Disclosure of Interest None Declared