The thesis concerns studies on several aspects of the ACPA response in UA and RA patients. One objective was to investigate the effect ACPA on the development of RA and how ACPA and other risk... Show moreThe thesis concerns studies on several aspects of the ACPA response in UA and RA patients. One objective was to investigate the effect ACPA on the development of RA and how ACPA and other risk factors could collectively contribute to the development of RA. The second aim was to increase knowledge on the development of the ACPA response itself Chapter 2 is a review on the percentage of patients with UA who develop RA Chapter 3 describes differences and similarities between ACPA-positive and ACPA-negative RA at first presentation to the rheumatologist and after follow-up. The strongest genetic risk factors, SE-alleles, were described to predispose only for ACPA-positive RA. In Chapter 4, it was investigated whether SE is a risk factor for ACPA-positive RA or for the development of ACPA. The contribution of HLA__DRB1 to the development of ACPA-negative RA was investigated in Chapter 5. In Chapter 6, it was determined whether SE-alleles interact with tobaccoexposure in the risk to develop ACPA-positive or ACPA-negative RA and whether different subtypes of SE interact differently with smoking. Chapter 7 evaluates whether tobaccoexposure also influences the isotype of ACPA. Chapters 8 and 9, describe different isotypes and the fine-specificity of the ACPA response. Finally, the results are summarized and discussed. Show less
This thesis investigated the association between several genetic factors and autoantibodies and the development of undifferentiated arthritis (UA) and rheumatoid arthritits (RA). Second, this... Show moreThis thesis investigated the association between several genetic factors and autoantibodies and the development of undifferentiated arthritis (UA) and rheumatoid arthritits (RA). Second, this thesis described a prediction model that estimates the chance to progress from UA to RA. The most important genetic risk factor for RA are the HLA-Class II alleles that encode for a common amino acid sequence, called the ‘Shared Epitope’. Investigating the progression to RA from UA revealed that the HLA-Shared Epitope alleles are not primarily a risk factor for RA but for the presence of anti-CCP antibodies, that are known to be specific for RA. Smoking in the presence of HLA-Shared Epitope alleles particularly increased the risk on anti-CCP-positive RA.. The HLA-DR3 alleles were associated with anti-CCP-negative RA. The presence of HLA-alleles encoding for D70ERAA correlated with a lower risk on RA and a less severe disease course. The presence of the PTPTN22 T-allele conferred an increased risk for both UA and RA. The knowledge on risk factors for RA-development was translated in a model that estimates the chance to progress to RA in patients that present with UA by using 9 clinical variables. The discriminative ability was high and this model allows individualized treatment decisions in UA. Show less
