In this thesis clinical and immunological studies in patients with undifferentiated (UA) and rheumatoid arthritis (RA) are described. Depending on the study population 6-55% of the patients who... Show moreIn this thesis clinical and immunological studies in patients with undifferentiated (UA) and rheumatoid arthritis (RA) are described. Depending on the study population 6-55% of the patients who presented with UA actually fulfilled the criteria for RA as defined by the ACR in 1987 over time. In the first four years, radiographic joint damage, disease activity and HAQ were comparable in patients with RA presenting with UA and patients presenting with RA. Treatment of UA patients with methotrexate resulted in postponing progression to RA and retarding radiographic joint damage. In UA patients who had low/intermediate pretreatment ACPA-levels and were treated with methotrexate, the incidence of RA was lower than in patients with high levels. The disease activity score that was used in RA patients was validated in patients with UA. To identify which patient with UA will progress to RA, a prediction rule was developed. In patients with RA, treatment with TNF-alpha resulted in recovery of regulatory T cells. The importance of these regulatory T cells was emphasized in the strength of the anti-inflammatory response to the human cartilage glycoprotein 39 in healthy individuals: it even suppressed other pro-inflammatory responses, whereas patients with RA reacted with a pro-inflammatory response Show less
Rheumatoid arthritis (RA) is a chronic inflammation of several joints caused by autoimmunity. HLA molecules are most important risk factor involved in RA development. Regarding the risk of RA... Show moreRheumatoid arthritis (RA) is a chronic inflammation of several joints caused by autoimmunity. HLA molecules are most important risk factor involved in RA development. Regarding the risk of RA development, three variants can be discriminated; the shared epitope increases the risk, DERAA-containing HLA molecules decrease the risk and a neutral variant. In this thesis we describe that a mother, in contrast to a father, with a DERAA-containing HLA-molecule confers a life-long protection to her child against RA development with and without passing the gene responsible for the HLA-molecule. Furthermore, we describe that the T cells of HLA-DR4 positive RA patients can react against certain peptides derived from the citrullinated (a post-translational modification) vimentin protein in a citrulline-specific manner. Next to HLA-molecules there are several other genetic factors involved in the risk of RA development, e.g. PTPN22 and CD40. For the PTPN22 SNP associated with RA development, we showed that information on the presence of the PTPN22 SNP next to the presence of ACPA (antibodies specific for RA patients) does not give additive value to the prediction of RA development. On the contrary, the SNP has an influence on the level of ACPA present in the patient. For a SNP in the CD40 gene, we showed that it influences the severity and progression of RA. Show less
