Genetic and prognostic factors in lupus

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease in which several organs and organ systems can be involved. SLE has is prevalent especially in young women, and has a prevalence of approx. 1 in 2.500 persons. One of the possible manifestations of SLE is renal involvement, lupus nephritis (LN). The exact pathogenesis of SLE is unknown, but genetic predisposition plays an important role. In this thesis we describe the results of analyses in SLE and LN patients with a focus on genetic and prognostic factors. In some of these analyses, patients with rheumatoid arthritis (RA) were included. The association of several known genetic factors with SLE was confirmed, but also some new associations were found. Association of SLE with chromosome 1q41-42 and the HLA locus were confirmed. We found evidence that polymorphisms in the gene encoding the complement component C1q are associated with SLE. In addition, we found a strong association of polymorphisms of the gene encoding the receptor for advanced glycation end products (RAGE) with SLE but also with RA. These associations with SLE had not been described before. Some RAGE polymorphisms were also associated with disease severity in SLE and LN. Analysis of a polymorphism in the gene encoding the CC chemokine receptor 5 (CCR5) showed no association with SLE, LN or RA. In a group of patients with a proliferative form of LN, we did not find a prognostic value of exact renal hemodynamic function tests.