ABSTRACT

The present study was carried out at the Institute of Clinical Research, Department of Rheumatology, and the Department of Clinical Immunology, Odense University Hospital, from 1999 to 2003 inclusive.

Systemic lupus erythematosus (SLE) is a chronic relapsing-remitting autoimmune disease characterized by widespread organ involvement and occurrence of a variety of autoantibodies.

The purposes of the present study were a) to determine the prevalence and annual incidence of SLE and disease flares in a complete community based lupus cohort, b) to determine the prevalence of selected autoantibodies and complaints/diseases among first-degree relatives (fdr.'s) and spouses to the lupus cohort, and c) to study peripheral blood T and B lymphocytes and monocytes in SLE-patients with varying degrees of disease activity, patients with newly diagnosed rheumatoid arthritis and healthy controls, with respect to surface markers, and expression of mRNA for selected cytokines and their receptors.

Ad a) Denmark is a low incidence lupus area but lupus prevalence is gradually increasing, although less pronounced than in neighbouring Nordic communities. Incomplete (I)-SLE is a benign disease variant which may, however, in an unpredictable manner convert into definite (D)-SLE. Two major D-SLE subsets of almost equal size can be identified according to flare rate, one having a long and quiescent course, the other exhibiting relapses alternating with remissions. Importantly, flares should be anticipated in particular among patients with nephropathy, infections and thrombocytopenia.

Ad b) Increased presence of ANAs in different serum dilutions was demonstrated among fdr.'s to this unselected cohort of lupus patients, hence supporting previous evidence from clinic based studies of an increased occurrence of autoantibodies in SLE fdr.'s. An effect of shared environment in adult life on factors determining ANA prevalence among lupus patients and their spouses appears to be negligible assessed by a low ANA prevalence in spouses. Present ANA seropositivity in fdr.'s was related to the criterial burden and cumulated damage among the corresponding lupus probands. There was an increased frequency of autoimmune traits among lupus fdr.'s. The study suggests an inherited genetic factor underlying the development of ANAs in fdr.'s to lupus patients. One or more combinations with environmental triggers or expression of additional genes are probably required to develop clinical SLE.

Ad c) The total numbers and frequency of plasma cells and B lymphocytes did not differ between groups even if BLyS mRNA expression by monocytes tended to be increased in inactive SLE. Since increased immunoglobulin and autoantibody production is a hall mark of SLE, quantification of circulating cells of B-lineage would not appear to be feasible in monitoring disease activity in lupus. SLE patients had normal circulating monocyte numbers, but decreased expression of mRNA for TNF- α , particularly in active disease, suggesting an inherent or acquired TNF- α abnormality in SLE. Notably, several T lymphocyte subsets were decreased in SLE including CD8 + cells, memory and naïve Tc lymphocytes. These findings apply to active as well as inactive disease thereby providing further evidence for defective T-B lymphocyte interaction in the pathogenesis of SLE.