Lupus more severe in patients with ancestry from southern Europe

Systemic lupus erythematosus (SLE) patients with a higher percentage of ancestry from southern Europe have more severe disease manifestations, according to new research presented today at EULAR 2008, the Annual Congress of the European League Against Rheumatism in Paris, France.

According to the results of the research, northern European ancestry is shown to be associated with the relatively milder mucocutaneous (skin) manifestations of SLE, whereas southern European ancestry contributes to more severe manifestations of the disorder such as nephritis (inflammation of the kidneys) and increased production of specific autoantibodies (antibodies that fail to recognise and therefore attack the body's own cells, tissues or organs).

SLE is a complex autoimmune disease characterised by chronic inflammation and damage to body tissues, which occurs as a result of the production of abnormal antibodies that target and cause damage to cells of the patient's body, including immune cells. SLE has the potential to affect a variety of areas of the body, including the heart, lungs, kidneys, joints, and/or nervous system. The course of the disease is unpredictable, with periods of illness (called flares) alternating with remission. Lupus can occur at any age but is most common in women, particularly of non-European descent. Until now, the relationship between specific European ancestry and SLE severity has not been studied.

Professor Lindsey A Criswell of the University of California, San Francisco, USA, who led the study, said: "Exploring the ancestry and genetic make-up of patients in relation to their disease today helps us to better understand the complex nature of SLE and why it manifests itself differently in different people. This study shows a clear correlation between specific European ancestry and SLE disease severity and autoantibody production, which may further assist in understanding the risk factors for this condition and should help us better understand and manage this disease in the future."

Researchers in this study examined 1,270 SLE patients from four independent cohorts who had at least 90% European ancestry according to continental ancestry-informative genetic markers. 1,409 genome-wide markers informative for northern versus southern European ancestry were then analysed to estimate the percentage of northern European ancestry for each subject using the STRUCTURE programme. The association between northern European ancestry and specific SLE subphenotypes, including autoantibody production, nephritis, arthritis and mucocutaneous manifestations was then explored.

Northern European ancestry was positively associated with photosensitivity (odds ratio=2.0, p<10-6) and discoid rash (odds ratio=1.9, p=0.01), which are relatively mild manifestations of SLE. It was inversely associated with anti-nuclear autoantibodies (odds ratio=0.38, p-value=0.0005), anticardiolipin antibodies (odds ratio=0.66, 95%, p-value =0.02), arthritis (odds ratio=0.62, p-value =0.003), and renal disorder (odds ratio=0.75, p-value =0.04).