Although mortality in patients with systemic lupus erythematosus (SLE) has decreased over the past three decades, infectious complications remain a significant cause of morbidity and mortality, accounting for approximately 20- 50% of all deaths. The profound influence of genetic background on susceptibility to infections has been well established. Recently, specific variants in the tumor necrosis factor alpha (TNFalpha) promoter and the genes encoding Fcgamma receptors and mannose binding lectin have been associated with an increased susceptibility to infections in certain populations. Polymorphisms affecting these same genes have also been associated with an increased risk of developing SLE or expression of specific lupus manifestations. However, the link between these genetic polymorphisms and risk of infections in SLE patients has never been examined.
The aims of this study are: a) to determine the incidence of specific polymorphisms in the TNFalpha promoter and the genes encoding Fcgamma receptors and mannose binding lectin in SLE patients b) characterize the frequency, type and severity of infectious complications in a group of SLE patients as compared with controls c) determine whether the presence of one or more polymorphisms in the genes of interest is associated with an increased risk of infectious complications in SLE. One hundred and five SLE patients and controls matched for age, sex and ethnicity will be assessed over an 18-month period to determine the incidence and severity of infectious complications. The incidence of genetic polymorphisms affecting these candidate genes and the frequency of infections will be compared between the two groups to determine the level of risk. The identification of genetic markers that would distinguish SLE patients at increased risk for infection would make a profound impact on the outcome of this disease by allowing clinicians to institute appropriate prophylactic therapies.
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