Association of systemic lupus erythematosus with low serum bilirubin levels

Objective: Systemic lupus erythematosus (SLE) is accompanied by severe oxidative stress. Bilirubin has been reported as a strong negative predictor of oxidative stress-mediated diseases, such as atherosclerosis. The objective of our study was to evaluate the association between serum bilirubin levels and SLE manifestation. Methods: The study was performed with 259 SLE patients, diagnosed according to American Rheumatism Association (ARA) criteria. A subset of these patients, having normal hepatic function (n = 218, mean age 39.5 years), was studied in greater detail to eliminate the possible confounding effects of any underlying or drug-induced liver disease on the serum bilirubin levels. Age-matched healthy subjects (n = 180) served as the control group. A standard biochemical and immunological work-up was performed on all subjects. Results: Compared to the controls, substantially lower levels of serum bilirubin were detected in SLE patients (p < 10(-5)); these were inversely correlated with disease activity and extent (p < 0.05). Furthermore, each 1 mol/L decrease in serum bilirubin was associated with a 37% increase in the odds for a positive SLE status [odds ratio (OR) 1.37, 95% confidence interval (CI) 1.28-1.47, p < 10(-5)]. Simultaneously, the odds of unconjugated hyperbilirubinaemia (a phenotypic sign of Gilbert's syndrome) were more than four times lower in SLE patients (OR 0.235, 95% CI 0.072-0.764, p = 0.016). Conclusion: Low serum bilirubin represented a strong predictor of the manifestation of SLE symptoms. The most likely explanation for this finding is the increased consumption of bilirubin due to the severe oxidative stress accompanying SLE. Subjects with higher serum bilirubin levels, such as those with Gilbert's syndrome, might be protected from the development of SLE.