Complement C3 serum levels in anorexia nervosa: a potential biomarker for the severity of disease?

Background: Anorexia nervosa carries the highest mortality rate of any psychiatric disorder. Even the most critically ill anorexic patients may present with normal 'standard' laboratory values, underscoring the need for a new sensitive biomarker. The complement cascade, a major component of innate immunity, represents a driving force in the pathophysiology of multiple inflammatory disorders. The role of complement in anorexia nervosa remains poorly understood. The present study was designed to evaluate the role of complement C3 levels, the extent of complement activation and of complement hemolytic activity in serum, as potential new biomarkers for the severity of anorexia nervosa. Patients and methods: This was a prospective cohort study on 14 patients with severe anorexia nervosa, as defined by a body mass index (BMI) < 14 kg/m(2). Serum samples were obtained in a biweekly manner until hospital discharge. A total of 17 healthy subjects with normal BMI values served as controls. The serum levels of complement C3, C3a, C5a, sC5b-9, and of the 50% hemolytic complement activity (CH50) were quantified and correlated with the BMIs of patients and control subjects. Results: Serum C3 levels were significantly lower in patients with anorexia nervosa than in controls (median 3.7 (interquartile range (IQR) 2.5-4.9) vs 11.4 (IQR 8.9-13.7, P < 0.001). In contrast, complement activation fragments and CH50 levels were not significantly different between the two groups. There was a strong correlation between index C3 levels and BMI (Spearman correlation coefficient = 0.71, P < 0.001). Conclusions: Complement C3 serum levels may represent a sensitive new biomarker for monitoring the severity of disease in anorexia nervosa. The finding from this preliminary pilot study will require further investigation in future prospective large-scale multicenter trials.