Scientists at the Proteomics Center at Children’s Hospital Boston identified a protein through mass spec techniques that serves as a biomarker for appendicitis in children. They report that this marker called leucine-rich alpha-2-glycoprotein (LRG) is also detectable in urine. Their findings will be published online June 23 in the Annals of Emergency Medicine.
The researchers examined 12 urine specimens using mass spectrometry instrumentation provided by Thermo Scientific. Of the samples, six were from patients with appendicitis, taken before and after appendectomy, and six were from patients without appendicitis. They identified 32 candidate biomarkers including many proteins associated with immune response and inflammation. To these 32 they added other 25 previously discovered marker candidates.
They then sought to validate these markers in 67 children seen at the hospital for suspected appendicitis over an 18-month period, 25 of whom ultimately had proven appendicitis. Seven promising urine biomarkers were identified. The best of them was LRG, which appears to be a specific marker of local inflammation. Research indicated near-perfect sensitivity with almost no false-negatives and near-perfect specificity with almost no false-positives, the investigators report.
LRG was strongly elevated in diseased appendices, even when those appendices appeared normal on imaging. Additionally, the amount of LRG correlated with the severity of the appendicitis as judged by histologic review of the appendix specimens.
Although mass spectrometry isn’t widely available clinically, urine LRG elevations were detected by immunoblotting, suggesting that a rapid clinical test such as a urine dipstick could be developed through further research. The team is now developing such a quantitative LRG urine assay and is working to further validate their findings.
The researchers note that since their study was limited to children, and that patterns of biomarkers likely vary in older patients, LRG testing would need to be studied in other clinical settings.