Clinical researchers at Children’s Hospital Boston have identified what seems to be an almost perfect marker for appendicitis. The substance, called leucine-rich alpha-2-glycoprotein (LRG), looks like a good candidate to be used for testing as it can be detected with immunoblotting, without a need for expensive mass spectrometers.
In the first phase, they examined 12 urine specimens — 6 from patients with appendicitis, taken before and after appendectomy, and 6 from patients without appendicitis — and identified 32 candidate biomarkers, including many proteins associated with immune response and inflammation. To these 32 they added other candidates found through gene expression studies and other means, yielding a total of 57 potential biomarkers. 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. The laboratory investigators testing for the markers were not told the patients’ clinical status, to ensure unbiased assessment of the test performance.
Seven promising urine biomarkers were identified. The best of them was leucine-rich alpha-2-glycoprotein (LRG), which appears to be a specific marker of local inflammation. It had an “area under the curve” value of 0.97, indicating near-perfect sensitivity (with almost no false-negatives) and near-perfect specificity (almost no false-positives). LRG was strongly elevated in diseased appendices, even when those appendices appeared normal on imaging, and 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.