ATP7B peptides could help improve Wilson disease diagnostics

Levels of the ATP7B peptide identifies Wilson disease (WD) with high reliability and can help reduce ambiguity regarding the diagnosis of the disease, a recent study has found.

The study included 264 WD dried blood spot samples (216 from patients, 48 from WD carriers), retrieved from five biorepositories, and 150 samples from normal controls. ATP7B levels were measured using immunoaffinity enrichment mass spectrometry.

Two ATP7B peptides were used in the present study as surrogates to measure total ATP7B protein concentrations. The mean concentrations in normal controls were 257.7±57.7 and 203.0±48.9 pmol/L for ATP7B peptides 887 and 1056, respectively. Disease cutoffs for the respective peptides were set at 114.0 and 80.8 pmol/L.

Overall, 92.1 percent (199 of 216) of all WD patients had at least one peptide fall below the disease threshold concentration. Among the 48 carriers, 16.7 percent (n=8) and 8.3 percent (n=4) had levels of ATP7B peptides 1056 and 887, respectively, lower than the diagnostic cutoffs.

Receiver operating characteristic curve analysis revealed an area under the curve of 0.98 for both ATP7B 1056 (95 percent confidence interval [CI], 0.97–0.99; p<0.0001) and ATP7B 887 (95 percent CI, 0.96–0.99; p<0.001). ATP7B 887 had a sensitivity and specificity of 91.2 percent and 98.1 percent, respectively.

“Clarity is brought to patients with ambiguous genetic results, significantly aiding in noninvasive diagnosis,” the researchers said. “A proposed diagnostic score and algorithm incorporating ATP7B peptide concentrations can be rapidly diagnostic and supplemental to current Leipzig scoring systems.”