A diagnostic blood test for Kawasaki disease?

Michael G Burke, MD

Kawasaki disease (KD) is associated with a gene expression pattern in the blood that differentiates it from the other infectious and inflammatory conditions with which KD is often clinically confused, a new study found. This suggests that a blood test based on measurements of the components of this 13-transcript gene expression signature could be developed to enable physicians to diagnose KD earlier and more accurately than they now can.

The study, which was conducted in pediatric centers in 4 different countries including the United States, had 2 groups of children. The training and test discovery group was comprised of 404 youngsters with infectious and inflammatory conditions, including KD, inflammatory diseases, and bacterial or viral infections, along with healthy controls. The independent validation group had 102 patients with KD, 72 of whom were in the first 7 days of illness (none had been ill for longer than 10 days), and 130 febrile controls. None of the participants had begun treatment with intravenous immunoglobulin.

At recruitment, investigators collected blood samples from all participants, which they evaluated for whole-blood gene expression. This analysis revealed that KD expressed 1600 genes differently than did other diseases and healthy controls. To identify a small signature group suitable for development as a diagnostic test, researchers pinpointed a 13-transcript signature in which some of the genes showed increased expression in KD compared with other infectious and inflammatory conditions and others decreased expression. In the discovery group, this signature distinguished KD from other infectious and inflammatory conditions with a sensitivity of 81.7% and specificity of 92.1%. In the validation group, the signature distinguished KD from febrile controls with a sensitivity of 85.9% and specificity of 89.1%.

Performance of the 13-transcript signature did differ depending on whether the child had clinically defined definite, highly probable, or possible KD, however, with diagnostic accuracy increasing with the certainty of clinical diagnosis. Also, performance was slightly reduced in patients who were diagnosed later than day 7 (Wright VJ, et al. JAMA Pediatr. August 6, 2018. Epub ahead of print.).

Thoughts from Dr. Burke

I can’t even count how many times I have explained to parents that we were considering KD but that the diagnosis was uncertain and there is no single blood test to make the answer clear. These researchers may be on the path to change that. Their work could lead to a practical, fast, accurate tool to help in diagnosis, especially for children with incomplete findings or an atypical course for KD.