Gene Transcript Abundance Profiles Distinguish Kawasaki Disease from Adenovirus Infection

Efforts to discern the etiology of acute febrile disease are hampered by the paucity of reliable discriminating clinical features, difficulties in obtaining appropriate specimens, insensitive methods for detecting known causative agents, and the lack of diagnostic tests for some conditions associated with fever, such as autoimmune diseases and adverse drug reactions. As a result, many acute febrile illnesses remain unexplained, especially in the early days after onset of clinical signs and symptoms. Molecular profiling of the host response offers an approach for classifying acutely ill hosts that complements traditional diagnostic approaches based on microbial detection [1]. Studies of human genome–wide transcript abundance patterns in peripheral blood suggest that these patterns might provide useful information about the disease mechanism, outcome, nature of the infectious agent, and diagnosis [2–6]. This last possibility has not been adequately explored, especially in the setting of a clinical syndrome that presents important diagnostic dilemmas. Kawasaki disease (KD) is an acute, self-limited inflammatory illness of infants and children [7]; ~25% of untreated patients develop coronary artery aneurysms or ectasia. Intravenous immunoglobulin (IVIG) reduces the rate of coronary artery aneurysms to ~5% when administered within the first 10 days of illness, but KD remains the leading cause of acquired pediatric heart disease in developed nations. Despite 30 years of research, no etiologic agent has been identified for KD. In the absence of a specific diagnostic test, KD is diagnosed according to clinical criteria, many of which are shared by other illnesses characterized by rash or fever, including adenovirus infections, streptococcal scarlet fever, and systemic drug reactions. Many children with KD consequently receive an erroneous or late diagnosis, which leads to delays in treatment and an increased risk of coronary artery aneurysm formation [8, 9]. We recently examined whole-blood genomewide transcript abundance patterns in patients with KD and identified specific transcript levels associated with the risk of subsequent failure to respond to IVIG therapy [4]. In the current study, we compared patterns of whole-blood gene expression in patients during the acute phase of KD with patterns found in patients during the early phase of 3 illnesses that have similar clinical presentations but well-defined alternative etiologies. We identified patterns of gene expression and corresponding biological programs that were different in patients with KD, compared to patients with the other illnesses, and we were able to distinguish between KD and adenovirus infection on the basis of gene expression patterns. The results from this study indicate that comparative analysis of host gene expression profiles is a promising approach for better understanding febrile illnesses and that such analysis may contribute to the development of a test for KD that enables more accurate and timely diagnosis.