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Published on: November 28, 2016
Comprehensive pathogen detection in sera of Kawasaki disease patients by high-throughput sequencing: a retrospective
Yuka Torii1, Kazuhiro Horiba1,2,3, Satoshi Hayano1
1Department of Pediatrics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
Insights
This study investigated pathogens in children with Kawasaki disease (KD). High-throughput sequencing found no single causative agent, but certain bacteria were more prevalent in KD patients, suggesting a potential immune trigger.
Area of Science:
- Pediatric Infectious Diseases
- Immunology
- Microbiology
Background:
- Kawasaki disease (KD) is an idiopathic childhood vasculitis affecting coronary arteries.
- The definitive causative pathogen for KD remains unknown.
- Diagnosis of KD is symptom-based, potentially after the triggering pathogen has diminished.
Purpose of the Study:
- To identify comprehensive pathogens in the sera of patients during the acute stage of Kawasaki disease.
- To utilize high-throughput sequencing (HTS) for pathogen detection in early-stage KD.
Main Methods:
- Sera from 12 KD patients and 12 controls were analyzed using HTS for DNA and RNA sequences.
- A custom bioinformatics pipeline, PATHDET, was employed to identify pathogen sequences.
- Equine infectious anemia was noted as a potential contaminant in RNA analysis.
Main Results:
- No specific RNA viruses were definitively linked to KD, excluding a known contaminant.
- DNA viruses, including human herpesvirus 6B and Anelloviridae, were found in both KD and control groups.
- Several bacterial genera (Acinetobacter, Pseudomonas, Delfita, Roseomonas, Rhodocyclaceae) were more frequently detected in KD sera.
Conclusions:
- No single pathogen was identified as the cause of Kawasaki disease in acute serum samples.
- While contamination is a concern, the increased prevalence of certain bacteria suggests they may act as immune system stimulants, potentially inducing KD.
Background:
Kawasaki disease (KD) is an idiopathic systemic vasculitis that predominantly damages coronary arteries in children. Various pathogens have been investigated as triggers for KD, but no definitive causative pathogen has been determined. As KD is diagnosed by symptoms, several days are needed for diagnosis. Therefore, at the time of diagnosis of KD, the pathogen of the trigger may already be diminished. The aim of this study was to explore comprehensive pathogens in the sera at the acute stage of KD using high-throughput sequencing (HTS).
Methods:
Sera of 12 patients at an extremely early stage of KD and 12 controls were investigated. DNA and RNA sequences were read separately using HTS. Sequence data were imported into the home-brew meta-genomic analysis pipeline, PATHDET, to identify the pathogen sequences.
Results:
No RNA virus reads were detected in any KD case except for that of equine infectious anemia, which is known as a contaminant of commercial reverse transcriptase. Concerning DNA viruses, human herpesvirus 6B (HHV-6B, two cases) and Anelloviridae (eight cases) were detected among KD cases as well as controls. Multiple bacterial reads were obtained from KD and controls. Bacteria of the genera Acinetobacter, Pseudomonas, Delfita, Roseomonas, and Rhodocyclaceae appeared to be more common in KD sera than in the controls.
Conclusion:
No single pathogen was identified in serum samples of patients at the acute phase of KD. With multiple bacteria detected in the serum samples, it is difficult to exclude the possibility of contamination; however, it is possible that these bacteria might stimulate the immune system and induce KD.
