CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Urine proteomics and diagnostic markers of Kawasaki disease
Kawasaki disease, or mucocutaneous lymph node syndrome, presents as a systematic vasculitis in children. Its etiology is unknown. Children with Kawasaki disease (KD) may have prolonged fever, inflammation of the oral mucosa, conjunctivitis, rash, extremity changes, and cervical lymphadenopathy. The incidence in American and European populations is about one in 10,000, but it may be as high as one in 100 in Japan. Kawasaki disease is the most common cause of acquired heart disease in the developed world, and diagnosis may be elusive since KD tends to mimic many other childhood illnesses. No definitive diagnostic test exists for early identification of KD. Investigators at Boston Children’s Hospital sought to identify unique markers for KD using high-accuracy mass spectrometry proteomics to analyze clinical urine specimens from patients with the disease. More than 2,000 unique proteins were analyzed. The authors found that the urine proteomes of patients with KD were enriched for cellular injury markers such as filamin and talin, immune regulators such as complement regulator CSMD3, immune pattern recognition receptor muclin, and immune cytokine protease meprin A. Significant elevations of filamin C and meprin A were detected in the serum and urine in two independent cohorts of patients with KD. Meprin A and filamin C also showed superior diagnostic performance in a blinded case-control study of patients with KD. The authors concluded that meprin A and filamin C showed particular promise as diagnostic markers based on receiver operating characteristic analysis. They stated that this discovery may lead to improved diagnosis and classification of children with KD and the development of novel therapeutic agents.
Kentsis A, Shulman A, Ahmed S, et al. Urine proteomics for discovery of improved diagnostic markers of Kawasaki disease. EMBO Mol Med. 2012;4:1–11.
Correspondence: Hanno Steen at hanno.steen@childrens.harvard.edu or Susan Kim at susan.kim@childrens.harvard.edu
Acute silent cerebral ischemic events in children with sickle cell anemia
Sickle cell anemia is the most common cause of overt stroke in children. Interventions, such as using transcranial Doppler ultrasonography screening to guide chronic transfusion therapy, has helped reduce the incidence of such strokes. However, despite transfusions, silent cerebral infarction (SCI) still occurs and is more common than stroke. SCI is not associated with motor or sensory impairment but results in neurocognitive deficits, which leads to poor school performance and increased risk for subsequent overt stroke. The authors proposed in this study that the recurrent and potentially reversible ischemia that occurs in many organ systems in sickle cell anemia may also occur in the brain. They conducted a study to determine if acute silent cerebral ischemic events (ASCIEs) could be detected in the asymp-
tomatic baseline state and were frequent and possibly transient. The investigators measured and compared the incidence of ASCIEs and progressive SCI in a group of children screened for SCI in the Silent Cerebral Infarct Transfusion trial. They also examined the clinical circumstances just prior to ASCIEs to help understand their causes. The authors studied 966 magnetic resonance imaging (MRI) scans from 732 children who were a mean age of 9.5 (standard deviation, 2.4) years and the majority of whom were male (51 percent) and had homozygous sickle cell anemia (93 percent). This group was further subdivided into ASCIE and SCI MRI groups to calculate incidence rates. The results showed that ASCIEs were detected on 1.3 percent of MRIs in 652 children, for an incidence of 47.3 events per 100 patient-years. Of the two of 10 children who had followup MRIs of the brain after ASCIEs, only one had a silent cerebral infarction in the same location as the ASCIE. Furthermore, the incidence of ASCIEs was statistically significantly higher than the incidence of progressive SCI. The authors concluded that children with sickle cell anemia have ongoing cerebral ischemia far more frequently than previously predicted. Furthermore, consideration of only easily visualized and permanent brain lesions, such as stroke and MRI, will miss the threat of ischemic injury in symptomatic children. The authors recommend further research to better understand the causes of ASCIEs and their treatment options.
Quinn CT, McKinstry RC, Dowling MM, et al. Acute silent cerebral ischemic events in children with sickle cell anemia. JAMA Neurol. 2013;70:58–64.
Correspondence: Michael R. DeBaun at mdebaun@vanderbilt.edun