New biomarkers of Kawasaki disease identified by urine proteomic analysis

Abstract

Kawasaki disease (KD) is an acute systemic vasculitis that mainly afflicts infants and young children. The symptoms of KD are similar to those of various febrile diseases. Here, we attempted to develop accurate diagnostic biomarkers of KD by performing urine proteomic analysis of samples from healthy controls, patients with KD, and patients with another febrile disease, pneumonia (two patients). We identified differentially expressed proteins (DEPs) in KD as compared to normal controls. We also constructed functional annotation and protein–protein interaction (PPI) networks of DEPs in KD and pneumonia. DEPs common to both KD and pneumonia were identified, as well as DEPs specific to KD. Compared to normal control, 43 and 62 DEPs were identified in KD and pneumonia, respectively. Serine hydroxymethyltransferase 1 is a hub protein of the KD‐specific PPI network. Thirteen DEPs common to both KD and pneumonia and 30 DEPs specific to KD were identified. Of these, the expression of eight DEPs could cluster normal and pneumonia samples into one group and cluster KD samples into another group based on hierarchical clustering. Our study identified several DEPs that may play a role in KD and that may serve as diagnostic biomarkers to distinguish patients with KD from both normal control and other febrile diseases.

Urine Proteomics: Evaluation of Different Sample Preparation Workflows for Quantitative, Reproducible, and Improved Depth of Analysis

“…The tryptic peptides were eluted via centrifugation for 1 min at 1000 g sequentially with 80 μL of TEAB, 80 μL of water/0.2%TFA, and 80 μL of 50% acetonitrile/0.2% TFA. The eluted peptides were vacuum-dried and dissolved in water/0.1% TFA before desalting …”

“…The mass spectrometer was set to repetitively scan m/z from 300 to 1400 (R = 120 000), followed by data-dependent MS/MS scans (R = 15 000) on the 20 most abundant ions with a minimum AGC of 8e 3 , normalized collision energy (NCE) of 27, dynamic exclusion of 30 s, with a repeat count of 1. The FTMS full-scan AGC target value was 3e 6 , whereas the MSn AGC was 2e 5 , respectively. The MS and MSn injection time was 32 ms; microscans were set at one.…”

“…Mass-spectrometry (MS)-based proteomics offers a highly parallel multiplexed platform that enables the quantification of large numbers of proteins and peptides. This approach has been successfully used to identify protein and peptide signatures that can aid in the diagnosis and prognosis of a wide range of conditions and diseases from urine. − …”

Neurological involvement, immune response, and biomarkers in Kawasaki disease along with its pathogenesis, therapeutic and diagnostic updates

“…Serinehydroxymethyl transferase may be an important hub macromolecule of the KD-specific PPI network. 30 Serum ferritin is understood to be a helpful biomarker for the prediction of IVIGnonresponsive KD, coronary artery abnormalities (CAAs), and macrophage activation syndrome (MAS) tendencies. 31 In a study, carboxyterminal propeptide of procollagen type I (PIPC), soluble suppressor of tumorigenicity II, galectin-3 (Gal-3), and growth-differentiation factor-15 were associated with the late convalescent blood cultures from a group of sixteen KD patients, who had an ejection fraction of less than 55% on their initial echocardiogram test.…”

Urinary N-telopeptide as a Biomarker of Disease Activity in Patients with Chronic Nonbacterial Osteomyelitis Who Have Not Received Bisphosphonates

“…Thus, current data do not support urinary NTx as a sensitive marker for CNO, but it may still have value in tracking disease flares after bisphos-phonate treatment. Other biomarkers using proteomic or metabolomic techniques, such as differentially expressed protein analysis or the analysis of urine metabolic profiles, may prove useful 7,8 .…”