Identification of candidate diagnostic serum biomarkers for Kawasaki disease using proteomic analysis

Kimura, Yayoi; Yanagimachi, Masakatsu; Ino, Yoko; Aketagawa, Mao; Matsuo, M.; Okayama, Akira; Shimizu, Hiroyuki; Oba, Kunihiro; Morioka, Ichiro; Imagawa, Tomoyuki; Kaneko, Tetsuji; Yokota, Shumpei; Hirano, Hisashi; Mori, Masaaki

doi:10.1038/srep43732

Cited by 50 publications

(39 citation statements)

References 33 publications

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“…We originally identified LRG as an inflammatory biomarker for autoimmune diseases such as rheumatoid arthritis and inflammatory bowel disease (IBD) 9 . Subsequent studies from our group and others have shown that LRG is increased in various immune-related diseases such as adult-onset Still's disease 19 , psoriasis 20 , juvenile idiopathic arthritis 21 , Kawasaki disease 22 , appendicitis 23 and cancers 24,25 , indicating that LRG elevation is not limited to autoimmune diseases. In addition, LRG may serve as a biomarker for several other disease conditions such as heart failure 26 , diabetes-related complications [27][28][29] and obesity 30 , which are not typical inflammatory www.nature.com/scientificreports www.nature.com/scientificreports/ diseases but may involve immunopathogenic mechanisms.…”

Section: Discussionmentioning

confidence: 89%

Leucine-rich alpha 2 glycoprotein is a new marker for active disease of tuberculosis

Fujimoto

Matsumoto

Serada

et al. 2020

Sci Rep

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Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is a global health problem. At present, prior exposure to Mtb can be determined by blood-based interferon-gamma release assay (IGRA), but active TB is not always detectable by blood tests such as CRP and ESR. This study was undertaken to investigate whether leucine-rich alpha-2 glycoprotein (LRG), a new inflammatory biomarker, could be used to assess active disease of TB. Cynomolgus macaques pretreated with or without Bacille Calmette-Guerin (BCG) vaccination were inoculated with Mtb to induce active TB. Blood was collected over time from these animals and levels of LRG as well as CRP and ESR were quantified. In the macaques without BCG vaccination, Mtb inoculation caused extensive TB and significantly increased plasma CRP and LRG levels, but not ESR. In the macaques with BCG vaccination, whereas Mtb challenge caused pulmonary TB, only LRG levels were significantly elevated. By immunohistochemical analysis of the lung, LRG was visualized in epithelioid cells and giant cells of the granulation tissue. In humans, serum LRG levels in TB patients were significantly higher than those in healthy controls and declined one month after anti-tubercular therapy. These findings suggest that LRG is a promising biomarker when performed following IGRA for the detection of active TB. Tuberculosis (TB) is a symptomatic disease caused by replicating Mycobacterium tuberculosis (Mtb). According to the WHO global tuberculosis report 2018 (https://www.who.int/tb/publications/global_report/en/), about 23% of the world's population is estimated to be latently infected with Mtb, Of these, up to 10% of humans develop active disease after Mtb infection 1 , which makes TB a major global health problem with the estimation of 10.4 million new cases and 1.7 million deaths in 2016 2. Importantly, 40% of estimated TB cases remain to be undiagnosed 2. Rapid detection of active TB is critical to reduce TB-related death. Recently-introduced interferon gamma release assay (IGRA) has better specificity than tuberculin skin test (TST) in TB screening and now become the standard for the identification of Mtb sensitization 1. Nevertheless, IGRA does not differentiate between active TB and resolved/latent infection 3. At present, sputum smear or culture of Mtb is still a gold standard for diagnosis of active TB. In addition, sputum culture is also a major biomarker for the evaluation of treatment 1,4,5. However, sputum test is assessable only when sputa of good quality were obtained from patients. Accordingly, sputum test is unavailable for infants with TB and patients with extrapulmonary tuberculosis. In addition, sputum test is not always available in resource-poor settings. Moreover, the sputum culture is not suitable for rapid decision making during therapy of outpatients, given that it requires long time before obtaining results 1. To detect Mtb in sputa in a rapid turnaround time, molecular diagnostics such as the GeneXpert MTB/RIF assay may be applicable 5. Nevertheless, this assay is ex...

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Section: Discussionmentioning

confidence: 89%

Leucine-rich alpha 2 glycoprotein is a new marker for active disease of tuberculosis

Fujimoto

Matsumoto

Serada

et al. 2020

Sci Rep

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“…However, none of them has been validated for clinical use. 60,61 Thus, more research is needed to identify a potential biomarker for KD that can be used in clinical practice.…”

Section: Biomarkers In Kdmentioning

confidence: 99%

Diagnosis of Kawasaki disease

2017

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Kawasaki disease (KD) is a medium vessel vasculitis with predilection for coronary arteries. Due to lack of a reliable confirmatory laboratory test, the diagnosis of KD is based on a constellation of clinical findings that appear in a typical temporal sequence. These diagnostic criteria have been modified from time to time and the most recent guidelines have been proposed by the American Heart Association (AHA) in 2017. However, several children may have incomplete or atypical forms of KD and the diagnosis can often be difficult, especially in infants and young children. In this review, we have detailed the steps involved in arriving at a diagnosis of KD and also highlight the important role of echocardiography in diagnosis and management of children with KD.

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“…Previous studies have focused on cytokines and chemokines during acute KD. However, these proteins are relatively non-specific and are elevated in many inflammatory processes ( 21 , 22 ).…”

Section: Introductionmentioning

confidence: 99%

Elevated Levels of Pentraxin 3 Correlate With Neutrophilia and Coronary Artery Dilation During Acute Kawasaki Disease

et al. 2020

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Kawasaki disease (KD) is the leading cause of acquired pediatric heart disease in the developed world as 25–30% of untreated patients and at least 5% of treated patients will develop irreversible coronary artery lesions (CAL). Pentraxin-3 (PTX-3) has been well-studied in inflammatory diseases, particularly in cardiovascular diseases associated with vascular endothelial dysfunction. We hypothesized that PTX-3 plays an important role in the development of KD-associated CAL and investigated the circulating levels of PTX-3 in the serum of KD patients. Children with acute KD were followed from diagnosis through normalization of the clinical parameters of inflammation (convalescent phase). Serum samples were obtained and echocardiograms were conducted at several phases of the illness: acute [prior to intravenous immunoglobulin (IVIG) treatment], sub-acute (5–10 days after IVIG treatment), and convalescent (1–4 months after KD diagnosis). Seventy children were included in the final cohort of the study, of whom 26 (37%) presented with CAL and 18 (26%) developed IVIG resistance. The patients included in this study came from diverse ethnic backgrounds, mostly with mixed ancestry/ ethnicity. Significantly increased PTX-3 levels were observed during the acute phase of KD compared to the sub-acute and the convalescent phases. The PTX-3 levels during acute KD were significantly higher among KD patients with CAL compared to patients with normal coronary arteries (NCA). Also, the PTX-3 levels were significantly higher in patients with IVIG resistance. Furthermore, the PTX-3 levels were significantly higher in IVIG-resistant KD patients with CAL as compared to the NCA group. Moreover, the PTX-3 levels were significantly correlated to coronary artery z-score during acute KD and to neutrophil counts throughout KD progression regardless of coronary artery z-score. Elevated PTX-3 levels correlated to elevated neutrophil counts, a known source of PTX-3 in acute inflammation and an important player in the development of KD vasculitis. We, therefore, suggest PTX-3 as a novel factor in the development of KD-associated CAL and propose neutrophil-derived PTX-3 as contributing to KD vascular dysfunction.

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Identification of candidate diagnostic serum biomarkers for Kawasaki disease using proteomic analysis

Cited by 50 publications

References 33 publications

Leucine-rich alpha 2 glycoprotein is a new marker for active disease of tuberculosis

Leucine-rich alpha 2 glycoprotein is a new marker for active disease of tuberculosis

Diagnosis of Kawasaki disease

Elevated Levels of Pentraxin 3 Correlate With Neutrophilia and Coronary Artery Dilation During Acute Kawasaki Disease

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