Serum leucine-rich α2-glycoprotein is a useful biomarker for monitoring disease activity in patients with adult-onset Still’s disease

Ha, You Jung; Kang, Eun Jin; Lee, S. W.; Park, Y. B.; Lee, S. K.; Song, Jung Soo; Choi, Sang Tae

doi:10.3109/03009742.2015.1016103

Cited by 21 publications

(15 citation statements)

References 14 publications

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“…Recently, LRG1 has been recognized as a proinflammatory marker and found to be elevated in patients with ulcerative colitis, type 1 diabetes or RA ( 26 – 29 ). A previous study demonstrated that the serum levels of LRG1 were significantly higher in AOSD patients than in RA patients and HC subjects ( 30 ), which was consistent with our results that the urinary levels of LRG1 increased in patients with AOSD compared to those in non-AOSD subjects. Moreover, we demonstrated that the levels of LRG1 were positively correlated with the serum levels of the inflammatory cytokines IL-1β, IL-6, and IL-18 ( Figure 3 ).…”

Section: Discussionsupporting

confidence: 93%

Urinary Proteomics Identifying Novel Biomarkers for the Diagnosis of Adult-Onset Still’s Disease

et al. 2020

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Adult-onset Still's disease (AOSD) is a systemic, multigenic autoinflammatory disease, and the diagnosis of AOSD must rule out neoplasms, infections, and other autoimmune diseases. Development of a rapid and efficient but non-invasive diagnosis method is urgently needed for improving AOSD therapy. In this study, we first performed a urinary proteomic study using isobaric tags for relative and absolute quantification (iTRAQ) labeling combined with liquid chromatography-tandem mass spectrometry analysis in patients with AOSD and healthy control (HC) subjects. The urinary proteins were enriched in pathways of the innate immune system and neutrophil degranulation, and we identified that the α-1-acid glycoprotein 1 (LRG1), orosomucoid 1 (ORM1), and ORM2 proteins were highly expressed in patients with AOSD. The elevated urine levels of LRG1, ORM1, and ORM2 were further validated by enzyme-linked immunosorbent assay in active patients with AOSD, disease controls, and HC subjects. Receiver operating characteristic curves showed that the areas under the curve of LRG1, ORM1, and ORM2 were 0.700, 0.837, and 0.736, respectively (all p < 0.05). Furthermore, we found that the urine levels of LRG1, ORM1, and ORM2 were positively correlated with the systemic score and erythrocyte sedimentation rate and that the urine levels of LRG1 were positively correlated with interleukin 1β (IL-1β), IL-6, and IL-18 levels, whereas the urine levels of ORM1 were positively correlated with the IL-1β level. Together, our study identified novel urinary markers for non-invasive and simple screening of AOSD.

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Section: Discussionsupporting

confidence: 93%

Urinary Proteomics Identifying Novel Biomarkers for the Diagnosis of Adult-Onset Still’s Disease

et al. 2020

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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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“…Increased LRG1 expression was also found in patients undergoing neurodegenerative diseases [ 23 ], acute appendicitis [ 9 ], hydrocephalus [ 24 ], heart failure [ 25 ], autoimmune diseases [ 12 ], and ageing [ 26 ]. LRG1 has also been suggested as promising biomarker in other disease entities, such as Still’s disease [ 27 ] and in peptidomics studies [ 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

LRG1 downregulation in allergic airway disorders and its expression in peripheral blood and tissue cells

Xie

Zhang

et al. 2016

J Transl Med

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BackgroundIncreased leucine-rich α2-glycoprotein-1 (LRG1) has been observed in plasma of individuals with various diseases. However, the role of LRG1 in allergic airway disease has not been investigated.ObjectiveTo explore the involvement of LRG1 in allergy and its cell origins.MethodsThe expression levels of LRG1 and its receptor transforming growth factor-beta receptor II (TGFBR2) in patients with allergic rhinitis (AR) and asthma (AS) were examined by flow cytometry, and enzyme-linked immunosorbent assay (ELISA).ResultsLRG1 and soluble TGFBR2 expression in plasma of patients with AR and AS were markedly lower than that of healthy control (HC) subjects. Large proportions of CD123 + HLA-DR−, CD16+, CD4+, CD8+, CD14+, and CD19+ cells expressed LRG1, although the percentages of LRG1+ cells in these cell populations were lower in AR and AS patients. Up to 89.8 and 15.5 % of dispersed mast cells expressed LRG1 and TGFBR2. Moreover, allergen extract exposure significantly reduced LRG1 and TGFBR2 expression in the plasma and leukocytes of patients with AR and AS.ConclusionsReduced LRG1 and TGFBR2 levels in patients with allergic airway disorders are likely caused by inhibitory actions of allergens in LRG1 producing cells. Thus, LRG1 may be a key regulatory factor of allergic responses.

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Serum leucine-rich α2-glycoprotein is a useful biomarker for monitoring disease activity in patients with adult-onset Still’s disease

Abstract: Serum LRG levels were increased in patients with AOSD and correlated well with disease activity measures. LRG may be a useful biomarker for distinguishing AOSD from RA and for monitoring the disease activity of AOSD.

Cited by 21 publications

References 14 publications

Urinary Proteomics Identifying Novel Biomarkers for the Diagnosis of Adult-Onset Still’s Disease

Urinary Proteomics Identifying Novel Biomarkers for the Diagnosis of Adult-Onset Still’s Disease

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

LRG1 downregulation in allergic airway disorders and its expression in peripheral blood and tissue cells

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