Leucine-rich Alpha-2 Glycoprotein As a Marker of Mucosal Healing in Inflammatory Bowel Disease

Overview

Journal Sci Rep

Specialty Science

Date 2021 May 28

PMID 34045529

Citations 33

Authors

Eriko Yasutomi

Toshihiro Inokuchi

Sakiko Hiraoka

Kensuke Takei

Shoko Igawa

Shumpei Yamamoto

Masayasu Ohmori

Shohei Oka

Yasushi Yamasaki

Hideaki Kinugasa

Masahiro Takahara

Keita Harada

Masaki Furukawa

Kouichi Itoshima

Ken Okada

Fumio Otsuka

Takehiro Tanaka

Toshiharu Mitsuhashi

Jun Kato

Hiroyuki Okada

Affiliations

Soon will be listed here.

Abstract

Leucine-rich alpha-2 glycoprotein (LRG) may be a novel serum biomarker for patients with inflammatory bowel disease. The association of LRG with the endoscopic activity and predictability of mucosal healing (MH) was determined and compared with those of C-reactive protein (CRP) and fecal markers (fecal immunochemical test [FIT] and fecal calprotectin [Fcal]) in 166 ulcerative colitis (UC) and 56 Crohn's disease (CD) patients. In UC, LRG was correlated with the endoscopic activity and could predict MH, but the performance was not superior to that of fecal markers (areas under the curve [AUCs] for predicting MH: LRG: 0.61, CRP: 0.59, FIT: 0.75, and Fcal: 0.72). In CD, the performance of LRG was equivalent to that of CRP and Fcal (AUCs for predicting MH: LRG: 0.82, CRP: 0.82, FIT: 0.70, and Fcal: 0.88). LRG was able to discriminate patients with MH from those with endoscopic activity among UC and CD patients with normal CRP levels. LRG was associated with endoscopic activity and could predict MH in both UC and CD patients. It may be particularly useful in CD.

Citing Articles

Leucine-rich alpha-2 glycoprotein as a superior biomarker to C-reactive protein for detecting small bowel lesions in Crohn's disease.

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Diagnostic accuracy and cut-off values of serum leucine-rich alpha-2 glycoprotein for Crohn's disease activity in the small bowel.

Okita M, Takenaka K, Hirai F, Ashizuka S, Iijima H, Bamba S J Gastroenterol. 2025; .

PMID: 39953247 DOI: 10.1007/s00535-025-02223-1.

Changes of leucine-rich alpha 2 glycoprotein could be a marker of changes of endoscopic and histologic activity of ulcerative colitis.

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References

Singh S, Feuerstein J, Binion D, Tremaine W . AGA Technical Review on the Management of Mild-to-Moderate Ulcerative Colitis. Gastroenterology. 2018; 156(3):769-808.e29. PMC: 6858923. DOI: 10.1053/j.gastro.2018.12.008. View

Feld L, Glick L, Cifu A . Diagnosis and Management of Crohn Disease. JAMA. 2019; 321(18):1822-1823. DOI: 10.1001/jama.2019.3684. View

Ballou S, Kushner I . C-reactive protein and the acute phase response. Adv Intern Med. 1992; 37:313-36. View

Hosomi S, Yamagami H, Itani S, Yukawa T, Otani K, Nagami Y . Sepsis Markers Soluble IL-2 Receptor and Soluble CD14 Subtype as Potential Biomarkers for Complete Mucosal Healing in Patients With Inflammatory Bowel Disease. J Crohns Colitis. 2017; 12(1):87-95. DOI: 10.1093/ecco-jcc/jjx124. View

Kawashima K, Ishihara S, Yuki T, Fukuba N, Sonoyama H, Kazumori H . Fecal Calprotectin More Accurately Predicts Endoscopic Remission of Crohn's Disease than Serological Biomarkers Evaluated Using Balloon-assisted Enteroscopy. Inflamm Bowel Dis. 2017; 23(11):2027-2034. DOI: 10.1097/MIB.0000000000001202. View

Mosli M, Zou G, Garg S, Feagan S, MacDonald J, Chande N . C-Reactive Protein, Fecal Calprotectin, and Stool Lactoferrin for Detection of Endoscopic Activity in Symptomatic Inflammatory Bowel Disease Patients: A Systematic Review and Meta-Analysis. Am J Gastroenterol. 2015; 110(6):802-19. DOI: 10.1038/ajg.2015.120. View

Langhorst J, Elsenbruch S, Koelzer J, Rueffer A, Michalsen A, Dobos G . Noninvasive markers in the assessment of intestinal inflammation in inflammatory bowel diseases: performance of fecal lactoferrin, calprotectin, and PMN-elastase, CRP, and clinical indices. Am J Gastroenterol. 2007; 103(1):162-9. DOI: 10.1111/j.1572-0241.2007.01556.x. View

Schoepfer A, Beglinger C, Straumann A, Trummler M, Renzulli P, Seibold F . Ulcerative colitis: correlation of the Rachmilewitz endoscopic activity index with fecal calprotectin, clinical activity, C-reactive protein, and blood leukocytes. Inflamm Bowel Dis. 2009; 15(12):1851-8. DOI: 10.1002/ibd.20986. View

Schoepfer A, Beglinger C, Straumann A, Trummler M, Vavricka S, Bruegger L . Fecal calprotectin correlates more closely with the Simple Endoscopic Score for Crohn's disease (SES-CD) than CRP, blood leukocytes, and the CDAI. Am J Gastroenterol. 2009; 105(1):162-9. DOI: 10.1038/ajg.2009.545. View

10.

Ma C, Lumb R, Walker E, Foshaug R, Dang T, Verma S . Noninvasive Fecal Immunochemical Testing and Fecal Calprotectin Predict Mucosal Healing in Inflammatory Bowel Disease: A Prospective Cohort Study. Inflamm Bowel Dis. 2017; 23(9):1643-1649. DOI: 10.1097/MIB.0000000000001173. View

11.

Hiraoka S, Inokuchi T, Nakarai A, Takashima S, Takei D, Sugihara Y . Fecal Immunochemical Test and Fecal Calprotectin Results Show Different Profiles in Disease Monitoring for Ulcerative Colitis. Gut Liver. 2017; 12(2):142-148. PMC: 5832338. DOI: 10.5009/gnl17013. View

12.

Walsh A, Kormilitzin A, Hinds C, Sexton V, Brain O, Keshav S . Defining Faecal Calprotectin Thresholds as a Surrogate for Endoscopic and Histological Disease Activity in Ulcerative Colitis-a Prospective Analysis. J Crohns Colitis. 2018; 13(4):424-430. DOI: 10.1093/ecco-jcc/jjy184. View

13.

Hiraoka S, Takashima S, Inokuchi T, Nakarai A, Takahara M, Harada K . The novel latex agglutination turbidimetric immunoassay system for simultaneous measurements of calprotectin and hemoglobin in feces. Intest Res. 2018; 17(2):202-209. PMC: 6505093. DOI: 10.5217/ir.2018.00086. View

14.

Inokuchi T, Kato J, Hiraoka S, Takashima S, Nakarai A, Takei D . Fecal Immunochemical Test Versus Fecal Calprotectin for Prediction of Mucosal Healing in Crohn's Disease. Inflamm Bowel Dis. 2016; 22(5):1078-85. DOI: 10.1097/MIB.0000000000000728. View

15.

Arai T, Takeuchi K, Miyamura M, Ishikawa R, Yamada A, Katsumata M . Level of Fecal Calprotectin Correlates With Severity of Small Bowel Crohn's Disease, Measured by Balloon-assisted Enteroscopy and Computed Tomography Enterography. Clin Gastroenterol Hepatol. 2016; 15(1):56-62. DOI: 10.1016/j.cgh.2016.08.015. View

16.

Nakarai A, Kato J, Hiraoka S, Kuriyama M, Akita M, Hirakawa T . Evaluation of mucosal healing of ulcerative colitis by a quantitative fecal immunochemical test. Am J Gastroenterol. 2012; 108(1):83-9. DOI: 10.1038/ajg.2012.315. View

17.

Naka T, Fujimoto M . LRG is a novel inflammatory marker clinically useful for the evaluation of disease activity in rheumatoid arthritis and inflammatory bowel disease. Immunol Med. 2019; 41(2):62-67. DOI: 10.1080/13497413.2018.1481582. View

18.

Fujimoto M, Serada S, Suzuki K, Nishikawa A, Ogata A, Nanki T . Leucine-rich α2 -glycoprotein as a potential biomarker for joint inflammation during anti-interleukin-6 biologic therapy in rheumatoid arthritis. Arthritis Rheumatol. 2015; 67(8):2056-60. DOI: 10.1002/art.39164. View

19.

Serada S, Fujimoto M, Ogata A, Terabe F, Hirano T, Iijima H . iTRAQ-based proteomic identification of leucine-rich alpha-2 glycoprotein as a novel inflammatory biomarker in autoimmune diseases. Ann Rheum Dis. 2009; 69(4):770-4. DOI: 10.1136/ard.2009.118919. View

20.

Serada S, Fujimoto M, Terabe F, Iijima H, Shinzaki S, Matsuzaki S . Serum leucine-rich alpha-2 glycoprotein is a disease activity biomarker in ulcerative colitis. Inflamm Bowel Dis. 2012; 18(11):2169-79. DOI: 10.1002/ibd.22936. View