Evaluation of Serum Leucine-Rich Alpha-2 Glycoprotein as a New Inflammatory Biomarker of Inflammatory Bowel Disease.

Tetsuhiro Yoshimura,Atsushi Mori,Kotaro Kuwaki,Keiichi Mitsuyama,Shuhei Fukunaga,Toshihiro Araki,Hidetoshi Takedatsu,Takuji Torimura,Hiroshi Yamasaki,Ryosuke Sakemi,Masaru Morita,Shinichiro Yoshioka,Kozo Tsuruta,Tânia Silvia Fröde

doi:10.1155/2021/8825374

Abstract

Studies on serum leucine-rich alpha-2 glycoprotein (LRG) in inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are scarce; the methods for estimating disease activity are less established, particularly for CD. This study is aimed at evaluating the utility of serum LRG as a potential inflammatory marker for IBD and to investigate the LRG gene expression in peripheral blood mononuclear cells (PBMCs) as a possible source of serum LRG. Overall, 98 patients with UC and 96 patients with CD were prospectively enrolled and clinically evaluated; 92 age-matched individuals served as the healthy controls. The blood samples were analyzed for serum LRG levels and routine laboratory parameters. Disease activity was assessed clinically and endoscopically. Finally, LRG gene expression in the PBMCs from a different cohort (41 patients with UC, 34 patients with CD, and 30 healthy controls) was examined. The serum LRG levels were higher during active disease than during inactive disease; additionally, serum LRG levels were positively correlated with clinical disease activity, C-reactive protein (CRP) levels, and other laboratory parameters in patients with UC and CD and with endoscopic disease activity in UC. UC and CD showed comparable areas under the curve (AUC) values for determining clinical remission and differentiating between endoscopic remission associated with LRG and CRP. The levels of LRG mRNA were also increased in PBMCs from patients with UC and CD and reflected disease activity. These data suggest that serum LRG, originated partially from PBMCs, is an inflammatory marker in UC and CD. A large-scale well-designed study should be conducted in the future to more accurately reveal the clinical significance of LRG in patients with IBD.

Highlights

Inflammatory bowel diseases (IBD), consisting of ulcerative colitis (UC) and Crohn’s disease (CD), are chronic disorders involving the gastrointestinal tract
Given the potential role of leucine-rich alpha-2 glycoprotein (LRG) as a biomarker for clinical and endoscopic disease activity in UC, we further investigated its diagnostic accuracy for detecting endoscopic remission and found that the areas under the curve (AUC) was similar for LRG and C-reactive protein (CRP), which differed from previous findings that showed a higher AUC for LRG than for CRP [20], the diagnostic criteria of endoscopic remission were different
We demonstrated for the first time that LRG gene expression in peripheral blood mononuclear cells (PBMCs) from UC and CD is increased and reflects the clinical disease activity, indicating that increased serum LRG observed in IBD is at least in part originating from PBMCs

Summary

Introduction

Inflammatory bowel diseases (IBD), consisting of ulcerative colitis (UC) and Crohn’s disease (CD), are chronic disorders involving the gastrointestinal tract. The infiltration and activation of inflammatory cells, and the production of a wide range of mediators, play significant roles in IBD [1, 2]. A reliable surrogate marker capable of mirroring intestinal inflammation and serving as a substitute for endoscopy is required. Blood-based biomarkers typically provide a noninvasive estimation of the inflammatory burden in IBD. Relatively few blood-based biomarkers have been extensively validated in IBD, and fewer still are in routine use in the clinical setting [2,3,4,5].

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