Editorial: Leucine-Rich Alpha-2 Glycoprotein Is Associated With Transmural Inflammation Assessed by Intestinal Ultrasound in Patients With Crohn's Disease

Abstract

In the era of ‘treat-to-target’ management of inflammatory bowel disease (IBD), non-invasive methods of disease assessment are increasingly utilised [1]. The rising incidence of IBD in newly industrialised countries poses additional challenges where access to ‘traditional’ methods of disease assessment, such as ileocolonoscopy, is more limited due to resource constraints [2]. Intestinal ultrasound (IUS) provides a real-time assessment of transmural inflammation and is useful for proactive and reactive monitoring of IBD [3-5]. Despite this, IUS is limited by inter-operator variability, the need for specialised training, and relatively limited worldwide availability [5]. Existing biomarkers such as C-reactive protein (CRP) and faecal calprotectin are often used with or without IUS [3] but these markers either lack sensitivity/specificity for active IBD or are limited by patient acceptability (e.g., for collection of faecal samples). Leucine-rich alpha-2 glycoprotein (LRG) is an alternative serum biomarker that is a predictor of both clinical and endoscopic activity in patients with Crohn's disease (CD) [6, 7].

Komatsu et al. [8] have expanded on existing evidence for LRG and have investigated it as a potential alternative to IUS in assessing transmural inflammation in CD. This single-centre, retrospective analysis of 97 patients and 213 IUS studies assessed the correlations between LRG and CRP with five validated IUS scores of CD activity. LRG was a significantly superior predictor of CD activity in most IUS indices when compared with CRP and the Crohn's Disease Activity Index, in all patients, and those in clinical remission. These findings are consistent with a similar study by Takenaka et al. [9] which evaluated the correlation between LRG and magnetic resonance enterography in CD.

The findings by Komatsu et al. [8] have promoted LRG as a feasible method of proactively assessing CD activity in patients who are clinically well. This allows for more timely healthcare interventions for individuals with ‘silent CD’ who have clinically quiescent disease but have an ongoing inflammatory burden and are at increased risk for adverse long-term health outcomes [10].

Despite the potential benefits of LRG as a biomarker in CD, several questions remain unanswered. The utility of LRG in individuals earlier in their disease course compared with a median disease duration of 10 years in this study by Komatsu et al. [8] is unclear. Furthermore, the associations of LRG with longitudinal CD outcomes, such as incident strictures or penetrating complications, hospitalisations, need for IBD surgery, and disability need closer interrogation. The utility of combining LRG with IUS in assessing such longer term health outcomes also requires assessment. LRG remains a relatively under-utilised biomarker worldwide. Further investigation of its accuracy in different ethnicities and regions, along with cost-effectiveness analyses in high- and low-income countries, will help to strengthen its position in the armamentarium of tools to assess IBD.

In conclusion, LRG correlates well with IUS findings in patients with CD and could become a useful biomarker for proactive monitoring of transmural inflammation in IBD.

Anna Mitchell: conceptualization, writing – original draft, writing – review and editing. Akhilesh Swaminathan: conceptualization, writing – original draft, writing – review and editing.

A.S. has received honoraria for educational activities from Janssen and Celltrion (unrelated to this manuscript).

This article is linked to Komatsu et al papers. To view these articles, visit https://doi.org/10.1111/apt.18430 and https://doi.org/10.1111/apt.18493.