Editorial: Leucine-Rich Alpha-2 Glycoprotein Is Associated With Transmural Inflammation Assessed by Intestinal Ultrasound in Patients With Crohn's Disease: Its Potential in Early-Stage Disease—Authors' Reply

Abstract

We greatly appreciate the insightful editorial by Drs. Mitchell and Swaminathan [1] discussing the utility of leucine-rich alpha-2 glycoprotein (LRG) as a non-invasive biomarker for assessing transmural inflammation in Crohn's disease (CD) determined by intestinal ultrasound (IUS) [2].

Our findings enhance the discussion by focusing on patients with early-stage CD. Among patients with disease duration of ≤ 1 year (26 IUS examinations) [3], LRG showed significant correlations with all evaluated IUS scores (Spearman's rank correlation coefficients [r_s], p < 0.05) with r_s values exceeding those observed in the overall study population (Table 1) [2]. The area under the curve was also numerically higher than that of overall study population (0.75, 0.85, 0.90, 0.84 and 0.85 for bowel wall thickness, Limberg score, Bowel Ultrasound Score, International Bowel Ultrasound Segmental Activity Score and Simple Ultrasound Score for Crohn's Disease, respectively). These results highlight that LRG can be an effective and even more accurate biomarker, in the early stages of CD, extending its utility beyond the median disease duration of 10 years, as described in our study [2]. This early correlation may have notable clinical implications. First, it underscores the potential of LRG to enable timely therapeutic interventions in patients newly diagnosed with CD, a critical period for preventing disease progression. Second, it emphasises LRG's role as a complementary biomarker to IUS, particularly when there is limited access to specialised imaging modalities. However, given the small sample size in this particular patient population, further studies are warranted.

To further explore the clinical relevance of LRG, we examined its association with surgical outcomes. Among 97 patients, seven underwent surgery within 1 year, and 12 during the observation period (days until surgery 1–1581). Comparison of the surgery and non-surgery groups revealed numerically higher LRG in the surgery group (20.4 vs. 17.6 μg/mL, p = 0.058), suggesting that higher LRG values may be associated with a higher risk of surgery, probably reflecting transmural inflammation. However, the predictive value was not statistically significant, due presumably to the limited sample size and the predominantly quiescent status of the patients. In addition, our preliminary analyses suggest that LRG may also be useful for predicting other adverse outcomes, such as treatment intensification and CD-related hospitalisations, when combined with IUS (manuscript under preparation), highlighting its potential utility in the context of a treat-to-target approach.

In conclusion, our findings suggest that LRG could serve as a valuable tool in managing CD, particularly in patients with short disease duration. Its good correlation with IUS scores and superior performance compared with C-reactive protein highlights its potential to enable timely therapeutic interventions during the critical early stages of disease progression. Further studies are warranted to explore its predictive power and combination with IUS to enhance clinical decision-making.

Moeko Komatsu: writing – original draft, conceptualization, data curation, formal analysis. Shintaro Sagami: conceptualization, writing – original draft. Taku Kobayashi: writing – original draft, conceptualization.

Moeko Komatsu has served as a speaker for AbbVie.Shintaro Sagami has served as a speaker for AbbVie, Eli Lilly, Janssen Pharmaceutical K.K., Gilead Sciences Inc., JIMRO Co. Ltd., KISSEI Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corporation, EA Pharma Co., Takeda Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd., and Zeria Pharmaceutical Co. Ltd., He has also held endowed chairs sponsored by AbbVie; JIMRO Co. Ltd., Zeria Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Mochida Pharmaceutical Co. Ltd., and EA Pharma Co. Ltd., and has received research grants from Bristol-Myers Squibb. Taku Kobayashi served as an advisory board member, consultant, or speaker for AbbVie, Activaid, Alfresa Pharma, Alimentiv, Bristol Myers Squibb, Celltrion, Covidien, EA Pharma, Eli Lilly, Ferring Pharmaceuticals, Galapagos, Gilead Sciences, Janssen Pharmaceuticals, JIMRO, Kissei Pharmaceutical, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Takeda, and Zeria Pharmaceutical, and has received research funding from AbbVie, Alfresa Pharma, EA Pharma, Gilead Sciences, Kyorin Pharmaceutical, Mochida Pharmaceutical, Nippon Kayaku, Otsuka Holdings, Pfizer, Sekisui Medical, Takeda, and Zeria Pharmaceutical. None of the funding received for this work was from any of the above organizations.

Guarantor of the article: Taku Kobayashi.

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.18463.