Scientific corner

Targeting neutrophils in inflammatory bowel disease: revisiting the role of adsorptive granulocyte and monocyte apheresis

Giorgos Bamias 1Evanthia Zampeli 2Eugeni Domènech 3 Expert Rev Gastroenterol Hepatol  2022 Jul 19;1-15. doi: 10.1080/17474124.2022.2100759.

Introduction: Inflammatory bowel disease (IBD) is a chronic immune-mediated disease of the gastrointestinal tract comprising Crohn’s disease (CD) and ulcerative colitis (UC). While any part of the digestive tract can be affected in CD, mucosal inflammation in UC is limited to the colon. Differences and similarities between the two conditions are reflected by their pathophysiology. Areas covered: An overview of immunological aspects, pharmacological management, and biomarkers of IBD is provided. The role of adsorptive granulocyte and monocyte apheresis (GMA) is reviewed including its primary and secondary effects on the immune system, as well as clinical studies in IBD (mainly UC), and potential biomarkers for adsorptive GMA. Expert opinion: In UC, adsorptive GMA with Adacolumn (Adacolumn®, JIMRO Co., Ltd. Takasaki, Gunma, Japan) selectively depletes elevated myeloid lineage leukocytes and has a range of beneficial secondary immune effects. Adsorptive GMA is a safe and effective non-pharmacological treatment option for UC. Pilot studies have reported promising results for adsorptive GMA in combination with biological agents, although larger studies are required. Fecal calprotectin concentrations, neutrophil counts in histological samples and/or the neutrophil/lymphocyte ratio in peripheral blood may prove to be useful biomarkers for predicting GMA effectiveness in the future.

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Inflammatory Bowel Disease and Neutrophil–Lymphocyte Ratio: A Systematic Scoping Review

Blake O. Langley 1,Sara E. Guedry 1,Joshua Z. Goldenberg 1,Douglas A. Hanes 1,Jennifer A. Beardsley 2 andJennifer Joan Ryan 1,

The findings of this systematic scoping review highlight the potential utility of NLR as an adjunctive IBD biomarker with broad applications, including differentiation from non-IBD controls, clinical and endoscopic disease activity differentiation, prediction of loss of response to treatment, and prediction of risk of complications. NLR has promise for guiding therapeutic decision making, specifically for predicting loss of response to IFX. In conclusion, NLR is an emerging IBD biomarker with potential utility at nearly every point in IBD management. As a potential IBD biomarker, NLR is particularly advantageous given that it is minimally invasive, economical, and accessible as it is easily calculated from blood count data routinely and serially monitored in patients with IBD. Additional research is justified to better understand if routine observation of NLR in research and clinical practice could beneficially impact the care of patients with IBD.

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Fecal Calprotectin is a Useful Biomarker for Predicting the Clinical Outcome of Granulocyte and Monocyte Adsorptive Apheresis in Ulcerative Colitis Patients: A Prospective Observation Study

Nobuhiro Ueno, Yuya Sugiyama, Yu Kobayashi, Yuki Murakami et al DOI:

In summary, we demonstrated the utility of FC as a biomarker for assessing ER after GMA and predicting CR at the early phase during GMA in patients with active UC. Assessing the baseline characteristics alone before GMA was not sufficient to predict CR. Our findings will benefit patients with active UC by allowing them to avoid undergoing unnecessary invasive procedures and will help establish new GMA therapeutic strategies.

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Novel Prognostic Biomarkers of Mucosal Healing in Ulcerative Colitis Patients Treated With Anti-TNF: Neutrophil-toLymphocyte Ratio and Platelet-to-Lymphocyte Ratio

Lorenzo Bertani 1Federico Rossari 2Brigida Barberio 3Maria Giulia Demarzo 4Gherardo Tapete 1Eleonora Albano 1Giovanni Baiano Svizzero 1Linda Ceccarelli 5Maria Gloria Mumolo 5Chiara Brombin 6Nicola de Bortoli 1Massimo Bellini 1Santino Marchi 1Giorgia Bodini 4Edoardo Savarino 3Francesco Costa 5

Inflamm Bowel Dis. 2020 Sep 18;26(10):1579-1587. doi: 10.1093/ibd/izaa062.

Background: Anti-tumor necrosis factor drugs (anti-TNFs) are widely used for the treatment of ulcerative colitis (UC). However, many patients experience loss of response during the first year of therapy. An early predictor of clinical remission and mucosal healing is needed. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are markers of subclinical inflammation poorly evaluated in UC patients treated with anti-TNFs. The aim of this multicenter study was to evaluate whether NLR and PLR could be used as prognostic markers of anti-TNF treatment response. Methods: Patients with UC who started anti-TNF treatment in monotherapy were evaluated. Patients with concomitant corticosteroid treatment ≥20 mg were excluded. We calculated NLR, PLR, and fecal calprotectin before treatment and after induction. The values of NLR and PLR were correlated with clinical remission and mucosal healing at the end of follow-up (54 weeks) using the Mann-Whitney U test and then multivariate analysis was conducted. Results: Eighty-eight patients were included. Patients who reached mucosal healing after 54 weeks of therapy displayed lower levels of both baseline NLR and PLR (P = 0.0001 and P = 0.04, respectively); similar results were obtained at week 8 (P = 0.0001 and P = 0.001, respectively). Patients who presented with active ulcers at baseline endoscopic evaluation had higher baseline NLR and PLR values compared with those without detected ulcers (P = 0.002 and P = 0.0007, respectively). Conclusions: Both NLR and PLR showed a promising role as early predictors of therapeutic response to anti-TNF therapy in UC patients. If confirmed in larger studies, classification and regression trees proposed in this article could be useful to guide clinical decisions regarding anti-TNF treatment.

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P614 The utility as a biomarker of faecal calprotectin for predicting the clinical outcome of granulocyte and monocyte adsorptive apheresis treatment in patients with ulcerative colitis

N UenoY MurakamiT IwamaT SasakiT KunogiK TakahashiK TanakaK AndoS KashimaY InabaK MoriichiH TanabeM TaruishiM FujiyaT Okumura, Journal of Crohn’s and Colitis, Volume 13, Issue Supplement_1, March 2019

Fcal is considered to be a useful and objective predictor of the efficacy of GMA treatment in UC patients and superior to symptomatic scores and blood parameters

Scientific corner

Faecal lactoferrin is a useful biomarker for mucosal healing in patients with ulcerative colitis during granulocyte and monocyte adsorptive apheresis therapy.

T Sagawa 1S Kakizaki 1T Tomizawa 1T Nakayama 1H Tanaka 1H Tojima 1K Sato 1M Kusano 2S Okamura 3M Yamada 1,Colorectal Dis. 2016 Jul;18(7):696-702. 

The faecal lactoferrin level is a useful biomarker of the mucosal findings in ulcerative colitis. Although endoscopy is the gold standard, the faecal lactoferrin level can be used as a biomarker during GMA therapy in patients with ulcerative colitis.

Scientific corner

Advantages of Fecal Lactoferrin Measurement during Granulocyte and Monocyte Adsorptive Apheresis Therapy in Ulcerative Colitis.

Keiichi Hashiguchi 1Fuminao TakeshimaYuko AkazawaKayoko MatsushimaHitomi MinamiHaruhisa MachidaNaoyuki YamaguchiKen ShiozawaKazuo OhbaKen OhnitaTatsuki IchikawaHajime IsomotoKazuhiko Nakao, Digestion. 2015;91(3):208-17.

Background: Fecal lactoferrin has been introduced as a useful tool for the diagnosis and monitoring of inflammatory bowel disease (IBD). The aim of this study was to assess if fecal lactoferrin can be employed to predict or estimate the effect of granulocyte and monocyte adsorptive apheresis (GMA) in ulcerative colitis (UC). Methods: This was a prospective study involving 21 patients with UC. Patients with moderately-to-severely active UC who were scheduled to undergo GMA were recruited. Changes in fecal lactoferrin concentration were compared between the GMA-responder and -nonresponder groups. Results: In the GMA-responder group, fecal lactoferrin significantly increased 1 week after the introduction of GMA and then significantly decreased after GMA sessions. Fecal lactoferrin concentrations were significantly higher in the GMA-responder group than in the GMA-nonresponder group at 1 and 2 weeks after the introduction of GMA. Multivariate logistic regression analysis revealed that fecal lactoferrin concentration 1 week after the introduction of GMA was the most contributing factor for the effectiveness of GMA in patients with UC. Conclusions: In the GMA-responder group, fecal lactoferrin concentration significantly increased 1 week after the introduction of GMA. Fecal lactoferrin may be beneficial for predicting clinical response of GMA in patients with UC at an early stage of GMA treatment.

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