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

Bertani, Lorenzo; Rossari, Federico; Barberio, Brigida; Demarzo, Maria Giulia; Tapete, G.; Albano, Eleonora Cavalcante; Svizzero, G. Baiano; Ceccarelli, L.; Mumolo, M.G.; Brombin, Chiara; Bortoli, Nicola de; Bellini, Massimo; Marchi, Santino; Bodini, Giorgia; Savarino, Edoardo; Costa, Francesco

doi:10.1093/ibd/izaa062

Cited by 47 publications

(45 citation statements)

References 37 publications

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“…This might explain the slightly higher NLRs (calculated as the ratio of both variables) in dogs with CE compared to people. 1,5 Further, it suggests species-specific differences in leukogram changes. However, interleukin-8 (the primary regulator of neutrophil responses and recruitment 4 ) is not dysregulated in canine CE.…”

Section: Discussionmentioning

confidence: 99%

Blood neutrophil-to-lymphocyte ratio (NLR) as a diagnostic marker in dogs with chronic enteropathy

Becher¹,

Suchodolski

Steiner

et al. 2021

J VET Diagn Invest

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Few routinely available biomarkers are clinically useful in assessing dogs with chronic enteropathy (CE) and aid in CE subclassification. The diagnostic potential of the blood neutrophil-to-lymphocyte ratio (NLR) has not been evaluated in canine CE. We evaluated the NLR in 93 dogs with CE (no steroid treatment for ≥2 wk prior) and tested for an association with clinical, clinicopathologic, and histologic characteristics and also with CE subclassification. NLR was significantly higher in CE dogs with severe clinical disease than dogs with mild clinical disease ( p = 0.047). Hypoalbuminemia ( p < 0.001), but not hypocobalaminemia, was associated with higher NLRs. NLR was correlated with fecal alpha1-proteinase inhibitor concentrations (ρ = 0.47) and the serum-to-fecal alpha1-proteinase inhibitor ratio (ρ = –0.48; both p < 0.001) but not with serum or fecal inflammatory markers nor with the overall histologic score (all p > 0.05). Dogs with steroid- or other immunosuppressant-responsive (IRE) or nonresponsive enteropathy (NRE) had significantly higher NLRs (median: 7.3) than dogs with food-responsive enteropathy (FRE; median: 3.0; p = 0.003), and a NLR ≥5.5 best distinguished both groups of dogs. No difference in NLR was detected between dogs with IRE and dogs diagnosed with NRE. These findings suggest that leukogram changes (i.e., NLR) could be clinically useful in canine CE, and that neutrophils might play a role in the systemic inflammatory response associated with canine CE. The NLR can be easily assessed on routine hematology and can potentially aid in the subclassification of dogs with CE based on the response to treatment.

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Section: Discussionmentioning

confidence: 99%

Blood neutrophil-to-lymphocyte ratio (NLR) as a diagnostic marker in dogs with chronic enteropathy

Becher¹,

Suchodolski

Steiner

et al. 2021

J VET Diagn Invest

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“…Similarly, in a Korean study, PLR among patients with severe UC was higher than that in patients with mild to moderate UC [ 21 ]. In an Italian study of 88 UC patients who started anti-TNF monotherapy, PLR was a useful prognostic biomarker of mucosal healing [ 22 ]. Platelet count and PLR might be cost-effective and easy-to-validate parameters for optimal treatment modality.…”

Section: Discussionmentioning

confidence: 99%

Association between platelet count and mucosal healing in Japanese patients with ulcerative colitis: a cross-sectional study

et al. 2020

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Background Mucosal healing (MH) has been indicated as the therapeutic goal for ulcerative colitis (UC). Platelet count is known as an inflammation evaluation. However, the association between platelet count and MH among patients with UC is still scarce. We therefore assessed this issue among Japanese patients with UC. Methods The study subjects consisted of 345 Japanese patients with UC. Platelet count was divided into quartiles on the basis of the distribution of all study subjects (low, moderate, high, and very high). Several endoscope specialists were responsible for evaluating MH and partial MH, which was defined as a Mayo endoscopic subscore of 0 and 0–1, respectively. Estimations of crude odds ratios (ORs) and their 95% confidence intervals (CIs) for partial MH and MH in relation to platelet count were performed using logistic regression analysis. Age, sex, CRP, steroid use, and anti-Tumor necrosis factor α (TNFα) preparation were selected a priori as potential confounding factors. Results The percentage of partial MH and MH were 63.2 and 26.1%, respectively. Moderate and very high was independently inversely associated with partial MH (moderate: OR 0.40 [95%CI 0.19–0.810], very high: OR 0.37 [95%CI 0.17–0.77], p for trend = 0.034). Similarly, moderate, high, and very high were independently inversely associated with MH (moderate: OR 0.37 [95% CI 0.18–0.73], high: OR 0.41 [95% CI 0.19–0.83], and very high: OR 0.45 [95% CI 0.21–0.94], p for trend = 0.033) after adjustment for confounding factors. Conclusions Among patients with UC, platelet count was independently inversely associated with MH

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“…Several biomarkers have been proposed in order to evaluate disease activity and predict therapeutic response to anti-TNF in UC patients (Verstockt et al, 2019;Bertani et al, 2020a;Bertani et al, 2020c;Barberio B. et al, 2020;Bertani et al, 2021). However, the role of Ig glycosylation has never been studied with this purpose.…”

Section: Introductionmentioning

confidence: 99%

Ig Glycosylation in Ulcerative Colitis: It’s Time for New Biomarkers

et al. 2021

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Background: Ulcerative colitis (UC) is a chronic relapsing disease, which needs a continue monitoring, especially during biological therapies. An increasing number of patients is treated with anti-Tumor Necrosis factor (TNF) drugs, and current research is focalized to identify biomarkers able to monitor the disease and to predict therapeutic outcome.Methods: We enrolled consecutive UC patients treated with anti-TNF, naïve to biologic drugs. Therapeutic outcome was evaluated after 54 weeks of treatment in terms of clinical remission (Partial Mayo Score -PMS- <2) and mucosal healing (Mayo Endoscopic Score <2). On serum samples collected at baseline and after 54 weeks of treatment, a Lectin-based ELISA assay was performed, and specific glycosylation patterns were evaluated by biotin-labelled lectins. We have also collected 21 healthy controls (NHS) samples, age and sex-matched.Results: Out of 44 UC patients enrolled, 22 achieved clinical remission and mucosal healing after 54 weeks. At baseline, when Protein A was used as coating, UC patients non-responders showed a reduced reactivity to Jacalin (JAC) in comparison with NHS (p = 0.04). After one year of treatment, a decrease in JAC binding was seen only in responders, in comparison with baseline (p = 0.04). When JAC binding was tested selecting IgG by means of Fab anti-IgG Fab, UC patients displayed an increased reactivity after anti-TNF therapy (p < 0,0001 vs controls). At baseline, PMS inversely correlates with JAC binding when Fab anti-IgG Fab was used in solid phase (r2 = 0,2211; p = 0,0033). Patients with higher PMS at baseline (PMS ≥5) presented lower binding capacity for JAC in comparison with NHS and with lower PMS patients (p = 0,0135 and p = 0,0089, respectively).Conclusion: Ig glycosylation was correlated with clinical and endoscopic activity in patients with UC. JAC protein A-selected Ig showed a possible role in predicting therapeutic effectiveness. If these data would be confirmed, Ig glycosylation could be used as biomarker in UC.

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

Cited by 47 publications

References 37 publications

Blood neutrophil-to-lymphocyte ratio (NLR) as a diagnostic marker in dogs with chronic enteropathy

Blood neutrophil-to-lymphocyte ratio (NLR) as a diagnostic marker in dogs with chronic enteropathy

Association between platelet count and mucosal healing in Japanese patients with ulcerative colitis: a cross-sectional study

Ig Glycosylation in Ulcerative Colitis: It’s Time for New Biomarkers

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