scholarly journals Utility of major basic protein, eotaxin-3, and mast cell tryptase staining for prediction of response to topical steroid treatment in eosinophilic esophagitis: analysis of a randomized, double-blind, double dummy clinical trial

2020 ◽  
Vol 33 (6) ◽  
Author(s):  
Evan S Dellon ◽  
John T Woosley ◽  
Sarah J McGee ◽  
Susan E Moist ◽  
Nicholas J Shaheen

Summary Inflammatory factors in eosinophilic esophagitis (EoE), including major basic protein (MBP), eotaxin-3 (EOT3) and mast cell tryptase (TRP), may predict treatment response to topical corticosteroids (tCS). We aimed to determine whether baseline levels of these markers predict response to tCS for EoE. To do this, we analyzed data from a randomized trial comparing two topical steroids for treatment of newly diagnosed EoE (NCT02019758). A pretreatment esophageal biopsy was stained for MBP, EOT3, and TRP to quantify tissue biomarker levels (cells/mm2). Levels were compared between histologic responders (<15 eos/hpf) and nonresponders (the primary outcome), and endoscopic responders (EREFS<2) and nonresponders. Complete histologic response (<1 eos/hpf) was also assessed, and area under the receiver operator characteristic curve (AUC) was calculated. We also evaluated whether baseline staining predicted symptom relapse in the trial’s off-treatment observation phase. Baseline samples were evaluable in 110/111 subjects who completed the randomized trial. MBP levels were higher in nonresponders (n = 36) than responders (704 vs. 373 cells/mm2; P = 0.007), but EOT3 and TRP levels were not statistically different. The combination of all three stains had an AUC of 0.66 to predict response. For complete histologic response, baseline TRP levels were higher in nonresponders (n = 69) than responders (370 vs. 268 mast cells/mm2; P = 0.01), with an AUC of 0.65. The AUC for endoscopic response was 0.68. Baseline staining did not predict symptom recurrence after remission. Pretreatment MBP, EOT3, and TRP levels were not strongly or consistently associated with histologic or endoscopic response to topical steroids. While elevated TRP levels may be associated with nonresponse compared with complete response, the magnitude and predictive utilities were modest. Novel methods for predicting steroid response are still required.

2014 ◽  
Vol 146 (5) ◽  
pp. S-664
Author(s):  
Evan S. Dellon ◽  
Olga Speck ◽  
Kimberly Woodward ◽  
Shannon Covey ◽  
Spencer Rusin ◽  
...  

2012 ◽  
Vol 107 (10) ◽  
pp. 1503-1511 ◽  
Author(s):  
Evan S Dellon ◽  
Xiaoxin Chen ◽  
Ryan C Miller ◽  
John T Woosley ◽  
Nicholas J Shaheen

2019 ◽  
Vol 32 (Supplement_1) ◽  
Author(s):  
R Tambucci ◽  
F Rea ◽  
M Malamisura ◽  
F Torroni ◽  
E F Romeo ◽  
...  

Abstract Introduction Since recently, after detection of eosinophilic predominant inflammation of esophagus a trial with proton-pump inhibitors (PPIs) was needed to individuate children with PPI-responsive esophageal eosinophilia (PPI-REE), only those non-responders received eosinophilic esophagitis (EoE) diagnosis. In 2018 updated international consensus suggested removing the PPI trial as a diagnostic criterion and consider PPIs as a treatment together with diets and topical steroids. The role of PPIs is evaluated in children with esophageal atresia (EA) and EoE versus EoE from general population. Method A retrospective chart review of both children with EA and EoE followed-up from at January 2005 has been performed. According to ESPGHAN guidelines published in 2014 patients showing eosinophilic inflammation received high-dose PPI trial to identified PPI-REE. Those non-responders were labeled as EoE and underwent to dietary and/or topical steroid treatment. Demographics and disease characteristics of EA patients with EoE were analyzed and compared with those with EoE from general population. Results Overall, 370 EA and 118 EoE patients were analyzed. Of them 15 EA-EoE patients were detected. Consequently, in our cohorts, 4.0% of EA patients developed EoE. Male-to-female prevalence ratio was of 2.55 with no difference in gender prevalence between groups. At diagnosis EoE-EA children were significantly younger compared to EoE group (mean: 5.1 vs 10.8 years; P < 0.0001). Peak EOS/HPF at diagnosis did not differ between groups (50.1 ± 26 vs 59.8 ± 29 EOS/HPF). No difference was observed in allergy prevalence between groups (53.8 vs 68.0%). PPI-REE was significantly more prevalent in EA-EoE group that in EoE group (66.6% vs 19.4%; P = 0.0004). Conclusion Similar gender distribution and high prevalence of allergy suggest that common genetic susceptibility factors for EoE exist. However, high prevalence of PPI-REE coupled early EoE onset might also suggest that other factors (e.g. esophageal motility disorders) might play a physiopathological role in EoE development in EA children. Our study suggests that a stepwise approach with PPIs as a first-line treatment for EoE management in EA children should still be considered.


Blood ◽  
1998 ◽  
Vol 92 (3) ◽  
pp. 1055-1061
Author(s):  
Glenn T. Furuta ◽  
Steven J. Ackerman ◽  
Lei Lu ◽  
Rachel E. Williams ◽  
Barry K. Wershil

Stem cell factor (SCF) is an important mast cell growth, differentiation, and survival factor. We investigated whether SCF influenced the response of mouse mast cells to an IgE-independent stimulus, eosinophil-derived granule major basic protein (MBP). Mouse bone marrow cultured mast cells (BMCMC) were derived in either concanavalin-stimulated mouse spleen conditioned medium (CM) or SCF. The cloned growth, factor-independent mast cell line Cl.MC/C57.1 was also studied. BMCMC in SCF exhibited cytochemical staining properties, protease and histamine content, and increased serotonin uptake consistent with more mature differentiated mast cells as compared with BMCMC in CM or Cl.MC/ C57.1 cells. BMCMC in SCF released serotonin,14C-labeled arachidonic acid metabolites and tumor necrosis factor-α (TNF-α) on stimulation with MBP, while no response was seen from either BMCMC in CM or Cl.MC/C57.1 cells. All three mast cell populations released mediators on stimulation with the cationic MBP analog, poly-L-arginine, indicating that the cationic charge did not explain the selective response of BMCMC in SCF to eosinophil-derived granule MBP. These findings show that SCF significantly influences mast cell differentiation and the responsiveness of mast cells to eosinophil-derived granule MBP. © 1998 by The American Society of Hematology.


1998 ◽  
Vol 114 ◽  
pp. A126-A127 ◽  
Author(s):  
GT Furuta ◽  
S Walsh ◽  
DA Antonioli ◽  
MY Wang ◽  
SJ Ackerman ◽  
...  

2017 ◽  
Vol 152 (5) ◽  
pp. S858 ◽  
Author(s):  
Swathi Eluri ◽  
Sara R. Selitsky ◽  
Joel S. Parker ◽  
Johnathan Hollyfield ◽  
Irina Perjar ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document