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Published on: February 28, 2021
TRANCE is a unique marker of chronic pancreatitis in children
Peter R Farrell1,2, Bomi Lee3, Faizan Ahmed2
1Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Cincinnati, Ohio, USA.
Insights
This study identified unique plasma biomarkers in pediatric chronic pancreatitis (CP) patients. TRANCE levels were elevated in CP, offering potential diagnostic insights for this condition.
Area of Science:
- Immunology
- Gastroenterology
- Pediatrics
Background:
- Pediatric acute pancreatitis (AP) and chronic pancreatitis (CP) require better diagnostic tools.
- Immune signaling pathways are implicated in pancreatitis pathogenesis.
- Identifying specific biomarkers can differentiate pediatric pancreatitis subtypes.
Purpose of the Study:
- To evaluate plasma chemokine and cytokine levels in pediatric CP patients.
- To compare these levels with pediatric AP patients and healthy controls (HCs).
- To identify unique biomarkers for pediatric CP.
Main Methods:
- Analyzed 247 immunoproteins in 146 pediatric participants (71 CP, 55 AP, 20 HCs) using NULISAseq.
- Utilized prospectively collected samples from a defined pediatric cohort.
- Employed multivariable logistic regression and AUC analysis for biomarker validation.
Main Results:
- Plasma analytes differentiated CP, AP, and HC groups (R2 = 0.13, P < 0.001).
- TRANCE, TWEAK, FLT-1, HGF, and TRAIL were elevated in pediatric CP versus AP/HC.
- A 5-protein model achieved an AUC of 0.94 for CP differentiation.
- Distinct cytokine profiles were observed in AP during acute flares and over time.
Conclusions:
- TRANCE is a potential biomarker, elevated in pediatric CP and decreased in AP flares.
- Specific immunoproteins differentiate pediatric pancreatitis subtypes.
- Further research into TRANCE and other analytes is warranted for CP pathogenesis.
Abstract:
BACKGROUNDElucidating immune signals through well-defined cohorts of pediatric acute pancreatitis (AP) and chronic pancreatitis (CP) patients is critical. This study aimed to evaluate plasma chemokine and cytokine levels in pediatric participants with CP, compared with AP and healthy controls (HCs), to identify unique biomarkers of CP.METHODSIndividuals were identified from a prospectively collected pediatric cohort (n = 146). Immunoproteins (n = 247) were measured using the NULISAseq platform on samples from individuals with CP (n = 71), AP (n = 55), and HCs (n = 20).RESULTSThe measured analytes showed separation among the 3 groups (R2 = 0.13, P < 0.001). In the CP group, TRANCE, TWEAK, FLT-1, HGF, and TRAIL were increased when compared with HC and AP patients (FDR-corrected P <0.05). A multivariable logistic regression model including all 5 proteins provided an AUC of 0.94 (0.93-0.96) for differentiating samples from CP versus AP or HC samples. In the AP group, CRP, IL-6, CD3E, ENRAGE, and MIF were elevated compared with HCs, while FGF-2, TAFA-5, IL-33, TRANCE, and CXCL12 were downregulated in the same acute time period (FDR-corrected P < 0.05). In the 21 patients with AP for whom follow-up samples were obtained, there was a notable decrease in sequential expression of IL-6 and CRP over 12 months and increased expression of CCL25, TAFA-5, and TRANCE proteins. Additionally, TRANCE was expressed on CP pancreatic tissue.CONCLUSIONSTRANCE was increased in pediatric patients with CP and decreased in those with AP during a flare. Future studies are needed to investigate the role of TRANCE and other analytes in the pathogenesis of CP.
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