P0219 The role of IP10 as a possible biomarker of Short Bowel Syndrome: a preliminary study
Authors: Pane C , Di Mattia M , Petito V , Foscarini E , Profeta F , Becherucci G , Masi L , Troisi S , Emoli V , Rondinone B , Turchini L , Gasbarrini A , Papa A , Scaldaferri F , Lopetuso L R 
Published: January 2025

Abstract

Background
Short Bowel Syndrome (SBS) indicates a complex gastrointestinal condition resulting from major surgical resections of the small intestine or congenital abnormalities, which results in insufficient absorption capacity1. SBS may be characterized by intestinal failure (IF), nutritional deficiencies and metabolic complications, coming along by the need for parenteral nutrition (PN)2.
SBS appears like a complication of severe gastrointestinal disorders, including Crohn’s disease (CD).
CD, SBS and IF might share some risk factors, but, to date, there are no biomarkers or pathophysiological markers available to indicate a higher risk of developing SBS3.
The aim of the current study is to identify circulating cytokines, that appears during chronic inflammation of the intestinal mucosa.

Methods
In order to analyze serum cytokines, 75 patients with CD have been enrolled and divided into 5 groups:
A1: SBS with IF and need for PN or intravenous fluids;
A3: SBS without IF and no active disease;
B: high risk of developing IF with multiple or extensive resection;
C1: low risk of developing IF with no resection;
C2: low risk of developing IF with resection.
Subsequent quantification of 19 cytokines of interest in serum samples was performed using the Human Cytokine Multiplex Assay (Bio-Rad Lab).

Results
Analysis of the serum cytokines of all groups under study revealed, relatively to the highest concentration, 6 cytokines: IP10, PDGF-BB, RANTES, MIP-1β, EOTAXIN, IL-9 (fig.1). A low concentration of cytokines with anti-inflammatory roles such as IL-4, IL1-RA and IL-13 is also evident. Especially, the higher serum concentration of IP10 in groups A1 and A3 (characterized by more severe disease) significantly emerges compared with other groups (fig.2). Significant differences between the groups can also be observed in the concentrations of PDGF-BB and RANTES, while no significant data are notable in the analysis of others.

Conclusion
IP-10 plays a key role in modulating the immune response, mainly through chemotaxis, by drawing immune cells toward sites of inflammation, perpetuating chronic inflammation4. Our results validate the role of IP-10 within the multifactorial nature of SBS. Moreover, the study could open the door to more in-depth research on the role of IP-10 as a possible biomarker of susceptibility to SBS and related diseases.

References
1.Massironi S, Cavalcoli F, Rausa E, Invernizzi P, Braga M, Vecchi M. Understanding short bowel syndrome: Current status and future perspectives. Dig Liver Dis. 2020;52(3):253-261. doi:10.1016/j.dld.2019.11.013
2.Pironi L, Konrad D, Brandt C, et al. Clinical classification of adult patients with chronic intestinal failure due to benign disease: An international multicenter cross-sectional survey. Clin Nutr. 2018;37(2):728-738. doi:10.1016/j.clnu.2017.04.013
3.Limketkai BN, Parian AM, Shah ND, Colombel JF. Short Bowel Syndrome and Intestinal Failure in Crohn’s Disease. Inflamm Bowel Dis. 2016;22(5):1209-1218. doi:10.1097/MIB.0000000000000698
4.Devito A. Alpha chemokines in Crohn’s disease. Clin Ter. 2015;166(2):e114-e117. doi:10.7417/CT.2015.1832

Fundings
2.1 "Rafforzamento e potenziamento della ricerca biomedica del SSN", finanziato dall’Unione europea – NextGenerationEU, CUP C53C22001140007. 2022 PNRR Project "Changing the future of intestinal failure in intestinal chronic inflammation: towards innovative predictive factors and therapeutic targets" code: PNRR-MAD-2022-12376791.