JPGN Journal Club June 2024: Anti-TNF Resistance in IBD and SIPR2 Pathways in Cholestasis with Prof Binita Kamath and Dr Jake Mann

JPGN Journal Club reports from the Milan venue of ESPGHAN’s 2024 annual meeting, seizing the opportunity to learn from those rarely in Europe – as today with Prof Binita Kamath, in transit between Toronto and Philadelphia professionally, who along with Dr Jake Mann will tag-team her way down the field shooting for goal with two articles of interest (Winter et al.’s Biomarkers predicting the effect of anti‐TNF treatment in paediatric and adult inflammatory bowel disease, from J Pediatr Gastroenterol Nutr 2024 May 2 doi: 10.1002/jpn3.12221, and Islam et al.’s A novel model to study mechanisms of cholestasis in human cholangiocytes reveals a role for the SIPR2 pathway, from Hepatol Commun 2024 Feb 268[3]:e0389).   In the study from Rotterdam (Prof J Escher, team leader), proteomics screening identified several species more abundant in material from persons who had developed resistance to anti-tumour necrosis factor inhibition than in persons without such resistance.  The numbers of subjects in these two cohorts ?  Small.  The p value of the increases in abundance seen ?  Slight.  Larger numbers called for, perhaps with different statistical handling – but a promising start and an interesting attack on the question of “What leads to treatment failure ? “ Prof Kamath stepped forward to explicate the work by Islam et al. – quite properly, since it is her team’s work.  Extrahepatic bile-duct cholangiocytes, grown as organoids, were challenged with taurocholic acid and other agents, and the cholangiocytes’ responses, categorised by pathways of involved molecules, were charted and analysed.  Of interest was that a hitherto little-studied molecule, sphingosine-1-phosphate receptor 2, was implicated as participating strongly :  New routes for investigation !     The information, viewpoints, and recommendations shared in this podcast are solely those of the hosts and guests, and may evolve over time as the field advances.