At the watershed between 2024 and 2025, some readers will have remembered this couplet: “Hark! It’s midnight, children dear. / Duck – here comes another year!” In paraphrase, then, duck – here comes another instalment of JPGN Journal Club, led by Dr. Jake Mann! Before we move along to the articles to which Jake wants us to pay attention, have a glance at what ESPGHAN is doing for you at https://www.espghan.org/knowledge-center:2025.I.30: Monothematic Conference on Steatotic Liver Dise...
At the watershed between 2024 and 2025, some readers will have remembered this couplet:
“Hark! It’s midnight, children dear. / Duck – here comes another year!”
In paraphrase, then, duck – here comes another instalment of JPGN Journal Club, led by Dr. Jake Mann! Before we move along to the articles to which Jake wants us to pay attention, have a glance at what ESPGHAN is doing for you at https://www.espghan.org/knowledge-center:
- 2025.I.30: Monothematic Conference on Steatotic Liver Disease in Children.
- III.05: GI Immunology Master Class: From Pathogenesis to Clinical Management of EGID, Coeliac Disease, and IBD.
- IV.02-04: A meeting on Nutritional Assessment in Artificially Fed Children with Chronic Intestinal Disorders.
- V.14-17: Don’t forget the Helsinki annual meeting!
Yes, the calendar is empty after that until early September, but then things get crowded. Sign up briskly, people, before the autumn’s offerings all are booked.
Jake’s choices for discussion today:
From J Pediatr Gastroenterol Nutr, by Anderson et al., writing from Helsinki and Stockholm:
“Serum bile acids early after portoenterostomy are predictive for native liver survival and portal hypertension in biliary atresia.”
The JPGN article provides evidence that, after hepatic portoenterostomy, monitoring serum bile-acid concentrations can supply prognostic information earlier and more sensitively regarding survival with the native liver or development of portal hypertension than monitoring serum bilirubin concentrations.
As physicians, we take trouble with diagnosis to improve our performance with prognosis – our priestcraft in foretelling the future has earned our profession the high regard in which it is intermittently held. If this new-ish approach to prognostication can be confirmed as effective, we’ll all be using it, for our patients’ and their families’ sakes and for our own sakes as well.
From J Exp Med, by Ghasempour et al., writing from Paris, Rotterdam, and Toronto inter alia:
“Human ITGAV variants are associated with immune dysregulation, brain abnormalities, and colitis.”
The article describing colitis associated with variants in the gene encoding integrin alpha-five (ITGAV) is almost as straightforward, once mystifying terminology is cleared away. Toward that end, a summing-up:
- Integrins are heterodimer transmembrane proteins that mediate cell interactions with the extracellular matrix and with other cells.
- Two integrins that include ITGAV, alpha-5-beta-6 and alpha-5-beta-8, activate transforming growth factor beta (TGF-β), which regulates aspects of chemotaxis and of cell proliferation, differentiation, and activation that modulate immune responses.
The results of Ghasempour et al. seem to have started with genomic searches in several children with immunodeficiency, complex congenital malformations, and colitis, with one child requiring colectomy. The searches uncovered variants in ITGAV. Expression of ITGAV in cell lines from the children was substantially but not entirely ablated, leading to reduced nuclear accumulation of the promoter-region DNA-binding transcriptional regulator S-mothers against decapentaplegic homologue 3 – yes, this is the protein’s actual name! – that TGF-β activates.
The cascade from upstream ITGAV expression to downstream disorders of the TGF-β pathway thus was documented. As it happens, variants in TGFB1, which encodes TGF-β, are found in children with faulty brain development and inflammatory bowel disease.
As the cherry on top of this sundae, when the zebrafish orthologue of ITGAV was ablated, nervous-system defects and gut inflammation resulted.
In short, then, another demonstration that TGFB1 and its targets are loci minoris resistentiae in at least some patients with inflammatory bowel disease. How long, then, before we shall clinically utilise TGF-β therapy in inflammatory bowel disease patients?
Literature
- Anderson L et al. Serum bile acids early after portoenterostomy are predictive for native liver survival and portal hypertension in biliary atresia. J Pediatr Gastroenterol Nutr 2024 Dec 31. DOI: 10.1002/jpn3.12451.
- Ghasempour S et al. Human ITGAV variants are associated with immune dysregulation, brain abnormalities, and colitis. J Exp Med 2024 Dec 2;221(12):e20240546. DOI: 10.1084/jem.20240546. Epub 2024 Nov 11. PMID: 39526957. PMCID: PMC11554753.
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