JPGN Journal Club: February 2024
Dr Alex Knisely today in JPGN Journal Club is in a dogfight against Dr Jake Mann – it’s Jake’s first solo flight as Journal Club pilot, will he be shot down? Jake first offers us, out of Berlin, with co-authors from European and Israeli centres, and published in J Pediatr Gastroenterol Nutr : Kalveram et al., Noninvasive scores are poorly predictive of histological fibrosis in pediatric fatty liver disease. Then he steers away from the sunlit uplands of JPGN and into the dark and stormy clouds of basic science, with, out of Aurora / Denver, Colorado, and claiming a double handful of co-authors on that side of the Atlantic and this, published in J Exp Med : Lui et al., A partial human LCK defect causes a T cell immunodeficiency with intestinal inflammation.
A tip of the school cap to Molesworth, N., here – and as any paediatric hepatopathologist would predict, the Berlin- based consortium found that clinical parameters and values for various biomarkers, assessed in differing combinations, did not identify or correctly stratify liver fibrosis, and that the proper set of tests to use in non-invasive diagnosis of liver fibrosis still awaits definition in paediatric fatty liver disease. To be regretted – in this histopathologist’s opinion – is that the extent of fibrosis was not verified by a review team ; that is, the co-authors contributed not glass slides bearing tissue sections but copies of reports. Not the firmest of foundations, then . . . Well, however they got there, the conclusion of the study was prima facie correct : Keep those biopsy specimens coming !
The Coloradans and their co-workers report from Immunology World, in which evaluation of two brothers, born to first-cousin parents, for features of immunodeficiency found that they harboured a novel variant in LCK, encoding lymphocyte-specific protein tyrosine kinase (LCK). The effects of the variant included chronic diarrhoea ; histopathologic assessment of bowel mucosa is not reported. In knock-in mice with the same variant in Lck, however, chronic intestinal mucosal inflammation was present – not a feature in Lck knock-out mice. Immunophenotyping in the siblings and in the mice found selective deficiency in numbers of regulatory T-cells. The lads were successfully treated with bone-marrow transplantation. The mice could be successfully treated by topping up regulatory T-cells or by depleting CD4-expressing T-cells. Aside from the effects that the variant had on orderly development of T-cell subsets, the report interested Jake (and our listeners, we hope!) because of parallels that can be drawn with genetic contributions to chronic inflammatory intestinal disease. Patients like these have a lot to teach us, Jake maintains, as – like every British boy’s hero, “Biggles” – he returns safely to his home airfield, mission accomplished and Alex foiled.
As always, happy listening – and happy reading !