3 research outputs found
A standardised model for stool banking for faecal microbiota transplantation : a consensus report from a multidisciplinary UEG working group
Background Faecal microbiota transplantation is an emerging therapeutic option, particularly for the treatment of recurrent Clostridioides difficile infection. Stool banks that organise recruitment and screening of faeces donors are being embedded within the regulatory frameworks described in the European Union Tissue and Cells Directive and the technical guide to the quality and safety of tissue and cells for human application, published by the European Council. Objective Several European and international consensus statements concerning faecal microbiota transplantation have been issued. While these documents provide overall guidance, we aim to provide a detailed description of all processes that relate to the collection, handling and clinical application of human donor stool in this document. Methods Collaborative subgroups of experts on stool banking drafted concepts for all domains pertaining to stool banking. During a working group meeting in the United European Gastroenterology Week 2019 in Barcelona, these concepts were discussed and finalised to be included in our overall guidance document about faecal microbiota transplantation. Results A guidance document for all domains pertaining to stool banking was created. This document includes standard operating manuals for several processes involved with stool banking, such as handling of donor material, storage and donor screening. Conclusion The implementation of faecal microbiota transplantation by stool banks in concordance with our guidance document will enable quality assurance and guarantee the availability of donor faeces preparations for patients.Peer reviewe
Temporal Regulation of Immune Response during GvHD via IL-33/ST2 axis
Similar abstract has been appporved for a conference (OAK22720).
IL-33 binding to the receptor suppression of tumorigenicity 2 (ST2) produces proinflammatory
and anti-inflammatory effects. Increased levels of soluble ST2 (sST2) are a
biomarker for steroid-refractory GVHD and mortality. However, whether sST2 has a role
as an immune modulator or only as a biomarker during GVHD was unclear. We show
increased IL-33 production by non-hematopoietic cells in the GI tract in mice postconditioning
and patients during GVHD. Exogenous IL-33 administration during the peak
inflammatory response worsened GVHD. Conversely, GVHD lethality and TNF-α
production was significantly reduced in il33-/- recipients. ST2 was upregulated on murine
and human alloreactive T cells and sST2 increased as experimental GVHD progressed.
Concordantly, st2-/- versus wildtype donor T cells had a marked reduction in GvHD
lethality and GI histopathology. Alloantigen-induced IL-18 receptor upregulation was
lower in st2-/- T cells, and linked to reduced IFN-Îł production by st2-/- versus wildtype T
cells during GVHD. Blockade of IL-33/ST2 interactions during allo-hematopoietic cell
transplantation by exogenous ST2-Fc infusions had a marked reduction in GVHD
lethality indicating a role of ST2 as a decoy receptor modulating GVHD. Together, these
studies point to targeting of the IL-33/ST2 axis as a novel and potent target for GVHD
therapy