P0195 Immune reconstitution following autologous hematopoietic stem cell transplantation with cyclophosphamide-free mobilization for refractory Crohn’s disease
E Saager, L Lutter, N Mahmmod, D Hoytema van Konijnenburg, E Delemarre, M van der Wal, B Oldenburg, F van Wijk, H FidderAbstract
Background
Autologous hematopoietic stem cell transplantation (aHSCT) has emerged as an effective therapeutic strategy for patients with severe chronic inflammatory conditions that are refractory to conventional treatment, including Crohn’s disease. The success of aHSCT is thought to be grounded in resetting the break of immunological tolerance, but the exact mechanisms underlying a favourable response remain incompletely understood.
Methods
We followed the immune reconstitution of 9 patients with severe refractory Crohn’s disease from one month until more than 2 years post-aHSCT. We performed flow cytometry to follow immune cell populations and functional T cells markers over time, in addition to Olink proteomics to study the inflammatory response in serum.
Results
Transplantation proceeded safely, without major adverse events in any of the 9 patients. aHSCT resulted in considerable improvement of disease status in 6 patients, with 3 patients classified as non-responders. After transplantation, we observed a strong change in the peripheral T-cell subset composition, with a reduction of the CD4/CD8 ratio and a reduction of naïve over effector memory (EM) T cells. Non-responders appeared distinct by a higher CD4/CD8 ratio and higher naïve over T-EM frequencies already before transplantation, and a smaller change in subset composition after transplantation. Remarkably, the local T-cell composition did not mirror the changes in the periphery, with an increased CD4/CD8 ratio in intestinal biopsies post-aHSCT, underscoring that a more detailed study of local versus peripheral responses to aHSCT is essential in aiding our understanding of its efficacy. Functionally, the changes in the peripheral T-cell profile were minimal and not clearly related to response. Although the pro-inflammatory profile was not altered, we did find a small but significant increase in the expression of regulatory markers.
Conclusion
aHSCT resulted in strong changes in the T-cell subset composition of Crohn’s disease patients, but only small changes in functional markers related to inflammation, regulation and homing. Non-responders could be distinguished at baseline by a different T-cell composition and also experienced less profound changes herein upon transplantation.