Autologous hematopoietic stem cell transplantation (aHSCT) has shown promise in patients with severe Crohn’s disease who do not respond to conventional treatments. While aHSCT is believed to reset immune tolerance, the precise mechanisms underlying its effectiveness remain unclear. A study examined immune reconstitution in nine patients for over two years following transplantation to better understand the immune changes associated with clinical response.
Researchers analyzed immune cell populations and inflammatory markers using flow cytometry and proteomic profiling. The results showed that six of the nine patients experienced significant disease improvement, while three were classified as non-responders. Across all patients, aHSCT led to notable shifts in peripheral T-cell composition, including a reduced CD4/CD8 ratio and a decrease in naïve T cells relative to effector memory T cells. However, non-responders displayed a distinct immune profile before transplantation, characterized by a higher CD4/CD8 ratio and greater naïve T-cell frequencies. These patients also exhibited less pronounced changes post-transplantation.
Interestingly, while peripheral immune changes were evident, local immune responses in intestinal biopsies did not mirror these shifts. Instead, an increased CD4/CD8 ratio was observed in the gut tissue following transplantation, suggesting that systemic and localized immune responses to aHSCT may differ.
This study highlights the importance of investigating the relationship between systemic and local immune responses in aHSCT-treated patients. Identifying baseline immune differences in responders versus non-responders may also help refine patient selection and improve treatment strategies for refractory Crohn’s disease.
