DOP084 Peripheral T cell repertoire reconstitution in Crohn's disease patients undergoing autologous HSCT
Corraliza A.M.*1, Masamunt M.C.1, Ricart E.1, Lόpez-García A.1, Le Bourhis L.2, Allez M.2, Panés J.1, Salas A.1
1IDIBAPS, Hospital Clínic, Gastroenterology, Barcelona, Spain 2Hôpital Saint-Louis, Inserm U1160, Paris, France
Hematopoietic stem cell transplant (HSCT) is considered a salvage therapy for patients with Crohn's disease (CD) refractory to current pharmacological therapies and in whom surgery is not suitable due to disease location or extension. It has been hypothesized that HSCT induces a “reset” of the immune system, producing a new non-autoimmune repertoire. Accurate and quantitative comparison of the regenerated T cell compartment relative to the baseline repertoire has not been performed in such patients.
Aim: To analyse the changes induced by HSCT in the peripheral blood T cell repertoire.
Fourteen CD patients were closely monitored at baseline and followed up for 1 year after receiving autologous HSCT. Blood samples were collected at baseline (pre-mobilization) and at 6 months and 1 year after HSCT. Samples from 3 healthy individuals at two different time points were analysed and used as control for TCR stability. We performed high-throughput deep TCRβ sequencing to track the presence and frequency of individual T cell clones in each patient across time-points, and to calculate the estimated diversity of the TCR repertoire. We correlated the latter with clinical outcome, and defined response to HSCT as a SES-CD<7 at 1 year. To quantitatively compare the repertoire similarity at two different time points, we used the Morisita-Horn index (M-H; range 0–1).
Monoclonal expansions in the T cell compartment are present at baseline in CD patients. This fact is associated with overall higher sample clonality compared to healthy individuals (p value = 0.02). Moreover, the number of TCR sequences at baseline is significantly lower in patients that do not achieve remission 1 year after HSCT compared to those that do (p value = 4×10–3). TCR clonality is further increased (p value = 1×10–3) 6 months after HSCT, reflecting the presence of highly expanded clones. The overall similarity between the repertoire at baseline and 6 months after HSCT was low (mean M-H=0.17), whereas a high degree of similarity (mean M-H=0.72) was observed between the repertoire at 6 months and 1 year. Nonetheless, an average of 14% of the clones present at baseline persists (with high frequency) at 6 months and 1 year after-HSCT regardless of response to treatment.
Patients with refractory CD who underwent HSCT present high TCR clonality at baseline compared to controls, suggesting the presence of expanded T cell clones. A lower baseline number of TCR sequences is associated with poor response to HSCT. HSCT induces dramatic changes the pre-existing TCRβ repertoire in blood. Nevertheless, a not negligible number of clones persist in the peripheral blood in high frequency following HSCT, regardless of the efficacy of the procedure.