Immunotyping of ITP Based on Different Platelet Destruction Mechanism Are Associated with Response to Splenectomy

In recent years, although the long-term remission rate of splenectomy is comparable to or even higher than that of other second-line treatments, the usage rate of splenectomy in patients with ITP has decreased year by year due to concerns about postoperative complications and uncertainty about the efficacy. Therefore, in this study, we constructed an immune atlas of peripheral blood and spleen form patients who underwent splenectomy by single-cell immune repertoire sequencing. By comparing the immune status of preoperative peripheral blood and intraoperative spleen tissue from the patients with response and non-response to splenectomy, we found activation, function and ISG response-related gene sets were enriched in each B subset in the peripheral blood and spleen from patients with response to splenectomy. Accordingly, BAFF and APRIL signaling between MCs and B cells were enhanced in these patients, which result in B cell hyperfunction and the production of autoantibodies. These results suggested that their platelets were destroyed primarily by antibody-mediated manner in patients with response to splenectomy. Instead, gene sets related to activation, function and cytotoxicity were enriched in T and NK cells in the peripheral blood and spleen from patients without response to splenectomy, and the MHC-I score of MCs was up-regulated in these patients, suggesting that their platelets mainly lysis by cytotoxic T cells. Thus, we further detected antibody-mediated and CTL-mediated platelet destruction associated immune indictors by flow cytometry and ELISA, the results showed anti-GPIIbIIIa titer was higher, while Ts percentage, CD8+/CD4+ and Th1/Th2 ratio were lower in preoperative peripheral blood from patients with response than those from patients without response. ROC analysis showed that the latter three indicators could effectively classify patients with antibody-mediated and CTL-mediated ITP, thus predicted splenectomy efficacy. In addition, by comparing the immune profiles of patients before and after splenectomy, it was found that the proportion of B cells in peripheral blood decreased after splenectomy, but the activation functions of B and T cells were significantly enhanced, which may partially compensate for the loss of humoral immunity caused by splenectomy. Therefore, the risk of long-term infection after operation may be lower than expected. We proceeded follow-up the ITP patients with (n=85) or without splenectomy(n=50) in our center in last 8 years and found that the infection rate of splenectomy patients was 5.88%, and that of non-operated patients was 12%, which confirmed our speculation. In conclusion, our study found that splenectomy had satisfactory clinical efficacy in patients with antibody-mediated platelet destruction, and the risk of long-term postoperative infection was not significantly increased compared with patients with ITP who did not undergo splenectomy.

No relevant conflicts of interest to declare.