Abstract

Abstract Background and Aims Desensitization therapy has enabled successful transplantation of renal allografts across the ABO blood group barrier, which significantly expands the living donor pool. Whether the B cell depletion induced by rituximab would affect the proportions of peripheral blood (PB) and lymph nodes (LN) T follicular helper (Tfh) and T follicular regulatory (Tfr) cells, whose survival depends on B cells, in ABO-incompatible kidney transplant recipients (ABOi-KTRs) is unknown. Method PB and LN samples were simultaneously collected on the day of transplantation from 14 ABOi-KTRs and 12 ABO-compatible KTRs (ABOc-KTRs) between January to October 2019. Additional PB from ABOi-KTRs was obtained before desensitization treatment (Rituximab+plasmapheresis+ immunosuppression). All recipients were undergone living donor transplantation. The frequency of B, Tfh (CD4+CXCR5+Foxp3-) and Tfr (CD4+CXCR5+Foxp3+) cells and the expression the PD-1, ICOS on Tfh and Tfr cells were quantified by flow cytometry. Results After desensitization treatment, significantly lower proportions of PB and LN B cells were observed in ABOi-KTRs (ABOi-a) when compared to ABOc and ABOi-b (ABOi-KTRs before desensitization) groups (Fig. A). Circulating Tfr cells decreased significantly after desensitization therapy, while no difference was found in LN Tfr cells (Fig. F). In addition, ABOi-a group showed higher expression of PD-1 on Tfr cell within PB, but lower within LN when compared to ABOi-b and ABOc groups, respectively (Fig. G). For Tfh proportion and its expression of PD-1 and ICOS within PB and LN, no significant difference was observed among groups (Fig. B-D). Significantly lower ratio of Tfr to Tfh was observed after ABO desensitization (Fig. E). Conclusion Our results indicated that ABO desensitization had significant suppression effects on B cells both within the PB and LN of ABOi-KTRs. In addition, the desensitization treatment mainly affected circulating Tfr cells, instead of Tfh cells, which shifted the balance between Tfr and Tfh cells towards Tfr cells in PB. Whereas, this treatment showed no influence on Tfh and Tfr populations within LN in ABOi-KTRs.

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