Rituximab can deplete B-cells; in kidney transplantation as induction or desensitization. Since as I know regulatory B-lymphocyte (BREG) phenotypes help prevent the rejection? (Please correct me if I am wrong.)Therefore, can RTX cause rejection worse instead of helping in the setting of acute cellular rejection?
Thank you very much!
Also, RTX increases the suppressive function of T-regulatory cells resulting in attenuation of pro-inflammatory CD4+ T cell responses... How can RTX do that? Since it deplete B-cells? How it also increases T-reg functions?
Thank you very much!
Wisit
Hi Wisit,
Clinically, there is little evidence for any immuno-regulatory mechanisms to be able to keep a rejection episode from occurring. This is likely because this is primarily dictated by whether the immunosuppression for the recipient is adequate for the degree of HLA mismatch with his/her donor. If the immunosuppression is inadequate, rejection (antibody +/- cellular) will override any immuno-regulatory effects.
Ritux tends to be used as induction when transplanting across pre-existing donor-specific antibody, sometimes following desensitization. The idea being that this will limit the strength of the memory B cell response you are likely to encounter in those cases. Overall, desensitization with Ritux induction shows better outcomes than desensitization without. It is hard to say whether Ritux can increase the risk for rejection because the only patients that would receive it are the ones at the highest risk for rejection already.
The clinical evidence that B regs can actually regulate an alloimmune response is indirect. The few patients that are spontaneously tolerant are characterized by a B cell gene signature in their blood when compared to non-tolerant patients (see: Newell, KA et. al. PMID:20501946). It has been speculated from that observation that B regs are involved in promoting transplantation tolerance.
I hope that helps.
Thank you very much, Dr.Hidalgo! This is really hepful explanation and reference.
Is it possible that Rituximab also decreases B regs and prevent tolerance, then increases risk for rejection?
Thank you once again,
Greatly appreciated!
Wisit
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