Combination of Total Lymphoid Irradiation, Low-Dose IVIG and ATG as Rescue Therapy for Highly Sensitized and Antibody-Mediated Rejection Renal Transplant Recipients.
Background: It is now clear that antibody- mediated rejection (AMR) is a major cause of graft failure. To avoid AMR, transplantation is preferably performed in non- or low-sensitized patients. For patients with pre-existing HLA antibodies due to pre-transplant sensitization or those with de novo HLA antibodies due to transplantation, elimination or reduction of HLA antibodies becomes critical to prevent AMR. Materials and Methods: In this clinical trial, we test the efficacy of a combination therapy of total lymphoid irradiation (TLI), low- dose intravenous immunoglobulin (IVIG), and anti-thymocyte globulin (ATG) with or without plasmapheresis (PP) in treating patients with HLA antibodies. Thirteen HLA antibody positive patients receiving renal transplants during 2009-2011 were enrolled in this study. Two cases with pre-existing HLA antibodies received combined therapy of TLI, PP, low-dose IVIG, and ATG induction. Eleven cases with de novo HLA antibodies and biopsy-proven AMR received TLI, low-dose IVIG, and ATG with or without PP.


RESULTS
Two sensitized patients with pre-existing HLA antibodies were successfully desensitized and able to accept renal transplantation without an observable AMR episode in 12 months of post-transplant follow-up. In 11 AMR cases with de novo HLA antibodies, only one patient failed to respond to the therapy and lost the allograft. In the other ten cases, the follow-up biopsies at one year post transplant showed no evidence of rejection and the patients had stable renal function. B cell proliferation was persistently inhibited in both desensitization and AMR patients.


CONCLUSIONS
Combined therapy of TLI, PP, low-dose IVIG, and ATG is an effective therapeutic measure to reduce the level of HLA antibodies and therefore to desensitize recipients pre-transplant and to reverse AMR post transplant. The potential mechanism of the therapy involves inhibition of B cell proliferation.
Dong
D
Zhu
Guisheng
G
Qi
Qunye
Q
Tang
Long
L
Li
Cheng
C
Yang
Miao
M
Lin
Boting
B
Wu
Ming
M
Xu
Junchao
J
Cai
Tongyu
T
Zhu
Ruiming
R
Rong
D000293:Adolescent; D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D049109:Cell Proliferation / Q000187:drug effects; D003131:Combined Modality Therapy; D003888:Desensitization, Immunologic / Q000379:methods*; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D006085:Graft Survival / Q000187:drug effects; D006680:HLA Antigens / Q000276:immunology*; D006648:Histocompatibility; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage*; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000401:mortality; D015182:Lymphatic Irradiation; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D000961:Antilymphocyte Serum; D015415:Biomarkers; D006680:HLA Antigens; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D007518:Isoantibodies