Case Report: Splenic Irradiation for the Treatment of Chronic Active Antibody-Mediated Rejection in Kidney Allograft Recipients With De Novo Donor-Specific Antibodies.

Lan Zhu,Gang Chen,Rula Sa,Zhiliang Guo,Junhua Li,Hui Guo

doi:10.3389/fimmu.2021.661614

Abstract

Chronic active antibody-mediated rejection (AMR) in renal transplantation is usually refractory to current conventional treatment with rituximab, plasmapheresis (PP), and intravenous immunoglobulins (IVIG). Splenic irradiation has been reported to be effective in the rescue of early severe acute AMR after kidney transplantation; however, its effect in chronic active AMR has not been reported to date. In order to reduce donor-specific antibody (DSA) and prevent the progression of chronic AMR, we used repetitive low-dose splenic irradiation, together with rituximab and PP/IVIG, in two living-related kidney transplant recipients with pathologically diagnosed chronic active AMR and the presence of long-term class II-de novo DSA. DSA monitoring and repeated renal biopsy revealed significantly reduced DSA levels as well as alleviated glomerulitis and peritubular capillaritis in both patients after treatment, and these therapies may have played a role in delaying the progression of chronic AMR. Although DSA levels in both patients eventually rebounded to some extent after treatment, serum creatinine increased slowly in one patient during the 16-month follow-up period and remained stable in the other during the 12-month follow-up period. Given the poor efficacy of conventional treatment at present, splenic irradiation may still be one of the treatment options for chronic active AMR.

Highlights

Chronic active antibody-mediated rejection (AMR) has long been recognized as the leading cause of late allograft loss in kidney transplantation [1, 2]
The development of de novo donor-specific antibody (DSA) after renal transplantation has been reported in 13%-30% of previously non-sensitized recipients [13]
De novo DSAs are mainly directed to donor HLA class II mismatches and can appear at any time after kidney transplantation [14,15,16].The long-term existence of de novo DSA after renal transplantation has been reported to be associated with the occurrence of chronic AMR, transplant glomerulopathy, and late graft loss [17]

Summary

INTRODUCTION

Chronic active antibody-mediated rejection (AMR) has long been recognized as the leading cause of late allograft loss in kidney transplantation [1, 2]. The pathology results showed moderate glomerulitis (g2), severe peritubular capillaritis (ptc3), mild peritubular capillary C4d deposition (C4d1), focal glomerular basement membrane double contours (cg2), peritubular capillary basement membrane multilayering (electron microscopy), and positive IgA deposition (++), which were diagnosed as mild chronic active AMR (Banff 2017 Schema), transplant glomerulopathy (TG), and recurrent IgA nephropathy (Figure 2A). The Flow-CDC test using isolated fresh donor lymphocytes as target cells showed a mildly positive result (8.87%) that was higher than that of the negative controls (cells only: 3.92%; cells + complement: 3.04%) (Figure 3B). After 4 weeks of treatment, the MFI levels of DSA significantly decreased (1:3 diluted serum; DR12-MFI: 1,742; DQA6-MFI: 1,222) and the Flow-CDC result became negative (3.74%) (Figure 3B). In the latest follow-up, his serum creatinine level was 133 mmol/L, and his total 24-hour urinary protein was 726 mg

DISCUSSION

Findings

ETHICS STATEMENT