Subclinical antibody‐mediated rejection due to anti‐human‐leukocyte‐antigen‐DR53 antibody accompanied by plasma cell‐rich acute rejection in a patient with cadaveric kidney transplantation

Abstract

ABSTRACT:A 56-year-old man who had undergone cadaveric kidney transplantation 21 months earlier was admitted to our hospital for a protocol biopsy; he had a serum creatinine level of 1.2 mg/dL and no proteinuria. Histological features showed two distinct entities: (i) inflammatory cell infiltration, in the glomerular and peritubular capillaries and (ii) focal, aggressive tubulointerstitial inflammatory cell infiltration, predominantly plasma cells, with mild tubulitis (Banff 13 classification: i2, t1, g2, ptc2, v0, ci1, ct1, cg0, cv0). Immunohistological studies showed mildly positive C4d immunoreactivity in the peritubular capillaries. The patient had donor specific antibody to human-leucocyte-antigen-DR53. We diagnosed him with subclinical antibody-mediated rejection accompanied by plasma cell-rich acute rejection. Both antibody-mediated rejection due to anti-human-leucocyteantigen -DR53 antibodies and plasma cell-rich acute rejection are known to be refractory and have a poor prognosis. Thus, we started plasma exchange with intravenous immunoglobulin and rituximab for the former and 3 days of consecutive steroid pulse therapy for the latter. Three months after treatment, a follow-up allograft biopsy showed excellent responses to treatment for both histological features. This case report considers the importance of an early diagnosis and appropriate intervention for subclinical antibody-mediated rejection due to donor specific antibody to humanleucocyte-antigen-DR53 and plasma cell-rich acute rejection.A recent study demonstrated that untreated subclinical antibody-mediated rejection (ABMR) is an important predictor of poor allograft outcomes.

Successful Treatment of Plasma Cell-Rich Acute Rejection Using Pulse Steroid Therapy Alone: A Case Report

“…Recipients with graft survival tended to be diagnosed earlier than did those with graft loss (average diagnosis time: 20.3 versus 40.9 months) [4]. Furthermore, among PCAR case reports, recipients with less than moderate interstitial inflammation (Banff classification: i1-2) tended to be diagnosed with PCAR earlier than were those with severe inflammation (Banff classification: i3) (average time 13.5 versus 24.7 months, p = 0.21 by Mann–Whitney test; Table 1) [5–11]. While these results suggest the importance of early PCAR diagnosis for prompt therapy and better allograft outcomes, whether an association exists between the timing of PCAR diagnosis and graft survival is still unknown.…”

“…Gärtner et al suggested that vascular rejection may be involved in poor graft outcomes in PCAR recipients [17]. Moreover, previous case reports of PCAR showed a tendency toward better allograft outcomes in recipients with mild or moderate interstitial infiltration (Banff classification: i1 and i2), compared with those with severe infiltration (i3) (Table 1) [5–11]. In contrast, a previous report of TCMR without PCAR showed that vascular rejection (Banff classification: ARII and ARIII) led to poorer allograft outcomes in recipients, similar to that seen with PCAR, but the severity of interstitial inflammation was not associated with graft survival [18].…”

Histopathological findings in transplanted kidneys

“…In previous studies, the response to antirejection therapy in PCAR, such as steroids, was less than satisfactory, with poor graft survival rates [105]. Some reports support the hypothesis that an antibody-mediated component participates in the graft injury of PCAR because it can be associated with both C4d staining and DSAs [99,103,106]. If there appears to be rapid progression of allograft dysfunction in the setting of significant plasma cell infiltration, then treatment modalities targeting both cellular and antibody-mediated pathways can be considered, although there are no data to support this line of treatment.…”

“…Most previous reports of subclinical rejection involved cellular rejection [93][94][95]. However, there are reports of allografts with histological manifestations of ABMR in the absence of functional deterioration of kidney function [30,[96][97][98][99]. Loupy et al suggested that subclinical TCMR was not associated with a significant effect on allograft outcome but triggered the appearance of de novo DSAs and progression to TG in a subset of patients.…”

Plasmapheresis Therapy in Kidney Transplant Rejection

“…Therefore, we suggest that DFPP aimed at AMR is significantly effective, cheap, and at low risks of infection. However, whether these interventions will improve the long-term kidney allograft survival is unclear [48]. It must be kept in mind that TPE can only remove antibodies, but drugs can suppress endogenous antibody rebound after depletion with TPE, and serves to restore antimicrobial immunoglobulins removed during plasmapheresis.…”