Plasma cell‐rich rejection accompanied by acute antibody‐mediated rejection in a patient with ABO‐incompatible kidney transplantation

Abstract

ABSTRACT:We report a case of plasma cell-rich rejection accompanied by acute antibody-mediated rejection in a patient with ABO-incompatible kidney transplantation. A 33-year-old man was admitted for an episode biopsy; he had a serum creatinine (S-Cr) level of 5.7 mg/dL 1 year following primary kidney transplantation. Histological features included two distinct entities: (1) a focal, aggressive tubulointerstitial inflammatory cell (predominantly plasma cells) infiltration with moderate tubulitis; and (2) inflammatory cell infiltration (including neutrophils) in peritubular capillaries. Substantial laboratory examination showed that the patient had donor-specific antibodies for DQ4 and DQ6. Considering both the histological and laboratory findings, we diagnosed him with plasma cell-rich rejection accompanied by acute antibody-mediated rejection. We started 3 days of consecutive steroid pulse therapy three times every 2 weeks for the former and plasma exchange with intravenous immunoglobulin (IVIG) for the latter histological feature. One month after treatment, a second allograft biopsy showed excellent responses to treatment for plasma cell-rich rejection, but moderate, acute antibody-mediated rejection remained. Therefore, we added plasma exchange with IVIG again. After treatment, allograft function was stable, with an S-Cr level of 2.8 mg/dL. This case report demonstrates the difficulty of the diagnosis of, and treatment for, plasma cell-rich rejection accompanied by acute antibody-mediated rejection in a patient with ABOincompatible kidney transplantation. We also include a review of the related literature.Both plasma cell-rich rejection (PCAR) and acute antibodymediated rejection (AMR) remain refractory rejection entities in spite of the recent development and establishment of immunosuppressive therapy. The former is characterized by the presence of mature plasma cells that comprise more than 10% of the inflammatory cell infiltration in a renal allograft.1 PCAR is a rare type of rejection noted in approximately 5-14% of patients with biopsy-proven acute rejection, but graft survival is poor and standard therapeutic options have yet to be generally established.2 The latter is a well-recognized type of rejection that is due in large part to antibodies to human leukocyte antigen (HLA) alleles. Recent studies have focused on not only HLA-DR compatibility, but also on that of HLA-DQ, since de novo DQ donor-specific antibodies (DSAbs) are the predominant HLA class II DSAbs found after transplantation. 3 We report here a refractory case of PCAR accompanied by AMR due to de novo DQ DSAbs 1 year after ABOincompatible, living-related kidney transplantation. CASE REPORTA 33-year-old Japanese man was admitted to our hospital for an episode biopsy 1 year following primary kidney transplantation. He was diagnosed with IgA nephropathy at the age of 31 years and received a living-related kidney transplantation at the age of 32 from his mother. ABO blood types were incompatible, and HLA alleles were mismatched at two bs_bs_ban...

Clinicopathological features and outcomes of kidney allografts in plasma cell‐rich acute rejection: A case series

“…reported that microvascular inflammation is associated with DSA positivity and recommended consideration of ABMR . Previous studies have reported that PCAR with poor outcome is associated with DSA or ABMR . An association between PCAR and ABMR cannot be definitively concluded from the results of the present study.…”

“…Several studies have reported that despite aggressive immunotherapy, some cases of rejection are refractory, and approximately 40–60% of patients develop graft loss within 1 year after a PCAR episode . Some cases were associated with donor‐specific antibodies (DSA) or ABMR . Assessing the pathophysiologic processes for this rare type of acute rejection is difficult, and the reasons for the poor outcomes seen with PCAR remain obscure.…”

Clinicopathological and immunohistochemical analysis of plasma cell‐rich rejection in renal transplantation: Involvement of intratubular Th1/Th2 balance in plasma cell enrichment

“…Recently several investigators have reported PCRR cases associated with antibody component and suggested that PCRR represents a prototype of AAMR or combined type of ATCR and AAMR . In our study, there were no significant differences in ATCR type based on the Banff classification and frequency of complicating AAMR between PCRRs and ATCRs.…”

“…Although PCRR has been considered a subtype of ATCR, methylprednisolone pulse (mPSL), a standard regimen for ATCR, is not usually adequately effective in cases of PCRR. Moreover, recent studies have suggested the distinctive characteristics of PCRR that differ from those of ATCR including long post‐transplant duration prior to rejection, poor graft survival and probable association with antibody components . Ultimately, PCRR is recognised as a refractory rejection and no ideal treatment for PCRR has been established.…”

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.…”