Plasma Cell-rich Acute Rejection Research Articles

MO1001THE OUTCOME OF PLASMA CELL-RICH ACUTE REJECTION IN KIDNEY TRANSPLANTATION, IS IT REALLY POOR?

Abstract Background and Aims The outcome of Plasma cell-rich acute rejection (PCAR) in kidney transplant is reported to be poor. However, PCAR which can be associated with any type of rejection, may not be considered as independent morphological prognostic feature. Different treatment modalities were prescribed with variable responses. We report here four cases of PCAR and describe their presentations, type of rejection, associated conditions and treatment outcome. Method Out of 1920 kidney transplant recipients under follow up in our centre from 1996 till 2019, four patients were reported to have PCAR according to 2007 Banff classification. They were re-evaluated based on 2015 Banff classification. The treatment protocol was tailored according to the type of rejection and associated conditions. Results The four patients, aged 28, 44, 46 and 54 years, had live unrelated renal transplant done somewhere abroad with no data about donor HLA typing. Two of them were females. One had high PRA and she was positive for HBsAg. One patient received induction immunosuppression with basiliximab. They all received prednisolone, mycophenolate and cyclosporine as the maintenance immunosuppression and had immediate graft function. Rejection happened between 23 to 180 months post-transplant. Two patients had acute T-cell mediated Banff 1A rejections with features consistent with early membranous nephropathy. One had acute T-cell mediated rejection Banff 1B and the fourth had borderline T-cell mediated rejection with morphological changes suggestive of chronic active antibody mediated rejection (AMR). Plasma cells constituted 10 to 30% of the interstitial infiltration. All patients received solumedrol pulse. Both patients with features of membranous nephropathy received rituximab and one of them had additionally IVIG. The patient with AMR received plasma exchange and IVIG. However, she did not receive rituximab as she was positive for HBsAg. All patients responded well to treatment and the mean improvement in eGFR was 12.8%, 24.9%, 40.3% and 39.1% at 1-, 3-, 6- and 12-months post treatment. Repeat kidney biopsy at 3 to 12 weeks post treatment showed resolution of plasma cell infiltration in all patients. Conclusion Outcome of PCAR management was favourable among our patients irrespective of the type of rejection and associated conditions.

Plasma cell rich acute rejection: Risk factors, treatment and outcomes.

Plasma cell-rich rejection is a rare and poorly defined entity. Its treatment is not clearly defined and has universally poor prognosis. More data should be published from various transplant centers around the world to identify the treatment that has the best outcomes and to formulate treatment guidelines for these cases. It is a retrospective analysis of kidney biopsies form 2008 to 2018. Four hundred biopsied were screened and 55 were found to have features of rejection and among them, 13 had plasma cell-rich rejection. Data of treatment given and the graft survival outcomes in these cases were retrieved by medical records. One patient had complete recovery, three had graft loss and the remaining nine had permanent decline in glomerular filtration rate. Decrease in immunosuppression and presence of infection are risk factors for plasma cell-rich acute rejection (PCAR). It can be acute cell-mediated rejection (ACR)/antibody-mediated rejection (AMR)/ACR+AMR. Resistant rejection, ACR+AMR, C4d positivity, and severe interstitial inflammation are poor prognostic factors. Overzealous decrease in immunosuppression should not be done. Management of immunosuppression during infection is most critical for the development of PCAR. Bortezomib is emerging as a therapeutic modality for the treatment of PCAR.

SUN-351 THE OUTCOME OF PLASMA CELL-RICH ACUTE REJECTION IN KIDNEY TRANSPLANTATION, IS IT REALLY POOR?

The outcome of Plasma cell-rich acute rejection (PCAR) in kidney transplant is reported to be poor. However, PCAR can present with any type of rejection and it may not be considered as independent prognostic morphological feature. Different treatment modalities were prescribed with variable responses. We report here four cases of PCAR and describe their presentations, type of rejection, associated conditions and treatment outcome. Out of 1920 kidney transplant recipients under follow up in our center, four patients were reported to have PCAR according to 2007 Banff classification. They were relooked at, based on the 2015 Banff classification. The treatment protocol was tailored according to the type of rejection and associated conditions. The four patients, aged 28, 44, 46 and 54 years, had live unrelated renal transplant done somewhere abroad with no data about donor HLA typing. Two of them were females. One had high PRA and she was positive for HBsAg. One patient received induction immunosuppression with basiliximab. They all received prednisolone, mycophenolate and cyclosporine as the maintenance immunosuppression and had immediate graft function. Rejection happened between 23 to 180 months post-transplant. Two patients had acute T-cell mediated Banff 1A rejections with features consistent with early membranous nephropathy. One had acute T-cell mediated rejection Banff 1B and the fourth had borderline T-cell mediated rejection with morphological changes suggestive of chronic active antibody mediated rejection (AMR). Plasma cells constituted 10 to 30% of the interstitial infiltration. All patients received solumedrol pulse. Both patients with features of membranous nephropathy received rituximab and one of them had additionally IVIG. The patient with AMR received plasma exchange and IVIG. However, she did not receive rituximab as she was positive for HBsAg. All patients responded to treatment and the mean improvement in eGFR was 20.5%, 21.4% and 11.2% at 1, 3 and 6 months post treatment. Repeat kidney biopsy at 3 to 12 weeks post treatment showed resolution of plasma cell infiltration in all patients. Outcome of PCAR management was favorable among our patients irrespective of the type of rejection and associated conditions.

Plasma Cell-Rich Acute Rejection in Renal Transplantation: A Case Report

Plasma cell-rich acute rejection (PCAR) is a rare type of allograft rejection in renal transplantation. It is characterized by the presence of mature plasma cells that compromise more than 10% of inflammatory cells infiltrating the renal graft. The pathogenesis of PCAR is unknown, appears late, and has been related mainly to insufficient immunosuppression or infections. The treatment is not clearly defined, and the graft survival is poor.Here, we report a case series of 3 Spanish patients diagnosed with PCAR accompanied by donor-specific antibodies (DSA) after kidney transplantation. Mean to diagnosis was 2-12 years post-transplantation, and they began with abrupt deterioration of renal function. All patients were women and had preceding viral infection. In addition, two of the three patients recognize a doubtful adherence to immunosuppression.About treatment, 2 of the 3 patients, because the biopsy of the renal graft showed signs suggestive of incipient antibody-mediated rejection (ABMR) (glomerulitis, capilaritis, transplant glomerulopathy), were started with corticosteroids, anti-thymoglobulin, plasmapheresis, and intravenous immunoglobulins. The last patient, who only showed PCAR at biopsy, was treated with corticosteroids and anti-thymoglobulin.After treatment, graft function improved in all of them, but one patient developed an ABMR and another required a dialysis program, all of which indicates the difficulty in management and treatment of PCAR.

Combined membranous glomerulonephritis and plasma cell-rich acute rejection in renal transplant recipient presented as nephrotic syndrome: case report and review of literature

Despite the contentious trials to improve the rates of acute rejection episodes and improve the renal allograft survival with potent immunosuppressants, the occurrence of more than 10 % of the inflammatory cells infiltrating renal allograft as mature plasma cells is uncommon and was recognized as plasma cell rich acute rejection (PCAR). Combination of PCAR with other glomerulopathies has not been reported before. Here, we report a case of late-onset PCAR associated with membranous glomerulonephritis (MGN) diagnosed at an early stage (2 years after transplantation). A 58-year-old male patient had end-stage kidney disease secondary to diabetic nephropathy and he was maintained on hemodialysis for 2 years until he underwent overseas living kidney transplantation. He presented to our center in Kuwait on the sixth day postoperatively, with stable renal function. He was maintained on steroid, cyclosporine, and mycophenolate mofetil. Two years after transplant, he developed picture of nephritic syndrome. His graft biopsy showed plasma cell-rich interstitial infiltrate associated with mild edema and focal tubulitis (PCACR) in addition to MGN. Further immunohistochemistry tests revealed both B-cell and T-cell markers (CD20 and CD3) were expressed in the lymphoplasmacytic infiltrate with predominant T lymphocytes. The possibility of multiple myeloma was ruled out. He received pulse steroid 1 g od for 3 days. His maintenance immunosuppression was intensified to tacrolimus-based regimen. Cluster differentiated lymphocyte count showed high CD-19 cells; therefore, we gave him a single dose of rituximab (375 mg/m2). Follow-up graft biopsy (1 month later) revealed MGN with complete resolution of plasma cells. His proteinuria started to improve after 4 months of management. He is enjoying stable graft function with controlled diabetes mellitus. PCAR is a treatable form of acute cellular rejection, and its combination with MGN will need special care with specific CD20 ablation therapy.

Allograft outcomes of treated children with kidney transplant who developed plasma cell-rich acute rejection (PCAR): A single center's experience.

PCAR is a rare form of ACR that may compromise renal allografts. This review evaluates the outcomes of a protocol used to treat PCAR (Study group), and compares these outcomes with a matched cohort with ACR (Control group). A retrospective analysis of 138 of pRTRs who underwent renal allograft biopsies between January 2008 and November 2016. Seven biopsies revealed in situ hybridization of EBER-negative PCAR (5%). Three Study group pRTRs lost their grafts within 3months after rejection (43%). None of the Control group pRTRs lost their graft during this period. At the time of rejection, eGFR was different between the Control and Study groups (27.0±19.9mL/min per m2 vs 40.0±10.6mL/min/1.73m2 , respectively; P<0.05). Among Study group pRTRs with functioning allografts (n=4), treatment resulted in an increase in eGFR from nadir levels (27.0±19.9 vs 55.6±18.3mL/min/1.73m2 , P<0.05). In the Study group, complications included neutropenia, BK and EBV viremia, and infusion-related hypotension and hypertension. (a) Graft loss in Study group while remaining high (43%) was lower than that reported in the published pediatric literature. (b) Our protocol was associated with improvement in eGFR in all surviving pRTRs within the Study group. (c) No life-threatening complications or malignancy were reported during the observation period.

Bortezomib Eliminates Plasma Cells From a Renal Graft in Plasma Cell–Rich Acute Rejection

Plasma cell–rich acute rejection (PCAR) and antibody-mediated rejection (ABMR), for which a standard treatment has not yet been established, are associated with poor graft survival after kidney transplantation. Here, we report a case series of 3 Japanese patients diagnosed with PCAR accompanied by ABMR. Steroid pulse therapy and rabbit antithymocyte globulin, plasma exchange, intravenous immunoglobulin, and rituximab therapies were sequentially performed in the first case. A graft biopsy after each treatment showed that plasma cell infiltration persisted. Five months after the initiation of rejection therapy, the patient was subjected to bortezomib therapy, which led to the partial elimination of plasma cells from the graft. However, the graft function gradually deteriorated, and hemodialysis treatment was warranted. In the other 2 cases, the patients received the same combination of therapy including bortezomib within a short period. Graft biopsies performed subsequently showed a marked decrease in the number of infiltrated plasma cells, and stabilization of renal graft function was achieved in both cases. Bortezomib, which targets plasma cells, is a potent drug that eliminates infiltrated plasma cells from the graft in PCAR. Thus, in addition to conventional therapy comprising plasma exchange, intravenous immunoglobulin, and rituximab against ABMR, bortezomib may be necessary to administer without any delay to control PCAR.

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

Plasma cell-rich acute rejection (PCAR) is a rare type of acute rejection in renal transplantation. Despite aggressive immunotherapy, approximately 40-60% of patients develop graft loss within 1 year after an episode of PCAR. However, the reason for this outcome remains obscure. This study retrospectively identified six patients with PCAR diagnosed between 2009 and 2015 at a single university hospital. Clinicopathological data were collected. Five of the six patients were male, and mean age at the onset of PCAR was 49.0 ±14.5 years. None of the patients showed overall poor adherence to medication. Mean time to diagnosis was 302 ±234 days post-transplantation. All patients had preceding or concurrent viral infection. Four patients developed PCAR alone and two patients developed PCAR with antibody-mediated rejection. One of the six patients showed both severe tubulointerstitial and microvascular inflammation (total of Banff tubulitis 't' + interstitial inflammation 'i' + glomerulitis 'g' + peritubular capillaritis 'ptc' scores >10). This patient had progressive worsening of graft function and re-initiated dialysis at 74 months after a PCAR episode. In addition, three of the six patients had long-term recurrence of PCAR. With the recurrence of PCAR, patients with both moderate tubulointerstitial and microvascular inflammation (total of Banff 't' + 'i' + 'g' + 'ptc' scores >6) had progressive worsening of graft function. In summary, the present results suggest that concurrent moderate to severe tubulointerstitial and microvascular inflammation may lead to poor outcomes of graft function after a PCAR episode.

Bortezomib Eliminates Plasma Cells from the Renal Graft in Plasma Cell-Rich Acute Rejection

Background Plasma cell–rich acute rejection (PCAR) and antibody- mediated rejection (ABMR) are associated with poor graft survival, and a standard treatment has not yet been established. Bortezomib is a proteasome inhibitor that induces apoptosis of plasma cells; however, there have been no reports that bortezomib is effective for PCAR accompanied by ABMR. Clinical Cases We report three Japanese patients diagnosed with PCAR accompanied by ABMR. Patient 1 was a 21-year-old man who had elevated serum creatinine 7 years after kidney transplantation. Steroid pulse therapy, rabbit antithymocyte globulin (rATG), plasma exchange (PEX), intravenous immunoglobulin (IVIG), and rituximab therapy were separately administered. Infiltrated plasma cells were persistent in the graft after each treatment, and 2 months later, he was treated with bortezomib, which led to the elimination of plasma cells from the graft. However, his graft function gradually deteriorated. Patient 2 was a 4-year-old girl who had elevated serum creatinine 1 year after kidney transplantation. Graft biopsy showed plasma cells infiltrated and clustered with CD20-positive cells in the renal graft (Figure 1). The combination therapy consisting of steroid, PEX, IVIG, rituximab, and bortezomib was administered. Infiltrated plasma cells were quickly eliminated from the graft (Figure 1), and stabilization of renal graft function has been achieved for 3 years. Patient 3 was a 36-year-old female who was diagnosed as ABMR with PCAR 6 years after kidney transplantation. She received the same therapy as patient 2 and plasma cells dramatically decreased in the graft. Pancytopenia and mild general fatigue were seen in patient 1 after bortezomib administration. Conclusions PCAR accompanied by ABMR is associated with a high risk of graft loss after kidney transplantation. Bortezomib, which targets plasma cells, is a potent medical agent that eliminates infiltrated plasma cells from the graft in PCAR. Full therapy, consisting of PEX, IVIG, and rituximab in addition to bortezomib, may be necessary to control PCAR accompanied by ABMR.

Management of Plasma Cell-Rich Acute Rejection in Living-Related Kidney Transplant: Role of Proteasome Inhibitor.

Plasma cell-rich acute rejection is an aggressive form of acute rejection that occurs late after transplant and is usually resistant to standard antirejection therapy. This study reports the safety, efficacy, and outcomes of plasma cell-rich acute rejection after treatment with bortezomib, a proteasome inhibitor, in 10 patients after a first living-related renal transplant. Plasma cell-rich acute rejection was diagnosed using the 2007 Banff classification. The treatment protocol for plasma cell-rich acute rejection included methylprednisolone (500 mg/kg), 7 sessions of plasmapheresis, antithymocyte globulin (3-5 mg/kg/day for 10 days), rituximab (2 doses at 375 mg/m2), and bortezomib (1 cycle at 1.3 mg/m2). The mean age of recipients and donors was 23.70 ± 11.39 and 37.30 ± 12.82 years, respectively. The mean time to plasma cell-rich acute rejection was 3.1 ± 2.5 years. The mean serum creatinine level at rejection was 4.8 ± 2.7 mg/dL. After treatment, serum creatinine decreased to 3.3 ± 1.8 mg/dL. Serum creatinine levels at 1-year and 2-year follow-up were 3.0 ± 2.3 and 3.3 ± 0.9 mg/dL, respectively. There was 1 graft failure due to recurrence of glomerulonephritis/de novo glomerulonephritis. No significant adverse effects were noted in the patients. Bortezomib successfully reverted plasma cell-rich acute rejection and stabilized graft function, with patients showing 2-year graft survival after rejection of 90%. Bortezomib-based treatment was successful in reverting plasma cell-rich acute rejection and stabilizing graft function, with graft survival of 90% at 2 years. Further studies with large cohorts and randomized trials with or without bortezomib will help in better evaluation of its efficacy, safety, and outcomes.

Immunohistopathologic Characterization of Plasma Cell-Rich Acute Rejection in Living-Related Renal Transplant Recipients.

Our aim was to analyze the immunohistopathologic features of plasma cell-rich acute rejection in a living-related renal transplant setting. Renal allograft biopsies of 50 cases of plasma cell-rich acute rejection were reviewed, and the main immunohistopathologic features were analyzed. The biopsies were studied using light microscopy, immunofluorescence, and immunohistochemistry and reported according to Banff classification. Biopsy findings were correlated with graft function and outcome. From February 2012 to December 2013, 50/1630 (3%) dysfunctional renal allograft biopsies showed plasma cell-rich acute rejection. Among acute changes, interstitial inflammation was of moderate degree in 8 cases (16%) and severe in 42 cases (84%). Mild tubulitis was found in 4 cases (8%), moderate tubulitis in 8 cases (16%), and severe tubulitis in 38 cases (76%). Glomerulitis was found in 2 cases (4%). No presence of arteritis was found. All plasma cell-rich acute rejection cases were of tubulointerstitial type, and most were of type IB. The mean percent of plasma cells on light microscopy in all cases was 28.8 ± 11.7%, and the range was 10% to 60%, with 46 cases (92%) showing plasma cell percent of ≥ 20%. The mean plasma cell percent on immunohistochemistry for CD138 was 29.0 ± 12.4%. Microvascular inflammation was found in 34 cases (68%). C4d testing was done by immunofluorescence in 22 cases (44%) and was positive in 8 cases (36%). Interstitial fibrosis/tubular atrophy was mild in 18 (36%), moderate in 28 (56%), and severe in 4 cases (8%). Plasma cell enrichment did not correlate with a variety of clinical and pathologic features (all P > .05). Plasma cell enrichment is not an independent prognostic morphologic feature and may represent either T-cell-mediated or antibody-mediated rejection or a mixture of these processes. Further investigations regarding its pathogenesis, accurate categorization, and treatment are needed.

Plasma cell-rich acute rejection of renal allograft: an unusual case of acute allograft dysfunction

We report a case of renal allograft dysfunction due to plasma cell-rich acute rejection (PCAR), which is an uncommon clinical entity with a wide range of differential diagnoses. Extensive diagnostic workup, treatment approach and outcome are discussed and we provide a brief summary of the current management dilemma. Nevertheless, the diagnosis of PCAR portends a poor prognosis and therefore timely diagnosis and intensification of treatment is crucial to prevent disease progression.

Expanding the antibody-mediated component of plasma cell-rich acute rejection: A case series.

Renal allograft rejection is mediated by T-cells (T-cell mediated rejection) or by donor-specific antibodies (DSAs) (antibody mediated rejection, ABMR). Plasma cell-rich acute rejection (PCAR) is a unique entity due to its peculiar morphology and poor prognostic behavior. All allograft biopsies done at our center from January 2013 to October 2014 were reviewed, and seven were identified with a diagnosis of PCAR with antibody mediated rejection (ABMR). The allograft biopsies were classified as per the Banff 2007 schema. Immunohistochemistry with C4d, SV 40, CD3, CD20, CD138, kappa and lambda light chain was performed. Total 210 allograft biopsies were performed in the study period of which seven biopsies (3.3%) were diagnosed as PCAR with ABMR. All these were late ABMRs (more than 6 months) with median posttransplant duration of 17 months. The allograft biopsy showed features of PCAR along with glomerulitis, peritubular capillaritis, and positive C4d. DSA was positive in six patients. All the patients were treated with standard therapeutic measures of acute cellular rejection (ACR) and ABMR including steroids, plasma exchange, rituximab and intravenous immunoglobulins. All the patients had persistent graft dysfunction or graft loss on follow-up.

Plasma cell-rich acute rejection: A morphologic archetype of combined cellular and humoral rejectione?

Plasma cell-rich acute rejection: A morphologic archetype of combined cellular and humoral rejectione?

The Role of Bortezomib in Pediatric Renal Transplant Recipients With Antibody Mediated Rejection.

Purpose: Bortezomib, a proteasome inhibitor has been used successfully to treat early antibody-mediated rejection(AMR) in adults. It is not known whether Bortezomib is safe and effective in pediatric kidney transplant recipients. It is also not known if it is effective in late AMR secondary to non-adherence. We utilized Bortezomib in IVIG/Rituximab resistant AMR. Methods: 8 patients with a mean age of 15.5 years(range 5-20 years), were treated with a bortezomib protocol that we adopted for pediatric kidney transplant patients using 4 doses of bortezomib(1.3 mg/m2 per dose × 4) per course at standard labeled doses. The bortezomib protocol also included a total of 7 rounds of plasma exchange and one round of rituximab at the beginning of the course and a round of high dose IVIG at the end. 1 patient had early acute AMR and 1 other patient had plasma cell rich Acute Cellular Rejection(ACR) on biopsy without DSA's. The remaining 6 patients had a combination of late AMR+/- ACR. Patients were monitored by serial donor specific anti-HLA antibody (DSA) determinations [Luminex/Labscreen beads] and quantified by conversion to fluorescence intensity to molecules of equivalent soluble fluorescence (MESF). Results: Of the 8 patients treated with bortezomib, no effect was observed in the patient with plasma cell rich ACR on biopsy. 1 patient suffered graft loss. In the serum at the time of pre-treatment biopsy, the mean sum of pre-treatment MFI of DSA's in the 7 patients was 25,579 (range 7457 - 43457). The same post-treatment was 24,663(range 4436-50082). In patients with coexisting ACR, 5 out of the 8 patients had an improvement in their Banff grade. Of the 7 patients that had C4d+ biopsies, 3 had reductions in their C4d staining. At the beginning of treatment the mean eGFR by the Schwartz method of 68.26 ml/min/1.73m2 (range 11.3 - 112) and post-treatment the mean was 80.41 ml/min/1.73m2( range 18 - 102.5). None of the patients experienced serious adverse events like peripheral neuropathy as defined by a predetermined protocol. Conclusion: We conclude that Bortezomib may have a modest effect in patients that showed denovo DSA's with AMR on biopsy due to non-adherence as determined by the % tacrolimus co-efficient of variation of by self-report due to a structured interview. In our experience the eGFR remained stable and there was a modest decrease in the MFI of DSA's and C4d staining. Bortezomib was not effective in treating plasma cell rich ACR.

Plasma Cell-Rich Acute Rejection With Monoclonal Gammopathy in a Renal Transplant Recipient

Plasma cell infiltration into a renal allograft comprises a spectrum of lesions from acute rejection to posttransplant lymphoproliferative disease. We report an unusual case of plasma cell infiltration into a renal allograft with monoclonal gammopathy. A 42-year-old woman was admitted because of graft dysfunction after noncompliance with immunosuppressive therapy for 5 months. A graft biopsy showed acute T-cell-mediated rejection and massive plasma cell infiltration. Despite initial treatment with steroids and antithymocyte globulin, there was persistence of graft dysfunction, monoclonal gammopathy, and plasma cell infiltration. Subsequent treatment with bortezomib improved graft function and caused the monoclonal gammopathy to resolve. Immunohistochemical evaluation of markers of B cells (CD20 and CD138) and the ratio of kappa-to-lambda light chain (15:1) showed that infiltrating cells were plasma cells producing kappa light chain. This suggested that plasma cell-rich acute rejection with monoclonal gammopathy in this patient might have been in an early stage of kappa light chain-producing posttransplant lymphoproliferative disease confined to the renal allograft, and that bortezomib may be effective in treating a patient with this condition.

A case of BK virus nephropathy and cytomegalovirus infection concurrent with plasma cell–rich acute rejection

The BK virus is a double-stranded DNA virus to which 90% of adults have been exposed. BK virus infections typically result in an oral or respiratory infection; however, BK virus reactivation is an infectious disease of concern in kidney transplant recipients. The prevalence of BK virus nephropathy (BKN) in kidney transplant recipients is approximately 5%, and most cases occur within one yr after kidney transplantation. Graft survival of BKN is reported to be 30-60%, and the standard treatment strategy for BKN is reducing immunosuppressive therapy and close monitoring for rejection. Viral infection is most common in the early post-transplantation phase, and BKN or acute rejection is one of the major factors involved in graft loss. However, in this report, we describe the successful management of BKN and cytomegalovirus infection concurrent with plasma cell-rich acute rejection.

Immunohistological study of a pediatric patient with plasma cell‐rich acute rejection

We report here the case of a girl who developed plasma cell-rich acute rejection (PCAR), a condition characterized by the presence of mature plasma cells infiltrating a renal allograft. The patient's creatinine level increased sharply to 4.3 mg/dL from 0.9 mg/dL at 19 months post-renal transplantation. She showed no response to methylprednisolone pulse therapy at a dose of 500 mg for three d but did show an immediate clinical and histopathological response to muromonab-CD3 (OKT3) administration. She had two episodes of PCAR recurrence and subsequently lost her graft. She had no evidences of antibody-mediated rejection including C4d deposition in peritubular capillaries and donor-specific antibodies during the entire follow-up period. To elucidate the pathogenesis of PCAR, immunohistological examination of infiltrating cells was performed. CD3-positive cells infiltration seemed to be associated with the CD138-positive cells infiltration, and the number of CD3-positive cells was increased preceding PCAR recurrence. Additionally, a rapid decrease in the number of CD138-positive cells and CD3-positive cells following the OKT3 administration was observed. This case suggests that T-cell mediated immune mechanisms might play a role in the development of PCAR.

Plasma cell-rich acute rejection of the renal allograft: A distinctive morphologic form of acute rejection?

This study was aimed at evaluating the clinicopathologic features of plasma cell-rich acute rejection (PCAR) of renal allograft and comparing them with acute cellular rejection (ACR), non-plasma cell-rich type. During a 2-year period, eight renal allograft biopsies were diagnosed as PCAR (plasma cells >10% of interstitial infiltrate). For comparison, 14 biopsies with ACR were included in the study. Detailed pretransplant data, serum creatinine at presentation, and other clinical features of all these cases were noted. Renal biopsy slides were reviewed and relevant immunohistochemistry performed for characterization of plasma cell infiltrate. The age range and duration of transplantation to diagnosis of acute rejection were comparable in both the groups. Histologically, the proportion of interstitial plasma cells, mean interstitial inflammation, and tubulitis score were higher in the PCAR group compared with cases with ACR. A significant difference was found in the outcome at last follow-up, being worse in patients with PCAR. This study shows that PCAR portends a poor outcome compared with ACR, with comparable Banff grade of rejection. Due to its rarity and recent description, nephrologists and renal pathologists need to be aware of this entity.

Plasma cell‐rich acute rejection after renal transplantation in a patient with pyoderma gangrenosum: a case report

A 40-yr-old female received a living-related renal transplantation on January 29, 2008. She had type I diabetes mellitus and pyoderma gangrenosum (PG). Induction immunosuppressive therapy consisted of tacrolimus, mycophenolate mofetil, basiliximab, and prednisolone. Intravenous methylprednisolone pulse therapy was administered to prevent ulceration at the surgical site. The postoperative outcome was almost uneventful, and renal graft function was well preserved for 11 months. Her graft function deteriorated on December 24, 2008 and thus an episode biopsy was performed. The histopathological findings were consistent with plasma cell-rich acute rejection (PCAR). During hospitalization, it was noted that the patient was non-compliant. We then performed steroid pulse therapy, and her graft function and histological findings improved. This is the first report of PCAR in a patient with PG who received a renal allograft. It was thought that PCAR was triggered because of her non-compliance. Thus, we should recognize the importance of enhancing compliance in transplant recipients.