bs_bs_banner
Nephrology 19, Suppl. 3 (2014) 31–34
Brief Communication
Plasma cell-rich rejection accompanied by acute antibody-mediated rejection in a patient with ABO-incompatible kidney transplantation MAIKO FURUYA,1 IZUMI YAMAMOTO,1 AKIMITSU KOBAYASHI,1 YASUYUKI NAKADA,1 NAOKI SUGANO,1 YUDO TANNO,1 ICHIRO OHKIDO,1 NOBUO TSUBOI,1 HIROYASU YAMAMOTO,2 KEITARO YOKOYAMA1 and TAKASHI YOKOO1 1 Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, and 2Department of Internal Medicine, Atsugi City Hospital, Kanagawa, Japan
KEY WORDS: acute antibody-mediated rejection, anti-DQ antibody, plasma cell-rich rejection. Correspondence: Dr Maiko Furuya, Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, 3-25-8, Nishi-shinbashi, Minato-ku, Tokyo 105-8471, Japan. Email: [email protected] doi:10.1111/nep.12245 Conflicts of interest: The authors have no competing interests and do not have any relationships to disclose.
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 © 2014 Asian Pacific Society of Nephrology
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 REPORT A 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 31
M Furuya et al.
Fig. 1 Clinical course. TAC, tacrolimus; MMF, mycophenolate mofetil; mPSL, metylprednisolone; PEX, plasma exchange; IVIG, intra) venous immunoglobulin; Cr, creatinine. ( Cr (mg/dL), ( ) U-Prot (g/day).
loci, B52 and DR8. The standard complement-dependent cytotoxicity cross-match test was negative. Immunosuppressive therapy consisted of tacrolimus, mycophenolate mofetil, metylprednisolone and basiliximab. The allograft had excellent early function, with an S-Cr level of 1.48 mg/dL 6 weeks before admission. However, one year after transplantation, his S-Cr level rapidly increased to 5.7 mg/dL, and he was admitted to our hospital for further evaluation, including the episode biopsy. The clinical course of the patient is shown in Figure 1. The allograft episode biopsy was performed one year following primary kidney transplantation. In the cortical area, focal interstitial mononuclear cell infiltration with mild interstitial fibrosis and tubular atrophy was identified, and moderate tubulitis was observed (Fig. 2). Plasma cells were detected in predominantly (more than 50% of inflammatory cells) the tubulointerstitial area (Fig. 2B). In addition, inflammatory cell infiltration (including neutrophils) was observed in peritubular capillaries (Fig. 2C). Immunohistological studies showed strong, linear, circumferential C4d immunoreactivity in peritubular capillaries. To exclude posttransplant lymphoproliferative disorder (PTLD), staining of kappa and lambda was carried out, but monoclonality was not seen. SV40- and EBER-positive cells were also not evident. Further evaluation for DSAbs using the flow cytometric panel reactive antibody method (Flow PRA) identified those against HLA class I (1.84%) and class II (53.52%). Additional screening with the LABScreen single antigen test (One Lamda, USA) identified anti-DQ4, 9, 7, 8, 2 and 6, but not DR8, DSAbs. Therefore, a donor DQ typing test was required, and we confirmed that our donor had 32
HLA-DQ4 and -DQ6. The mean fluorescence intensity (MFI) values are 2701 for anti-HLA-DQ4 Ab but less than 1579 for anti-HLA-DQ6 Ab. Taken together, these findings indicated that acute AMR occurred due to de novo anti-DQ4 and antiDQ6 antibodies. Finally, we diagnosed our patient with PCAR accompanied by acute AMR type II. The Banff ‘07 classification was t2, i2, g0, v0, ptc3, ct1, ci1, cg0, cv0, ptcbmml0 and ah0. We treated him with 3 consecutive days of intravenous steroid pulse therapy (methylprednisolone, 500 mg/day) every 3 weeks and administered intravenous immunoglobulin (IVIG) and plasma exchange (PEX). The S-Cr level gradually decreased from 5.7 to 2.75 mg/dL and did not decrease thereafter. To evaluate the efficacy of the treatment, we performed a second biopsy on day 37. The second biopsy specimen revealed peritubular capillaries with neutrophil infiltration, focal and moderate. Tubulointerstitial inflammatory cells are focal and there were much less plasma cells infiltration compared with previous renal biopsy. We diagnosed the patient with residual AMR type II. The Banff classification was t0, i1, g0, v0, ptc2, ct1, ci1, cg0, cv0, ptcbmml1 and ah0. For treatment of the residual refractory AMR, we performed an additional three sessions of PEX and IVIG. In addition, we administered rituximab (200 mg/body) on day 44, because his CD19/20 level increased to 9.2% and 10.3%. The S-Cr level did not increase further and was stable at 2.8 mg/dL. The patient was discharged from our hospital on day 58. After leaving hospital, in spite of the above therapy, his S-Cr level was not decreased less than 2.7 mg/dL. The additional biopsy was performed 2 years after kidney transplan© 2014 Asian Pacific Society of Nephrology
Plasma cell-rich rejection
Fig. 2 Light microscopic findings of the first biopsy. (A) Focal interstitial mononuclear cell infiltration with mild interstitial fibrosis and tubular atrophy was identified, and moderate tubulitis was observed (HE, ×40). (B) Plasma cells were detected in predominantly the tubulointerstitial area (PAS, ×400). (C) Inflammatory cell infiltration, including neutrophils, was observed in peritubular capillaries (PAS, ×400).
tation and found the obstinate mild peritubular capillaritis and mild capillary basement membrane thickening. Further analysis showed de novo anti-DQ4 antibodies increased to 14 315 on MFI values. Again, for treatment of the obstinate refractory AMR, we performed an additional three sessions of PEX and IVIG. In addition, we administered rituximab (200 mg/body) because his CD19/20 level increased to 1.5% and 2%. His S-Cr level was still high at the S-Cr level of 2.8 mg/dL 30 months after kidney transplantation.
DISCUSSION In this study, we report a refractory case of PCAR accompanied by acute AMR. This case report helps to inform at least two debates: (1) the difficulties of diagnosis and management of PCAR when it is accompanied by AMR; and (2) the difficulties of diagnosis of AMR when it is resultant of antiHLA-DQ antibody in ABO-incompatible kidney transplantation, because HLA-DQ antigen screening is not always required. PCAR is characterized by the presence of mature plasma cells that comprise more than 10% of the inflammatory cell infiltration in a renal graft.1 This pathologic finding is noted in approximately 5–14% of patients with biopsy-proven acute rejection. Although therapy for this condition has not been generally established, graft survival is poor.2 To diagnose PCAR, physicians should pay attention to PTLD caused by Epstein-Barr (EB) viral infection, because the treatment for PTLD is contrary to that for PCAR.4 In our case, we confirmed that there was no monoclonality for kappa and lambda by immunohistochemistry. In addition, EBER stain© 2014 Asian Pacific Society of Nephrology
ing was negative by in situ hybridization. Authorities stated that there could be an AMR variant of PCAR. C4d-positive PCAR with circulating DSAbs responds adequately to treatment aimed at AMR, such as rituximab and IVIG combination therapy. On the other hand, C4d-negative PCAR is intractable to treatment. In our case, treatment aimed at AMR showed good response. Current anti-humoral therapies in transplantation and autoimmune disease do not target the mature antibody-producing plasma cells. Matthew et al. reported that bortezomib therapy may be effective for treating mixed rejection (AMR and acute T cellmediated rejection) with minimal toxicity and for sustaining reduction of DSAb and non-DSAb levels.5 In this context, a strategy for treating PCAR needs to be established in the future. The importance of HLA matching in kidney transplantation is well recognized, with HLA-DR compatibility having the greatest influence on outcome.6,7 Recent studies have demonstrated that HLA class II DSAbs have a greater effect than class I DSAbs.8,9 More recent studies showed that de novo DQ DSAbs are the predominant HLA class II DSAbs found after transplantation.3,10 Those reports showed that 17.8– 18.2% of patients developed de novo HLA DSAbs after kidney transplantation, and 10–13.8% of patients had de novo DQ DSAbs. Moreover, of the HLA DSAb-positive patients, 54.3– 77.8% developed de novo DQ DSAbs. Significantly, graft survival was worse and AMR occurred at a higher incidence in de novo DQ DSAb-positive cases compared with all other cases.3,10 Considering these reports, AMR due to de novo DQ DSAbs could be a prominent cause for deteriorating kidney function in this case. HLA-DQ typing before kidney trans33
M Furuya et al.
plantation promises early detection of AMR, especially in the case of ABO-incompatible kidney transplantation. In conclusion, we report an obstinate refractory case of PCAR accompanied by AMR due to de novo DQ DSAbs 1 year after ABO-incompatible kidney transplantation. The causes of PCAR are not well understood, but this case could be a variant of AMR. Treatment aimed at AMR, including rituximab, IVIG and PEX combination therapy, was effective in our case. Establishing an appropriate treatment for PCAR is a forthcoming challenge. In addition, since de novo DQ DSAbs are the predominant class II DSAbs present after kidney transplantation and are associated with inferior allograft outcomes, HLA typing – not only HLA-A, B, and DR loci but also HLA-DQ – promises earlier and better treatment of patients with kidney transplantation.
REFERENCES 1. Adrogue HE, Soltero L, Land GA et al. Immunoglobulin therapy for plasma cell-rich rejection in the renal allograft. Transplantation 2006; 82: 567.
34
2. Charney DA, Nadasdy T, Lo AW et al. Plasma cell-rich acute renal allograft rejection. Transplantation 1999; 68: 791. 3. Willicombe M, Brookes P, Sergeant R et al. De novo DQ donor-specific antibodies are associated with a significant risk of antibody-mediated rejection and transplant glomerulopathy. Transplantation 2012; 94: 172–7. 4. Rokshana S, Lesley R. The post-transplant lymphoproliferative disorder – A literature review. Pediatr. Nephrol. 2004; 19: 369. 5. Chandrasekar P, Ljungman PT. Antifungal therapy strategies in hematopoietic stem-cell transplant recipients: Early treatment options for improving outcomes. Transplantation 2008; 86: 189. 6. Ting A, Morris PJ. Powerful effect of HLA-DR matching on survival of cadaveric renal allografts. Lancet 1980; 2: 282. 7. Gillks WR, Bradley BA, Gore SM et al. Substantial benefits of tissue matching in renal transplantation. Transplantation 1987; 43: 669. 8. Terasaki PI, Ozawa M, Castro R. Four-year follow-up of a prospective trial of HLA and MICA antibodies on kidney graft survival. Am. J. Transplant. 2007; 2: 408. 9. Willicombe M, Roufosse C, Brookes P et al. Antibody-mediated rejection after alemtuzumab induction: Incidence, risk factors, and predictors of poor outcome. Transplantation 2011; 92: 176. 10. DeVos JM, Gaber AO, Knight RJ et al. Donor-specific HLA-DQ antibodies may contribute to poor graft outcome after renal transplantation. Kidney Int. 2012; 82: 598.
© 2014 Asian Pacific Society of Nephrology
Nephrology 19, Suppl. 3 (2014) 31–34
Brief Communication
Plasma cell-rich rejection accompanied by acute antibody-mediated rejection in a patient with ABO-incompatible kidney transplantation MAIKO FURUYA,1 IZUMI YAMAMOTO,1 AKIMITSU KOBAYASHI,1 YASUYUKI NAKADA,1 NAOKI SUGANO,1 YUDO TANNO,1 ICHIRO OHKIDO,1 NOBUO TSUBOI,1 HIROYASU YAMAMOTO,2 KEITARO YOKOYAMA1 and TAKASHI YOKOO1 1 Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, and 2Department of Internal Medicine, Atsugi City Hospital, Kanagawa, Japan
KEY WORDS: acute antibody-mediated rejection, anti-DQ antibody, plasma cell-rich rejection. Correspondence: Dr Maiko Furuya, Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, 3-25-8, Nishi-shinbashi, Minato-ku, Tokyo 105-8471, Japan. Email: [email protected] doi:10.1111/nep.12245 Conflicts of interest: The authors have no competing interests and do not have any relationships to disclose.
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 © 2014 Asian Pacific Society of Nephrology
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 REPORT A 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 31
M Furuya et al.
Fig. 1 Clinical course. TAC, tacrolimus; MMF, mycophenolate mofetil; mPSL, metylprednisolone; PEX, plasma exchange; IVIG, intra) venous immunoglobulin; Cr, creatinine. ( Cr (mg/dL), ( ) U-Prot (g/day).
loci, B52 and DR8. The standard complement-dependent cytotoxicity cross-match test was negative. Immunosuppressive therapy consisted of tacrolimus, mycophenolate mofetil, metylprednisolone and basiliximab. The allograft had excellent early function, with an S-Cr level of 1.48 mg/dL 6 weeks before admission. However, one year after transplantation, his S-Cr level rapidly increased to 5.7 mg/dL, and he was admitted to our hospital for further evaluation, including the episode biopsy. The clinical course of the patient is shown in Figure 1. The allograft episode biopsy was performed one year following primary kidney transplantation. In the cortical area, focal interstitial mononuclear cell infiltration with mild interstitial fibrosis and tubular atrophy was identified, and moderate tubulitis was observed (Fig. 2). Plasma cells were detected in predominantly (more than 50% of inflammatory cells) the tubulointerstitial area (Fig. 2B). In addition, inflammatory cell infiltration (including neutrophils) was observed in peritubular capillaries (Fig. 2C). Immunohistological studies showed strong, linear, circumferential C4d immunoreactivity in peritubular capillaries. To exclude posttransplant lymphoproliferative disorder (PTLD), staining of kappa and lambda was carried out, but monoclonality was not seen. SV40- and EBER-positive cells were also not evident. Further evaluation for DSAbs using the flow cytometric panel reactive antibody method (Flow PRA) identified those against HLA class I (1.84%) and class II (53.52%). Additional screening with the LABScreen single antigen test (One Lamda, USA) identified anti-DQ4, 9, 7, 8, 2 and 6, but not DR8, DSAbs. Therefore, a donor DQ typing test was required, and we confirmed that our donor had 32
HLA-DQ4 and -DQ6. The mean fluorescence intensity (MFI) values are 2701 for anti-HLA-DQ4 Ab but less than 1579 for anti-HLA-DQ6 Ab. Taken together, these findings indicated that acute AMR occurred due to de novo anti-DQ4 and antiDQ6 antibodies. Finally, we diagnosed our patient with PCAR accompanied by acute AMR type II. The Banff ‘07 classification was t2, i2, g0, v0, ptc3, ct1, ci1, cg0, cv0, ptcbmml0 and ah0. We treated him with 3 consecutive days of intravenous steroid pulse therapy (methylprednisolone, 500 mg/day) every 3 weeks and administered intravenous immunoglobulin (IVIG) and plasma exchange (PEX). The S-Cr level gradually decreased from 5.7 to 2.75 mg/dL and did not decrease thereafter. To evaluate the efficacy of the treatment, we performed a second biopsy on day 37. The second biopsy specimen revealed peritubular capillaries with neutrophil infiltration, focal and moderate. Tubulointerstitial inflammatory cells are focal and there were much less plasma cells infiltration compared with previous renal biopsy. We diagnosed the patient with residual AMR type II. The Banff classification was t0, i1, g0, v0, ptc2, ct1, ci1, cg0, cv0, ptcbmml1 and ah0. For treatment of the residual refractory AMR, we performed an additional three sessions of PEX and IVIG. In addition, we administered rituximab (200 mg/body) on day 44, because his CD19/20 level increased to 9.2% and 10.3%. The S-Cr level did not increase further and was stable at 2.8 mg/dL. The patient was discharged from our hospital on day 58. After leaving hospital, in spite of the above therapy, his S-Cr level was not decreased less than 2.7 mg/dL. The additional biopsy was performed 2 years after kidney transplan© 2014 Asian Pacific Society of Nephrology
Plasma cell-rich rejection
Fig. 2 Light microscopic findings of the first biopsy. (A) Focal interstitial mononuclear cell infiltration with mild interstitial fibrosis and tubular atrophy was identified, and moderate tubulitis was observed (HE, ×40). (B) Plasma cells were detected in predominantly the tubulointerstitial area (PAS, ×400). (C) Inflammatory cell infiltration, including neutrophils, was observed in peritubular capillaries (PAS, ×400).
tation and found the obstinate mild peritubular capillaritis and mild capillary basement membrane thickening. Further analysis showed de novo anti-DQ4 antibodies increased to 14 315 on MFI values. Again, for treatment of the obstinate refractory AMR, we performed an additional three sessions of PEX and IVIG. In addition, we administered rituximab (200 mg/body) because his CD19/20 level increased to 1.5% and 2%. His S-Cr level was still high at the S-Cr level of 2.8 mg/dL 30 months after kidney transplantation.
DISCUSSION In this study, we report a refractory case of PCAR accompanied by acute AMR. This case report helps to inform at least two debates: (1) the difficulties of diagnosis and management of PCAR when it is accompanied by AMR; and (2) the difficulties of diagnosis of AMR when it is resultant of antiHLA-DQ antibody in ABO-incompatible kidney transplantation, because HLA-DQ antigen screening is not always required. PCAR is characterized by the presence of mature plasma cells that comprise more than 10% of the inflammatory cell infiltration in a renal graft.1 This pathologic finding is noted in approximately 5–14% of patients with biopsy-proven acute rejection. Although therapy for this condition has not been generally established, graft survival is poor.2 To diagnose PCAR, physicians should pay attention to PTLD caused by Epstein-Barr (EB) viral infection, because the treatment for PTLD is contrary to that for PCAR.4 In our case, we confirmed that there was no monoclonality for kappa and lambda by immunohistochemistry. In addition, EBER stain© 2014 Asian Pacific Society of Nephrology
ing was negative by in situ hybridization. Authorities stated that there could be an AMR variant of PCAR. C4d-positive PCAR with circulating DSAbs responds adequately to treatment aimed at AMR, such as rituximab and IVIG combination therapy. On the other hand, C4d-negative PCAR is intractable to treatment. In our case, treatment aimed at AMR showed good response. Current anti-humoral therapies in transplantation and autoimmune disease do not target the mature antibody-producing plasma cells. Matthew et al. reported that bortezomib therapy may be effective for treating mixed rejection (AMR and acute T cellmediated rejection) with minimal toxicity and for sustaining reduction of DSAb and non-DSAb levels.5 In this context, a strategy for treating PCAR needs to be established in the future. The importance of HLA matching in kidney transplantation is well recognized, with HLA-DR compatibility having the greatest influence on outcome.6,7 Recent studies have demonstrated that HLA class II DSAbs have a greater effect than class I DSAbs.8,9 More recent studies showed that de novo DQ DSAbs are the predominant HLA class II DSAbs found after transplantation.3,10 Those reports showed that 17.8– 18.2% of patients developed de novo HLA DSAbs after kidney transplantation, and 10–13.8% of patients had de novo DQ DSAbs. Moreover, of the HLA DSAb-positive patients, 54.3– 77.8% developed de novo DQ DSAbs. Significantly, graft survival was worse and AMR occurred at a higher incidence in de novo DQ DSAb-positive cases compared with all other cases.3,10 Considering these reports, AMR due to de novo DQ DSAbs could be a prominent cause for deteriorating kidney function in this case. HLA-DQ typing before kidney trans33
M Furuya et al.
plantation promises early detection of AMR, especially in the case of ABO-incompatible kidney transplantation. In conclusion, we report an obstinate refractory case of PCAR accompanied by AMR due to de novo DQ DSAbs 1 year after ABO-incompatible kidney transplantation. The causes of PCAR are not well understood, but this case could be a variant of AMR. Treatment aimed at AMR, including rituximab, IVIG and PEX combination therapy, was effective in our case. Establishing an appropriate treatment for PCAR is a forthcoming challenge. In addition, since de novo DQ DSAbs are the predominant class II DSAbs present after kidney transplantation and are associated with inferior allograft outcomes, HLA typing – not only HLA-A, B, and DR loci but also HLA-DQ – promises earlier and better treatment of patients with kidney transplantation.
REFERENCES 1. Adrogue HE, Soltero L, Land GA et al. Immunoglobulin therapy for plasma cell-rich rejection in the renal allograft. Transplantation 2006; 82: 567.
34
2. Charney DA, Nadasdy T, Lo AW et al. Plasma cell-rich acute renal allograft rejection. Transplantation 1999; 68: 791. 3. Willicombe M, Brookes P, Sergeant R et al. De novo DQ donor-specific antibodies are associated with a significant risk of antibody-mediated rejection and transplant glomerulopathy. Transplantation 2012; 94: 172–7. 4. Rokshana S, Lesley R. The post-transplant lymphoproliferative disorder – A literature review. Pediatr. Nephrol. 2004; 19: 369. 5. Chandrasekar P, Ljungman PT. Antifungal therapy strategies in hematopoietic stem-cell transplant recipients: Early treatment options for improving outcomes. Transplantation 2008; 86: 189. 6. Ting A, Morris PJ. Powerful effect of HLA-DR matching on survival of cadaveric renal allografts. Lancet 1980; 2: 282. 7. Gillks WR, Bradley BA, Gore SM et al. Substantial benefits of tissue matching in renal transplantation. Transplantation 1987; 43: 669. 8. Terasaki PI, Ozawa M, Castro R. Four-year follow-up of a prospective trial of HLA and MICA antibodies on kidney graft survival. Am. J. Transplant. 2007; 2: 408. 9. Willicombe M, Roufosse C, Brookes P et al. Antibody-mediated rejection after alemtuzumab induction: Incidence, risk factors, and predictors of poor outcome. Transplantation 2011; 92: 176. 10. DeVos JM, Gaber AO, Knight RJ et al. Donor-specific HLA-DQ antibodies may contribute to poor graft outcome after renal transplantation. Kidney Int. 2012; 82: 598.
© 2014 Asian Pacific Society of Nephrology
