Rituximab Therapy for Acute Humoral Rejection After Kidney Transplantation

Faguer, Stanislas; Kamar, Nassim; Guilbeaud-Frugier, Céline; Fort, Marylise; Modesto, Anne; Mari, Arnaud; Ribes, David; Cointault, Olivier; Lavayssière, Laurence; Guitard, Joëlle; Durand, Dominique; Rostaing, Lionel

doi:10.1097/01.tp.0000261113.30757.d1

Cited by 192 publications

(160 citation statements)

References 19 publications

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“…Rituximab has been clinically applied in the treatment of B cells related diseases including multiple myeloma (11). Tyden et al (12) found the effectiveness of Rituximab in patients with renal transplant rejection due to mismatched ABO blood type.…”

Section: Discussionmentioning

confidence: 99%

CD20 Expression in the Transplanted Kidney of Patients with Graft Loss and Transient Allograft Dysfunction

Han¹,

Shi²,

Cai³

et al. 2012

Journal of Medical Biochemistry

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Summary: This study aimed to explore the relationship between the infiltration of CD20+ B cells and the survival time of a renal allograft and to investigate the role of infiltrated B cells in the rejection of the renal allograft. A total of 40 patients with renal allograft loss due to refractory rejection and 20 patients with transient renal allograft dysfunction were recruited. Renal biopsy was done and CD20 expression was detected by immunohistochemistry. In addition, the survival time of the renal allograft was also obtained. The relationships between the CD20 expression and the survival time of the renal allograft and graft loss due to rejection were analyzed. The associations of gender, age and clinicopathogical types with the CD20 expression were also investigated. The proportion of patients positive for CD20 in the transplanted kidney was higher in patients receiving nephrectomy of the allograft due to rejection than in those with transient allograft dysfunction. The diffuse infiltration of CD20+ B cells was considered as positive staining. In 40 samples from patients with graft loss, 19 had diffuse infiltration of CD20+ B cells (47.5%). In 19 patients positive for CD20, hyperacute rejection was found in 1 patient, acute rejection in 5 and chronic rejection in 13. Statistical analysis showed the CD20 expression was not associated with the age and gender of donors and recipients, regimen for immunosuppressive treatment, cold/warm ischemia time and secondary transplantation. CD20+ B cell infiltration predicts a poor prognosis of patients with kidney transplantation and is one of the risk factors of graft loss. Keywords: renal allograft, rejection, CD20, B cellsKratak sadr`aj: Cilj ove studije bio je da se ispita odnos izme|u infiltracije CD20+ B }elija i vremena pre`ivljavanja bubre`nog alografta, kao i da se istra`i uloga infiltriranih B }elija u odbacivanju bubre`nog alografta. Obuhva}eno je ukupno 40 pacijenata sa gubitkom bubre`nog alografta usled refraktornog odbacivanja i 20 pacijenata sa prolaznom disfunkcijom bubre`nog alografta. Izvr{ena je biopsija bubrega a ekspresija CD20 detektovana je imunohistohemijski. Pored toga, utvr|eno je vreme pre`ivljavanja bubre`nog alografta. Analizirani su odnosi izme|u ekspresije CD20 i vremena pre`ivljavanja bubre`nog alografta i gubitka grafta usled odbacivanja. Tako|e je ispitana povezanost pola, uzrasta i klini~ko-patolo{kih tipova i ekspresije CD20. Propor cionalno vi{e pacijenata kod kojih je na|ena ekspresija CD20 u presa|enom bubregu bilo je me|u pacijentima podvrgnutim nefrektomiji alografta usled odbacivanja nego me|u onima sa prolaznom disfunkcijom alografta. Difuzna infiltracija CD20+ B }elija ozna~ena je kao pozitivno bojenje. Od 40 uzo raka od pacijenata sa gubitkom grafta, kod 19 je otkrivena difuzna infiltracija CD20+ B }elija (47,5 %). Od 19 pacijenata pozitivnih na CD20, kod 1 je prona|eno hiperakutno odbacivanje, kod 5 akutno odbacivanje a hroni~no odbacivanje kod 13 subjekata. Statisti~ka analiza je pokazala da ekspresija CD20 nije povezana sa ...

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Section: Discussionmentioning

confidence: 99%

CD20 Expression in the Transplanted Kidney of Patients with Graft Loss and Transient Allograft Dysfunction

Han¹,

Shi²,

Cai³

et al. 2012

Journal of Medical Biochemistry

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“…We were unable to perform c4d staining due to unavailability of the technique in our institution. Treatment options include plasmapheresis, high-dose corticosteroid pulses, and IVIG with varying success rate (4,5). Some of these antibodymediated rejection episodes are refractory to conventional treatments.…”

Section: Discussionmentioning

confidence: 99%

“…Becker et al fi rst reported successful treatment of such a steroid-resistant rejection episode with rituximab (6). Since then a number of case series and reports have been published with regards to success of rituximab in this particular indication (4,6). Rituximab is a chimeric murine/human anti CD 20 antibody which directly inhibits B cell proliferation by antibody-dependent, cell-mediated, and complement-mediated cytotoxicity (7).…”

Section: Discussionmentioning

confidence: 99%

Successful Treatment of Refractory Acute Humoral Allograft Rejection with Single Dose Rituximab

Solak¹,

Atalay²,

Türk³

2010

Turk Neph Dial Transpl

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Acute humoral rejection (AHR) is a rare event; however it can potentially lead to graft loss in up 40% of cases after 1 year of transplantation. A number of features like re-transplantation, ABO incompatibility and positive lymphocyte cross-match portend a high risk for AHR. We performed a retransplantation to a 23-year-old female patient who had lost her fi rst allograft due to polyomavirus nephropathy. After the second transplantation, she developed AHR that was confi rmed by allograft biopsy. We instituted steroid pulses for three days, alternate-day thymoglobulin, plasmapheresis and intravenous immunoglobulin. Despite this therapy, renal function did not improve; therefore as a last resort we administered singledose rituximab. Later on the course her urine output increased and kidney function recovered. In conclusion, rituximab can be tried as a last line of therapy in refractory AHR episodes. KEYWORDS: Refractory acute humoral rejection, Renal allograft, Rituximab ÖZAkut humoral rejeksiyon (AHR) nadir bir olaydır, ancak transplantasyondan 1 yıl sonrasında greft kayıplarının %40'ı kadarından sorumlu olabilir. Tekrarlayan transplantasyon, ABO kan grubu uyumsuzluğu ve pozitif lenfosit cross-match gibi bazı özellikler AHR için yüksek risk teşkil eder. İlk transplant böbreğini poliomavirüs enfeksiyonu nedeniyle kaybeden 23 yaşındaki kadın hastaya ikinci böbrek naklini yapıldı. Hastada nakil sonrası, böbrek biyopsisi ile konfi rme edilen AHR gelişti. Üç gün boyunca günlük pulse steroid, günaşırı timoglobulin ve plazmaferez uygulandı. Daha sonra IVIG verildi. Bu tedavilere rağmen böbrek fonksiyonları iyileşmedi. Son çare olarak hastaya tek doz rituximab uyguladık verildi. Hastanın idrar çıkışı ve fonksiyonları iyileşti. Sonuç olarak, refrakter AHR episodlarında rituximab son tedavi seçeneği olarak denenebilir. ANAHTAR SÖZCÜKLER:Refrakter akut humoral rejeksiyon, Renal allograft, Rituximab

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“…[7][8][9] Anti-CD20 antibodies (rituximab) have been used as rescue therapy for CD20-mediated refractory acute rejection with successful outcomes. 7,[10][11][12][13][14][15] Herein, we report a case of refractory acute cellular rejection with clusters of CD20-positive lymphocyte graft infiltrates, resistant to steroid pulses, plasmapheresis, and switching of immunosuppressive drug regimen, which was successfully treated with anti-CD20 antibodies.…”

Section: Introductionmentioning

confidence: 99%

“…26,27 However, rituximab has been successful in only 75% of recipients with positive DSAs and C4d-positive humoral rejection, raising the question of effective use of rituximab without CD20 phenotyping of the graft cellular infiltrate. 12 The presence of CD20-positive lymphocyte clusters in the allograft interstitium represents a severe subset of cellular rejection. 9 The infiltrating CD20-positive B cells may function as efficient antigen-presenting cells for indirect allorecognition, forming intrarenal ectopic lymphoid structures and leading to development of chronic allograft dysfunction.…”

mentioning

confidence: 99%

Refractory CD20 Positive Cellular Rejection in Living Kidney Transplant: A Case Report and Review of Literature

Akl

Sheashaa²,

Rahim³

et al. 2019

Exp Clin Transplant

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Transplant is the optimal therapy for patients with end-stage renal disease. Acute cellular rejection refractory to treatment remains a major risk factor for graft loss and poor outcomes. In this study, we describe a 39-year-old man who received a living-related kidney transplant. Two days after transplant, the patient displayed acute deterioration of graft function. Conventional anti-rejection therapy was initiated, but graft function did not improve. Biopsy revealed acute cellular rejection (grade IIA), and C4d and HLA antibodies were negative. Immuno histochemistry phenotyping revealed clusters of CD20-positive lymphocytes, with 80% being CD3 positive. Rituximab was prescribed, and graft function improved dramatically. After 1 week, a second graft biopsy was done due to lagging of graft function, shown by serum creatinine of 2.1 mg/dL. Biopsy revealed regenerating acute tubular necrosis with disappearance of the CD20-positive lymphocyte cluster infiltrates. Two year, after transplant, the patient's graft function maintained stable. Phenotyping of the cellular infiltrate is important as it may lead to a proper selection of immunosuppression and consequent improvement of graft outcome. Key words: Acute humoral rejection, B-cell-mediated rejection, CD20-mediated rejection, Renal transplantation, Rituximab IntroductionTransplant remains the optimal treatment for patients with end-stage renal disease. 1 Acute graft rejection remains a common complication and affects long-term graft survival. 2,3 Advances in immunosuppressive protocols have led to improvements in acute graft rejection episodes. 3-6 However, acute graft rejection, especially antibody-mediated rejection (AMR), can cause graft loss in some patients and can shorten graft function time in others. The presence of CD20-positive cells in the graft has been associated with poor reversibility of graft function and a trend toward poor graft survival even without AMR. 7-9 Anti-CD20 antibodies (rituximab) have been used as rescue therapy for CD20-mediated refractory acute rejection with successful outcomes. 7,10-15 Herein, we report a case of refractory acute cellular rejection with clusters of CD20-positive lymphocyte graft infiltrates, resistant to steroid pulses, plasmapheresis, and switching of immunosuppressive drug regimen, which was successfully treated with anti-CD20 antibodies. Case ReportA 39-year-old-male with type 2 insulin-dependent diabetes presented with end-stage kidney disease and with both kidneys having small size. The patient had been on regular hemodialysis for 3 years.The patient received a right iliac renal allograft from his 27-year-old brother. The sibling donor had a different compatible blood group, one mismatched HLA DR, negative repeated complement-dependent crossmatch test, and 7% donor nonspecific panel reactive antibody (PRA) class I and 0% PRA class II. There were no complications during the transplant procedure and postoperative period, with total ischemia time of 55 minutes and immediate diuresis. Induction immunosuppr...

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Rituximab Therapy for Acute Humoral Rejection After Kidney Transplantation

Cited by 192 publications

References 19 publications

CD20 Expression in the Transplanted Kidney of Patients with Graft Loss and Transient Allograft Dysfunction

CD20 Expression in the Transplanted Kidney of Patients with Graft Loss and Transient Allograft Dysfunction

Successful Treatment of Refractory Acute Humoral Allograft Rejection with Single Dose Rituximab

Refractory CD20 Positive Cellular Rejection in Living Kidney Transplant: A Case Report and Review of Literature

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