ABSTRACT
Abstract Introduction: Sensitization to human leukocyte antigen is a barrier to. Few data have been published on desensitization using polyvalent human intravenous immunoglobulin (IVIG) alone. Methods: We retrospectively reviewed the of 45 patients with a positive complement-dependent cytotoxicity crossmatch (CDCXM) or flow cytometry crossmatch (FCXM) against living donors from January 2003 to December 2014. Of these, 12 were excluded. Patients received monthly IVIG infusions (2 g/kg) only until they had a negative T-cell and B-cell FCXM. Results: During the 33 patients, 22 (66.7%) underwent living donor kidney transplantation, 7 (21.2%) received a deceased donor graft, and 4 (12.1%) did not undergo transplantation. The median class I and II panel reactive antibodies for these patients were 80.5% (range 61%-95%) and 83.0% (range 42%-94%), respectively. Patients (81.8%) had a positive T-cell and/or B-cell CDCXM and 4 (18.2%) had a positive T-cell and/or B-cell FCXM. Patients underwent transplantation after a median of 6 (range 3-16). The median donor-specific antibody mean fluorescence intensity sum was 5057 (range 2246-11,691) before and 1389 (range 934-2492) after desensitization (p = 0.0001). Mean patient follow-up time after transplantation was 60.5 (SD, 36.8) months. Nine patients (45.0%). Death-censored graft survival at 1, 3, and 5 years after transplant was 86.4, 86.4, and 79.2%, respectively and patient survival was 95.5, 95.5, and 83.7%, respectively. Conclusions: Desensitization using IVIG alone is an effective strategy, allowing successful transplantation in 87.9% of these highly sensitized patients.
Resumo Introdução: Sensibilização HLA é uma barreira ao transplante em pacientes sensibilizados. Há poucos dados publicados sobre dessensibilização utilizando somente imunoglobulina intravenosa humana polivalente (IgIV). Métodos: Revisamos retrospectivamente prontuários de 45 pacientes com prova cruzada positiva por citotoxicidade dependente do complemento (CDCXM) ou citometria de fluxo (FCXM) contra doadores vivos, de Janeiro/2003-Dezembro/2014. Destes, excluímos 12. 33 pacientes receberam infusões mensais de IgIV (2 g/kg) apenas até apresentarem FCXM células T e B negativa. Resultados: Durante dessensibilização, 22 pacientes (66,7%) realizaram transplante renal com doador vivo, 7 (21,2%) receberam enxerto de doador falecido, 4 (12,1%) não realizaram transplante. A mediana do painel de reatividade de anticorpos classes I e II para estes pacientes foi 80,5% (intervalo 61%-95%) e 83,0% (intervalo 42%-94%), respectivamente. 18 pacientes (81,8%) apresentaram CDCXM célula T e/ou B positiva; 4 (18,2%) apresentaram FCXM célula T e/ou B positiva. Pacientes realizaram transplante após mediana de 6 (intervalo 3-16) infusões. A mediana da somatória da intensidade média de fluorescência do anticorpo específico contra o doador foi 5057 (intervalo 2246-11.691) antes e 1389 (intervalo 934-2492) após dessensibilização (p = 0,0001). O tempo médio de acompanhamento do paciente pós transplante foi 60,5 (DP, 36,8) meses. Nove pacientes (45,0%) não apresentaram rejeição e 6 (27,3%) apresentaram rejeição mediada por anticorpos. Sobrevida do enxerto censurada para óbito em 1, 3, 5 anos após transplante foi 86,4; 86,4; 79,2%, respectivamente, e sobrevida do paciente foi 95,5; 95,5; 83,7%, respectivamente. Conclusões: Dessensibilização utilizando apenas IgIV é uma estratégia eficaz, permitindo transplante bem-sucedido em 87,9% destes pacientes altamente sensibilizados.
ABSTRACT
OBJECTIVE: The significance of pretransplant, donor-specific antibodies on long-term patient outcomes is a subject of debate. This study evaluated the impact and the presence or absence of donor-specific antibodies after kidney transplantation on short- and long-term graft outcomes. METHODS: We analyzed the frequency and dynamics of pretransplant donor-specific antibodies following renal transplantation from a randomized trial that was conducted from 2002 to 2004 and correlated these findings with patient outcomes through 2009. Transplants were performed against a complement-dependent T- and B-negative crossmatch. Pre- and posttransplant sera were available from 94 of the 118 patients (80%). Antibodies were detected using a solid-phase (LuminexH), single-bead assay, and all tests were performed simultaneously. RESULTS: Sixteen patients exhibited pretransplant donor-specific antibodies, but only 3 of these patients (19%) developed antibody-mediated rejection and 2 of them experienced early graft losses. Excluding these 2 losses, 6 of 14 patients exhibited donor-specific antibodies at the final follow-up exam, whereas 8 of these patients (57%) exhibited complete clearance of the donor-specific antibodies. Five other patients developed ''de novo'' posttransplant donor-specific antibodies. Death-censored graft survival was similar in patients with pretransplant donor-specific and non-donor-specific antibodies after a mean follow-up period of 70 months. CONCLUSION: Pretransplant donor-specific antibodies with a negative complement-dependent cytotoxicity crossmatch are associated with a risk for the development of antibody-mediated rejection, although survival rates are similar when patients transpose the first months after receiving the graft. Our data also suggest that early posttransplant donor-specific antibody monitoring should increase knowledge of antibody dynamics and their impact on long-term graft outcome.
Subject(s)
Adolescent , Adult , Female , Humans , Middle Aged , Young Adult , Antibodies/immunology , Blood Grouping and Crossmatching , Graft Rejection/immunology , Graft Survival/immunology , Kidney Transplantation/immunology , Tissue Donors , Cross-Sectional Studies , Cyclosporine/therapeutic use , Follow-Up Studies , Graft Rejection/prevention & control , HLA Antigens/immunology , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/adverse effects , Tacrolimus/therapeutic useABSTRACT
INTRODUÇÃO: O objetivo deste estudo foi avaliar prospectivamente os anticorpos anti-HLA após o transplante renal e associar estes achados com episódios de rejeição aguda, marcação por C4d e sobrevida do enxerto. MÉTODOS: Foram avaliados 926 soros de 111 pacientes no primeiro ano pós-transplante ou até a perda do enxerto. Os anticorpos foram analisados por PRA-ELISA (Panel Reactive Antibodies by Enzyme Linked Immuno Sorbent Assay). Anticorpos anti-HLA doador-específicos foram detectados por provas-cruzadas e caracterizados pelo método de microesferas marcadas com antígenos HLA. Episódios de rejeição aguda foram classificados conforme os Critérios de Banff 97, atualizados em 2003. RESULTADOS: Conforme o PRA-ELISA pós-transplante os pacientes foram classificados em 5 Grupos: Grupo A (n=80): sem evidência de anticorpos pré e pós-transplante; Grupo B (n=8): pacientes com anticorpos de novo; Grupo C (n=5): pacientes sensibilizados que permaneceram com mesmo nível de PRA-ELISA; Grupo D (n=4): pacientes sensibilizados que elevaram o nível de PRA-ELISA e Grupo E (n=14): pacientes sensibilizados que diminuíram o nível de PRA-ELISA durante o primeiro ano pós-transplante. A incidência de rejeição aguda foi de 23,4%. Pacientes dos Grupos B, C e D apresentaram mais episódios de rejeição aguda (respectivamente, 57%; 60% e 100%) que os dos Grupos A (18%) e E (7%), (p<0,001). Rejeições ocorridas no Grupo A foram histologicamente menos severas do que as dos outros Grupos (p=0,03) e com menor incidência de C4d+ (p<0,001). Entre os pacientes com rejeição aguda, 44% deles apresentaram anticorpos no momento da rejeição, sendo que em 90% dos casos esses anticorpos foram doadorespecíficos. Rejeição mediada por células, ou seja, sem anticorpos e com C4d-, ocorreu em 56% dos casos. A incidência global de rejeição mediada por anticorpos (RMA) foi de 11%. A sobrevida do enxerto censurada para óbito foi menor em pacientes com rejeição aguda (p<0,001), especialmente naqueles com anticorpos...
INTRODUCTION: The aim was to follow prospectively anti-HLA antibodies (Abs) after kidney transplantation and to evaluate their association with acute rejection episodes, C4d staining and graft survival. METHODS: We analyzed 926 sera from 111 transplanted patients until graft lost or during 1 year posttransplant. The antibodies were analyzed using Panel Reactive Antibodies by Enzyme Linked Immuno Sorbent Assay (PRA-ELISA). Donor-specific antibodies (DSA) were detected by crossmatch tests and characterized by single antigen beads. Acute rejections (AR) were classified by Banff 97 criteria, updated in 2003. RESULTS: According to post-transplant PRAELISA the patients were classified in 5 groups: Group A (n=80): no evidence of Abs pre and post-transplant; Group B (n=8): patients with Abs de novo; Group C (n=5): sensitized patients who sustained the same PRA-ELISA levels; Group D (n=4): sensitized patients who increased PRA-ELISA levels and Group E (n=14): sensitized patients who decreased PRA-ELISA levels during the first year. The overall incidence of acute rejection was 23,4%. Patients from Groups B, C and D had more AR (respectively, 57%; 60% and 100%) than patients from Groups A (18%) and E (7%), (p<0.001). Patients from Group A had lower Banff scores than other groups (p=0.03) and lower rates of C4d positivity on AR biopsies (p<0.001). Among patients with AR, 44% of them had antibodies which appeared/increased during the AR episodes, and 90% were DSA. AR were pure cell-mediated (C4d-/Abs-) in 56% of the cases. The overall incidence of antibody-mediated rejection (AMR) was 11%. One-year censored graft survival was lower in patients with AR (p<0.001), specially in those with DSA (p<0.001), C4d+ (p=0.003), and AMR (p<0.003). CONCLUSION: Our data suggest that monitoring of anti- HLA antibodies post-transplantation is an useful tool for the diagnosis of antibody-mediated responses, and has prognostic implications in terms of graft survival.