Desensitization using IVIG alone for living-donor kidney transplant: impact on donor-specific antibodies / Dessensibilização usando somente IgIV para transplante renal com doador vivo: impacto nos anticorpos específicos contra o doador

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.

Desensitization using IVIG alone for living-donor kidney transplant: impact on donor-specific antibodies.

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.

Dynamics of anti-human leukocyte antigen antibodies after renal transplantation and their impact on graft outcome.

The purpose of this study was to sequentially monitor anti-HLA antibodies and correlate the results with antibody-mediated rejection (AMR), graft survival (GS), and graft function (GF). We collected sera from 111 kidney transplant recipients on transplant days 0, 7, 14, 30, 60, 90, 180, and 360 and analyzed PRA levels by ELISA. DSAs were analyzed by single-antigen beads in rejecting kidneys. At pre-transplant, 79.3% of the patients were non-sensitized (PRA = 0%) and 20.7% were sensitized (PRA > 1%). After transplant, patients were grouped by PRA profile: no anti-HLA antibodies pre- or post-transplant (group HLApre-/post-; n = 80); de novo anti-HLA antibodies post-transplant (group HLApre-/post+; n = 8); sensitized pre-transplant/increased PRA post-transplant (group HLApre+/post↑; n = 9); and sensitized pre-transplant/decreased PRA post-transplant (group HLApre+/post↓; n = 14). De novo anti-HLA antibodies were detected at 7-180 d. In sensitized patients, PRA levels changed within the first 30 d post-transplant. Incidence of AMR was higher in HLApre-/post+ and HLApre+/post↑ than in HLApre-/post-, and HLApre+/post↓ (p < 0.001) groups. One-yr death-censored GS was 36% in group HLApre+/post↑, compared with 98%, 88% and 100% in groups HLApre-/post-, HLApre-/post+, and HLApre+/post↓, respectively (p < 0.001). Excluding first-year graft losses, GF and GS were similar among the groups. In conclusion, post-transplant antibody monitoring can identify recipients at higher risk of AMR.