Avaliação do efeito da imunossupressão do transplante renal na imunidade humoral e celular adquirida pela vacinação contra o SARS-CoV-2
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Data
2024-06-26
Autores
Foresto, Renato Demarchi [UNIFESP]
Orientadores
Pestana, José Osmar Medina de Abreu [UNIFESP]
Tipo
Tese de doutorado
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Objetivo: O objetivo primário do estudo foi avaliar o efeito da imunossupressão do transplante renal sobre a imunidade humoral e celular gerada pelas vacinas anti-SARS-CoV-2.
Métodos: Estudo clínico prospectivo com intervenção de mundo real, realizado em centro único, incluindo pacientes adultos com doença renal crônica em estágio avançado, vacinados contra o SARS-CoV-2 e sem COVID-19 prévia. Foram comparadas a sororreversão de anticorpos IgG, títulos de anticorpos IgG, anticorpos neutralizantes e resultados de teste de detecção de IFN-Ƴ entre pacientes submetidos ao transplante renal e pacientes que permaneceram em diálise. Foram realizadas coletas de sangue na inclusão e nos meses 1, 3, 6 e 12 do seguimento para as análises.
Resultados: Foram incluídos 113 pacientes no grupo transplante e 108 no grupo diálise. A idade (54,0 vs. 45,4 anos) e o tempo em diálise (25,0 vs. 51,9 meses) foram inferiores no transplante. Um paciente apresentou sororreversão no transplante e 3 na diálise nos 12 meses, sem diferença estatística. Os títulos de anticorpos IgG no transplante foram inferiores ao longo de 12 meses (M1: 10.809,3±12.621,7 vs. 15.267,8±16.096,2 UI/mL; M3: 12.215,5±12.885,8 vs. 15.016,2±15.346,1 UI/mL; M6: 12.540,4±13, 010,7 vs. 18.503,5±14.581,0 UI/mL; M12: 12.369,1±13.189,9 vs. 12.818,2±12.171,6 UI/mL p=0,005). As taxas de anticorpos neutralizantes foram elevadas e semelhantes (98,9% vs. 97,5%; p=0,831). Houve elevada proporção de resultados indeterminados de IFN-Ƴ, sem tendência definida nos grupos. No seguimento, o grupo transplante apresentou maior número de COVID-19 (37 vs. 16; p=0,002), apesar de ter recebido maior número de doses adicionais de vacina (141 vs. 73; p<0,001).
Conclusão: Em comparação com pacientes em diálise, receptores de transplante renal apresentaram títulos mais baixos de IgG e taxas semelhantes de sororreversão e anticorpos neutralizantes. A imunidade celular apresentou elevada proporção de resultados indeterminados, dificultando sua interpretação. Embora o grupo transplante tenha recebido mais reforços, a incidência de COVID-19 neste grupo foi mais elevada.
Objective: The primary objective of the study was to evaluate the effect of renal transplant immunosuppression on humoral and cellular immunity generated by anti-SARS-CoV-2 vaccines. Methods: Prospective clinical study with real-world intervention, carried out in a single center, including adult patients with advanced stage chronic kidney disease, vaccinated against SARS-CoV-2 and without previous COVID-19. The seroreversion of IgG antibodies, IgG antibody titers, neutralizing antibodies and IFN-Ƴ detection test results were compared between patients undergoing kidney transplantation and patients who remained on dialysis. Blood samples were collected at inclusion and in months 1, 3, 6 and 12 of follow-up for analysis. Results: We included 113 patients in the transplant group and 108 in the dialysis group. Age (54.0 vs. 45.4 years) and time on dialysis (25.0 vs. 51.9 months) were lower in transplantation. One patient presented seroreversion during transplantation and 3 during dialysis within 12 months, with no statistical difference. IgG antibody titers at transplantation were lower over 12 months (M1: 10,809.3±12,621.7 vs. 15,267.8±16,096.2 IU/mL; M3: 12,215.5±12,885.8 vs. 15,016. 2±15,346.1 IU/mL; M6: 12,540.4±13, 010.7 vs. 12,818.2±12,171. 6 IU/mL p=0.005). Neutralizing antibody rates were high and similar (98.9% vs. 97.5%; p=0.831). There was a high proportion of indeterminate IFN-Ƴ results, with no defined trend in the groups. During follow-up, the transplant group had a higher number of COVID-19 cases (37 vs. 16; p=0.002), despite having received a greater number of additional doses of vaccine (141 vs. 73; p<0.001). Conclusion: Compared with dialysis patients, kidney transplant recipients had lower IgG titers and similar rates of seroreversion and neutralizing antibodies. Cellular immunity presented a high proportion of indeterminate results, making interpretation difficult. Although the transplant group received more boosters, the incidence of COVID-19 in this group was higher.
Objective: The primary objective of the study was to evaluate the effect of renal transplant immunosuppression on humoral and cellular immunity generated by anti-SARS-CoV-2 vaccines. Methods: Prospective clinical study with real-world intervention, carried out in a single center, including adult patients with advanced stage chronic kidney disease, vaccinated against SARS-CoV-2 and without previous COVID-19. The seroreversion of IgG antibodies, IgG antibody titers, neutralizing antibodies and IFN-Ƴ detection test results were compared between patients undergoing kidney transplantation and patients who remained on dialysis. Blood samples were collected at inclusion and in months 1, 3, 6 and 12 of follow-up for analysis. Results: We included 113 patients in the transplant group and 108 in the dialysis group. Age (54.0 vs. 45.4 years) and time on dialysis (25.0 vs. 51.9 months) were lower in transplantation. One patient presented seroreversion during transplantation and 3 during dialysis within 12 months, with no statistical difference. IgG antibody titers at transplantation were lower over 12 months (M1: 10,809.3±12,621.7 vs. 15,267.8±16,096.2 IU/mL; M3: 12,215.5±12,885.8 vs. 15,016. 2±15,346.1 IU/mL; M6: 12,540.4±13, 010.7 vs. 12,818.2±12,171. 6 IU/mL p=0.005). Neutralizing antibody rates were high and similar (98.9% vs. 97.5%; p=0.831). There was a high proportion of indeterminate IFN-Ƴ results, with no defined trend in the groups. During follow-up, the transplant group had a higher number of COVID-19 cases (37 vs. 16; p=0.002), despite having received a greater number of additional doses of vaccine (141 vs. 73; p<0.001). Conclusion: Compared with dialysis patients, kidney transplant recipients had lower IgG titers and similar rates of seroreversion and neutralizing antibodies. Cellular immunity presented a high proportion of indeterminate results, making interpretation difficult. Although the transplant group received more boosters, the incidence of COVID-19 in this group was higher.
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FORESTO, Renato Demarchi. Avaliação do efeito da imunossupressão do transplante renal na imunidade humoral e celular adquirida pela vacinação contra o SARS-CoV-2. 2024. 179 f. Tese (Doutorado em Nefrologia) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP). São Paulo, 2024.