Non-Invasive Monitoring for Rejection in Kidney Transplant Recipients After SARS-CoV-2 mRNA Vaccination

SARS-CoV-2 mRNA 疫苗接种后肾移植受体排斥反应的无创监测

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作者:Ayman Al Jurdi, Rodrigo B Gassen, Thiago J Borges, Zhabiz Solhjou, Frank E Hullekes, Isadora T Lape, Orhan Efe, Areej Alghamdi, Poojan Patel, John Y Choi, Mostafa T Mohammed, Brigid Bohan, Vikram Pattanayak, Ivy Rosales, Paolo Cravedi, Camille N Kotton, Jamil R Azzi, Leonardo V Riella

Conclusions

SARS-CoV-2 mRNA vaccination in KTRs did not elicit a significant alloimmune response. About half of KTRs who develop anti-wild-type spike antibodies after two mRNA vaccine doses have neutralizing responses against the Delta variant. There was no association between anti-viral humoral and cellular responses.

Methods

To address this issue, we conducted a prospective, multi-center study of 58 adult KTRs receiving mRNA-BNT162b2 or mRNA-1273 vaccines. We used multiple complementary non-invasive biomarkers for rejection monitoring including serum creatinine, proteinuria, donor-derived cell-free DNA, peripheral blood gene expression profile (PBGEP), urinary CXCL9 mRNA and de novo donor-specific antibodies (DSA). Secondary outcomes included development of anti-viral immune responses against the wild-type and Delta variant of SARS-CoV-2.

Results

At a median of 85 days, no KTRs developed de novo DSAs and only one patient developed acute rejection following recent conversion to belatacept, which was associated with increased creatinine and urinary CXCL9 levels. During follow-up, there were no significant changes in proteinuria, donor-derived cell-free DNA levels or PBGEP. 36% of KTRs in our cohort developed anti-wild-type spike antibodies, 75% and 55% of whom had neutralizing responses against wild-type and Delta variants respectively. A cellular response against wild-type S1, measured by interferon-γ-ELISpot assay, developed in 38% of KTRs. Cellular responses did not differ in KTRs with or without antibody responses. Conclusions: SARS-CoV-2 mRNA vaccination in KTRs did not elicit a significant alloimmune response. About half of KTRs who develop anti-wild-type spike antibodies after two mRNA vaccine doses have neutralizing responses against the Delta variant. There was no association between anti-viral humoral and cellular responses.

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