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

Frontiers in Immunology

Orhan Efe¹  Frank E. Hullekes¹  Ayman Al Jurdi¹  Leonardo V. Riella¹  Thiago J. Borges¹  Rodrigo B. Gassen¹  Isadora T. Lape¹  Mostafa T. Mohammed²  Ivy Rosales³  Vikram Pattanayak³  Brigid Bohan⁴  Paolo Cravedi⁵  Camille N. Kotton⁶  John Y. Choi⁷  Areej Alghamdi⁷  Zhabiz Solhjou⁷  Jamil R. Azzi⁷  Poojan Patel⁷ 

[1] Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, United States;Clinical Pathology Department, Minia University, Minya, Egypt;Department of Pathology, Massachusetts General Hospital, Boston, MA, United States;Histocompatibility Laboratory, Massachusetts General Hospital, Boston, MA, United States;Renal Division, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States;Transplant and Immunocompromised Host Infectious Diseases Infectious Diseases Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States;Transplantation Research Center, Renal Division, Brigham and Women’s Hospital, Boston, MA, United States;

关键词: SARS-CoV-2;    COVID-19;    kidney transplant;    vaccine;    rejection;    monitoring;   

DOI  :  10.3389/fimmu.2022.838985

来源: DOAJ

【 摘 要 】

IntroductionStudies have shown reduced antiviral responses in kidney transplant recipients (KTRs) following SARS-CoV-2 mRNA vaccination, but data on post-vaccination alloimmune responses and antiviral responses against the Delta (B.1.617.2) variant are limited.Materials and methodsTo 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.ResultsAt 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.ConclusionsSARS-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.

【 授权许可】

Unknown