Temporary reduction of immunosuppression enhances production of anti‐S antibody against severe acute respiratory syndrome coronavirus 2 after vaccination in kidney transplant recipients

Abstract

Objectives The study identified factors affecting anti‐S immunoglobulin G production after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in kidney transplant recipients. Methods Serum samples were prospectively collected from kidney transplant recipients, live kidney donors, and healthy volunteers 1 month after receiving the second dose of SARS‐CoV‐2 vaccine, and anti‐S immunoglobulin G titers were measured. The mycophenolate mofetil dose was reduced before vaccination in some immunologically low‐risk recipients. Results A total of 151 kidney transplant recipients, 74 live kidney donors, and 50 healthy volunteers were included. Kidney transplant recipients had significantly lower titers of anti‐S immunoglobulin G than donors and healthy volunteers (1377 ± 246, 8310 ± 932, and 9908 ± 1040 AU/ml, respectively). Only 67.3% of kidney transplant recipients, compared to 100% of donors and healthy volunteers, were positive for anti‐S immunoglobulin G. Among the kidney transplant recipients, the anti‐S titer was higher in younger recipients, those with higher peripheral blood lymphocyte counts and glomerular filtration rates, those without a history of antithymocyte globulin use, and those who had discontinued or received a reduced dose of mycophenolate mofetil. Younger age, higher lymphocyte count, glomerular filtration rate, and mycophenolate reduction were significantly associated with anti‐S immunoglobulin G > 1000 AU/ml in nominal logistic regression analysis. There were no rejection episodes after mycophenolate modification in kidney transplant recipients. Conclusions Anti‐S immunoglobulin G production after vaccination was attenuated in kidney transplant recipients. Mycophenolate mofetil cessation or reduction is a modifiable means to enhance anti‐S immunoglobulin G production in immunosuppressed kidney transplant recipients.

Mycophenolic Acid Exposure Determines Antibody Formation Following SARS‐CoV‐2 Vaccination in Kidney Transplant Recipients: A Nested Cohort Study

“…For KTRs on TMT with high immunological risk for rejection or graft loss, AUC‐guided personalized dosing to a lower range might be a better strategy to balance between risks of allo‐immunity and antibody formation. Multiple nonrandomized studies have recently described the positive effect of mycophenolic acid withdrawal on seroconversion rates and antibody titers, supporting such a strategy 28–30 . In contrast, a recent randomized trial showed no statistical significant difference in seroconversion rate and IgG titers between KTRs in which mycophenolate was temporarily halted or continued, with seroconversion rates of 80% and 67% after three vaccination doses, respectively 31 .…”

“…Multiple nonrandomized studies have recently described the positive effect of mycophenolic acid withdrawal on seroconversion rates and antibody titers, supporting such a strategy. [28][29][30] In contrast, a recent randomized trial showed no statistical significant difference in seroconversion rate and IgG titers between KTRs in which mycophenolate was temporarily halted or continued, with seroconversion rates of 80% and 67% after three vaccination doses, respectively. 31 There are, however, two important limitations to mention.…”

SARS-CoV-2-specific immune responses converge in kidney disease patients and controls with hybrid immunity

“…In addition, this KTR also developed S-specific CD4+ and CD8+ T-cells. This intra-group variation could be explained by the 19-year period after transplantation, which was accompanied with decreased use of immunosuppressive drugs for this individual, compared to less than a 10-year period for the two other KTRs 38 , 39 .…”

Neutralizing antibody responses and cellular responses against SARS-CoV-2 Omicron subvariant BA.5 after mRNA SARS-CoV-2 vaccination in kidney transplant recipients

“…A large cohort study (N = 1804) also reported similar ndings 22 . Several studies demonstrated that IgG positivity is signi cantly associated with MMF cessation or dose reduction 23,24 . Tomiyama et al reported that the seropositivity rate was 95% after the third dose of the vaccine in liver transplant recipients, and only 48% among them were taking MMF 11 .…”