scholarly journals Immune Responses to SARS-CoV-2 Infection and Vaccination in Dialysis Patients and Kidney Transplant Recipients

2021 ◽  
Vol 10 (1) ◽  
pp. 4
Author(s):  
Patrick Affeldt ◽  
Felix Carlo Koehler ◽  
Karl August Brensing ◽  
Vivien Adam ◽  
Julia Burian ◽  
...  

Dialysis patients and kidney transplant (KTX) recipients suffer from an impaired immune system and show a decreased response to the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccination. We performed a retrospective analysis of 1505 serological SARS-CoV-2 measurements obtained from 887 dialysis patients and 86 KTX recipients. The results were separated by patient subgroups (dialysis/KTX) as well as SARS-CoV-2 status. The latter criterion included SARS-CoV-2-naïve patients with or without COVID-19 vaccination and convalescent patients receiving a booster shot. Serologies of 27 vaccinated healthy individuals served as the reference group. Vaccine-induced cellular immune response was quantified by an interferon-γ release assay in 32 KTX recipients. We determined seroconversion rates of 92.6%, 93.4%, and 71.4% in dialysis patients vaccinated with either BNT162b2, mRNA-1273, or AZD1222, respectively. Vaccination-induced anti-SARS-CoV-2 antibody titers were lower in dialysis patients compared to healthy individuals, and vaccination with mRNA-1273 induced higher titers than BNT162b2. The initial seroconversion rate was 39.5% in KTX recipients vaccinated with BNT162b2. A linear regression model identified medication with mycophenolate-mofetil/mycophenolic acid as an independent risk factor for missing seroconversion. Within a cohort of 32 KTX recipients, cellular and humoral immune reactivity to SARS-CoV-2 was detectable in three patients only. Conclusively, vaccine-induced seroconversion rates were similar in dialysis patients compared to healthy individuals but were strongly impaired in KTX recipients. Anti-SARS-CoV-2 IgG titers elicited by double active immunization were significantly lower in both cohorts compared to healthy individuals, and immune responses to vaccination vanished quickly.

Kidney360 ◽  
2021 ◽  
pp. 10.34067/KID.0003512021
Author(s):  
Thilo Kolb ◽  
Svenja Fischer ◽  
Lisa Müller ◽  
Nadine Lübke ◽  
Jonas Hillebrandt ◽  
...  

Background: Kidney failure patients on dialysis or after renal transplantation have a high risk for severe COVID-19 infection and vaccination against SARS-CoV-2 is the only expedient prophylaxis. Generally, immune responses are attenuated in kidney failure patients, however, systematic analyses of immune responses to SARS-CoV-2 vaccination in dialysis patients and in kidney transplant recipients (KTR) are still missing. Methods: In this prospective multicentric cohort study, antibody responses COVID-19 mRNA vaccines (BNT162b2; Biontech/Pfizer or mRNA-1273; Moderna) were measured in 32 dialysis patients and in 28 KTRs. SARS-CoV-2-specific antibodies and neutralization capacity were evaluated and compared to controls (n=78) in a similar age-range. Results: After the first vaccination, SARS-CoV-2-specific antibodies were nearly undetectable in kidney failure patients. After the second vaccination, 93% of the controls and 88% of dialysis patients but only 37% of KTRs developed SARS-CoV-2-specific IgG above cut-off. Moreover, mean IgG levels were significantly lower in KTRs (54±93 BAU/ml) compared to dialysis patients (503±481 BAU/ml, p<0.01). Both KTRs as well as dialysis patients had significantly lower IgG levels compared to controls (1992±2485 BAU/ml; p<0.001 and p<0.01). Importantly, compared to controls, neutralizing antibody titers were significantly lower in KTRs and dialysis patients. After the second vaccination, 76% of KTRs did not show any neutralization capacity against SARS-CoV-2 suggesting impaired seroprotection. Conclusions: Kidney failure patients show a significantly weaker antibody response compared to controls. Most strikingly, only one out four KTRs developed neutralizing antibodies against SARS-CoV-2 after two doses of vaccine. These data suggest that vaccination strategies need modification in immune transplant and dialysis patients.


2020 ◽  
Vol 98 (6) ◽  
pp. 1540-1548 ◽  
Author(s):  
Kitty J. Jager ◽  
Anneke Kramer ◽  
Nicholas C. Chesnaye ◽  
Cécile Couchoud ◽  
J. Emilio Sánchez-Álvarez ◽  
...  

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Ondrej Viklicky ◽  
Jiri Klema ◽  
Petra Mrazova ◽  
Daniel Abramowicz ◽  
Marc Abramowicz ◽  
...  

Abstract Background and Aims TOMOGRAM, multicenter study founded by DESCARTES ERA/EDTA WG, aims to identify transcriptomic and genomic signatures of operational tolerance (OT) in recently identified cohort of OT kidney transplant recipients. Method RNA sequencing of peripheral blood was evaluated in 15 OT patients recently identified by TOMOGRAM consortium in 8 European countries, 23 stable patients (≥ 15 years on immunosuppression, STA), 14 CABMR patients (≥ 1 year, CR), 14 non-transplant CNI-treated patients and 14 healthy controls (HC). Differential expression was performed using DESEq2 and gene annotation analysis using Enrichr. Besides immunosuppression unadjusted model, robust negative-binomial regression model was created to adjust for immunosuppression intake. The models was trained on homogeneous group of STA patients. Results Using model unadjusted for immunosuppression, no differences in transcriptomic profiles between OT, STA and HC groups were identified. Nine transcripts were upregulated and 2 downregulated in OT compared CR group. The number of deregulated transcripts substantially increased when the model was adjusted for immunosuppression. Gene annotation analysis of top ranked deregulated 1109 transcripts (FC&gt;2, adjusted p value &lt;0.0001) showed deregulation of biological processes related to interferon-γ-mediated signaling pathway (p=1.4*10-5), response to cytokine (p=1.5*10-5), type I interferon signaling pathway (p=0.00036), regulation of I-kappaB kinase/NF-kappaB signaling (p=0.0021), cytokine-mediated signaling pathway (p=0.019) and neutrophil mediated immunity (p=0.033). While interferon-γ-mediated and type I interferon signaling were related to transcripts increased in CR, neutrophils associated transcripts were increased in OT. Analysis of cell types transcripts showed enrichment of CD19 B cells (p=1.6*10-9) in CR, while CD56NK cells (p=2.5*10-11) and CD8 T cells (p=1.6*10-11) transcripts predominated in OT. To reveal probability of operational tolerance inside STA group, 13 transcripts able to discriminate OT and CR cohorts with high AUC (&gt;0.89) were used in PCA analysis (ADGRG3, ATG2A, GDPD5, IL16, MX2, SLA2, PRKD2, SLIRP, GNLY, SRCAP, ARGHAP9, IGHM, CD5). The high probability of OT signature was found in a single STA patient. Conclusion Contrary to previous reports which pointed out towards naïve B cell signatures, unique OT patients exhibit other specific immunosuppression-independent transcriptomic profiles.


2016 ◽  
Vol 17 (1) ◽  
pp. 281-286 ◽  
Author(s):  
D. Kumar ◽  
V. H. Ferreira ◽  
P. Campbell ◽  
K. Hoschler ◽  
A. Humar

2006 ◽  
Vol 80 (7) ◽  
pp. 3495-3505 ◽  
Author(s):  
Yiping Chen ◽  
Jennifer Trofe ◽  
Jennifer Gordon ◽  
Renaud A. Du Pasquier ◽  
Prabir Roy-Chaudhury ◽  
...  

ABSTRACT Reactivation of the polyomavirus BK (BKV) causes polyomavirus nephropathy (PVN) in kidney transplant (KTx) recipients and may lead to loss of the renal allograft. We have identified two HLA-A*0201-restricted nine-amino-acid cytotoxic T lymphocyte (CTL) epitopes of the BKV major capsid protein VP1, VP1p44, and VP1p108. Using tetramer staining assays, we showed that these epitopes were recognized by CTLs in 8 of 10 (VP1p44) and 5 of 10 (VP1p108) HLA-A*0201+ healthy individuals, while both epitopes elicited a CTL response in 10 of 10 KTx recipients with biopsy-proven PVN, although at variable levels. After in vitro stimulation with the respective peptides, CTLs directed against VP1p44 were more abundant than against VP1p108 in most healthy individuals, while the converse was true in KTx recipients with PVN, suggesting a shift in epitope immunodominance in the setting of active BKV infection. A strong CTL response in KTx recipients with PVN appeared to be associated with decreased BK viral load in blood and urine and low anti-BKV antibody titers, while a low or undetectable CTL response correlated with viral persistence and high anti-BKV antibody titers. These results suggest that this cellular immune response is present in most BKV-seropositive healthy individuals and plays an important role in the containment of BKV in KTx recipients with PVN. Interestingly, the BKV CTL epitopes bear striking homology with the recently described CTL epitopes of the other human polyomavirus JC (JCV), JCV VP1p36 and VP1p100. A high degree of epitope cross-recognition was present between BKV and corresponding JCV-specific CTLs, which indicates that the same population of cells is functionally effective against these two closely related viruses.


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