Biomarkers to assess donor-reactive T-cell responses in kidney transplant patients

2016 ◽  
Vol 49 (4-5) ◽  
pp. 329-337 ◽  
Author(s):  
Elena Crespo ◽  
Oriol Bestard
Keyword(s):  
T Cell ◽  
Kidney Transplant ◽  
T Cell Responses ◽  
Cell Responses ◽  
Transplant Patients ◽  
Kidney Transplant Patients

scholarly journals Comparison of humoral and cellular responses in kidney transplant recipients receiving BNT162b2 and ChAdOx1 SARS-CoV-2 vaccines

2021 ◽  
Author(s):  
Maria Prendecki ◽  
Tina Thomson ◽  
Candice L Clarke ◽  
Paul Martin ◽  
Sarah Gleeson ◽  
...  
Keyword(s):  
T Cell ◽  
Kidney Transplant ◽  
T Cell Responses ◽  
Cellular Responses ◽  
Control Group ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Cell Responses ◽  
Transplant Patients ◽  
Kidney Transplant Patients

Background Attenuated immune responses to mRNA SARS-CoV-2 vaccines have been reported in solid organ transplant recipients. Most studies have assessed serological responses alone, and there is limited immunological data on vector-based vaccines in this population. This study compares the immunogenicity of BNT162b2 with ChAdOx1 in kidney transplant patients, assessing both serological and cellular responses. Methods 920 patients were screened for spike protein antibodies (anti-S) following 2 doses of either BNT162b2 (n=490) or ChAdOx1 (n=430). 106 patients underwent assessment with T-cell ELISpot assays. 65 health care workers were used as a control group. Results Anti-S was detected in 569 (61.8%) patients. Seroconversion rates in infection-naïve patients who received BNT162b2 were higher compared with ChAdOx1, at 269/410 (65.6%) and 156/358 (43.6%) respectively, p<0.0001. Anti-S concentrations were higher following BNT162b, 58(7.1-722) BAU/ml, compared with ChAdOx1, 7.1(7.1-39) BAU/ml, p<0.0001. Calcineurin inhibitor monotherapy, vaccination occurring >1st year post-transplant and receiving BNT162b2 was associated with seroconversion. Only 28/106 (26.4%) of patients had detectable T-cell responses. There was no difference in detection between infection-naïve patients who received BNT162b2, 7/40 (17.5%), versus ChAdOx1, 2/39 (5.1%), p=0.15. There was also no difference in patients with prior infection who received BNT162b2, 8/11 (72.7%), compared with ChAdOx1, 11/16 (68.8%), p=0.83. Conclusions. Enhanced humoral responses were seen with BNT162b2 compared with ChAdOx1 in kidney transplant patients. T-cell responses to both vaccines were markedly attenuated. Clinical efficacy data is still required but immunogenicity data suggests weakened responses to both vaccines in transplant patients, with ChAdOx1 less immunogenic compared with BNT162b2.

Effector Antitumor and Regulatory T Cell Responses Influence the Development of Nonmelanoma Skin Cancer in Kidney Transplant Patients

2017 ◽  
Vol 101 (9) ◽  
pp. 2102-2110 ◽  
Author(s):  
Elena Crespo ◽  
Loreto Fernandez ◽  
Marc Lúcia ◽  
Edoardo Melilli ◽  
Ricardo Lauzurica ◽  
...  
Keyword(s):  
T Cell ◽  
Skin Cancer ◽  
Kidney Transplant ◽  
Regulatory T Cell ◽  
T Cell Responses ◽  
Nonmelanoma Skin Cancer ◽  
Cell Responses ◽  
Transplant Patients ◽  
Kidney Transplant Patients

scholarly journals SARS-CoV-2-specific humoral and cellular immunity in renal transplant and haemodialysis patients treated with convalescent plasma

2020 ◽  
Author(s):  
Monika Lindemann ◽  
Adalbert Krawczyk ◽  
Sebastian Dolff ◽  
Margarethe Konik ◽  
Hana Rohn ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
T Cell ◽  
Kidney Disease ◽  
Plasma Treatment ◽  
Kidney Transplant ◽  
Antiviral Treatment ◽  
T Cell Responses ◽  
Close Monitoring ◽  
Cell Responses ◽  
Alternative Treatment Option

AbstractBackgroundWhen patients with chronic kidney disease are infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) they can face two specific problems: Virus-specific immune responses may be impaired and remdesivir, an antiviral drug described to shorten the time to recovery, is contraindicated. Antiviral treatment with convalescent plasma could be an alternative treatment option.MethodsIn this case series we present two kidney transplant recipients and two patients dependent on haemodialysis who were infected with SARS-CoV-2 and received convalescent plasma. Antibodies against the spike 1 protein of SARS-CoV-2 were determined sequentially by IgG ELISA and neutralization assay and specific T cell responses by interferon-gamma ELISpot.ResultsPrior to treatment, in three patients antibodies were undetectable by ELISA (ratio < 1.1), corresponding to low neutralizing antibody titers (≤ 1:40). One patient was also negative to the ELISpot and two showed weak responses. After convalescent plasma treatment we observed an increase of SARS-CoV-2-specific antibodies (IgG ratio and neutralization titer) and of specific T cell responses. After intermittent clinical improvement one kidney transplant recipient again developed typical symptoms at day 12 after treatment and received a second cycle of convalescent plasma treatment. Altogether, three patients clinically improved and could be discharged from hospital. However, one multimorbid female in her early eighties deceased.ConclusionsOur data suggest that the success of convalescent plasma therapy may only be temporary in patients with chronic kidney disease; which requires an adaptation of the treatment regimen. Close monitoring after treatment is needed for this patient group.

Massive elevation of procalcitonin plasma levels in the absence of infection in kidney transplant patients treated with pan-T-cell antibodies

2001 ◽  
Vol 27 (6) ◽  
pp. 987-991 ◽  
Author(s):  
R. Sabat ◽  
C. Höflich ◽  
W.D. Döcke ◽  
F. Kern ◽  
H.-D. Volk ◽  
...  
Keyword(s):  
T Cell ◽  
Kidney Transplant ◽  
Plasma Levels ◽  
Transplant Patients ◽  
Kidney Transplant Patients

BK Polyomavirus–Specific CD8 T-Cell Expansion In Vitro Using 27mer Peptide Antigens for Developing Adoptive T-Cell Transfer and Vaccination

2020 ◽  
Author(s):  
Maud Wilhelm ◽  
Amandeep Kaur ◽  
Marion Wernli ◽  
Hans H Hirsch
Keyword(s):  
T Cells ◽  
T Cell ◽  
Kidney Transplant ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Responses ◽  
Bk Polyomavirus

Abstract Background BK polyomavirus (BKPyV) remains a significant cause of premature kidney transplant failure. In the absence of effective antivirals, current treatments rely on reducing immunosuppression to regain immune control over BKPyV replication. Increasing BKPyV-specific CD8 T cells correlate with clearance of BKPyV DNAemia in kidney transplant patients. We characterized a novel approach for expanding BKPyV-specific CD8 T cells in vitro using 27mer-long synthetic BKPyV peptides, different types of antigen-presenting cells, and CD4 T cells. Methods Langerhans cells and immature or mature monocyte-derived dendritic cells (Mo-DCs) were generated from peripheral blood mononuclear cells of healthy blood donors, pulsed with synthetic peptide pools consisting of 36 overlapping 27mers (27mP) or 180 15mers (15mP). BKPyV-specific CD8 T-cell responses were assessed by cytokine release assays using 15mP or immunodominant 9mers. Results BKPyV-specific CD8 T cells expanded using 27mP and required mature Mo-DCs (P = .0312) and CD4 T cells (P = .0156) for highest responses. The resulting BKPyV-specific CD8 T cells proliferated, secreted multiple cytokines including interferon γ and tumor necrosis factor α, and were functional (CD107a+/PD1–) and cytotoxic. Conclusions Synthetic 27mP permit expanding BKPyV-specific CD8 T-cell responses when pulsing mature Mo-DCs in presence of CD4 T cells, suggesting novel and safe approaches to vaccination and adoptive T-cell therapies for patients before and after kidney transplantation.

scholarly journals CD4 + T cell lymphopenia predicts mortality from Pneumocystis pneumonia in kidney transplant patients

2020 ◽  
Vol 34 (9) ◽  
Author(s):  
Tilo Freiwald ◽  
Stefan Büttner ◽  
Nardos T. Cheru ◽  
Despina Avaniadi ◽  
Simon S. Martin ◽  
...  
Keyword(s):  
T Cell ◽  
Kidney Transplant ◽  
Pneumocystis Pneumonia ◽  
Cd4 T Cell ◽  
Transplant Patients ◽  
T Cell Lymphopenia ◽  
Kidney Transplant Patients

scholarly journals CD45RC Expression of Circulating CD8+ T Cells Predicts Acute Allograft Rejection: A Cohort Study of 128 Kidney Transplant Patients

2019 ◽  
Vol 8 (8) ◽  
pp. 1147 ◽  
Author(s):  
Lemerle ◽  
Garnier ◽  
Planchais ◽  
Brilland ◽  
Subra ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Kidney Transplant ◽  
Cd8 T Cells ◽  
De Novo ◽  
Predictive Biomarkers ◽  
Transplant Patients ◽  
History Of ◽  
Kidney Transplant Patients ◽  
A Prospective Study

Predictive biomarkers of acute rejection (AR) are lacking. Pre-transplant expression of CD45RC on blood CD8+ T cells has been shown to predict AR in kidney transplant (KT) patients. The objective of the present study was to study CD45RC expression in a large cohort of KT recipients exposed to modern immunosuppressive regimens. CD45RC expression on T cells was analyzed in 128 KT patients, where 31 patients developed AR, of which 24 were found to be T-cell mediated (TCMR). Pre-transplant CD4+ and CD8+ CR45RChigh T cell proportions were significantly higher in patients with AR. The frequency of CD45RChigh T cells was significantly associated with age at transplantation but was not significantly different according to gender, history of transplantation, pre-transplant immunization, and de novo donor specific anti-Human Leucocyte Antigen (HLA) antibody. Survival-free AR was significantly better in patients with CD8+ CD45RChigh T cells below 58.4% (p = 0.0005), but not different according to CD4+ T cells (p = 0.073). According to multivariate analysis, CD8+ CD45RChigh T cells above 58.4% increased the risk of AR 4-fold (HR 3.96, p = 0.003). Thus, pre-transplant CD45RC expression on CD8+ T cells predicted AR, mainly TCMR, in KT patients under modern immunosuppressive therapies. We suggest that CD45RC expression should be evaluated in a prospective study to validate its usefulness to quantify the pre-transplant risk of AR.

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