scholarly journals Establishment of an ELISpot Assay to Detect Cellular Immunity against S. pneumoniae in Vaccinated Kidney Transplant Recipients

Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1438
Author(s):  
Anja Gäckler ◽  
Nils Mülling ◽  
Kim Völk ◽  
Benjamin Wilde ◽  
Ute Eisenberger ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Cellular Immunity ◽  
Elispot Assay ◽  
Pneumococcal Infection ◽  
Organ Transplant ◽  
Pneumococcal Vaccination ◽  
Cellular Responses ◽  
Interferon Γ ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

In organ transplant recipients, the rate of invasive pneumococcal diseases is 25 times greater than in the general population. Vaccination against S. pneumoniae is recommended in this cohort because it reduces the incidence of this severe form of pneumococcal infection. Previous studies indicate that transplant recipients can produce specific antibodies after pneumococcal vaccination. However, it remains unclear if vaccination also induces specific cellular immunity. In the current study on 38 kidney transplant recipients, we established an interferon-γ ELISpot assay that can detect serotype-specific cellular responses against S. pneumoniae. The results indicate that sequential vaccination with the conjugated vaccine Prevenar 13 and the polysaccharide vaccine Pneumovax 23 led to an increase of serotype-specific cellular immunity. We observed the strongest responses against the serotypes 9N and 14, which are both components of Pneumovax 23. Cellular responses against S. pneumoniae correlated positively with specific IgG antibodies (r = 0.32, p = 0.12). In conclusion, this is the first report indicating that kidney transplant recipients can mount specific cellular responses after pneumococcal vaccination. The ELISpot we established will allow for further investigations. These could help to define, for example, factors influencing specific cellular immunity in immunocompromised cohorts or the duration of cellular immunity after vaccination.

ELISpot assay as a sensitive tool to detect cellular immunity following influenza vaccination in kidney transplant recipients

2006 ◽  
Vol 120 (3) ◽  
pp. 342-348 ◽  
Author(s):  
Monika Lindemann ◽  
Oliver Witzke ◽  
Peter Lütkes ◽  
Melanie Fiedler ◽  
Ernst Kreuzfelder ◽  
...  
Keyword(s):  
Influenza Vaccination ◽  
Kidney Transplant ◽  
Cellular Immunity ◽  
Elispot Assay ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Sensitive Tool

TO005OPERATIONAL TOLERANCE IN KIDNEY TRANSPLANT RECIPIENTS: TOMOGRAM TRANSCRIPTOMIC STUDY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Ondrej Viklicky ◽  
Jiri Klema ◽  
Petra Mrazova ◽  
Daniel Abramowicz ◽  
Marc Abramowicz ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Kidney Transplant ◽  
Type I Interferon ◽  
Gene Annotation ◽  
Interferon Γ ◽  
Type I ◽  
Transplant Recipients ◽  
Interferon Signaling ◽  
Kidney Transplant Recipients ◽  
Operational Tolerance

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>2, adjusted p value <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 (>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.

scholarly journals Sex-Specific Differences in HLA Antibodies after Pneumococcal Vaccination in Kidney Transplant Recipients

Vaccines ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 84 ◽  
Author(s):  
Lindemann ◽  
Oesterreich ◽  
Wilde ◽  
Eisenberger ◽  
Muelling ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
De Novo ◽  
Pneumococcal Vaccination ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Current Data ◽  
Class I ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Hla Antibodies

In transplant recipients vaccination against Streptococcus pneumoniae is recommended to reduce mortality from invasive pneumococcal disease. It is still debated if vaccination in transplant recipients triggers alloresponses. Therefore, it was our aim to define if vaccination with Prevenar 13®, a 13-valent, conjugated pneumococcal vaccine (Pfizer, New York, NY, USA) that acts T cell dependently, induces human leukocyte antigen (HLA) antibodies in clinically stable kidney transplant recipients. Forty-seven patients were vaccinated once with Prevenar 13® and HLA antibodies were determined prior to vaccination and at month 1 and 12 thereafter. In parallel, pneumococcal IgG antibodies were measured. Using Luminex™ Mixed Beads technology (One Lambda/Thermo Fisher, Canoga Park, CA, USA) we observed overall no change in HLA antibodies after vaccination. Pneumococcal antibodies increased significantly at month 1 (p < 0.0001) and remained elevated at month 12 (p < 0.005). A more detailed analysis of HLA antibodies showed that in 18 females HLA class I and II antibodies increased significantly at month 1 and 12 (p < 0.05); whereas in 29 males HLA class I and II antibodies tended to decrease. Using Luminex™ Single Antigen Beads assay, no de novo donor-specific HLA antibodies were detected after vaccination. In conclusion, the current data indicate that females may be more susceptible to the induction of (non-specific) HLA antibodies after vaccination.

scholarly journals SARS-CoV-2-specific Humoral and Cell-mediated Immune Responses after Immunization with Inactivated COVID-19 Vaccine in Kidney Transplant Recipients (CVIM 1 Study)

2021 ◽  
Author(s):  
Jackrapong Bruminhent ◽  
Chavachol Sethaudom ◽  
Pongsathon Chaumdee ◽  
Sarinya Boongird ◽  
Sasisopin Kiertiburanakul ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Organ Transplant ◽  
Calcineurin Inhibitors ◽  
Neutralizing Antibody ◽  
Cell Mediated Immunity ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Cell Responses ◽  
Clinical Trials Registry

Immunogenicity following inactivated SARS-CoV-2 vaccination among solid organ transplant recipients has not been assessed. Seventy-five patients (37 kidney transplant [KT] recipients and 38 non-transplant controls) received two doses, at 4-week intervals, of an inactivated whole-virus SARS-CoV-2 vaccine. SARS-CoV-2-specific humoral (HMI) and cell-mediated immunity (CMI) were measured before, 4 weeks post-first dose, and 2 weeks post-second dose. The median age of KT recipients was 50 years (IQR, 42 to 54) and 89% were receiving calcineurin inhibitors/mycophenolate/corticosteroid regimens. The median time since transplant was 4.5 years (IQR, 2 to 9.5). Among 35 KT patients, anti-RBD IgG titer after vaccination was not significantly different to baseline, but was significantly lower than in controls (7.8 [95%CI 0.2 to 15.5] vs 2,691 [95%CI 1,581 to 3,802], p<0.001) as well as the percentage of surrogate virus neutralizing antibody inhibition (2 [95% CI -1 to 6] vs 71 [95%CI 61 to 81], p<0.001). However, the mean of SARS-CoV-2 mixed peptides-specific T-cell responses measured by enzyme-linked immunospot assays was significantly increased compared with baseline (66 [95%CI 36 to 99] vs. 34 [95%CI 19 to 50] T-cells/10^6 PBMCs, p=0.02) and comparable to that in controls. Our findings revealed weak HMI and marginal CMI responses in fully vaccinated KT recipients receiving inactivated SARS-CoV-2 vaccine. (Thai Clinical Trials Registry, TCTR20210226002).

scholarly journals B and T cell responses after a third dose of SARS-CoV-2 vaccine in Kidney Transplant Recipients

2021 ◽  
Author(s):  
Eva Schrezenmeier ◽  
Hector Rincon-Arevalo ◽  
Ana-Luisa Stefanski ◽  
Alexander Potekhin ◽  
Henriette Staub-Hohenbleicher ◽  
...  
Keyword(s):  
T Cell ◽  
Kidney Transplant ◽  
Immunosuppressive Treatment ◽  
Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
The Third ◽  
Cellular Analysis ◽  
Cell Immunity

Background: Accumulating evidence suggests that solid organ transplant recipients, as opposed to the general population, show strongly impaired responsiveness towards standard SARS-CoV-2 mRNA-based vaccination, demanding alternative strategies for protection of this vulnerable group. Methods: In line with recent recommendations, a third dose of either heterologous ChAdOx1 (AstraZeneca) or homologous BNT162b2 (BioNTech) was administered to 25 kidney transplant recipients (KTR) without humoral response after 2 doses of BNT162b2, followed by analysis of serological responses and vaccine-specific B- and T-cell immunity. Results: 9/25 (36%) KTR under standard immunosuppressive treatment seroconverted until day 27 after the third vaccination, while one patient developed severe COVID-19 infection immediately after vaccination. Cellular analysis seven days after the third dose showed significantly elevated frequencies of viral spike protein receptor binding domain specific B cells in humoral responders as compared to non-responders. Likewise, portions of spike-reactive CD4+ T helper cells were significantly elevated in seroconverting patients. Furthermore, overall frequencies of IL-2+, IL-4+ and polyfunctional CD4+ T cells significantly increased after the third dose, whereas memory/effector differentiation remained unaffected. Conclusions: Our data suggest that a fraction of transplant recipients benefits from triple vaccination, where seroconversion is associated with quantitative and qualitative changes of cellular immunity. At the same time, the study highlights that modified vaccination approaches for immunosuppressed patients still remain an urgent medical need.

scholarly journals Identification of Risk Factors for Multiple Non-Melanoma Skin Cancers in Italian Kidney Transplant Recipients

Medicina ◽  
2019 ◽  
Vol 55 (6) ◽  
pp. 279 ◽  
Author(s):  
Elisa Zavattaro ◽  
Paolo Fava ◽  
Federica Veronese ◽  
Giovanni Cavaliere ◽  
Daniela Ferrante ◽  
...  
Keyword(s):  
Risk Factors ◽  
Kidney Transplant ◽  
Organ Transplant ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Skin Cancers ◽  
Increased Risk ◽  
History Of ◽  
Solar Lentigo ◽  
Melanoma Skin

Background and objectives: Non-melanoma skin cancers (NMSCs) represent the most frequently encountered malignancy in organ transplant recipients and their incidence increases proportionally to the duration of immunosuppression. Furthermore, patients of this group often develop multiple and more aggressive cancers and, to date, risk factors for the development of multiple NMSCs have not been yet established. The present study aimed to identify risk factors for multiple NMSCs in a cohort of Italian kidney transplant recipients (KTRs). Materials and Methods: We consecutively included all KTRs referring to two post-transplant outpatient clinics of North-Western Italy between 2001 and 2017. In this cohort, we evaluated different clinical (endogenous and exogenous) risk factors in order to establish their correlation with NMSCs. Results: 518 KTRs were included, of which 148 (28.6%) developed keratinocyte cancers, with a single tumor in 77 subjects, two skin cancers in 31 patients, 3 in 21 patients, whereas at least 4 NMSCs developed in 19 KTRs. We observed an increased risk of the development of cutaneous neoplasms for the male gender, old age at transplantation (>50 years), light phototype, solar lentigo, history of sunburns, or chronic actinic damage. Considering patients affected by multiple keratinocyte neoplasms, we observed a significant association of actinic damage and solar lentigo with an increased risk of NMSCs; their significance was confirmed even at the multivariable model. Conclusions: Our results confirm the role played by chronic cutaneous actinic damage in carcinogenesis on KTRs and highlight the significance of individualized periodic dermatological screening.

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