Human Cytomegalovirus (HCMV)-Specific Antibody Response and Development of Antibody-Dependent Cellular Cytotoxicity Against HCMV After Lung Transplantation

2020 ◽  
Vol 222 (3) ◽  
pp. 417-427
Author(s):  
Hannes Vietzen ◽  
Irene Görzer ◽  
Claudia Honsig ◽  
Peter Jaksch ◽  
Elisabeth Puchhammer-Stöckl
Keyword(s):  
Human Cytomegalovirus ◽  
Lung Transplant ◽  
Enzyme Linked Immunosorbent Assay ◽  
Transplant Recipients ◽  
Antibody Dependent Cellular Cytotoxicity ◽  
Specific Antibody Response ◽  
Healthy Control ◽  
Severe Infections ◽  
Lung Transplant Recipients ◽  
The Impact

Abstract Background Human cytomegalovirus (HCMV) may cause severe infections in lung transplant recipients (LTRs). The impact of the host antibody (AB)-dependent cytotoxicity (ADCC) on HCMV is still unclear. Therefore, we analyzed the AB-response against HCMV glycoprotein B (gB) and the pentameric complex (PC) and the ADCC response in HCMV-seropositive (R+) LTRs and in seronegative recipients of positive organs (D+/R−). Methods Plasma samples were collected from 35 R+ and 28 D+/R− LTRs for 1 (R+) or 2 (D+/R−) years posttransplantation and from 114 healthy control persons. The PC- and gB-specific ABs were assessed by enzyme-linked immunosorbent assay. The ADCC was analyzed by focal expansion assay and CD107 cytotoxicity assay. Results In R+ LTRs, significantly higher gB-specific AB levels developed within 1 year posttransplantation than in controls (immunoglobulin [Ig]G1, P < .001; IgG3, P < .001). In addition, higher levels of ADCC were observed by FEA and CD107 assay in R+ patients compared with controls (P < .001). In 23 D+R− patients, HCMV-specific ABs developed. Antibody-dependent cytotoxicity became detectable 3 months posttransplantation in these, with higher ADCC observed in viremic patients. Depletion of gB- and PC-specific ABs revealed that, in particular, gB-specific Abs were associated with the ADCC response. Conclusions We show that a strong ADCC is elicited after transplantation and is especially based on gB-specific ABs.

scholarly journals Analysis and Fine Specificity of the HCMV-Specific Cell-Free and Cell-Associated Antibody-Dependent Cellular Phagocytosis (ADCP) Responses in Lung Transplant Recipients

2021 ◽  
Vol 22 (15) ◽  
pp. 8206
Author(s):  
Simone Eberhard ◽  
Hannes Vietzen ◽  
Irene Görzer ◽  
Peter Jaksch ◽  
Elisabeth Puchhammer-Stöckl
Keyword(s):  
Lung Transplant ◽  
Study Cohort ◽  
Specific Cell ◽  
Transplant Recipients ◽  
Post Transplantation ◽  
Severe Infections ◽  
Hcmv Replication ◽  
Lung Transplant Recipients ◽  
High Level ◽  
The Impact

Human Cytomegalovirus (HCMV) may cause severe infections in transplant recipients. HCMV-replication can be limited by HCMV-specific antibody responses. The impact of the antibody-dependent cellular phagocytosis (ADCP) on inhibition of HCMV-replication in natural infections has not been clarified. Therefore, we investigated the HCMV-specific ADCP response in a study cohort of lung-transplant recipients (LTRs) with different donor (D) and recipient (R) HCMV-serostatus. Follow-up plasma samples from 39 non/low-viremic and 36 highly viremic (>1000 HCMV copies/mL plasma) LTRs were collected for one (R+ LTRs) or two (D+/R− LTRs) years post-transplantation. The HCMV-specific ADCP responses were assessed by focal expansion assays (FEA) and flow-cytometry. In all LTRs, ADCP responses were detected against HCMV-infected cells and cell-free virions. When measured in fibroblasts as well as with cell-free virus, the HCMV-specific ADPC response was higher in LTRs than in HCMV-seropositive healthy controls. In D+/R− LTRs, a significant ADCP response developed over time after the receipt of an HCMV positive lung, and a level of <19 IE+ cells/focus in the FEA on fibroblasts was associated with further protection from high-level viremia. Taken together, a strong HCMV-specific ADCP response is elicited in transplant recipients, which may contribute to protection from high-level viremia in primary HCMV infection.

The Impact of Donor Asphyxiation or Drowning on Pediatric Lung Transplant Recipients

2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Laura Seese ◽  
Arman Kilic ◽  
Harma K. Turbendian ◽  
Pablo G. Sanchez ◽  
Carlos E. Diaz-Castrillon ◽  
...  
Keyword(s):  
Lung Transplant ◽  
Transplant Recipients ◽  
Lung Transplant Recipients ◽  
The Impact

scholarly journals Early protein expression profile in bronchoalveolar lavage fluid and clinical outcomes in primary graft dysfunction after lung transplantation

2020 ◽  
Vol 58 (2) ◽  
pp. 379-388
Author(s):  
Anna E Frick ◽  
Stijn E Verleden ◽  
Sofie Ordies ◽  
Annelore Sacreas ◽  
Robin Vos ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Lung Transplantation ◽  
Lung Transplant ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Enzyme Linked Immunosorbent Assay ◽  
Transplant Recipients ◽  
Primary Graft Dysfunction ◽  
Graft Dysfunction ◽  
Lung Transplant Recipients

Abstract OBJECTIVES Primary graft dysfunction (PGD) remains a major post-transplant complication and is associated with increased morbidity and mortality. Mechanisms evoking PGD are not completely clear, but inflammation plays a central role. We investigated the association between PGD and inflammatory proteins present in immediate postoperative bronchoalveolar lavage. METHODS All double-lung recipients transplanted at our institution from 2002 to 2018 were included in our study. We retrospectively selected 80 consecutive lung transplant recipients with different PGD grades (n = 20 for each PGD grades 0–1 to 2–3). In bronchoalveolar lavage performed within the first 24 h after donor aortic cross-clamping following lung transplantation, concentrations of 30 cytokines, chemokines and growth factors were assessed by enzyme-linked immunosorbent assay (ELISA) and correlated with donor and recipient demographics and outcomes. For analysis, 2 groups were defined: ‘mild’ PGD (grade 0–1) and ‘severe’ PGD (grades 2–3). RESULTS Significant differences between mild and severe PGD were found in 8 biomarkers [interleukin (IL)-6, IL-10, IL-13, eotaxin, granulocyte colony-stimulating factor, interferon γ, macrophage inflammatory protein 1α, surfactant protein D (SP-D); P &lt; 0.05]. Increased IL-10 and IL-13, but none of the other proteins, were associated with short-term outcome (longer time to extubation; P = 0.005 and P &lt; 0.0001; increased intensive care unit stay; P = 0.012 and P &lt; 0.0001; and hospital stay; P = 0.041 and P = 0.002). There were no significant differences in donor and recipient characteristics between the groups. CONCLUSIONS Expression profiles of key inflammatory mediators in bronchoalveolar lavage fluid differed significantly between lung transplant recipients with severe versus mild PGD and correlated with clinical outcome variables. Further research should focus on the early mechanisms leading to PGD.

scholarly journals 1737. Impact of Therapeutic Drug Monitoring (TDM) of Azole Prophylaxis in Lung Transplant Recipients on the Development of Positive Fungal Events

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S636-S636
Author(s):  
Anooj Shah ◽  
Carly D’Agostino ◽  
Kathleen Cunningham ◽  
Clare Kane ◽  
Michael G Ison ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Lung Transplant ◽  
Study Groups ◽  
Fungal Species ◽  
Therapeutic Drug ◽  
Transplant Recipients ◽  
Lung Transplant Recipients ◽  
Index Value ◽  
The Impact

Abstract Background The utility and clinical impact of therapeutic drug monitoring (TDM) of prophylactic azole antifungals in lung transplant recipients is not well described. The objective of this study was to investigate the impact of TDM of azole prophylaxis in lung transplant recipients on the development of positive fungal events. Methods A retrospective analysis was performed on 47 lung transplant recipients between 2013 and 2018 at Northwestern Memorial Hospital. A positive fungal event was defined as fungal species on BAL culture and/or positive BAL Aspergillus galactomannan (GM) with an index value ≥1.0. Study groups were defined based on attainment of therapeutic trough levels after initiation of oral therapy (therapeutic if posaconazole level ≥0.7 μg/mL or voriconazole ≥1–5.5 μg/mL, subtherapeutic if ≥2 consecutive levels of posaconazole <0.7 μg/mL or voriconazole <1 μg/mL after initial dose increase). Results There were no differences in baseline characteristics (Figure 1). There were a total of 11 fungal events with 3 (12.0%) occurring in the therapeutic cohort and 8 (36.4%) in those subtherapeutic (P = 0.08). In the 5 patients with a positive GM, the mean index was 2.02 ± 0.95. 7/30 (23.3%) of patients on posaconazole had a fungal event, with 2/7 (28.6%) requiring treatment at the time of event. For patients on voriconazole, 4/17 (23.5%) had a fungal event, with 1/4 (25.0%) requiring treatment. Mean time to fungal event was 164.5 ± 8.9 days vs. 135.9 ± 13.7 days in the therapeutic and subtherapeutic group, respectively (P = 0.05). All patients on posaconazole suspension who experienced a fungal event were subtherapeutic (3/3, 100%) compared with the majority of patients on posaconazole delayed release (DR) tablets who achieved therapeutic levels (17/22, 77.3%). Mean posaconazole trough level observed in the patients receiving DR tablet was 2.15 ± 0.95 μg/mL. Conclusion There was an association between two consecutive subtherapeutic azole prophylaxis levels and positive fungal events indicating a role for TDM in lung transplant recipients. Time to fungal event post-transplant was shorter in subtherapeutic patients. As anticipated, the use of posaconazole suspension resulted in subtherapeutic levels. This study presents an opportunity for further research of the impact of TDM on clinical outcomes to optimize patient care. Disclosures All authors: No reported disclosures.

Diversity of antiviral-resistant human cytomegalovirus in heart and lung transplant recipients

2010 ◽  
Vol 13 (2) ◽  
pp. 145-153 ◽  
Author(s):  
J.M. Iwasenko ◽  
G.M. Scott ◽  
Z. Naing ◽  
A.R. Glanville ◽  
W.D. Rawlinson
Keyword(s):  
Human Cytomegalovirus ◽  
Lung Transplant ◽  
Transplant Recipients ◽  
Lung Transplant Recipients

The Impact of Pandemic Influenza A H1N1 2009 on Australian Lung Transplant Recipients

2011 ◽  
Vol 11 (3) ◽  
pp. 568-574 ◽  
Author(s):  
B. J. H. Ng ◽  
A. R. Glanville ◽  
G. Snell ◽  
M. Musk ◽  
M. Holmes ◽  
...  
Keyword(s):  
Pandemic Influenza ◽  
Influenza A ◽  
Lung Transplant ◽  
Transplant Recipients ◽  
Influenza A H1n1 ◽  
Lung Transplant Recipients ◽  
The Impact

The impact of genetic polymorphisms, diltiazem, and demographic variables on everolimus trough concentrations in lung transplant recipients

2014 ◽  
Vol 28 (5) ◽  
pp. 590-597 ◽  
Author(s):  
Kelly E. Schoeppler ◽  
Christina L. Aquilante ◽  
Tyree H. Kiser ◽  
Douglas N. Fish ◽  
Martin R. Zamora
Keyword(s):  
Genetic Polymorphisms ◽  
Lung Transplant ◽  
Demographic Variables ◽  
Transplant Recipients ◽  
Trough Concentrations ◽  
Lung Transplant Recipients ◽  
The Impact

scholarly journals Human Cytomegalovirus Load in Plasma and Bronchoalveolar Lavage Fluid: A Longitudinal Study of Lung Transplant Recipients

2004 ◽  
Vol 190 (6) ◽  
pp. 1076-1083 ◽  
Author(s):  
Glen P. Westall ◽  
Alexandra Michaelides ◽  
Trevor J. Williams ◽  
Greg I. Snell ◽  
Thomas C. Kotsimbos
Keyword(s):  
Longitudinal Study ◽  
Bronchoalveolar Lavage ◽  
Human Cytomegalovirus ◽  
Lung Transplant ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Transplant Recipients ◽  
Lung Transplant Recipients
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