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

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.

2020 ◽  
Vol 222 (3) ◽  
pp. 417-427
Author(s):  
Hannes Vietzen ◽  
Irene Görzer ◽  
Claudia Honsig ◽  
Peter Jaksch ◽  
Elisabeth Puchhammer-Stöckl

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 &lt; .001; IgG3, P &lt; .001). In addition, higher levels of ADCC were observed by FEA and CD107 assay in R+ patients compared with controls (P &lt; .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.


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

2016 ◽  
Vol 07 (02) ◽  
pp. 430-445 ◽  
Author(s):  
Susan Sereika ◽  
Annette DeVito Dabbs ◽  
Steven Handler ◽  
Elizabeth Schlenk ◽  
Yun Jiang

SummaryTo describe lung transplant recipients (LTRs’) acceptance and use of mobile technology for health self-monitoring during the first year post-transplantation, and explore correlates of the use of technology in the 0 to 2, >2 to ≤6, >6 to ≤12, and 0 to 12 months.Secondary analysis of data from 96 LTR assigned to use Pocket PATH®, a smartphone application, for daily health self-monitoring in a randomized controlled trial. Use of Pocket PATH was categorized as low, moderate, and high use. Proportional odds models for ordinal logistic regression were employed to explore correlates of use of technology.LTR reported high acceptance of Pocket PATH at baseline. However, acceptance was not associated with actual use over the 12 months (p=0.45∼0.96). Actual use decreased across time intervals (p<0.001). Increased self-care agency was associated with the increased odds of higher use in women (p=0.03) and those less satisfied with technology training (p=0.02) in the first 2 months. Higher use from >2 to ≤6 months was associated with greater satisfaction with technology training (OR=3.37, p=0.01) and shorter length of hospital stay (OR=0.98, p=0.02). Higher use from >6 to ≤12 months was associated with older age (OR=1.05, p=0.02), lower psychological distress (OR=0.43, p=0.02), and better physical functioning (OR=1.09, p=0.01). Higher use over 12 months was also associated with older age (OR=1.05, p=0.007), better physical functioning (OR=1.13, p=0.001), and greater satisfaction with technology training (OR=3.05, p=0.02).Correlates were different for short- and long-term use of mobile technology for health self-monitoring in the first year post-transplantation. It is important to follow up with LTR with longer hospital stay, poor physical functioning, and psychological distress, providing ongoing education to improve their long-term use of technology for health self-monitoring.Citation: Jiang Y, Sereika SM, DeVito Dabbs A, Handler SM, Schlenk EA. Acceptance and use of mobile technology for health self-monitoring in lung transplant recipients during the first year post-transplantation.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S636-S636
Author(s):  
Anooj Shah ◽  
Carly D’Agostino ◽  
Kathleen Cunningham ◽  
Clare Kane ◽  
Michael G Ison ◽  
...  

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.


2011 ◽  
Vol 11 (3) ◽  
pp. 568-574 ◽  
Author(s):  
B. J. H. Ng ◽  
A. R. Glanville ◽  
G. Snell ◽  
M. Musk ◽  
M. Holmes ◽  
...  

2014 ◽  
Vol 28 (5) ◽  
pp. 590-597 ◽  
Author(s):  
Kelly E. Schoeppler ◽  
Christina L. Aquilante ◽  
Tyree H. Kiser ◽  
Douglas N. Fish ◽  
Martin R. Zamora

2017 ◽  
Vol 36 (4) ◽  
pp. S410
Author(s):  
A.L. Hulbert ◽  
C. Benedetti ◽  
K. Beermann ◽  
A. Gray ◽  
M. Hartwig ◽  
...  

2020 ◽  
Vol 30 (2) ◽  
pp. 140-143
Author(s):  
Anahli Patel ◽  
Yelena Chernyak

Transplant recipients have significant psychosocial stressors due to unique posttransplant sequela that results in an increased incidence of psychopathology. Posttransplant psychological interventions, especially in lung transplant recipients, are understudied, as the focus of prior research has emphasized pretransplant interventions. However, posttransplant psychological stability affects medical outcomes. The importance of posttransplant psychological intervention is highlighted. Recommendations exist which call for attention to specific psychological domains in the posttransplant recovery period and highlight the impact of psychological rehabilitation on overall wellness and success in recovery. A novel psychological rehabilitation intervention is outlined as a response to posttransplant intervention recommendations to demonstrate implementation.


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