Core signature of rejection-associated cytokines and chemokines in endomyocardial biopsies after heart transplantation.

Background: Rejection remains a limiting factor for survival after heart transplantation (HTx), and predictive biomarkers are still missing. Therefore, we aimed to define the cytokine/chemokine microenvironment in endomyocardial biopsies (EMB) and plasma after HTx and to identify patterns that reflect ischemia/reperfusion injury as well as allograft rejection. Therefore, we hypothesize distinct cytokine/chemokine patterns in heart biopsies with histopathologically proven rejection compared with the microenvironment in unsuspicious biopsies.

HCMV Variants Expressing ULBP2 Enhance the Function of Human NK Cells via its Receptor NKG2D.

The immunosuppressed state of transplant patients allows opportunistic pathogens such as human cytomegalovirus (HCMV) to cause severe disease. Therefore, inducing and boosting immunity against HCMV in recipients prior to organ transplantation is highly desirable, and accordingly, the development of an HCMV vaccine has been identified as a clinically relevant priority. Such vaccines need to be highly attenuated while eliciting specific and protective immune responses.

CD14CD16 monocytes are the main producers of Interleukin-10 following clinical heart transplantation.

Introduction: Following heart transplantation, a cascade of immunological responses is initiated influencing the clinical outcome and long-term survival of the transplanted patients. The anti-inflammatory cytokine interleukin-10 (IL-10) was shown to be elevated in the blood of heart transplant recipients directly after transplantation but the releasing cell populations and the composition of lymphocyte subsets following transplantation have not been thoroughly studied.

Methods: We identified immune cells by immunophenotyping and analyzed intracellular IL-10 production in peripheral blood mononuclear cells (PBMC) of heart transplanted patients (n= 17) before, directly after and 24h post heart transplantation.

Composition of perfusion solutions and kinetics define differential cytokine/chemokine secretion in a porcine cardiac arrest model of lung preservation.

Background: lung perfusion (EVLP) uses continuous normothermic perfusion to reduce ischemic damage and to improve post-transplant outcomes, specifically for marginal donor lungs after the donation after circulatory death. Despite major efforts, the optimal perfusion protocol and the composition of the perfusate in clinical lung transplantation have not been identified. Our study aims to compare the concentration levels of cytokine/chemokine in different perfusion solutions during EVLP, after 1 and 9 h of cold static preservation (CSP) in a porcine cardiac arrest model, and to correlate inflammatory parameters to oxygenation capacities.

Age-related cytokine imbalance in the thymus in sudden infant death syndrome (SIDS).

Background: Sudden infant death syndrome (SIDS) has been considered to be triggered by a combination of underlying immune dysregulation and infections. The thymus is a crucial lymphatic organ responsible for T cell development in infancy. We hypothesized that an altered thymic immune status may be detectable by intrathymic cytokine profiling in SIDS.

Immediate major dynamic changes in the T- and NK-cell subset composition after cardiac transplantation.

Early kinetics of lymphocyte subsets involved in tolerance and rejection following heart transplantation (HTx) are barely defined. Here, we aimed to delineate the early alloimmune response immediately after HTx. Therefore, blood samples from 23 heart-transplanted patients were collected before (pre-), immediately (T0), 24 hours (T24), and 3 weeks (3 wks) after HTx.

Third SARS-CoV-2 vaccination and breakthrough infections enhance humoral and cellular immunity against variants of concern.

Introduction: SARS-CoV-2 vaccination is the leading strategy to prevent severe courses after SARS-CoV-2 infection. In our study, we analyzed humoral and cellular immune responses in detail to three consecutive homologous or heterologous SARS-CoV-2 vaccinations and breakthrough infections.

Methods: Peripheral blood samples of n=20 individuals were analyzed in the time course of three SARS-CoV-2 vaccinations and/or breakthrough infection.

Pulmonary immune profiling of SIDS: impaired immune maturation and age-related cytokine imbalance.

Background: For sudden infant death syndrome (SIDS), an impaired immunocompetence has been discussed for a long time. Cytokines and chemokines are soluble immune mediators (SIM) whose balance is essential for the immune status. We hypothesized that an imbalanced immune response might contribute to the etiology of SIDS.

Donor NK and T Cells in the Periphery of Lung Transplant Recipients Contain High Frequencies of Killer Cell Immunoglobulin-Like Receptor-Positive Subsets.

Introduction: For end-stage lung diseases, double lung transplantation (DLTx) is the ultimate curative treatment option. However, acute and chronic rejection and chronic dysfunction are major limitations in thoracic transplantation medicine. Thus, a better understanding of the contribution of immune responses early after DLTx is urgently needed.

Endothelial dysfunction contributes to severe COVID-19 in combination with dysregulated lymphocyte responses and cytokine networks.

The systemic processes involved in the manifestation of life-threatening COVID-19 and in disease recovery are still incompletely understood, despite investigations focusing on the dysregulation of immune responses after SARS-CoV-2 infection. To define hallmarks of severe COVID-19 in acute disease (n = 58) and in disease recovery in convalescent patients (n = 28) from Hannover Medical School, we used flow cytometry and proteomics data with unsupervised clustering analyses. In our observational study, we combined analyses of immune cells and cytokine/chemokine networks with endothelial activation and injury.

Identification of distinct secretory patterns and their regulatory networks of ischemia versus reperfusion phases in clinical heart transplantation.

Background: Ischemia/reperfusion injury (IRI) is associated with inflammatory responses contributing to the development of primary graft dysfunction (PGD) and rejection. Here, we investigated the pathophysiology of IRI and the early phase after heart transplantation (HTx) regarding its cytokine/chemokine and endothelial networks.

Methods: Using multiplex technology, we assessed protein concentrations in plasma samples of HTx recipients (n = 11) pre-, postoperatively, 24 h and 3 weeks after HTx.

Differential effects of Belatacept on virus-specific memory versus de novo allo-specific T cell responses of kidney transplant recipients and healthy donors.

Belatacept, Nulojix®, inhibits the interaction of CD28 on naïve T cells with B7.1/B7.2 (CD80/86) on antigen presenting cells, leading to T cell hyporesponsiveness and anergy and is approved as immunosuppressive drug in kidney transplantation.