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Metabolic pathways regulate immune responses and disrupted metabolism leads to immune dysfunction and disease. Coronavirus disease 2019 (COVID-19) is driven by imbalanced immune responses, yet the role of immunometabolism in COVID-19 pathogenesis remains unclear. By investigating 87 patients with confirmed SARS-CoV-2 infection, 6 critically ill non���COVID-19 patients, and 47 uninfected controls, we found an immunometabolic dysregulation in patients with progressed COVID-19. Specifically, T cells, monocytes, and granulocytes exhibited increased mitochondrial mass, yet only T cells accumulated intracellular reactive oxygen species (ROS), were metabolically quiescent, and showed a disrupted mitochondrial architecture. During recovery, T cell ROS decreased to match the uninfected controls. Transcriptionally, T cells from severe/critical COVID-19 patients showed an induction of ROS-responsive genes as well as genes related to mitochondrial function and the basigin network. Basigin (CD147) ligands cyclophilin A and the SARS-CoV-2 spike protein triggered ROS production in T cells in vitro. In line with this, only PCR-positive patients showed increased ROS levels. Dexamethasone treatment resulted in a downregulation of ROS in vitro and T cells from dexamethasone-treated patients exhibited low ROS and basigin levels. This was reflected by changes in the transcriptional landscape. Our findings provide evidence of an immunometabolic dysregulation in COVID-19 that can be mitigated by dexamethasone treatment.

The B cell activating factor BAFF has gained importance in the context of kidney transplantation due to its role in B cell survival. Studies have shown that BAFF correlates with an increased incidence of antibody-mediated rejection and the development of donor-specific antibodies. In this study, we analyzed a defined cohort of kidney transplant recipients who were treated with standardized immunosuppressive regimens according to their immunological risk profile. The aim was to add BAFF as an awareness marker in the course after transplantation to consider patient’s individual immunological risk profile. Included patients were transplanted between 2016 and 2018. Baseline data, graft function, the occurrence of rejection episodes, signs of microvascular infiltration, and DSA kinetics were recorded over 3 years. BAFF levels were determined 14 d, 3 and 12 months post transplantation. Although no difference in graft function could be observed, medium-risk patients showed a clear dynamic in their BAFF levels with low levels shortly after transplantation and an increase in values of 123% over the course of 1 year. Patients with high BAFF values were more susceptible to rejection, especially antibody-mediated rejection and displayed intensified microvascular inflammation; the combination of high BAFF + DSA puts patients at risk. The changing BAFF kinetics of the medium risk group as well as the increased occurrence of rejections at high BAFF values enables BAFF to be seen as an awareness factor. To compensate the changing immunological risk, a switch from a weaker induction therapy to an intensified maintenance therapy is required. Supplementary Information The online version contains supplementary material available at 10.1007/s12026-021-09205-4.

Background B-cell-activating factor (BAFF) is associated with donor-specific antibodies (DSA) and poorer outcomes after renal transplantation (RTx). We examined the effects of anti-BAFF treatment on B cells, expression of costimulatory molecules and cytokines, germinal centers (GCs), and DSA formation in an RTx model in rats. Methods Anti-BAFF antibody was injected on days 3, 17, 31, and 45 after allogeneic RTx. Rats received reduced dose cyclosporine A for 28 or 56 days to allow chronic rejection and DSA formation. Leukocytes, B-cell subsets, and DSA were measured using flow cytometry; expression of cytokines and costimulatory molecules was measured by quantitative polymerase chain reaction, and GCs and T follicular helper were assessed using immunohistochemistry. Rejection was evaluated by a nephropathologist. Results Anti-BAFF treatment reduced the frequency of B cells in allografts and spleen. Naive B cells were strongly reduced by anti-BAFF treatment in all compartments. Messenger RNA expression of interleukin-6 and the costimulatory molecules CD40 and inducible T cell costimulator ligand was significantly reduced in anti-BAFF-treated rats. GC area was smaller and plasmablasts/plasma cell numbers lower in anti-BAFF-treated rats, which was reflected by less DSA in certain IgG subclasses. Conclusions Anti-BAFF treatment interferes with humoral responses at multiple levels in this model of allogeneic RTx.

BACKGROUND Declining numbers of deceased donors and prolonged waiting time emphasize the importance of living kidney donation. Furthermore, because of the changing age structures with increasingly older recipients, the question of acceptance of older donors is becoming more relevant. However, sufficient long-term outcome data, especially for older donors - including histopathological analysis - are lacking. The aim of this study was to analyze the Regensburg Living Donor Cohort with regard to age