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Higher CD19+ CD25+ Bregs are independently associated with better graft function in renal transplant recipients

Research Abstract

The Identification of B cell subsets with regulatory functions might open the way to new therapeutic strategies in the field of transplantation, which aim to reduce the dose of immunosuppressive drugs and prolong the graft survival. CD25 was proposed as a marker of a B-cell subset with an immunosuppressive action termed Bregs. The effect of CD19 + CD25 + Bregs on graft function in renal transplant recipients has not yet been elucidated. We investigated a potential impact of CD19 + CD25 + Bregs on renal graft function as well as a possible interaction of CD19 + CD25 + Bregs with peripheral Tregs in healthy controls, end-stage kidney disease patients (ESKD), and renal transplant recipients. Moreover, we aimed to investigate the association of CD19 + CD25 + Bregs with serum IL-10, TGF-ß1, and IFN-γ in the same study groups.

Research Authors
Eman H. Ibrahim, Mostafa G. Aly, Gerhard Opelz, Christian Morath, Martin Zeier, Caner Süsal, Douaa M. Sayed, Eman Hassan, Naruemol Ekpoom & Volker Daniel
Research Date
Research Department
Research Journal
BMC nephrology
Research Member
Research Publisher
BioMed Central
Research Vol
22
Research Website
https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-021-02374-2
Research Year
2021

Serum Zinc Levels in Chronic Kidney Disease patients, Hemodialysis Patients, and Healthy Controls: Systematic Review and Meta-analysis

Research Abstract

Objectives

Chronic kidney disease (CKD) patients are liable to changes in zinc homeostasis through anorexia and dietary restrictions, as well as hemodialysis (HD). Changes in zinc homeostasis might predispose CKD and HD patients to specific adverse effects, including erythropoietin-resistant anemia, oxidative stress, atherosclerosis, and cardiovascular disease. Since serum zinc levels are rarely measured in CKD and HD patients, zinc supplementations do not represent a routine therapy for CKD and dialysis patients. Therefore, in this meta-analysis, we aimed to assess serum zinc levels in CKD and HD patients compared with healthy controls (HC). In addition, we investigated whether HD affects serum zinc levels by comparing serum zinc levels in HD versus CKD patients and comparing serum zinc pre- versus post-HD.

Methods

A comprehensive search of databases was conducted to identify either observational studies or randomized trials that assessed serum zinc levels in either CKD and /or HD patients in comparison to HC. We conducted a random-effects meta-analysis.

Results

Our meta-analysis included 42 studies with a total of 4161 participants, of whom 460 represented CKD patients, whereas 2047 patients represented HD patients. 1654 participants were healthy controls. Both CKD and HD patients showed lower serum zinc levels compared with HC (mean difference = -22.86 μg/dl, 95% CI [-33.25, -12.46]; mean difference = -13.64 μg/dl, 95% CI [-21.47, -53.80], respectively). CKD and HD patients showed no significant difference in serum zinc levels (mean difference = 15.39, 95% CI [-8.91, 39.68]). Pre-HD serum zinc levels were significantly lower than those post-HD (mean difference = -7.51 μg/dl, 95% CI [-14.24, -0.78]).

Conclusion

Occurrence of Lower serum zinc levels in CKD and HD patients than in HC appears to be more frequent than reported in daily clinical practice. An increase in the frequency of zinc measurement might be beneficial.

Research Authors
Anas Elgenidy, Mostafa Atef Amin, Ahmed K Awad, Faeq Husain-Syed, Mostafa G Aly
Research Date
Research Department
Research Journal
Journal of Renal Nutrition
Research Member
Research Year
2022

Immunogenicity and reactogenicity of homologous mRNA-based and vector-based SARS-CoV-2 vaccine regimens in patients receiving maintenance dialysis

Research Abstract

Patients receiving maintenance dialysis (MD) are vulnerable to COVID-19-related morbidity and mortality. Currently, data on SARS-CoV-2-specific cellular and humoral immunity post-vaccination in this population are scarce.

We conducted a prospective single-center study exploring the specific cellular (interferon-γ and interleukin-2 ELISpot assays) and humoral immune responses (dot plot array and chemiluminescent microparticle immunoassay [CMIA]) at 4 weeks and 6 weeks following a single dose or a complete homologous dual dose SARS-CoV-2 vaccine regimen in 60 MD patients (six with a history of COVID-19).

Our results show that MD patients exhibit a high seroconversion rate (91.7%) but the anti-spike IgG antibodies (CMIA) tend to wane rapidly after full immunization. Only 51.7% of the patients developed T cell immune response. High anti-spike IgG antibodies may predict a better cellular immunity …

Research Authors
Hristos Karakizlis, Christian Nahrgang, Kevin Strecker, Jiangping Chen, Mostafa Aly, Heiko Slanina, Christian G Schüttler, Isla Esso, Martin Wolter, Darina Todorova, Sönke Jessen, Andrea Adamik, Claudio Ronco, Werner Seeger, Rolf Weimer, Martina Sester, H
Research Date
Research Department
Research Journal
Clinical Immunology
Research Member
Research Pages
108961
Research Publisher
Academic Press
Research Year
2022

Relationship of transitional regulatory B and regulatory T cells and immunosuppressive drug doses in stable renal transplant recipients

Research Abstract

Objectives

Regulatory B cells (Bregs) and T cells (Tregs) are thought to be involved in the regulation of graft acceptance in renal transplant recipients. However, mechanisms that affect Breg differentiation and interaction with Tregs are rather unclear.

Methods

Using eight-color-fluorescence flow cytometry, Tregs and CD19+ CD24hiCD38hi Bregs were analyzed in whole blood samples of 80 stable kidney transplant recipients, 20 end-stage renal disease (ESRD) patients and 32 healthy controls (HC). In addition, differentiation of Bregs and Tregs was studied in different micromilieus using cocultures with strongly enriched B-lymphocytes and autologous peripheral blood mononuclear cells stimulated with CpG and phytohemagglutinin.

Results

Bregs were higher in HC than in ESRD patients and lowest in transplant recipients. Bregs were higher early as compared to late posttransplant. Posttransplant, high Bregs were associated with higher glomerular filtration rate (GFR) and lower C-reactive protein (CRP). Higher doses and blood levels of ciclosporine, tacrolimus, and mycophenolate mofetil as well as higher doses of steroids were not associated with low Bregs. In contrast, most Treg subsets were lower when blood levels of ciclosporine, tacrolimus, and mycophenolate mofetil were higher. Tregs were not associated with Bregs, GFR, CRP plasma levels, and occurrence of rejection or infection. In vitro, differentiation of Bregs was strongly dependent on T cell support and was blocked by excessive or lacking T-cell help. Tregs were not associated with Breg numbers in vitro.

Conclusion

Bregs appear to be insensitive to high doses of posttransplant immunosuppressive drugs. The protracted Breg decrease posttransplant might be caused by impaired T cell support attributable to immunosuppressive drugs.

Research Authors
Eman H Ibrahim, Mostafa Aly, Christian Morath, Douaa M Sayed, Naruemol Ekpoom, Gerhard Opelz, Caner Süsal, Volker Danie
Research Date
Research Department
Research Journal
Immunity, Inflammation and Disease
Research Member
Research Pages
1252-1271
Research Vol
Vol.9
Research Website
https://doi.org/10.1002/iid3.473
Research Year
2021
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