Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Schuller, M.
Flow Cytometric B Cell Phenotyping before and after Kidney Transplantation – Potential Predictors of SARS-CoV-2 Vaccination Response within the Circulating B Cell Pool
PhD-Studium (Doctor of Philosophy); Humanmedizin; [ Dissertation ] Medizinische Universität Graz; 2024. pp. 112
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Eller Philipp
- Malli Roland
- Altmetrics:
- Abstract:
- Introduction: Kidney transplantation (KT) is the preferred form of kidney replacement therapy considering morbidity, mortality and quality of life. To avoid allograft rejection, KT comes at the cost of chronic immunosuppression, which harbors an increased risk of infection. Current immunosuppressive treatments are primarily targeted towards T cells. B cells (BCs) have historically been disregarded or reduced to their, potentially detrimental, role as alloantibody producers, but BCs may also provide humoral immunity and exert antibody-independent functions with relevance in transplantation. The COVID-19 pandemic has posed a dual threat for kidney transplant recipients (KTRs), as they are particularly vulnerable to severe courses, while antibody response to vaccination has been suboptimal. In this study, we investigated the changes of BCs and BC subpopulations from before to one year after KT. Additionally, we screened for potential predictors within the peripheral BC pool for vaccination response. Methods: A total of 105 KTRs were screened, and blood samples were taken prior to the hemodialysis session before transplantation (T1) and one year after transplantation (T2). Due to incomplete follow-up, death or graft loss 71 KTRs were included in our T1/T2 cohort. Peripheral blood mononuclear cells (PBMCs) were isolated at both timepoints and stained for flow cytometric analysis of leucocytes and BC subpopulations using the markers CD19, IgM, IgD, CD24, CD27, CD86, CD5 and CD38. For the vaccination subcohort, we analyzed antibody response to mRNA-based SARS-CoV-2 vaccination (mRNA-1273 or BNT162b2) in 40 out of 71 KTRs, for whom this data was available. Spearman rank-based correlation between BC subpopulations at T2 and antibody titers were calculated. Results: From T1 to T2, leucocyte numbers increased by virtue of monocyte and granulocyte expansion while lymphocytes remained stable. CD19+ BCs trended for increased abundance at T2. Naïve BCs, the largest BC subset, were found at similar frequencies and absolute numbers at both timepoints. Plasmablasts and transitional BCs (TrBCs) were profoundly reduced at T2, whereas double negative BCs increased in abundance. In the memory BC (mBC) pool, IgM-only mBCs and class-switched mBCs were reduced at T2. IgD-only mBCs and unswitched mBCs remained similar. Diminished frequencies and counts of activated CD86+ and tolerogenic CD27- CD5+ BCs were observed at T2. Only 50% of KTRs (n= 20) developed detectable antibody titers after two doses of SARS-CoV-2 vaccination. Antibody levels correlated with TrBC counts and frequencies at T2. Responders displayed increased TrBC abundance compared to non-responders without any detectable antibodies. Conclusion: Flow cytometric phenotyping of circulating BCs revealed profound compositional changes from the CKD G5 to the stable KT setting. Particularly small subsets like PBs and TrBCs were decreased after transplantation. By showing that TrBCs correlated with antibody levels after SARS-CoV-2 vaccination, we provide evidence that quantitative and qualitative changes of the BC pool may be of clinical relevance. Our findings of TrBCs as predictors of humoral response need to be confirmed in larger and prospective studies, potentially expanding to other vaccines.