Can Double-Negative B Cells and Marginal Zone B Cells Have a Potential Impact on the Outcome of Kidney Transplantation?
Abstract
1. Introduction
2. Methods
2.1. Study Patients
2.1.1. Inclusion Criteria
2.1.2. Exclusion Criteria
2.2. Study Schedule
2.3. Ethical Approval and Consent to Participate
2.4. Immunosuppressive Regimen
2.5. Flow Cytometry of B-Cell Subpopulations
- Anti-CD19 PC5.5 clone J3-119, Beckman Coulter, Beckman Coulter, Inc., Sykesville, MD, USA;
- Anti-CD27 PE-Dylight 594 clone LT27, EXBIO, Praha SA, Czech Republic;
- Anti-CD45-PC7 clone J33 Beckman Coulter, Beckman Coulter, Inc., Sykesville, MD, USA;
- Anti-IgD clone IA6-2 Thermo Scientific LSG, Lagoas Park, Porto Salvo, Portugal;
- Anti-IgM PE clone, SA-DA4 Beckman Coulter, Beckman Coulter, Inc., Sykesville, MD, USA.
2.6. Statistics
3. Results
3.1. Patient Characteristics
3.2. Differences in DN and MZB B-Cell Populations at Different Study Time Points: DN and MZ B Cells Underwent Changes During the 12-Month Follow-Up Period
3.3. How the DN and MZ Β Cell Populations Were Affected by Different Factors That Influence the Outcome of Kidney Transplantation
3.4. MZ B Cells in Relation to the Prediction of Rejection
3.5. Frequencies and Absolute Numbers of MZ and DN B Cells in Relation to Graft Function at Different Time Points During Study Follow-Up
3.6. Effect of Induction Immune Therapy on DN and MZ B Cells at Different Time Points
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Study Sample | N: 71 |
---|---|
Characteristics of recipients | |
Sex | Female: 20/Male: 51 28.17/71.83% |
Age in years | 48.5 (39, 60) |
Type of donors | Deceased/brain death: 50 (70%) Living: 21 (30%) |
Preemptive recipients | 7 (9.86%) |
Dialysis patient candidates for transplantation | |
Type of dialysis | HD: 64 (81%) CAPD: 7 (19%) |
Duration of dialysis (months) | 87 (34–127) |
Distribution of underlying kidney disease | |
Polycystic kidney disease | 14 (19.7%) |
Primary glomerulonephritis IgA nephropathy Membranous nephropathy Focal segmental glomerulosclerosis Membranoproliferative glomerulonephritis | 12 (17%) 5 (7%) 3 (4.25%) 2 (2.83%) 2 (2.83%) |
Reflux nephropathy | 6 (8.4%) |
Diabetes mellitus | 6 (8.4%) |
Nephrosclerosis/hypertension | 8 (11.25%) |
Urinary tract infections/stones | 5 (7%) |
Other | 12 (17%) |
Unknown | 8 (11.25%) |
Information on transplantation, graft function | |
Delayed graft function | Yes: 12 (24%) No: 38 (76%) |
Cold ischemia time (hours) | 19.2 (4.6) |
eGFR (mL/min/1.73 m2) | 52 (36–89) |
Recipients with rejection | 11 (15.5%) |
Induction therapy | |
Basiliximab, N (%) | 63 (88.7%) |
Anti-thymocyte globulin, N(%) | 8 (11.3%) |
T0 1 | T3 1 | T6 1 | T12 1 | p 2 | Post Hoc 3 Comparison | |
---|---|---|---|---|---|---|
%Double negative, (CD19+IgD−CD27), DN | 11.9 (7.8, 18.6) | 10.1 (7.7, 13.8) | 13.1 (8.8, 18.8) | 13.6 (9.2, 17.7) | 0.004 | ns |
#Double negative (CD19+IgD−CD27−), DN | 10 (5.8, 19) | 11 (5.3, 18) | 11 (6.1, 17.5) | 12 (7.9, 21) | ns | ns |
%Marginal zone B cells (CD19+IgD+IgM+CD27+), MZB | 26.6 (11.2, 38.1) | 25.6 (14.4, 42.2) | 22.8 (11.3, 41.6) | 30 (19.5, 44.3) | ns | ns |
#(CD19+IgD+IgM+CD27+), MZB | 5 (1.7, 10.4) | 6 (2.8, 15) | 3 (1, 10) | 7 (5, 11) | 0.005 | ns |
Univariate Regression | |||||
---|---|---|---|---|---|
Frequency of Cell Population | 95% Confidence Interval | ||||
β | Ν | p | Lower | Upper | |
Double negative, DN | |||||
Age of the recipient | −0.04 | 71 | 0.5 | −0.17 | 0.09 |
Type of donor (deceased/living) | 1.6 | 71 | 0.3 | −1.8 | 5 |
Cold ischemia time, CIT | −0.04 | 71 | 0.7 | −0.20 | 0.13 |
Delayed graft function, DGF | 2.8 | 71 | 0.093 | −0.49 | 6.1 |
Dialysis vintage | −0.01 | 64 | 0.05 | −0.04 | 0.02 |
Marginal zone B cells, MZB | |||||
Age of the recipient | 0.07 | 71 | 0.7 | −0.27 | 0.42 |
Type of donor (deceased/living) | −1.2 | 71 | 0.8 | −10 | 8 |
Cold ischemia time, CIT | −0.19 | 71 | 0.5 | −0.28 | 0.6 |
DGF | −4.1 | 71 | 0.4 | −13 | 4.7 |
Dialysis vintage | 0.04 | 64 | 0.4 | −0.04 | 0.12 |
Univariate Regression | Multivariate Regression | ||||||||
---|---|---|---|---|---|---|---|---|---|
Absolute Numbers of Cells | 95% Confidence Interval | 95% Confidence Interval | |||||||
β | Ν | p | Lower | Upper | β | p | Lower | Upper | |
Double negative, DN | |||||||||
Age of the recipient | −0.47 | 71 | 0.01 | −0.47 | −0.82 | −0.27 | 0.3 | −0.75 | 0.21 |
Type of donor (deceased/living) | 11 | 71 | 0.023 | 1.5 | 20 | 5.9 | 0.6 | −15 | 27 |
Cold ischemia time, CIT | −0.49 | 71 | 0.031 | −0.94 | −0.05 | −0.1 | 0.8 | −1 | 0.84 |
Delayed graft function, DGF | −2.0 | 71 | 0.7 | −12 | 7.5 | ||||
Dialysis vintage | −0.12 | 64 | 0.005 | −0.12 | −0.21 | −0.05 | 0.4 | −0.17 | 0.07 |
Marginal zone B cells, MZB | |||||||||
Age of the recipient | −0.19 | 71 | 0.079 | −0.19 | 0.02 | −0.11 | 0.3 | −0.35 | 0.12 |
Type of donor (deceased/living) | 5.6 | 71 | 0.052 | −0.05 | 11 | 6.4 | 0.3 | −5 | 18 |
Cold ischemia time, CIT | −0.20 | 71 | 0.2 | −0.47 | 0.07 | 0.2 | 0.5 | −0.34 | 0.74 |
DGF | −5.4 | 71 | 0.047 | −11 | −0.07 | −4.4 | 0.12 | −10 | 1.2 |
Dialysis vintage | 0.00 | 64 | >0.9 | −0.04 | 0.03 |
Kidney Transplant Recipients (N: 71) | Recipients Experiencing Rejection (N: 11) | Recipients Free of Rejection (N: 60) | p-Value * | |
---|---|---|---|---|
Age of recipients | 49 (40, 57) | 49 (38.25, 57) | 48 (43, 52) | 0.968 |
Sex (female/male) | 19/52 | 3/8 | 16/44 | 1.000 |
Donor type (deceased/living) | 50/21 | 7/4 | 43/17 | 0.721 |
DGF | 21/71 | 6/11 | 15/60 | 0.072 |
Frequency and Absolute Number of Cells at Pre-Transplant Time (T0) | Rejection | p-Value Wilcoxon Rank Sum Test | |
---|---|---|---|
Rejection Free, (N = 60) Median (IQR) | Rejection, (N = 11) Median (IQR) | ||
% DN | 12 (8, 19) | 9 (7, 15) | 0.5 |
# DN | 10 (6, 19) | 9 (6, 18) | 0.8 |
% MZB | 31 (9, 39) | 17 (9, 27) | 0.5 |
# MZB | 5.2 (1.1, 11.8) | 4.2 (1.8, 6.3) | 0.7 |
Cell Population at 12 Months Post-Transplant | Rejection | p-Value Wilcoxon Rank Sum Test | |
---|---|---|---|
Rejection Free, N = 60 Median (IQR) | Rejection, N = 11 Median (IQR) | ||
% DN | 12.9 (8.7, 17.9) | 14.4 (12.7, 17.6) | 0.2 |
# DN | 12 (8, 21) | 11 (9, 25) | 0.7 |
% MZB | 31 (20, 45) | 20 (13, 26) | 0.064 |
# MZB | 7 (5, 11) | 9 (6, 10) | >0.9 |
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Fouza, A.; Fylaktou, A.; Daoudaki, M.; Talimtzi, P.; Tagkouta, A.; Vagiotas, L.; Katsanos, G.; Tsoulfas, G.; Antoniadis, N. Can Double-Negative B Cells and Marginal Zone B Cells Have a Potential Impact on the Outcome of Kidney Transplantation? J. Clin. Med. 2025, 14, 3312. https://doi.org/10.3390/jcm14103312
Fouza A, Fylaktou A, Daoudaki M, Talimtzi P, Tagkouta A, Vagiotas L, Katsanos G, Tsoulfas G, Antoniadis N. Can Double-Negative B Cells and Marginal Zone B Cells Have a Potential Impact on the Outcome of Kidney Transplantation? Journal of Clinical Medicine. 2025; 14(10):3312. https://doi.org/10.3390/jcm14103312
Chicago/Turabian StyleFouza, Ariadni, Asimina Fylaktou, Maria Daoudaki, Persefoni Talimtzi, Anneta Tagkouta, Lampros Vagiotas, Georgios Katsanos, Georgios Tsoulfas, and Nikolaos Antoniadis. 2025. "Can Double-Negative B Cells and Marginal Zone B Cells Have a Potential Impact on the Outcome of Kidney Transplantation?" Journal of Clinical Medicine 14, no. 10: 3312. https://doi.org/10.3390/jcm14103312
APA StyleFouza, A., Fylaktou, A., Daoudaki, M., Talimtzi, P., Tagkouta, A., Vagiotas, L., Katsanos, G., Tsoulfas, G., & Antoniadis, N. (2025). Can Double-Negative B Cells and Marginal Zone B Cells Have a Potential Impact on the Outcome of Kidney Transplantation? Journal of Clinical Medicine, 14(10), 3312. https://doi.org/10.3390/jcm14103312