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Alterations in Peripheral Blood B Cell Subpopulations in Kidney Transplant Recipients With DSA

B. Ramaswami,1 R. Ippolito,2 B. Elinoff,1 M. Marrari,3 K. Hadi,1 C. Macedo,1 D. Metes,1 A. Shields,4 R. Alloway,5 A. Zeevi,3 F. Lakkis,1 E. Woodle,4 G. Chalasani.1,2

1Surgery & STI(1), Medicine(2), Pathology(3), University of Pittsburgh, Pittsburgh
2Surgery(4) & Medicine(5), University of Cincinnati College of Medicine, Cincinnati.

Meeting: 2015 American Transplant Congress

Abstract number: C252

Keywords: Alloantibodies, B cells, FACS analysis, Kidney transplantation

Session Information

Session Name: Poster Session C: Translational Biomarkers and Immune Monitoring

Session Type: Poster Session

Date: Monday, May 4, 2015

Session Time: 5:30pm-6:30pm

 Presentation Time: 5:30pm-6:30pm

Location: Exhibit Hall E

Peripheral blood B cell subpopulations were assessed over time (1, 3, 6, 9, and 12 months) in living donor kidney transplant recipients undergoing thymoglobulin (n = 32) or basiliximab induction (n = 24) and were prospectively monitored for DSA. There were no significant differences observed in age, gender, race, HLA mismatches, PRA at transplantation and maintenance immunosuppression between patients who did or did not develop DSA. B cells were characterized by FACS after exclusion of dead cells and non-B cells. All patients with DSA, irrespective of thymoglobulin or basiliximab induction, showed a significant decrease in B cell numbers at time of DSA in contrast to those without DSA (⇓24.5% vs. ↑28% from baseline, p >0.05, n = 7 – 9). Patients who developed DSA after thymoglobulin induction showed delayed recovery of B cell numbers that remained decreased even at 1 year in those with concomitant rejection. Moreover, B cells expressing CD5, a negative regulator of B cell activation, were significantly decreased in patients with DSA while IgG memory B cells continued to increase over time (⇓71.7% vs. ↑95.2%, and ↑101.7% vs. ⇓63.8%, respectively, from baseline, p >0.05, n = 4 – 5). After basiliximab induction, only patients who developed DSA showed a persistent decline in CD25+ B cells that have immunomodulatory functions. Also, a higher ratio of total memory to CD24+ memory (immunomodulatory, pre-pro-IL10+) B cells at transplantation was found in patients with DSA (3.8±0.9 vs. 2.1±0.8, p >0.05, n = 4 – 6) followed by an increase in atypical memory B cells compared to those without DSA (↑158% vs. ⇓21.4%, p >0.05, n = 4 – 6). These findings suggest that altered homeostasis and activation of B cells possibly led to changes in memory vs. immunomodulatory B cells contributing to the development of DSA.

In summary, patients who developed DSA under thymoglobulin or basiliximab induction showed similar trends such as decreased B cell numbers and yet dissimilar changes in B cell subpopulations suggesting distinct underlying mechanisms of DSA development (eg. altered homeostatic cytokines, increase in memory B cells, and decrease in regulatory B cells or function).

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To cite this abstract in AMA style:

Ramaswami B, Ippolito R, Elinoff B, Marrari M, Hadi K, Macedo C, Metes D, Shields A, Alloway R, Zeevi A, Lakkis F, Woodle E, Chalasani G. Alterations in Peripheral Blood B Cell Subpopulations in Kidney Transplant Recipients With DSA [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/alterations-in-peripheral-blood-b-cell-subpopulations-in-kidney-transplant-recipients-with-dsa/. Accessed May 10, 2025.

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