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Renal Transplant Recipients (RTR) with Immune Mediated Graft Injury Display Significant Alterations within the Peripheral B Cell Phenotype

A. Cherukuri, A. Salama, C. Carter, B. Clark, R. Baker

St. James's University Hospital, Leeds, United Kingdom
UCL, London, United Kingdom

Meeting: 2013 American Transplant Congress

Abstract number: A645

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Phenotypic characterization of PBMCs constitutes part of the immune signature for operational tolerance in RTR. Alterations in the PBMCs of RTR with biopsy proven microcirculation injury are less well understood.

Herein, we analysed various lymphocyte subsets and Donor Specific Antibody (DSA) in the peripheral blood of healthy volunteers (HV) and RTR and assessed their relationship with graft function.

A total of 110 subjects were included in this study: HV (n=18); stable function (n=45); GD-NI: graft dysfunction-non immunological (n=22); GD-I: graft dysfunction-immunological (n=25). Absolute numbers of lymphocytes in the peripheral blood were quantified using Trucount beads. Lymphocyte subsets within the T and B cell compartments were analysed and compared across the patient groups (Significant differences are shown in Table-1). There were no significant differences in the numbers of the recent thymic emigrants, naÏve, central or effector memory CD4+T cells. Within the GD-I group, 30% of the patients with no DSAs had significantly higher number of CD19+CD24hiCD38hi (TRS) cells along with higher B-NaÏve-memory ratio and a marginally higher proportion of Tregs. TRS cells which were reduced in RTR with biopsy proven microcirculation injury were found to contain a significant number of the CD19+CD5+CD1dhi cells which correspond to regulatory mouse B-10 cells. In a separate series of experiments we demonstrated that these cells exhibit regulatory properties in vitro.

(95% CI) HV Stable GD-NI GD-I P-value
CD3+ cells (/ΜL) 1496 (1168-1824) 1144 (1011-1277) 1154 (874-1435) 1123 (921-1325) <0.05
CD4+ cells (/ΜL) 878 (730-1025) 650 (563-738) 646 (461-831) 616(491-741) <0.01
CD19+ cells (/ΜL) 349 (223-475) 257 (216-297) 136(101-171) 140 (93-188) <0.01
NK cells (/ΜL) 274 (218-330) 238 (201-275) 205 (154-258) 139 (91-187) <0.01
T regs 6.7% (5.8%-7.7%) 5.1% (4.6%-5.5%) 4.6% (4%-5.2%) 4.5% (3.6%-5.3%) <0.01
TRS B cells 14% (11%-17%) 11% (9%-12%) 8% (6%-10%) 5% (3%-7%) <0.01
TRS-T1/T2 ratio 0.3 (0.2-0.4) 0.22 (0.17-0.25) 0.2 (0.15-0.25) 0.09 (0.03-1) <0.01
B-naive/memory ratio 3 (1.5-4.4) 7.6 (6-9) 9.6 (3.8-16) 3.8 (2-5.7) <0.01
CD24hiCD27+ B cells 22.5% (17%-28%) 13% (9%-17%) 14% (9%-18%) 21% (15%-26%) <0.05

We have shown significant differences within the B cell compartment with a significant reduction in the regulatory type B subsets in patients with biopsy proven immunological graft injury. Such a phenotype has to be studied prospectively to assess its clinical utility.

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To cite this abstract in AMA style:

Cherukuri A, Salama A, Carter C, Clark B, Baker R. Renal Transplant Recipients (RTR) with Immune Mediated Graft Injury Display Significant Alterations within the Peripheral B Cell Phenotype [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/renal-transplant-recipients-rtr-with-immune-mediated-graft-injury-display-significant-alterations-within-the-peripheral-b-cell-phenotype/. Accessed April 22, 2021.

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