Purpose: B cell subsets could be used as biomarkers to modulate therapy regimens in kidney transplant patients. B cell subsets occur with varying proportions within the B cell pool and the composite of these proportions provide a B cell signature (BCS). These proportions can be affected by therapies and reflect the “immune status” of the individual. We evaluated the effects of Thymoglobulin and conventional immunosuppressive therapy on specific B cell subsets within nonmemory compartments in the B cell pools of kidney transplant (Tx) patients. Hypothesis: We hypothesized that BCSs post-Thymoglobulin would be significantly altered compared to pre-Tx and healthy controls. Methods: Kidney Tx patients received low dose thymoglobulin (1.5 mg /kg); cumulative dose was less than 5 mg/kg. Maintenance immunosuppression consisted of tacrolimus, MMF, and prednisone. PBMCs and serum was collected from healthy individuals (n=26), pre-Tx (n=18), post-Tx 1 month (n=11), and post-Tx 3 months (n=7). PBMCs were assessed using 7-color flow cytometry and FlowJo Software. Serum BAFF levels were measured using ELISA. BCS and BAFF levels were assessed for statistical significance using unpaired t test and Welch's correction. Results: We observed a significant difference in T1 subset between healthy and post-Tx 1 month (p = 0.0059), healthy and post-Tx 3 months (p = 0.0005), and pre-Tx and post-3 month (p = 0.0033). In T2 subsets, significant differences were observed between healthy and pre-Tx (p = 0.0336), healthy and post-3 months (p = 0.0092), and pre-Tx and post-3 months (p = 0.2779). The mature naive subset showed significant differences between healthy and pre-Tx (p = 0.0437), and healthy and post-3 months (p = 0.0013). ELISA results showed BAFF levels were significant between pre-Tx and post-1 month (p = 0.0003), but not significant between pre-Tx and post-3 months (p = 0.1257). Conclusions: BCS from healthy, pre- and post- transplant displayed unique profiles. A larger transplant patient sample size is currently being assessed to provide data on what specific B cell subsets Thymoglobulin targets. In the future, BCS profiles could be correlated with clinical parameters of graft function and provide a method for monitoring non-sensitized patients for susceptibility to AMR and a basis for modulating treatment to prevent rejection.

CITATION INFORMATION: Benitez A, Milford T, Torralba K, Payne K, De Vera M. B Cell Signature Profiling in Kidney Transplant Patients on Thymoglobulin. Am J Transplant. 2016;16 (suppl 3).

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