Purpose: Donor specific antibodies (DSA) that emerge following transplantation are indicative of allogenic sensitization and a predisposing factor for antibody mediated rejection. Though various methods of alloantibody detection exist, a timely and accurate test to identify allo-sensitization has not been clinically available. Here, we report, a study monitoring emergence of CD38+/CD138+ plasma cells in the circulation after allo-sensitization as an early marker of DSA development.

Methods: A transgenic mouse model of HLA.A2 sensitization with skin allograft was utilized. DSA IgM and IgG were measured in a flow-cytometric antibody binding assay using a HLA.A2 expressing human T-cell lymphoma line (ATCC 120.1) as target. CD38+/CD138+ plasma cells in peripheral blood and in the spleens were measured in multi-perimeter FACS. Cellular kinetics of blood plasma cells, its correlations with alloantibody levels and splenic plasma cells during de novo DSA responses were investigated.

Results: FACS analysis of PBMC demonstrated that only [frac14] of naïve adult mice (C57BL/j6 at Day 0, n=12) had low frequency (0.025%+0.043%) of CD38+/CD138+ cells in the blood. After allogenic sensitization all mice (n=12) had detectable CD38+/CD138+ cells in the blood. Cellular kinetics showed that CD38+/CD138+ plasma cells increased significantly at Day 7 (frequency: 0.3+0.07%, p=0.003 vs. Day 0), Day 14 (0.3+0.07, p=0.001), Day 21 (0.1+0, p=0.0025) and Day 28 (0.175+0.04, p=0.0028). The increase in CD38+/CD138+ plasma cells in the blood at Day 7 preceded the increases of DSA IgM (peaked at Day 14) and IgG (peaked at day 21) and corresponded to increases of CD138+ cells in the spleens.

Conclusion: Results demonstrated that the occurring frequency of CD38+/CD138+ plasma cells in peripheral blood increases significantly following allogenic sensitization and expansion of blood circulating plasma cells precedes peak titers of IgM and IgG DSA, suggesting that detection of plasma cells in peripheral blood may be of use in earlier detection of allo-sensitization with attendant graft injury.

CITATION INFORMATION: Chai N-.N., Wu G., Kim I., Jordan S., Klein A. Analysis of Circulating CD38+/CD138+ Plasma Cells during Development of De Novo Donor Specific Antibody Responses Am J Transplant. 2017;17 (suppl 3).

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