Anti-MS4A1 Monoclonal antibody, clone 3I8 [Biotin]

Background. Recently, several B cell-related markers have been described to be upregulated during operational tolerance in kidney allograft recipients. Little data exist on these markers during allograft rejection. Methods. In this study, we investigated regulation-associated B-cell phenotypes in peripheral blood mononuclear cells (PBMCs) of kidney transplant recipients with (n = 21) and without (n = 22) acute rejection (AR). We also determined expression levels of the B cell-related genes, MS4A1, TCL1A, and CD79B, in PBMCs and isolated B cells. Patient samples were analyzed before transplantation at discharge and at time of AR before initiation of antirejection therapy or at matching timepoints in patients with stable graft function. Results. On transplantation, the peripheral CD19(+)CD24(hi)CD38(hi) transitional B cell subset strongly declined, regardless of the subsequent occurrence of AR. In contrast, the CD19(+)CD27(+)CD24(hi) subset remained stable after transplantation in both patients groups. MS4A1 gene expression levels in PBMC were comparable between patient groups at all timepoints. In contrast, TCL1A expression levels increased in stable patients, but decreased in patients at the time of AR in both PBMC and isolated B cells. CD79B expression levels in stable patients were unaltered after transplantation in PBMC but showed an increase in the B cell fraction at discharge. At the time of AR, CD79B gene expression was significantly lower compared to stable patients, being most apparent in the B-cell fraction. Conclusion. These results suggest that, in addition to being markers for immunologic unresponsiveness, gene expression levels of TCL1A and CD79B may also identify immune activation in the setting of kidney transplantation.

Gene expression profiling has emerged as a powerful strategy to define transcriptional mechanism activated in organ transplantation. We performed a pilot feasibility study of mRNA-based pancreas transplant biopsy stratification. The mRNAs expression of 32 genes, observed in renal transplant dysfunction, and 10 pancreas-specific genes were evaluated in 26 pancreas transplant biopsy specimens by quantitative real-time polymerase chain reaction using TaqMan Low Density Array technology. Unsupervised 2D hierarchical clustering segregated the biopsies in two main cluster branches, A and B. Six of seven patients (85.7%) in cluster A and 6 of 19 (31.6%) in cluster B retained functioning pancreas allograft. CD20/MS4A1 mRNA and protein, in addition to CD 3 protein, were detected in four specimens in cluster B. Three of those four pancreas transplants were subsequently lost. Our study demonstrates the potential association of gene expression with clinical outcome of pancreas transplants and justifies further studies in an independent cohort.