Anti-ITGAX monoclonal antibody, clone N418 [FITC]

Background. We have shown that genomic biomarkers in peripheral blood provide evidence of early graft rejection and may offer an important option for posttransplant monitoring, and we are working to improve this signature to maximize assay performance. Methods. This clinical refinement study (n = 79) used gene expression profiling in a case-control design to compare whole blood samples between normal subjects (n = 20) and patients with (n = 20) or without (n = 39) biopsy-confirmed acute rejection (BCAR). Results. Gene expression in peripheral blood from subjects with BCAR before treatment differed significantly from that of normal subjects and transplant recipients without BCAR. Hierarchical clustering and principal component analysis showed that samples obtained 1 to 5 days after the start of treatment of BCAR were segregated across both groups before treatment or without BCAR and that this was closely related to the time lag between treatment and sampling. Genes differentially expressed during BCAR included FKSG49, LMAN2, NFYC, LIMK2, JUNB, NASP, MALAT1, ITGAX, HLA-J, FKBP1A, and RBMS1, and gene ontology analysis highlighted changes in networks related to cytoskeletal reorganization, apoptosis, and immune signaling, whereas after treatment change highlighted pathways of cellular metabolism, cell-cycle regulation, DNA damage, and apoptosis. Conclusion. Gene expression in the peripheral blood is associated with BCAR, and the pattern of expression changes rapidly after treatment. This may offer a potential tool for diagnosis of rejection and immunologic monitoring of response to treatment, which is now being evaluated in a large multicenter international study.

Dendritic cells (DC) are specialized antigen-presenting cells, responsible for peripheral immune responses. Recently, resident brain dendritic cells (bDC) were identified and functionally characterized in the young adult Itgax (CD11c) EYFP+ transgenic mouse brain. In the present study, we describe changes in number, phenotype, and source of bDC in the aging mouse brain. Immunohistochemistry and fluorescent activated cell sorting (FACS) analysis revealed an age-related increase in bDC with a concomitant rise in the expression of immune activation markers MHCII, CD80, and CD86. Quantification of immunolabeled bDC in the cortex, corpus callosum, and cerebellum of the aged brain revealed a 2- to 5-fold increase. In contrast, either no change or a decrease in bDC was noted in regions of adult neurogenesis. Chimeras (wild type host/EYFP+ bone marrow) suggest that the increase of EYFP+ cells in the aging brain is in part due to an accumulation of peripherally derived cells. Collectively, the numerical and phenotypic changes in bDC indicate these cells may serve as an important immune component in the functional and anatomic alterations associated with aging. (C) 2012 Elsevier Inc. All rights reserved.