Ibrutinib suppresses alloantibody responses in a mouse model of allosensitization.

Background: Ibrutinib is a Bruton's tyrosine Kinase (BTK) antagonist that inhibits B cell receptor (BCR) signaling. Complete BTK deficiency is associated with absence of B-cells. Ibrutinb is currently approved by FDA for treatment of B-cell malignancies, including Waldenström macroglobulinaemia.

Immunological characterization of de novo and recall alloantibody suppression by CTLA4Ig in a mouse model of allosensitization.

It is well known that CTLA4Ig inhibits allogenic T-cell activation in transplantation. The immunological features and mechanisms associated with alloantibody suppression by CTLA4Ig, however, are poorly understood. Here, we used a mouse model of allosensitization to evaluate the efficacy of CTLA4Ig (abatacept) in suppression of donor-specific antibody (DSA) during de novo and recall alloantibody responses.

Anti-interleukin 6 receptor antibodies attenuate antibody recall responses in a mouse model of allosensitization.

Background: Interleukin (IL)-6 is a regulatory cytokine for T helper type 17 (Th17) and Treg cells and a potent stimulus for B/plasma cells. The current study evaluated the effect of IL-6 receptor (IL-6R) blockade with an antiYIL-6R monoclonal (mMR16-1) in alloantibody recall responses.

Methods: A mouse model of human leukocyte antigen (HLA).

Anti-CD3ε induces splenic B220lo B-cell expansion following anti-CD20 treatment in a mouse model of allosensitization.

Antibodies targeting T cells and B cells are increasingly used for immunosuppression in clinical transplantation. However, the impact of T-cell depletion by antibodies on B-cell homeostasis is poorly understood. Using a mouse model of allosensitization with skin allograft, we investigated whether targeting T cells by anti-CD3ε alters peripheral B-cell homeostasis and alloantibody responses following B-cell depletion by anti-CD20.

Immunologic parameters and viral infections in patients desensitized with intravenous immunoglobulin and rituximab.

Desensitization with IVIG and rituximab followed by transplantation with alemtuzumab or daclizumab induction is an effective clinical protocol. Here, we examined the effects of this protocol on immune cell number, T cell function by Cylex ImmuKnow®, CMV-specific CD8+ T cell (CMV-Tc) activity, total and viral-specific immunoglobulin levels and viral infections. In 17 highly HLA-sensitized (HS) patients who received desensitization, CD19+ cells were undetectable immediately after desensitization, while other immune cells were unchanged.

Intracellular IFNgamma production in CD3 negative cells exposed to allo-antigens is an indicator of prior sensitization.

Background: Sensitization to HLA antigens (Ags) is a significant obstacle to kidney transplantation and risk factor for antibody-mediated rejection (AMR). Current screening methods to assess HLA Ag exposure include various antibody assays. However, tools to accurately measure cell-mediated immunity to allo-Ags in a clinical setting are lacking.

Flow cytometric isolation and phenotypic characterization of two subsets of ED2(+) (CD163) hepatic macrophages in rats.

Aims: Macrophages in the liver are well known for their functional heterogeneity. However, subpopulations of the hepatic macrophages are not well defined.

Methods: Two subsets of hepatic macrophages isolated from rats via FACS with immunolabeling of ED2 (anti-CD163) antibody were studied for phenotypic and functional characteristics.

Anti-CD20 antibody suppresses anti-HLA antibody formation in a HLA-A2 transgenic mouse model of sensitization.

Background: B cell depletion by anti-CD20 antibody is used in desensitization protocols and for treatment of antibody-mediated rejection (AMR). However, little is known about the efficacy and the mechanism(s) of action.

Methods: A mouse model of HLA sensitization was used to study the effectiveness of anti-CD20 treatment on B cell depletion and anti-HLA antibody suppression.

Differential beta-adrenoceptor expression induced by nerve growth factor infusion into the canine right and left stellate ganglia.

Background: Nerve growth factor (NGF) infusion into the right stellate ganglion (RSG) is antiarrhythmic, while NGF infusion into the left stellate ganglion (LSG) is proarrhythmic in dogs with myocardial infarction (MI) and complete atrioventricular block (CAVB). This functional asymmetry suggests differential neural remodeling.

Objectives: To test the hypothesis that NGF infusion into the RSG and the LSG can lead to differential beta-adrenoceptor (beta-AR) expression in dogs with MI and CAVB.

Proteinase and growth factor alterations revealed by gene microarray analysis of human diabetic corneas.

Purpose: To identify proteinases and growth factors abnormally expressed in human corneas of donors with diabetic retinopathy (DR), additional to previously described matrix metalloproteinase (MMP)-10 and -3 and insulin-like growth factor (IGF)-I.

Methods: RNA was isolated from 35 normal, diabetic, and DR autopsy human corneas ex vivo or after organ culture. Amplified cRNA was analyzed using 22,000-gene microarrays (Agilent Technologies, Palo Alto, CA).

Transcriptomic fingerprinting of bone marrow-derived hepatic beta2m-/Thy-1+ stem cells.

The aim of the present study was to determine if the bone marrow (BM) beta2m-/Thy-1+ stem cells isolated from common bile duct ligated (CBDL) rats possess hepatocyte-like characteristics in their global gene expression profiles. The Affymetrix RG U34A arrays were used to conduct transcriptomic profiling on BM beta2m-/Thy-1+ stem cells isolated from CBDL and control rats as well as primary hepatocytes. Forty-one probe sets were up-regulated more than 2-fold in CBDL-derived beta2m-/Thy-1+ BM stem cells compared to control BM stem cells.

Increased expression of membrane type 3-matrix metalloproteinase in human atherosclerotic plaque: role of activated macrophages and inflammatory cytokines.

Background: Matrix metalloproteinases (MMPs) are thought to play a prominent role in atherogenesis and destabilization of plaque. Pericellularly localized membrane-type (MT)-MMPs activate secreted MMPs. We investigated the hypothesis that MT3-MMP is expressed in human atherosclerotic plaques and is regulated by locally produced inflammatory cytokines and oxidized low-density lipoprotein (Ox-LDL).