Venous Thrombosis in Acquired Hemophilia: The Complex Management of Competing Pathologies.

 Venous thrombosis is rare in the setting of factor VIII (FVIII) deficiency. Cases of deep vein thrombosis (DVT) have been described in hemophiliacs after recent major surgery, or in association with the administration of FVIII concentrate and activated prothrombin complex concentrates, but occurrence of spontaneous DVT is even more uncommon.  We describe the challenging management of extensive DVT in a patient with acquired hemophilia A with concurrent hemorrhagic manifestations and review similar published cases.

Relative Frequencies of Alloantigen-Specific Helper CD4 T Cells and B Cells Determine Mode of Antibody-Mediated Allograft Rejection.

Humoral alloimmunity is now recognized as a major determinant of transplant outcome. MHC glycoprotein is considered a typical T-dependent antigen, but the nature of the T cell alloresponse that underpins alloantibody generation remains poorly understood. Here, we examine how the relative frequencies of alloantigen-specific B cells and helper CD4 T cells influence the humoral alloimmune response and how this relates to antibody-mediated rejection (AMR).

Germinal Center Alloantibody Responses Mediate Progression of Chronic Allograft Injury.

Different profiles of alloantibody responses are observed in the clinic, with those that persist, often despite targeted treatment, associated with poorer long-term transplant outcomes. Although such responses would suggest an underlying germinal center (GC) response, the relationship to cellular events within the allospecific B cell population is unclear. Here we examine the contribution of germinal center (GC) humoral alloimmunity to chronic antibody mediated rejection (AMR).

Data regarding transplant induced germinal center humoral autoimmunity.

This data is related to the research article entitled "Germinal center humoral autoimmunity independently mediates progression of allograft vasculopathy" (Harper et al., 2016) [2]. The data presented here focuses on the humoral autoimmune response triggered by transferred allogeneic CD4 T cells and includes details on: (a) the recipient splenic germinal center (GC) response; (b) augmentation of humoral autoimmunity and accelerated heart allograft rejection following transplantation from donors primed against recipient; (c) flow cytometric analysis of donor and recipient CD4 T cells for signature markers of T follicular helper cell differentiation; (d) donor endothelial cell migration in response to column purified autoantibody from recipient sera; (e) analysis of development of humoral responses in recipients following adoptive transfer of donor CD4 T cells and; (f) the development of humoral autoimmunity in mixed haematopoietic chimeric mice.

Germinal center humoral autoimmunity independently mediates progression of allograft vasculopathy.

The development of humoral autoimmunity following organ transplantation is increasingly recognised, but of uncertain significance. We examine whether autoimmunity contributes independently to allograft rejection. In a MHC class II-mismatched murine model of chronic humoral rejection, we report that effector antinuclear autoantibody responses were initiated upon graft-versus-host allorecognition of recipient B cells by donor CD4 T-cells transferred within heart allografts.

CD8 T-cell recognition of acquired alloantigen promotes acute allograft rejection.

Adaptive CD8 T-cell immunity is the principal arm of the cellular alloimmune response, but its development requires help. This can be provided by CD4 T cells that recognize alloantigen "indirectly," as self-restricted allopeptide, but this process remains unexplained, because the target epitopes for CD4 and CD8 T-cell recognition are "unlinked" on different cells (recipient and donor antigen presenting cells (APCs), respectively). Here, we test the hypothesis that the presentation of intact and processed MHC class I alloantigen by recipient dendritic cells (DCs) (the "semidirect" pathway) allows linked help to be delivered by indirect-pathway CD4 T cells for generating destructive cytotoxic CD8 T-cell alloresponses.

BAFF and associated TNF superfamily members in renal transplantation: an end to BLySful ignorance.

: The emergence of B-cell-activating factor and its related family members as critical mediators for B-cell development and survival has led to the development of a number of new agents aimed at controlling complicated chronic pathologies with an underlying humoral component. Currently being trialed in autoimmunity, these agents also hold much promise for preventing the insidious humoral responses that are increasingly associated with early failure of kidney transplants. This review discusses some of the pertinent aspects of B-cell-activating factor biology and considers how recent advances in our understanding of this signaling axis could be exploited to improve clinical outcomes in renal transplantation.

Regulation of allograft survival by inhibitory FcγRIIb signaling.

Fcγ receptors (FcγR) provide important immunoregulation. Targeting inhibitory FcγRIIb may therefore prolong allograft survival, but its role in transplantation has not been addressed. FcγRIIb signaling was examined in murine models of acute or chronic cardiac allograft rejection by transplanting recipients that either lacked FcγRIIb expression (FcγRIIb(-/-)) or overexpressed FcγRIIb on B cells (B cell transgenic [BTG]).

Flexible, task-dependent use of sensory feedback to control hand movements.

We tested whether changing accuracy demands for simple pointing movements leads humans to adjust the feedback control laws that map sensory signals from the moving hand to motor commands. Subjects made repeated pointing movements in a virtual environment to touch a button whose shape varied randomly from trial to trial-between squares, rectangles oriented perpendicular to the movement path, and rectangles oriented parallel to the movement path. Subjects performed the task on a horizontal table but saw the target configuration and a virtual rendering of their pointing finger through a mirror mounted between a monitor and the table.

Near-optimal human adaptive control across different noise environments.

A person learning to control a complex system needs to learn about both the dynamics and the noise of the system. We evaluated human subjects' abilities to learn to control a stochastic dynamic system under different noise conditions. These conditions were created by corrupting the forces applied to the system with noise whose magnitudes were either proportional or inversely proportional to the sizes of subjects' control signals.

Properties of synergies arising from a theory of optimal motor behavior.

We consider the properties of motor components, also known as synergies, arising from a computational theory (in the sense of Marr, 1982) of optimal motor behavior. An actor's goals were formalized as cost functions, and the optimal control signals minimizing the cost functions were calculated. Optimal synergies were derived from these optimal control signals using a variant of nonnegative matrix factorization.