Disappearance of a High Response Factor VIII Inhibitor in a Hemophiliac with AIDS

Abstract

The eradication of a high-response Factor VIII inhibitor in patients with severe hemophilia A is extremely rare even with prolonged immunosuppressive therapy. This report presents a patient with severe hemophilia A, in whom the disappearance of such an inhibitor coincided with the development of the acquired immunodeficiency syndrome (AIDS). Laboratory studies demonstrated a marked decrease in helper T-cells and marked depression of cell-mediated immunity by in vivo and in vitro testing. In addition, humoral immune responses were abnormal. Thus, anamnestic antibody formation to different antigens was absent and in vitro pokeweed mitogen-induced immunoglobulin synthesis by the patient's B-cells was markedly impaired even in the presence of normal T-cells. These findings indicate that the disappearance of the Factor VIII inhibitor and the lack of an anamnestic antibody response to infused Factor VIII observed in this patient may be secondary to a humoral immunodeficiency associated with AIDS.

A role for thrombin in the initiation of the immune response to therapeutic factor VIII

“…The first evidence that this antibody response is T-cell mediated came from hemophilic patients who were also infected with HIV. [8][9][10][11] In these case reports, when patients' T-cell levels decreased as a consequence of the HIV infection, so did their anamnestic response to FVIII. When CD4 counts rose in response to antiretroviral drugs, they again began to form inhibitory antibodies.…”

“…The immune response to FVIII is T-cell dependent in humans [8][9][10][11] and mice. 12,13 A typical T cell-dependent antibody response begins when an immature antigen-presenting cell (APC; eg, dendritic cell) encounters a "danger" signal.…”

The incidence of factor VIII and factor IX inhibitors in the hemophilia population of the UK and their effect on subsequent mortality, 1977–99

“…HIV infection was associated with substantially increased mortality during the study period [16,17]. A further increase was not seen with inhibitors, and indeed some HIV positive patients who had inhibitors may lose them as their immune function deteriorates [25,26].…”

Endocytic receptor for pro-coagulant factor VIII: Relevance to inhibitor formation

“…T-cell receptors of T lymphocytes that were found to proliferate in the presence of FVIII, preferentially use Vβ genes of the BV2, BV5 and BV9 families (30). Interestingly, patients with a history of high inhibitor titers were found to lose their FVIII inhibitor following infection by HIV (31)(32)(33). This was associated with a drop in CD4+ T cell counts, and the lack of an anamnestic immune response upon subsequent intravenous administration of therapeutic FVIII.…”