Biomedical subjects

William Stohl

Publications and source records attributed to William Stohl.

22 records · Page 2Linked to original sources

PubMed2002

BLyS and APRIL form biologically active heterotrimers that are expressed in patients with systemic immune-based rheumatic diseases.

BLyS and APRIL are two members of the TNF superfamily that are secreted by activated myeloid cells and have costimulatory activity on B cells. BLyS and APRIL share two receptors, TACI and BCMA, whereas a third receptor, BAFF-R, specifically binds BLyS. Both BLyS and APRIL have been described as homotrimeric molecules, a feature common to members of the TNF superfamily. In this study, we show that APRIL and BLyS can form active heterotrimeric molecules when coexpressed and that circulating heterotrimers are present in serum samples from patients with systemic immune-based rheumatic diseases. These findings raise the possibility that active BLyS/APRIL heterotrimers may play a role in rheumatic and other autoimmune diseases and that other members of the TNF ligand superfamily may also form active soluble heterotrimers.

Animals↗

PubMed2002

B lymphocyte stimulator protein-associated increase in circulating autoantibody levels may require CD4+ T cells: lessons from HIV-infected patients.

To assess the helper T cell dependence of B lymphocyte stimulator (BLyS) protein-driven autoantibody production in vivo, serum levels of BLyS protein, total IgG, and anti-IgG anti-phospholipid (aPhL) autoantibodies from HIV-infected patients (n = 105) with varying degrees of CD4+ cell depletion and healthy control donors at low risk for HIV (n = 64) were determined. Peripheral blood mononuclear cells from these subjects were stained for surface expression of BLyS protein. Monocyte surface expression and serum levels of BLyS protein were increased in HIV-infected patients as were serum total IgG and IgG aPhL autoantibody levels. No associations were detected between increased serum BLyS protein levels and patient age, sex, disease duration, history of opportunistic infection or malignancy, or serum total IgG levels. However, serum levels of IgG aPhL autoantibodies were greater in patients with high serum BLyS protein levels than in those with normal serum BLyS protein levels. Importantly, this association between serum levels of BLyS protein and IgG aPhL was appreciated only in patients who were not severely CD4+ cell-depleted and not in patients who were severely CD4+ cell-depleted (peripheral blood CD4+ cell counts <or= 200/mm(3)). Thus, BLyS protein may preferentially facilitate IgG autoantibody production in vivo in a helper T cell-dependent manner. This raises the possibility that the combination of a BLyS protein antagonist with an agent that targets (helper) T cells may have salutary synergistic effects on autoantibody production in diseases such as systemic lupus erythematosus.

Adult↗

PubMed2002

B lymphocyte stimulator protein levels in systemic lupus erythematosus and other diseases.

The size of the known members of the tumor necrosis factor ligand and receptor superfamilies has burgeoned in the past few years. Among the novel tumor necrosis factor ligand and receptor superfamily members recently described is B lymphocyte stimulator (BLyS; Human Genome Sciences, Rockville, MD) protein. By virtue of its ability to promote B-cell survival, expansion, and differentiation, it likely plays an important contributory role in systemic lupus erythematosus pathogenesis and propagation. In addition, it may play a similar role in other systemic immune-based rheumatic diseases, and becomes a legitimate candidate target for antagonist biologic agents.

Animals↗

PubMed2002

Systemic lupus erythematosus: a blissless disease of too much BLyS (B lymphocyte stimulator) protein.

B lymphocyte stimulator (BLyS) protein is among the novel tumor necrosis factor (TNF) ligands and receptor superfamily members recently described. BLyS protein can promote B cell survival, expansion, and differentiation both and. Constitutive overexpression of BLyS protein can result in systemic lupus erythematosus (SLE)-like disease in mice, and circulating levels of BLyS protein are elevated in a subset of human SLE patients. Treatment of SLE mice with a BLyS protein antagonist ameliorates disease progression and enhances survival. By inference, BLyS protein may also play an important contributory role in pathogenesis and/or propagation of human SLE and becomes a legitimate candidate target for antagonist biologic agents.

Animals↗