IFN signaling inhibits osteogenesis in human SLE bone marrow.

Background: Bone marrow mesenchymal stem cells are multipotent adult stem cells that can differentiate into osteoblasts, adipocytes, and chondrocytes. Our recently published data demonstrate that systemic lupus erythematous bone marrow mesenchymal stem cells produce increased quantities of interferon β based on a positive feedback loop involving the innate signaling molecule mitochondrial antiviral signaling protein. Moreover, this pathway contributes to human systemic lupus erythematous bone marrow mesenchymal stem cell senescence-like features.

Failure of B Cell Tolerance in CVID.

Common variable immunodeficiency (CVID) comprises a group of related disorders defined by defects in B cell function and antibody production. Concurrent autoimmune features are common, but the underlying pathogenic mechanisms of autoimmunity in CVID are poorly understood. Overlap in some clinical and laboratory features suggests a shared pathogenesis, at least in part, with systemic lupus erythematosus (SLE).

B cell targeted therapies in autoimmune disease.

Purpose Of Review: FDA-approved B cell-targeted therapy has expanded to a multitude of autoimmune diseases ranging from organ specific diseases, like pemphigus and multiple sclerosis, to systemic diseases such as ANCA-associated vasculitis, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In this review, we discuss the variability in response to B cell-targeted therapies with a focus on the diversity of human B cells and plasma cells, and will discuss several of the promising new B cell-targeted therapies.

Recent Finding: The pathogenic roles for B cells include autoantibody-dependent and autoantibody-independent functions whose importance may vary across diseases or even in subsets of patients with the same disease.

Peripheral Blood B Cell Depletion after Rituximab and Complete Response in Lupus Nephritis.

Background And Objectives: Incomplete peripheral blood B cell depletion after rituximab in lupus nephritis might correlate with inability to reduce tubulointerstitial lymphoid aggregates in the kidney, which together could be responsible for inadequate response to treatment. We utilized data from the Lupus Nephritis Assessment with Rituximab (LUNAR) study to characterize the variability of peripheral blood B cell depletion after rituximab and assess its association with complete response in patients with lupus nephritis.

Design, Setting, Participants, & Measurements: We analyzed 68 participants treated with rituximab.

Modeling of human dermal absorption of octamethylcyclotetrasiloxane (D(4)) and decamethylcyclopentasiloxane (D(5)).

In this study, data for human dermal absorption of octamethylcyclotetrasiloxane, D(4), and decamethylcyclopentasiloxane, D(5), through axilla skin in vivo are interpreted using pharmacokinetic models of dermal absorption by adding the dermal exposure route to inhalation physiologically based pharmacokinetics models developed previously. The compartmental model describing dermal absorption of these compounds included volatilization of the applied chemical from the skin surface, diffusion of absorbed chemical back to the skin surface and evaporation of this chemical from the skin surface after the applied dose had cleared from the application site, uptake from the skin compartment into blood, and a storage compartment within the skin. Data from exposures in volunteers (i.