Challenges in understanding Sjögren's syndrome - improved insights into the pathogenesis generate hope for innovative therapies?

The reviews in this series on Sjögren syndrome provide an up-to-date summary and perspectives on the pathogenesis of this interesting entity with glandular and frequently systemic manifestations, the value of preclinical models, and our current understanding of therapeutic approaches. The last of these includes what has been learned from trials blocking tumor necrosis factor and, more recently, anti-CD20 therapy. Potential therapeutic targets, such as blockade of the B cell-activating factor, the role of interferon-alpha, and targeting CD22, are discussed

Vasculitis: mechanisms involved and clinical manifestations

Systemic vasculitis, an inflammatory necrotizing disease of the blood vessel walls, can occur secondary to autoimmune diseases, including connective tissue diseases. Various pathogenic mechanisms have been implicated in the induction of vasculitis, including cell-mediated inflammation, immune complex-mediated inflammation and autoantibody-mediated inflammation. This inflammatory activity is believed to contribute to accelerated atherosclerosis, and also leads to increased risk for cardiovascular events in patients with rheumatoid arthritis and systemic lupus erythematosus. Endothelial cell activation is a common pathogenic pathway in the systemic vasculitis associated with rheumatoid arthritis and systemic lupus erythematosus, with elevated levels of endothelin-1 potentially inducing vascular dysregulation

Selecting B cells and plasma cells to memory

Humoral immunity appears to be based on immunological memory provided by memory plasma cells, which secrete protective antibodies, and memory B cells, which react to antigen challenge by differentiating into plasma cells. How these differentiation pathways relate to each other, how cells are selected into these memory populations, and how these populations are maintained remains enigmatic

Developments in lupus 2006

Published reports in 2006 on systemic lupus erythematosus are reviewed with regard to preclinical and clinical studies on disturbances of the immune system including co-stimulation, cytokines and recent insights into new therapeutic approaches. Increasing knowledge of components of the innate immune system, such as certain receptors (Toll-like receptors, Fc receptors and complement receptors) and cytokines as well as immune cells (dendritic cells, plasmacytoid cells and neutrophils) supports their immunopathogenic relevance and enhance our understanding of the pathogenic complexity of lupus. Although it remains to be shown which of those could be targets for therapy or biomarkers, lymphocyte-directed therapy is currently under promising clinical investigation

B cell subset distribution in human bone marrow is stable and similar in left and right femur: An instructive case

The bone marrow (BM) is, in addition to being the site of B cell development, a tissue that harbors long-lived plasma cells (PC), the cells that protect the body against foreign antigens by continuous production of antibodies. Nothing is known about the long-term stability and functionality of both B cells and PC in the BM at the individual donor level since repeated sampling possibilities outside of oncology are scarce. Here, we had the opportunity to obtain BM samples from a patient undergoing bilateral total hip arthroplasty half a year apart. We observed that the frequencies of the analyzed B cell and PC subsets were similar despite a time of six months in between and sampling on left and right side of the body. Additionally, B cell receptor stimulation led to comparable results. Our data suggest that composition and functionality of B cells are stable in the BM of adults at the individual donor level