The Journal of immunology : official journal of the American Association of Immunologists
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Plasma B lymphocyte stimulator and B cell differentiation in idiopathic pulmonary fibrosis patients.
We hypothesized B cells are involved in the pathogenesis of idiopathic pulmonary fibrosis (IPF), a progressive, restrictive lung disease that is refractory to glucocorticoids and other nonspecific therapies, and almost invariably lethal. Accordingly, we sought to identify clinically associated B cell-related abnormalities in these patients. Phenotypes of circulating B cells were characterized by flow cytometry. ⋯ The 25% of IPF subjects with the greatest BLyS values also had diminished 1-y survival (46 ± 11%), compared with those with lesser BLyS concentrations (81 ± 5%) (hazard ratio = 4.0, 95% confidence interval = 1.8-8.7, p = 0.0002). Abnormalities of B cells and BLyS are common in IPF patients, and highly associated with disease manifestations and patient outcomes. These findings have implications regarding IPF pathogenesis and illuminate the potential for novel treatment regimens that specifically target B cells in patients with this lung disease.
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C-reactive protein (CRP) is an acute-phase protein that plays an important defensive role in innate immunity against bacterial infection, but it is also upregulated in many noninfectious diseases. The generic function of this highly conserved molecule in diseases that range from infection, inflammation, trauma, and malignancy is not well understood. In this article, we demonstrate that CRP defends the human body against the toxicity of histones released into the circulation after extensive cell death. ⋯ CRP is able to compete with phospholipid-containing liposomes for the binding to histones. This explains how CRP prevents histones from integrating into cell membranes, which would otherwise induce calcium influx as the major mechanism of cytotoxicity caused by extracellular histones. Because histone elevation occurs in the acute phase of numerous critical illnesses associated with extensive cell death, CRP detoxification of circulating histones would be a generic host defense mechanism in humans.
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During the 2009 pandemic H1N1 influenza A virus (pH1N1) outbreak, obese individuals were at greater risk for morbidity and mortality from pandemic infection. However, the mechanisms contributing to greater infection severity in obese individuals remain unclear. Although most individuals lacked pre-existing, neutralizing Ab protection to the novel pH1N1 virus, heterologous defenses conferred from exposure to circulating strains or vaccination have been shown to impart protection against pH1N1 infection in humans and mice. ⋯ Further, obese mice had elevated viral titers, greater lung inflammation and lung damage, and more cytotoxic memory CD8(+) T cells in the lung airways. Although obese mice had more regulatory T cells (Tregs) in the lung airways than did lean controls during the pH1N1 challenge, Tregs isolated from obese mice were 40% less suppressive than Tregs isolated from lean mice. In sum, excessive inflammatory responses to pH1N1 infection, potentially owing to greater viral burden and impaired Treg function, may be a novel mechanism by which obesity contributes to greater pH1N1 severity.