Arthritis and rheumatism
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Arthritis and rheumatism · May 2010
Adipocytokines, insulin resistance, and coronary atherosclerosis in rheumatoid arthritis.
The prevalence of subclinical coronary atherosclerosis is increased in patients with rheumatoid arthritis (RA), and the increased risk is associated with insulin resistance. Adipocytokines have been linked to obesity, insulin resistance, inflammation, and coronary heart disease in the general population. This study was undertaken to examine the hypothesis that adipocytokines affect insulin resistance and coronary atherosclerosis among patients with RA. ⋯ Leptin is associated with insulin resistance in patients with RA but, paradoxically, attenuates the effects of insulin resistance on coronary calcification.
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Arthritis and rheumatism · May 2010
Anti-citrullinated protein antibodies bind surface-expressed citrullinated Grp78 on monocyte/macrophages and stimulate tumor necrosis factor alpha production.
Anti-citrullinated protein antibodies (ACPAs), which are the most specific autoantibody marker in patients with rheumatoid arthritis (RA), correlate with disease activity; however, the role of ACPAs in RA pathogenesis has not been elucidated. We hypothesized that ACPAs may directly stimulate mononuclear cells to produce inflammatory cytokines. Thus, we identified cognate antigens of ACPAs on monocyte/macrophages and examined their immunopathologic roles in the pathogenesis of RA. ⋯ We clearly demonstrated that ACPAs enhance NF-kappaB activity and TNFalpha production in monocyte/macrophages via binding to surface-expressed citrullinated Grp78.
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Arthritis and rheumatism · May 2010
Expanding the phenotypic spectrum of lupus erythematosus in Aicardi-Goutières syndrome.
Aicardi-Goutières syndrome (AGS) is an early-onset encephalopathy resembling congenital viral infection that is characterized by basal ganglia calcifications, loss of white matter, cerebrospinal fluid (CSF) lymphocytosis, and elevated interferon-alpha levels in the CSF. Studies have shown that AGS is an autosomal-recessive disease linked to mutations in 5 genes, encoding the 3'-repair DNA exonuclease 1 (TREX1), the 3 subunits of ribonuclease H2 (RNASEH2A-C), and sterile alpha motif domain and HD domain-containing protein 1 (SAMHD1). In this study we further characterized the phenotypic spectrum of this disease. ⋯ These findings expand the phenotypic spectrum of lupus erythematosus in AGS and provide further insight into its disease mechanisms by showing that activation of the innate immune system as a result of inherited defects in nucleic acid metabolism could lead to systemic autoimmunity.
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Arthritis and rheumatism · May 2010
Spinal tumor necrosis factor alpha neutralization reduces peripheral inflammation and hyperalgesia and suppresses autonomic responses in experimental arthritis: a role for spinal tumor necrosis factor alpha during induction and maintenance of peripheral inflammation.
In addition to the sensitization of pain fibers in inflamed tissues, the increased excitability of the spinal cord is an important mechanism of inflammatory pain. Furthermore, spinal neuronal excitability has been suggested to play a role in modulating peripheral inflammation. This study was undertaken to test the hypothesis that spinal actions of the proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) add significantly to both hyperalgesia and maintenance of peripheral inflammation. ⋯ Our findings indicate that spinal TNFalpha plays an important role in both pain signaling and modulation of peripheral inflammation. Thus, neutralizing this cytokine at the spinal site not only represents a putative therapeutic option for different pain syndromes, but may be directly used to attenuate peripheral inflammation.