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Human Autoimmune Diseases (human + autoimmune_diseases)
Selected AbstractsApoptosis: A review of pro-apoptotic and anti-apoptotic pathways and dysregulation in diseaseJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 6 2008Mauria A. O'Brien DVM Abstract Objective , To review the human and veterinary literature on the biology of apoptosis in health and disease. Data Sources , Data were examined from the human and veterinary literature identified through Pubmed and references listed in appropriate articles pertaining to apoptosis. Human Data Synthesis , The role of apoptosis in health and disease is a rapidly growing area of research in human medicine. Apoptosis has been identified as a component of human autoimmune diseases, Alzheimer's disease, cancer, and sepsis. Veterinary Data Synthesis , Research data available from the veterinary literature pertaining to apoptosis and its role in diseases of small animal species is still in its infancy. The majority of veterinary studies focus on oncologic therapy. Most of the basic science and human clinical research studies use human blood and tissue samples and murine models. The results from these studies may be applicable to small animal species. Conclusions , Apoptosis is the complex physiologic process of programmed cell death. The pathophysiology of apoptosis and disease is only now being closely evaluated in human medicine. Knowledge of the physiologic mechanisms by which tissues regulate their size and composition is leading researchers to investigate the role of apoptosis in human diseases such as cancer, autoimmune disease and sepsis. Because it is a multifaceted process, apoptosis is difficult to target or manipulate therapeutically. Future studies may reveal methods to regulate or manipulate apoptosis and improve patient outcome. [source] Abnormal B-cell cytokine responses a trigger of T-cell,mediated disease in MS?ANNALS OF NEUROLOGY, Issue 4 2010Amit Bar-Or MD, FRCP Objective To study antibody-independent contributions of B cells to inflammatory disease activity, and the immune consequences of B-cell depletion with rituximab, in patients with multiple sclerosis (MS). Methods B-Cell effector-cytokine responses were compared between MS patients and matched controls using a 3-signal model of activation. The effects of B-cell depletion on Th1/Th17 CD4 and CD8 T-cell responses in MS patients were assessed both ex vivo and in vivo, together with pharmacokinetic/pharmacodynamic studies as part of 2 rituximab clinical trials in relapsing,remitting MS. Results B Cells of MS patients exhibited aberrant proinflammatory cytokine responses, including increased lymphotoxin (LT):interleukin-10 ratios and exaggerated LT and tumor necrosis factor (TNF)-, secretion, when activated in the context of the pathogen-associated TLR9-ligand CpG-DNA, or the Th1 cytokine interferon-,, respectively. B-Cell depletion, both ex vivo and in vivo, resulted in significantly diminished proinflammatory (Th1 and Th17) responses of both CD4 and CD8 T cells. Soluble products from activated B cells of untreated MS patients reconstituted the diminished T-cell responses observed following in vivo B-cell depletion in the same patients, and this effect appeared to be largely mediated by B-cell LT and TNF,. Interpretation We propose that episodic triggering of abnormal B-cell cytokine responses mediates ,bystander activation' of disease-relevant proinflammatory T cells, resulting in new relapsing MS disease activity. Our findings point to a plausible mechanism for the long-recognized association between infections and new MS relapses, and provide novel insights into B-cell roles in both health and disease, and into mechanisms contributing to therapeutic effects of B-cell depletion in human autoimmune diseases, including MS. ANN NEUROL 2010;67:452,461 [source] Antibodies to native myelin oligodendrocyte glycoprotein in children with inflammatory demyelinating central nervous system disease,ANNALS OF NEUROLOGY, Issue 6 2009Fabienne Brilot PhD Objective Myelin oligodendrocyte glycoprotein (MOG) is a candidate target antigen in demyelinating diseases of the central nervous system (CNS). Although MOG is encephalitogenic in different animal models, the relevance of this antigen in human autoimmune diseases of the CNS is still controversial. Methods We investigated the occurrence and biological activity of antibodies to native MOG (nMOG) in 47 children during a first episode of CNS demyelination (acute disseminated encephalomyelitis [ADEM], n = 19 and clinical isolated syndrome [CIS], n = 28) by a cell-based bioassay. Results High serum immunoglobulin G (IgG) titers to nMOG were detected in 40% of children with CIS/ADEM but 0% of the control children affected by other neurological diseases, healthy children, or adults with inflammatory demyelinating diseases, respectively. By contrast, IgM antibodies to nMOG occurred in only 3 children affected by ADEM. Children with high anti-nMOG IgG titer were significantly younger than those with low IgG titer. Anti-nMOG IgG titers did not differ between the ADEM and CIS group, and did not predict conversion from CIS to MS during a mean 2-year follow-up. However, intrathecal IgG anti-MOG antibody synthesis was only seen in CIS children. IgG antibodies to nMOG not only bound to the extracellular domain of nMOG, but also induced natural killer cell-mediated killing of nMOG-expressing cells in vitro. Interpretation Overall, these findings suggest nMOG as a major target of the humoral immune response in a subgroup of children affected by inflammatory demyelinating diseases of the CNS. Children may provide valuable insight into the earliest immune mechanisms of CNS demyelination. Ann Neurol 2009;66:833,842 [source] Insights into the role of fibroblasts in human autoimmune diseasesCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2005T. J. Smith Summary Traditional wisdom has considered fibroblasts as contributing to the structural integrity of tissues rather than playing a dynamic role in physiological or pathological processes. It is only recently that they have been recognized as comprising diverse populations of cells exhibiting complex patterns of biosynthetic activity. They represent determinants that react to stimuli and help define tissue remodelling through the expression of molecules imposing constraints on their cellular neighbourhood. Moreover, fibroblasts can initiate the earliest molecular events leading to inflammatory responses. Thus they must now be viewed as active participants in tissue reactivity. In this short review, I will provide an overview of contemporary thought about the contribution of fibroblasts to the pathogenesis of autoimmune processes through their expression of, and responses to, mediators of inflammation and tissue remodelling. [source] | ||||||||||