AARDA-funded Research

 

Autoimmune Research on PubMed

Here is a list of 10 recent published autoimmunity papers from PubMed.gov

pubmed: autoimmune NCBI: db=pubmed; Term=autoimmune

  • Nutritional Management of Metabolic Endotoxemia: A Clinical Review.
    by Brown BI on January 1, 1970 at 12:00 am

    Nutritional Management of Metabolic Endotoxemia: A Clinical Review. Altern Ther Health Med. 2017 Jul;23(4):42-54 Authors: Brown BI Abstract Context • Diet-induced, metabolic endotoxemia is emerging as an important contributory factor to the development of a wide range of chronic diseases, including cardiometabolic, autoimmune, psychiatric, and neurodegenerative illnesses. Emerging human clinical studies have demonstrated that diet and dietary components are potent modifiers of circulating endotoxins and can be used to reduce plasma levels significantly and improve metabolic health. Objective • The aim of the current study was to explore briefly the concept of metabolic endotoxemia and its relationship to disease development, to examine the influence of diet and dietary components on circulating endotoxins, and, finally, discuss the clinical relevance of nutritional interventions for management of metabolic endotoxemia. Design • The researcher performed a literature review of dietary and nutritional interactions with metabolic endotoxemia with a focus on studies relevant to clinical practice. Setting • The study took place at the UK College of Nutrition and Health (London, England). Results • Improving dietary quality, optimizing the intake of phytonutrient-rich foods, improving micronutrient status, consuming fermented foods, manipulating the gut microflora with prebiotics and probiotics, and using specific nutritional supplements, such as glutamine, lactoferrin, resveratrol, and berberine, have been shown to be effective in targeting metabolic endotoxemia. Conclusions • Diet, dietary components, and nutritional supplements, including prebiotics and probiotics, have demonstrated the ability to provide clinically important reductions in circulating endotoxins and improve related sequels, such as inflammation and other negative health markers. The development of personalized nutritional interventions for the management of metabolic endotoxemia is a promising area for future research due to the potential of such interventions to improve multiple aspects of human health and mitigate a wide range of chronic diseases. PMID: 28646814 [PubMed - in process […]

  • Prevalence of immune-related systemic adverse events in patients treated with anti-Programmed cell Death 1/anti-Programmed cell Death-Ligand 1 agents: A single-centre pharmacovigilance database analysis.
    by Le Burel S, Champiat S, Mateus C, Marabelle A, Michot JM, Robert C, Belkhir R, Soria JC, Laghouati S, Voisin AL, Fain O, Mékinian A, Coutte L, Szwebel TA, Dunogeant L, Lioger B, Luxembourger C, Mariette X, Lambotte O on January 1, 1970 at 12:00 am

    Prevalence of immune-related systemic adverse events in patients treated with anti-Programmed cell Death 1/anti-Programmed cell Death-Ligand 1 agents: A single-centre pharmacovigilance database analysis. Eur J Cancer. 2017 Jun 21;82:34-44 Authors: Le Burel S, Champiat S, Mateus C, Marabelle A, Michot JM, Robert C, Belkhir R, Soria JC, Laghouati S, Voisin AL, Fain O, Mékinian A, Coutte L, Szwebel TA, Dunogeant L, Lioger B, Luxembourger C, Mariette X, Lambotte O Abstract AIM: The growing use of immune checkpoint inhibitors (ICIs) is associated with the occurrence of immune-related adverse events (irAEs). Few data are published on systemic, immunohaematological and rheumatic irAEs. In a pharmacovigilance database analysis, we screened for these irAEs and calculated their prevalence. PATIENTS AND METHODS: Participants were recruited via Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie (REISAMIC)(1) a French registry of grade ≥2 irAEs occurring in ICI-treated patients. The pathologies of interest were systemic autoimmune and inflammatory diseases, rheumatic diseases and immune cytopenia. RESULTS: Out of 908 patients treated with anti-Programmed cell Death 1 (PD1)/anti-Programmed cell Death-Ligand 1 (PD-L1) agents (together with an anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) agent in 40 cases) between December 2012 and December 2016 at a single centre, 21 patients experienced systemic irAEs. The types and the prevalence of irAEs were as follows: immune thrombocytopenia (0.2%), Sjögren syndrome (0.3%), rheumatoid arthritis (0.2%), polymyalgia rheumatica (0.2%), psoriatic arthritis (0.2%), seronegative polyarthritis (0.7%) and sarcoidosis (0.2%). Patients with Sjögren syndrome or seronegative polyarthritis were more likely to have received combination therapy with ipilimumab (2.5% for both). We described these 21 cases, together with nine additional cases from five other centres. Most irAE were moderately severe (grade 2, 63%). The median time to onset was 57°days (interquartile range (IQR) 24-117). The ICI was withdrawn in 12 cases, 25 patients (83%) received corticosteroids, and five patients (17%) received immunosuppressant/immunomodulatory agents. The irAEs resolved fully or partially in 28 cases (93%). CONCLUSION: Although systemic, immunohaematological and rheumatic diseases are rarely associated with ICI use, the prevalence is higher when two ICIs are combined. Corticosteroids are often effective and may enable the continued administration of ICIs. Studies designed to identify at-risk patients are warranted. PMID: 28646772 [PubMed - as supplied by publisher […]

  • Wogonin attenuates inflammation by activating PPAR-γ in alcoholic liver disease.
    by Li HD, Chen X, Yang Y, Huang HM, Zhang L, Zhang X, Zhang L, Huang C, Meng XM, Li J on January 1, 1970 at 12:00 am

    Wogonin attenuates inflammation by activating PPAR-γ in alcoholic liver disease. Int Immunopharmacol. 2017 Jun 21;50:95-106 Authors: Li HD, Chen X, Yang Y, Huang HM, Zhang L, Zhang X, Zhang L, Huang C, Meng XM, Li J Abstract Alcoholic liver disease (ALD) is one of the predominant causes of liver-related morbidity and mortality worldwide. However, effective therapy for ALD is still lacking. Wogonin, a major flavonoid compound, is found in Scutellaria baicalensis Georgi. Accumulating studies have revealed that wogonin possesses anti-inflammatory and anti-tumour activities in various models. However, the hepatoprotective activity of wogonin in ALD is still obscure. In this study, we found that wogonin significantly attenuated inflammatory response in EtOH-fed mice, and reduced the expression of inflammatory cytokines such as TNF-α and IL-6 in EtOH-induced RAW264.7 cells. Furthermore, our findings showed that wogonin remarkably induced the expression of PPAR-γ in vivo and in vitro. Compared with the wogonin-treated group, blockade of PPAR-γ with inhibitor (T0070907) or PPAR-γ small interfering (si)-RNA were applied in RAW264.7 cells to evaluate the involvement of wogonin in alleviating EtOH-induced inflammation. Moreover, forced expression of PPAR-γ further suppressed the expression of TNF-α and IL-6 when treated with wogonin on EtOH-induced RAW264.7 cells. In addition, it was demonstrated that wogonin remarkably suppressed PPAR-γ-meditated phosphorylation and activation of NF-κB-P65. In conclusion, our results indicated that wogonin may serve as an effective modulator of PPAR-γ by down-regulating NF-κB pathway, thereby attenuated inflammatory response in ALD. PMID: 28646664 [PubMed - as supplied by publisher […]

  • Interferon-β regulates dendritic cell activation and migration in experimental autoimmune encephalomyelitis.
    by Pennell LM, Fish EN on January 1, 1970 at 12:00 am

    Interferon-β regulates dendritic cell activation and migration in experimental autoimmune encephalomyelitis. Immunology. 2017 Jun 24;: Authors: Pennell LM, Fish EN Abstract CD11c+ dendritic cells (DCs) exert a critical role as antigen-presenting cells in regulating pathogenic T cells in multiple sclerosis (MS). To determine whether the therapeutic benefit of interferon (IFN)-β treatment for MS is in part influenced by IFN regulation of DC function, we examined the immunophenotype of DCs derived from IFN-β(+/+) and IFN-β(-/-) mice using a myelin oligodendrocyte glycoprotein (MOG) peptide-induced mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Our earlier work identified that IFN-β(-/-) mice exhibit earlier onset and more rapid progression of neurologic impairment compared with IFN-β(+/+) mice. In this study we show that LPS-/MOG peptide-stimulated IFN-β(-/-) DCs secrete cytokines associated with pathologic Th17 rather than Treg polarization and exhibit increased CD80 and MHCII expression when compared to stimulated IFN-β(+/+) DCs. IFN-β(-/-) DCs from mice immunized to develop EAE induce greater proliferation of MOG-transgenic CD4+ T cells and promote IL-17 production by these T cells. Adoptive transfer of MOG peptide-primed IFN-β(-/-) DCs into IFN-β(+/+) and IFN-β(-/-) mice immunized to develop EAE resulted in their rapid migration into the CNS of recipient mice, prior to onset of disease, which we attribute to failed STAT1-mediated inhibition of CCR7. Taken together, our data support immunoregulatory roles for IFN-β in the activation and migration of DCs during EAE. This article is protected by copyright. All rights reserved. PMID: 28646573 [PubMed - as supplied by publisher […]

  • Control of autoimmune inflammation using liposomes to deliver positive allosteric modulators of metabotropic glutamate receptors.
    by Gammon JM, Adapa AR, Jewell CM on January 1, 1970 at 12:00 am

    Related Articles Control of autoimmune inflammation using liposomes to deliver positive allosteric modulators of metabotropic glutamate receptors. J Biomed Mater Res A. 2017 Jun 24;: Authors: Gammon JM, Adapa AR, Jewell CM Abstract Multiple sclerosis (MS) is an autoimmune disease where myelin is incorrectly recognized as foreign and attacked by the adaptive immune system. Dendritic cells (DCs) direct adaptive immunity by presenting antigens to T cells, therefore serving as a target for autoimmune therapies. N-Phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC), a positive allosteric modulator of metabotropic glutamate receptor 4 (mGluR4), can promote regulatory T cells by altering cytokine secretion to bias T cell differentiation. The therapeutic potential of PHCCC, however, is hindered by dose-limiting toxicity, poor solubility, and the need for frequent dosing. We hypothesized liposomal delivery of PHCCC might enable safe, effective delivery of this hydrophobic drug to exploit metabolism as a means of controlling inflammation in self-reactive immune cells. PHCCC was readily encapsulated in liposomes modified with polyethylene glycol. Under sink conditions, controlled release resulted in 58% of drug released into media over 18 hours. Culture of primary DCs with PHCCC liposomes reduced pro-inflammatory cytokine secretion while reducing toxicity four-fold compared with soluble PHCCC. During co-culture of DCs with myelin-reactive T cells from transgenic mice, PHCCC liposomes reduced T cell proliferation and interferon gamma secretion. These results support the potential of using liposomes to promote tolerance through biocompatible delivery of metabolic modulators. This article is protected by copyright. All rights reserved. PMID: 28646511 [PubMed - as supplied by publisher […]

  • Neuroprotective effects of G-CSF administration in microglia-mediated reactive T cell activation in vitro.
    by Peng W on January 1, 1970 at 12:00 am

    Related Articles Neuroprotective effects of G-CSF administration in microglia-mediated reactive T cell activation in vitro. Immunol Res. 2017 Jun 23;: Authors: Peng W Abstract G-CSF is a growth factor that has known neuroprotective effects in a variety of experimental brain injury models. As both antigen-presenting microglia and reactive T cells are key components in the development and progression of EAE, the aim of this study is to investigate the neuroprotective effects of recombinant human G-CSF, as administered in microglia-mediated reactive T cell assay in vitro. Our results indicate that G-CSF treatment has no apparent effect for the resting un-activated microglia. G-CSF pre-protection of microglia increased protective cytokine IL-4 production and effectively inhibited the productions of NO and other inflammatory mediators (IFN-γ, TNF-α, IL-1β, IL-17, and chemokine MCP-1) after LPS stimulation. G-CSF suppressed the proliferative response of microglia-mediated MOG35-55 reactive T cells. G-CSF-microglia-T cells increased IL-4 and IL-10 secretions and decreased IFN-γ, TNF-α, and IL-17 productions. G-CSF significantly elevated CD4(+)CD25(+) regulatory T cell subset in microglia-mediated reactive T cells. Moreover, G-CSF inhibited MHC-II expression of microglia after LPS activation or in the interactions of microglia and reactive T cells. G-CSF administration induced the apoptosis and enhanced the G0/G1 to S phase transition and elevated the gene expression of apoptosis markers in microglia-mediated reactive T cells after stimulated by specific antigen MOG35-55. These findings reveal that G-CSF administration potently neuroprotects the central nervous system (CNS) from immune-mediated damage in microglia-mediated reactive T cell activation. Apoptosis of reactive T cells in CNS is important in attenuating the development of autoimmune CNS diseases. G-CSF administration has neuroprotective effects in CNS and the potential to be a therapeutic agent in multiple sclerosis. PMID: 28646409 [PubMed - as supplied by publisher […]

  • The Changing Landscape of Alopecia Areata: An Introduction.
    by Han G on January 1, 1970 at 12:00 am

    Related Articles The Changing Landscape of Alopecia Areata: An Introduction. Adv Ther. 2017 Jun 23;: Authors: Han G Abstract Alopecia areata is an extremely common autoimmune condition affecting hair. Severe forms of alopecia areata exist, with existing treatments consisting of systemic immunosuppressants with numerous side effects. Recently, breakthroughs have been made in both understanding the pathogenesis of alopecia areata and the treatment thereof, which hold the promise of being able to target severe cases of alopecia areata with more efficacy and better tolerability. This article serves as an introduction to review papers from two of the leading researchers in the field of alopecia areata. PMID: 28646391 [PubMed - as supplied by publisher […]

  • Nogo-A antibodies enhance axonal repair and remyelination in neuro-inflammatory and demyelinating pathology.
    by Ineichen BV, Kapitza S, Bleul C, Good N, Plattner PS, Seyedsadr MS, Kaiser J, Schneider MP, Zörner B, Martin R, Linnebank M, Schwab ME on January 1, 1970 at 12:00 am

    Related Articles Nogo-A antibodies enhance axonal repair and remyelination in neuro-inflammatory and demyelinating pathology. Acta Neuropathol. 2017 Jun 23;: Authors: Ineichen BV, Kapitza S, Bleul C, Good N, Plattner PS, Seyedsadr MS, Kaiser J, Schneider MP, Zörner B, Martin R, Linnebank M, Schwab ME Abstract Two hallmarks of chronic multiple sclerosis lesions are the absence of significant spontaneous remyelination and primary as well as secondary neurodegeneration. Both characteristics may be influenced by the presence of inhibitory factors preventing myelin and neuronal repair. We investigated the potential of antibodies against Nogo-A, a well-known inhibitory protein for neuronal growth and plasticity, to enhance neuronal regeneration and remyelination in two animal models of multiple sclerosis. We induced a targeted experimental autoimmune encephalomyelitis (EAE) lesion in the dorsal funiculus of the cervical spinal cord of adult rats resulting in a large drop of skilled forelimb motor functions. We subsequently observed improved recovery of forelimb function after anti-Nogo-A treatment. Anterograde tracing of the corticospinal tract revealed enhanced axonal sprouting and arborisation within the spinal cord gray matter preferentially targeting pre-motor and motor spinal cord laminae on lesion level and above in the anti-Nogo-A-treated animals. An important additional effect of Nogo-A-neutralization was enhanced remyelination observed after lysolecithin-induced demyelination of spinal tracts. Whereas remyelinated fiber numbers in the lesion site were increased several fold, no effect of Nogo-A-inhibition was observed on oligodendrocyte precursor proliferation, migration, or differentiation. Enhancing remyelination and promoting axonal regeneration and plasticity represent important unmet medical needs in multiple sclerosis. Anti-Nogo-A antibodies hold promise as a potential new therapy for multiple sclerosis, in particular during the chronic phase of the disease when neurodegeneration and remyelination failure determine disability evolution. PMID: 28646336 [PubMed - as supplied by publisher […]

  • Electroporation as a vaccine delivery system and a natural adjuvant to intradermal administration of plasmid DNA in macaques.
    by Todorova B, Adam L, Culina S, Boisgard R, Martinon F, Cosma A, Ustav M, Kortulewski T, Le Grand R, Chapon C on January 1, 1970 at 12:00 am

    Related Articles Electroporation as a vaccine delivery system and a natural adjuvant to intradermal administration of plasmid DNA in macaques. Sci Rep. 2017 Jun 23;7(1):4122 Authors: Todorova B, Adam L, Culina S, Boisgard R, Martinon F, Cosma A, Ustav M, Kortulewski T, Le Grand R, Chapon C Abstract In vivo electroporation (EP) is used to enhance the uptake of nucleic acids and its association with DNA vaccination greatly stimulates immune responses to vaccine antigens delivered through the skin. However, the effect of EP on cutaneous cell behavior, the dynamics of immune cell recruitment and local inflammatory factors, have not been fully described. Here, we show that intradermal DNA vaccination combined with EP extends antigen expression to the epidermis and the subcutaneous skin muscle in non-human primates. In vivo fibered confocal microscopy and dynamic ex vivo imaging revealed that EP promotes the mobility of Langerhans cells (LC) and their interactions with transfected cells prior to their migration from the epidermis. At the peak of vaccine expression, we detected antigen in damaged keratinocyte areas in the epidermis and we characterized recruited immune cells in the skin, the hypodermis and the subcutaneous muscle. EP alone was sufficient to induce the production of pro-inflammatory cytokines in the skin and significantly increased local concentrations of Transforming Growth Factor (TGF)-alpha and IL-12. Our results show the kinetics of inflammatory processes in response to EP of the skin, and reveal its potential as a vaccine adjuvant. PMID: 28646234 [PubMed - in process […]

  • Direct oral anticoagulants for treatment of HIT: update of Hamilton experience and literature review.
    by Warkentin TE, Pai M, Linkins LA on January 1, 1970 at 12:00 am

    Related Articles Direct oral anticoagulants for treatment of HIT: update of Hamilton experience and literature review. Blood. 2017 Jun 23;: Authors: Warkentin TE, Pai M, Linkins LA Abstract Direct oral anticoagulants (DOACs) are attractive options for treatment of heparin-induced thrombocytopenia (HIT). We report our continuing experience in Hamilton, Canada, since January 1, 2015 (when we completed our prospective rivaroxaban for HIT study) using rivaroxaban for serologically-confirmed HIT (4Ts score ≥4 points, PF4/heparin immunoassay-positive, serotonin-release assay positive). We also performed a literature review of HIT treatment using a DOAC (rivaroxaban, apixaban, dabigatran, edoxaban). Our analysis focused on patients who received DOAC therapy for acute HIT, either as primary therapy (group A), or as secondary therapy (group B; initial treatment using a non-DOAC/non-heparin anticoagulant with transition to a DOAC during HIT-associated thrombocytopenia). Our primary endpoint was occurrence of objectively-documented thrombosis during DOAC therapy of acute HIT. We found recovery without new, progressive, or recurrent thrombosis occurred in all 10 Hamilton patients with acute HIT treated with rivaroxaban. Including these new data, the literature review identified a thrombosis rate of 1/46 patients (2.2%; 95%CI; 0.4-11.3%) in patients treated with rivaroxaban during acute HIT (group A = 25; group B = 21); major hemorrhage was seen in 0/46 patients. Similar outcomes in smaller numbers of patients were observed with apixaban (n = 12) and dabigatran (n = 11). DOACs offer simplified management of selected patients, as illustrated by a case of persisting ("autoimmune") HIT (99-day platelet recovery with parallel waning of serum-induced heparin-independent serotonin-release) with successful outpatient rivaroxaban management of HIT-associated thrombosis. Evidence supporting efficacy and safety of DOACs for acute HIT is increasing, with the largest experience reported for rivaroxaban. PMID: 28646118 [PubMed - as supplied by publisher […]