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INTRODUCTION: Guillain-Barré syndrome (GBS) is a monophasic immune neuropathic disorder characterized by acute paralysis. A significant portion of patients are left with residual deficits, which presents a considerable global healthcare challenge. The precise mechanisms underlying GBS pathogenesis are not fully elucidated. Recent studies have focused on postinfectious molecular mimicry and identified involvement of IgG autoantibodies and innate immune effectors in GBS. Intravenous immunoglobulins (IVIg) and plasma exchange (PE) are two established evidence-based immunomodulatory treatments for GBS, but a significant proportion of GBS patients fails to respond adequately to either therapy. This emphasizes an urgent need for novel and more potent treatments. AREAS COVERED: We discuss novel immunomodulatory therapies presently at different phases of preclinical and clinical investigation. Some drugs in development target pathophysiologic mechanisms such as IgG autoantibody catabolism and complement activation, which are relevant to GBS. EXPERT OPINION: There is an unmet need for more effective immune therapies for GBS. New immunomodulatory therapies under development may provide more potent options for GBS patients who do not respond to IVIg or PE. Future directions may include incorporating neuroprotective interventions based on evolving understanding of mechanisms underlying nerve injury and axonal degeneration.
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Background and Objectives: This study presents results from a survey of physicians performing electrodiagnostic studies to assess average volume. We also assessed how different factors (trainees, technologists, age of the physician, and case complexity) affected volume. Productivity is an important factor for physicians across practice settings. However, unlike evaluation and management services for neurologists, there are no published data for benchmarks of average volume of electrodiagnostic studies. Methods: A 34-question survey was designed collecting information on demographics, electrodiagnostic study volume, technologists, trainees, referrals, and case complexity. The anonymous survey was disseminated through a QR code or hyperlink to multiple online neurology, physical medicine and rehabilitation, electromyography, and neuromuscular forums. The primary outcome was EMG volume including number of EMGs per half-day and EMG volume per year. We conducted bivariate association analysis between primary outcomes and respondent characteristics using the Pearson χ2 test. Multivariable regression models determined factors associated with each of our outcome variables. Results: A total of 201 respondents initiated the survey. 71% were certified in adult neurology, 19.6% in physical medicine and rehabilitation, and 2.7% in pediatric neurology. 37.5% practiced in academic medicine. The remaining respondents were from private practice, group, solo, hospital employed, or other. 83% of respondents allotted a dedicated half-day to performing EMGs. The median number of EMGs scheduled during a half-day was within 3-4 (45%). 30% and 7% scheduled 5-6 or more than 7 patients per half-day, respectively. The median number of EMGs performed per year was within 251-500 (37%). Discussion: This national, cross-sectional survey evaluates average metrics of EMG volume. Our survey showed that the median number of EMGs annually lies between 251 and 500 studies (37%). In addition, for those respondents who allotted a dedicated half-day to performing EMGs, the median number of EMG studies scheduled per half-day lies between 3 and 4 studies (45%). In multivariate analysis, respondent characteristics of age of the physician (older than 45), working with nerve conduction technologists, and holding the position of EMG director were associated with increased EMG volume.
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Anti-ganglioside antibodies (anti-Gg Abs) have been linked to delayed/poor clinical recovery in both axonal and demyelinating forms of Guillain-Barrè Syndrome (GBS). In many instances, the incomplete recovery is attributed to the peripheral nervous system's failure to regenerate. The cross-linking of cell surface gangliosides by anti-Gg Abs triggers inhibition of nerve repair in both in vitro and in vivo axon regeneration paradigms. This mechanism involves the activation of the small GTPase RhoA, which negatively modulates the growth cone cytoskeleton. At present, the identity/es of the receptor/s responsible for transducing the signal that ultimately leads to RhoA activation remains poorly understood. The aim of this work was to identify the transducer molecule responsible for the inhibitory effect of anti-Gg Abs on nerve repair. Putative candidate molecules were identified through proteomic mass spectrometry of ganglioside affinity-captured proteins from rat cerebellar granule neurons (Prendergast et al., 2014). These candidates were evaluated using an in vitro model of neurite outgrowth with primary cultured dorsal root ganglion neurons (DRGn) and an in vivo model of axon regeneration. Using an shRNA-strategy to silence putative candidates on DRGn, we identified tumor necrosis factor receptor 1A protein (TNFR1A) as a transducer molecule for the inhibitory effect on neurite outgrowth from rat/mouse DRGn cultures of a well characterized mAb targeting the related gangliosides GD1a and GT1b. Interestingly, lack of TNFr1A expression on DRGn abolished the inhibitory effect on neurite outgrowth caused by anti-GD1a but not anti-GT1b specific mAbs, suggesting specificity of GD1a/transducer signaling. Similar results were obtained using primary DRGn cultures from TNFR1a-null mice, which did not activate RhoA after exposure to anti-GD1a mAbs. Generation of single point mutants at the stalk region of TNFR1A identified a critical amino acid for transducing GD1a signaling, suggesting a direct interaction. Finally, passive immunization with an anti-GD1a/GT1b mAb in an in vivo model of axon regeneration exhibited reduced inhibitory activity in TNFR1a-null mice compared to wild type mice. In conclusion, these findings identify TNFR1A as a novel transducer receptor for the inhibitory effect exerted by anti-GD1a Abs on nerve repair, representing a significant step forward toward understanding the factors contributing to poor clinical recovery in GBS associated with anti-Gg Abs.
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Peripheral nerve injury (PNI) resulting from trauma or neuropathies can cause significant disability, and its prognosis deteriorates with age. Emerging evidence suggests that gut dysbiosis and reduced fecal short-chain fatty acids (SCFAs) contribute to an age-related systemic hyperinflammation (inflammaging), which hinders nerve recovery after injury. This study thus aimed to evaluate the pro-regenerative effects of a rejuvenating fecal microbiota transplant (FMT) in a preclinical PNI model using aged mice. Aged C57BL/6 mice underwent bilateral crush injuries to their sciatic nerves. Subsequently, they either received FMT from young donors at three and four days after the injury or retained their aged gut microbiota. We analyzed gut microbiome composition and SCFA concentrations in fecal samples. The integrity of the ileac mucosal barrier was assessed by immunofluorescence staining of Claudin-1. Flow cytometry was utilized to examine immune cells and cytokine production in the ileum, spleen, and sciatic nerve. Various assessments, including behavioural tests, electrophysiological studies, and morphometrical analyses, were conducted to evaluate peripheral nerve function and repair following injury. Rejuvenating FMT reversed age-related gut dysbiosis by increasing Actinobacteria, especially Bifidobacteriales genera. This intervention also led to an elevation of gut SCFA levels and mitigated age-related ileac mucosal leakiness in aged recipients. Additionally, it augmented the number of T-helper 2 (Th2) and regulatory T (Treg) cells in the ileum and spleen, with the majority being positive for anti-inflammatory interleukin-10 (IL-10). In sciatic nerves, rejuvenating FMT resulted in increased M2 macrophage counts and a higher IL-10 production by IL-10+TNF-α- M2 macrophage subsets. Ultimately, restoring a youthful gut microbiome in aged mice led to improved nerve repair and enhanced functional recovery after PNI. Considering that FMT is already a clinically available technique, exploring novel translational strategies targeting the gut microbiome to enhance nerve repair in the elderly seems promising and warrants further evaluation.
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Vieillissement , Transplantation de microbiote fécal , Microbiome gastro-intestinal , Souris de lignée C57BL , Régénération nerveuse , Animaux , Souris , Transplantation de microbiote fécal/méthodes , Microbiome gastro-intestinal/physiologie , Régénération nerveuse/physiologie , Mâle , Lésions des nerfs périphériques/thérapie , Inflammation/métabolisme , Inflammation/thérapie , Dysbiose/thérapie , Nerf ischiatique/traumatismesRÉSUMÉ
Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-Barrè syndrome, mostly related to halted axon regeneration. Cross-linking of cell surface gangliosides by anti-ganglioside antibodies triggers inhibition of nerve repair in in vitro and in vivo paradigms of axon regeneration. These effects involve the activation of the small GTPase RhoA/ROCK signaling pathways, which negatively modulate growth cone cytoskeleton, similarly to well stablished inhibitors of axon regeneration described so far. The aim of this work was to perform a proof of concept study to demonstrate the effectiveness of Y-27632, a selective pharmacological inhibitor of ROCK, in a mouse model of axon regeneration of peripheral nerves, where the passive immunization with a monoclonal antibody targeting gangliosides GD1a and GT1b was previously reported to exert a potent inhibitory effect on regeneration of both myelinated and unmyelinated fibers. Our results demonstrate a differential sensitivity of myelinated and unmyelinated axons to the pro-regenerative effect of Y-27632. Treatment with a total dosage of 9 mg/kg of Y-27632 resulted in a complete prevention of anti-GD1a/GT1b monoclonal antibody-mediated inhibition of axon regeneration of unmyelinated fibers to skin and the functional recovery of mechanical cutaneous sensitivity. In contrast, the same dose showed toxic effects on the regeneration of myelinated fibers. Interestingly, scale down of the dosage of Y-27632 to 5 mg/kg resulted in a significant although not complete recovery of regenerated myelinated axons exposed to anti-GD1a/GT1b monoclonal antibody in the absence of toxicity in animals exposed to only Y-27632. Overall, these findings confirm the in vivo participation of RhoA/ROCK signaling pathways in the molecular mechanisms associated with the inhibition of axon regeneration induced by anti-GD1a/GT1b monoclonal antibody. Our findings open the possibility of therapeutic pharmacological intervention targeting RhoA/Rock pathway in immune neuropathies associated with the presence of anti-ganglioside antibodies and delayed or incomplete clinical recovery after injury in the peripheral nervous system.
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We report the presence of a male Haemaphysalis semermis collected from the domestic cat, Felis catus in an aboriginal village located in Pahang, Malaysia. This paper constitutes a new host record of this tick species, and also the first documentation of the infestation of companion animals other than domestic dogs (Canis lupus) by H. semermis in Malaysia. Additionally, we have included an updated host index of the tick species in Southeast Asia.
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Carnivora , Felidae , Ixodidae , Tiques , Animaux , Chats , Mâle , Chiens , Malaisie , Parcs de loisirsRÉSUMÉ
We report two new records of chewing lice from avian pets in Peninsular Malaysia: Colpocephalum apivorus Tendeiro, 1958 from an Oriental honey buzzard (Pernis ptilorhynchus (Temminck, 1821)), and Myrsidea splendenticola Klockenhoff, 1973 from an albino house crow (Corvus splendens Vieillot, 1817). The scarcity of louse records from avian pets and wild birds, and the lack of louse research in Malaysia are discussed.
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Amblycera , Maladies des oiseaux , Corneilles , Miel , Ischnocera , Pédiculoses , Animaux , Pédiculoses/médecine vétérinaire , Malaisie , OiseauxRÉSUMÉ
@#We report two new records of chewing lice from avian pets in Peninsular Malaysia: Colpocephalum apivorus Tendeiro, 1958 from an Oriental honey buzzard (Pernis ptilorhynchus (Temminck, 1821)), and Myrsidea splendenticola Klockenhoff, 1973 from an albino house crow (Corvus splendens Vieillot, 1817). The scarcity of louse records from avian pets and wild birds, and the lack of louse research in Malaysia are discussed.
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The taxonomy of ticks of the subgenus Boophilus has been extensively debated and is often complicated by the high intraspecific variation of morphological features between species. Notably, the cattle tick Rhipicephalus microplus is a species complex consisting of Rhipicephalus annulatus, Rhipicephalus australis and the three mitochondrial clades (A-C) of R. microplus. To gain insight into the taxonomic status of this species complex, we performed morphological and molecular analyses on these cattle ticks across four states in peninsular Malaysia. We morphologically identified 60 males and 104 females of R. microplus, 298 males and 374 females of R. australis, and one R. annulatus male in our field collection, of which the latter two species have never been recorded in Malaysia. However, all three morphologically identified species were molecularly assigned as R. microplus clade A based on the barcoding cytochrome oxidase subunit I (COI) analysis. The discrepancy between morphological and genetic data highlights an urgent need for further exploration and in-depth research into the taxonomic status of these sympatric tick species.
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Maladies des bovins , Coléoptères , Rhipicephalus , Infestations par les tiques , Animaux , Bovins , Maladies des bovins/génétique , Femelle , Malaisie , Mâle , Phylogenèse , Rhipicephalus/anatomie et histologie , Infestations par les tiques/médecine vétérinaireRÉSUMÉ
OBJECTIVES: Intravenous immunoglobulin (IVIg) is used for treatment of acute neurologic conditions such as Guillain-Barre syndrome, chronic inflammatory demyelinating polyradiculoneuropathy relapse, and myasthenia gravis exacerbation. Precision dosing (adjusted or ideal body weight) is proposed to conserve IVIg. There have been no published studies comparing clinical outcomes in traditional dosing (actual body weight) with precision dosing. In 2014, our institution began dosing patients with precision dosing. This decision was largely performed by administration rather than physicians' preference. We sought to analyze our retrospective data to understand the change in dosing methods with neurologic outcomes. METHODS: We performed a retrospective review of all patients hospitalized at a single center who received IVIg for myasthenia gravis, Guillain-Barre syndrome, and chronic inflammatory demyelinating polyradiculoneuropathy from January 2010 to October 2017. We collected baseline information and clinical outcomes including mortality, readmission, need for second rescue treatment, length of stay, discharge disposition, treatment-related adverse events, and modified research council posttreatment sum score. RESULTS: Length of stay was significantly shorter with precision dosing. There was no statistically significant difference in discharge disposition, readmission, rescue treatment, or modified research council posttreatment sum score with precision dosing. CONCLUSION: Precision dosing did not adversely affect short-term neurologic outcomes.
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Syndrome de Guillain-Barré , Polyradiculonévrite inflammatoire démyélinisante chronique , Syndrome de Guillain-Barré/traitement médicamenteux , Humains , Immunoglobulines par voie veineuse , Récidive tumorale locale , Polyradiculonévrite inflammatoire démyélinisante chronique/traitement médicamenteux , Études rétrospectivesRÉSUMÉ
Soft ticks (Acari: Argasidae) are the second major family of the blood feeding metastriates and vectors of a number of viral and bacterial pathogens for both humans and animals. Despite the growing effort on tick surveillance and studies worldwide, there is still limited information on the soft tick distribution in the island nations of Southeast Asia, especially species that are medically and veterinarily important. With the aim to provide an overview of the current status of knowledge on soft tick distribution in the island nations of Southeast Asia (Malaysia, Singapore, Brunei, Indonesia, the Philippines and Timor-Leste), this article reviews the species of soft ticks (Acari: Argasidae) and their associated hosts and pathogens, with the addition of a pictorial summary and list of tick species discovered in this region. The most prevalent soft tick genus is Carios, and the host species most associated with findings of soft ticks in this region are bats, particularly of the Pteropodidae and Vespertilionidae families. Furthermore, the only known pathogen originating from soft ticks in the island nations of Southeast Asia was the Keterah virus, which was isolated from Argas pusillus tick in Malaysia.
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Tiques , Animaux , Asie du Sud-Est/épidémiologie , Humains , Iles , Malaisie , Tiques/classification , Tiques/microbiologie , Tiques/virologieRÉSUMÉ
Immunoglobulin G (IgG) therapy is an established long-term treatment in chronic inflammatory demyelinating polyneuropathy (CIDP) that is commonly administered intravenously (IVIg). The subcutaneous immunoglobulin (SCIg) administration route is a safe and effective alternative option, approved by the United States Food and Drug Administration (FDA) in 2018, for maintenance treatment of adults with CIDP. Physicians and patients alike need to be aware of all their treatment options in order to make informed decisions and plan long-term treatment strategies. In this review, we collate the evidence for SCIg in CIDP from all published studies and discuss their implications and translation to clinical practice. We also provide guidance on the practicalities of how and when to transition patients from IVIg to SCIg and ongoing patient support. Evidence suggests that IVIg and SCIg have comparable long-term efficacy in CIDP. However, SCIg can provide additional benefits for some patients, including no requirement for venous access or premedication, and reduced frequency of systemic adverse events. Local-site reactions are more common with SCIg than IVIg, but these are mostly well-tolerated and abate with subsequent infusions. Data suggest that many patients prefer SCIg following transition from IVIg. SCIg preference may be a result of the independence and flexibility associated with self-infusion, whereas IVIg preference may be a result of familiarity and reliance on a healthcare professional for infusions. In practice, individualizing maintenance dosing based on disease behavior and determining the minimally effective IgG dose for individuals are key considerations irrespective of the administration route chosen.
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Immunisation passive , Immunoglobuline G/usage thérapeutique , Polyradiculonévrite inflammatoire démyélinisante chronique/traitement médicamenteux , Humains , Immunoglobuline G/administration et posologie , Perfusions sous-cutanéesRÉSUMÉ
Guillain-Barré syndrome (GBS) is an autoimmune peripheral neuropathy and a common cause of neuromuscular paralysis. Preceding infection induces the production of anti-ganglioside (GD) antibodies attacking its own peripheral nerves. In severe proximal peripheral nerve injuries that require long-distance axon regeneration, motor functional recovery is virtually nonexistent. Damaged axons fail to regrow and reinnervate target muscles. In mice, regenerating axons must reach the target muscle within 35â¯days (critical period) to reform functional neuromuscular junctions and regain motor function. Successful functional recovery depends on the rate of axon regeneration and debris removal (Wallerian degeneration) after nerve injury. The innate-immune response of the peripheral nervous system to nerve injury such as timing and magnitude of cytokine production is crucial for Wallerian degeneration. In the current study, forced expression of human heat shock protein (hHsp) 27 completely reversed anti-GD-induced inhibitory effects on nerve repair assessed by animal behavioral assays, electrophysiology and histology studies, and the beneficial effect was validated in a second mouse line of hHsp27. The protective effect of hHsp27 on prolonged muscle denervation was examined by performing repeated sciatic nerve crushes to delay regenerating axons from reaching distal muscle from 37â¯days up to 55â¯days. Strikingly, hHsp27 was able to extend the critical period of motor functional recovery for up to 55â¯days and preserve the integrity of axons and mitochondria in distal nerves. Cytokine array analysis demonstrated that a number of key cytokines which are heavily involved in the early phase of innate-immune response of Wallerian degeneration, were found to be upregulated in the sciatic nerve lysates of hHsp27 Tg mice at 1â¯day postinjury. However, persistent hyperinflammatory mediator changes were found after chronic denervation in sciatic nerves of littermate mice, but remained unchanged in hHsp27 Tg mice. Taken together, the current study provides insight into the development of therapeutic strategies to enhance muscle receptiveness (reinnervation) by accelerating axon regeneration and Wallerian degeneration.
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Protéines du choc thermique , Régénération nerveuse , Névrite auto-immune expérimentale , Lésions des nerfs périphériques , Animaux , Axones , Souris , Nerf ischiatiqueRÉSUMÉ
PURPOSE OF REVIEW: This article reviews the clinical features, diagnosis and differential diagnosis, prognosis, pathogenesis, and current and upcoming treatments of Guillain-Barré syndrome (GBS). RECENT FINDINGS: GBS is an acute inflammatory neuropathic illness with striking clinical manifestations and significant morbidity. A substantial proportion of patients with GBS do not respond to current immunomodulatory therapies (ie, plasma exchange and IV immunoglobulin [IVIg]), highlighting the need for new therapies. Prognostic models that can accurately predict functional recovery and the need for artificial ventilation have emerged. These models are practical, and online calculators are available for clinical use, facilitating early recognition of patients with poor outcome and the opportunity to personalize management decisions. Clinical and experimental studies have identified innate immune effectors (complement, macrophage lineage cells, and activating Fcγ receptors) as important mediators of inflammatory nerve injury. Two complement inhibitors are undergoing clinical testing for efficacy in GBS. SUMMARY: GBS is the most common cause of acute flaccid paralysis in the United States and worldwide. New treatments for GBS have not emerged since the 1990s. Our understanding of the pathogenesis of this disorder has progressed, particularly over the past decade; as a result, new therapeutic agents targeting different components of the complement cascade are at advanced stages of clinical development.
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Syndrome de Guillain-Barré/diagnostic , Syndrome de Guillain-Barré/physiopathologie , Syndrome de Guillain-Barré/thérapie , Adulte , Femelle , HumainsRÉSUMÉ
Proteins in saliva are needed for preprocessing food in the mouth, maintenance of tooth mineralization, and protection from microbial pathogens. Novel insights into human lineage-specific functions of salivary proteins and clues to their involvement in human disease can be gained through evolutionary studies, as recently shown for salivary amylase AMY1 and salivary agglutinin DMBT1/gp340. However, the entirety of proteins in saliva, the salivary proteome, has not yet been investigated from an evolutionary perspective. Here, we compared the proteomes of human saliva and the saliva of our closest extant evolutionary relatives, chimpanzees and gorillas, using macaques as an outgroup, with the aim to uncover features in saliva protein composition that are unique to each species. We found that humans produce a waterier saliva, containing less than half total protein than great apes and Old World monkeys. For all major salivary proteins in humans, we could identify counterparts in chimpanzee and gorilla saliva. However, we discovered unique protein profiles in saliva of humans that were distinct from those of nonhuman primates. These findings open up the possibility that dietary differences and pathogenic pressures may have shaped a distinct salivary proteome in the human lineage.
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Primates/métabolisme , Salive/composition chimique , Protéines et peptides salivaires/analyse , Animaux , Évolution biologique , Gorilla gorilla/génétique , Gorilla gorilla/métabolisme , Humains , Macaca/génétique , Macaca/métabolisme , Pan troglodytes/génétique , Pan troglodytes/métabolismeRÉSUMÉ
Intravenous immunoglobulins (IVIg) are standard treatment for Guillain-Barré syndrome (GBS). Their exact mechanisms of action are versatile and not fully understood. One possible mechanism is neutralization of circulating autoantibodies via binding to anti- idiotypic antibodies forming idiotype-anti-idiotype dimeric IgG immune complexes. To examine the role of immune complex formation as mechanism of action for IVIg in GBS, 34 C57Bl/6 mice were either treated with anti-ganglioside antibodies and IVIg or IVIg and PBS alone, whereas eight additional mice were treated either with anti-ganglioside autoantibodies and IVIg or anti-ganglioside autoantibodies alone. Subsequently IgG dimer formation was assessed by high performance liquid chromatography (HPLC) and enzyme- linked immunosorbent assay (ELISA). In addition, IgG dimer formation was measured in sera of eight GBS patients who were treated with IVIg. In mice, a significant increase of dimeric IgG after administration of anti-ganglioside antibodies and IVIg could be observed. Re-monomerized IgG dimers showed immunoreactivity against gangliosides and serum immunoreactivity was significantly reduced after IVIg infusion. Likewise also in GBS patients, IgG dimer formation could be detected after IVIg treatment. Our data indicate that dimeric IgG immune complexes contain anti-idiotypic antibodies and provide proof of concept that IVIg treatment in GBS results in measurable amounts of IgG dimers. Larger patient cohorts are needed to evaluate serum IgG dimer increase as a possible marker for treatment response in GBS. Graphical Abstract Mechanism of action: Intravenous immunoglobulins (IVIg) and anti-ganglioside antibodies form dimeric IgG immune complexes, preventing axonal damage in Guillain-Barré Syndrome.
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Autoanticorps/sang , Syndrome de Guillain-Barré/sang , Syndrome de Guillain-Barré/traitement médicamenteux , Immunoglobuline G/sang , Immunoglobulines par voie veineuse/administration et posologie , Adulte , Animaux , Autoanticorps/immunologie , Marqueurs biologiques/sang , Femelle , Syndrome de Guillain-Barré/immunologie , Humains , Immunoglobuline G/immunologie , Mâle , Souris , Souris de lignée C57BL , Adulte d'âge moyenRÉSUMÉ
Spontaneous autoimmune peripheral polyneuropathy (SAPP) is a reproducible mouse model of chronic inflammatory peripheral neuropathy in female non-obese diabetic mice deficient in co-stimulatory molecule, B7-2 (also known as CD86). There is evidence that SAPP is an interferon-γ, CD4+ T-cell-mediated disorder, with autoreactive T-cells and autoantibodies directed against myelin protein zero involved in its immunopathogenesis. Precise mechanisms leading to peripheral nerve system inflammation and nerve injury including demyelination in this model are not well defined. We examined the role of activating Fc-gamma receptors (FcγRs) by genetically ablating Fcγ-common chain (Fcer1g) shared by all activating FcγRs in the pathogenesis of this model. We have generated B7-2/ Fcer1g-double null animals for these studies and found that the neuropathic disease is substantially ameliorated in these animals as assessed by behavior, electrophysiology, immunocytochemistry, and morphometry. Our current studies focused on characterizing systemic and endoneurial inflammation in B7-2-null and B7-2/ Fcer1g-double nulls. We found that accumulation of endoneurial inflammatory cells was significantly attenuated in B7-2/ Fcer1g-double nulls compared to B7-2-single nulls. Whereas, systemically the frequency of CD4+ regulatory T cells and expression of immunosuppressive cytokine, IL-10, were significantly enhanced in B7-2/ Fcer1g-double nulls. Overall, these findings suggest that elimination of activating FcγRs modulate nerve injury by altering endoneurial and systemic inflammation. These observations raise the possibility of targeting activating FcγRs as a treatment strategy in acquired inflammatory demyelinating neuropathies.
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Maladies auto-immunes/métabolisme , Polyneuropathies/métabolisme , Récepteurs du fragment Fc des IgG/métabolisme , Animaux , Maladies auto-immunes/immunologie , Axones/anatomopathologie , Antigène CD86/déficit , Antigène CD86/génétique , Numération cellulaire , Cytokines/métabolisme , Délétion de gène , Régulation de l'expression des gènes , Lipopolysaccharides/pharmacologie , Activation des macrophages/effets des médicaments et des substances chimiques , Souris , Gaine de myéline/physiologie , Nerfs périphériques/anatomopathologie , Polyneuropathies/immunologie , Récepteur Fc/déficit , Récepteur Fc/génétique , Lymphocytes T régulateurs/cytologie , Lymphocytes T régulateurs/effets des médicaments et des substances chimiques , Lymphocytes auxiliaires Th2/effets des médicaments et des substances chimiques , Lymphocytes auxiliaires Th2/métabolismeRÉSUMÉ
BACKGROUND: Research is a critical component amongst the strategies to improve health outcomes of any country. The role of research assumes greater importance in Africa as it carries a larger share of the global burden of diseases, blindness, and low vision. "Vision 2020- the Right to Sight" is a WHO-IAPB collaborated initiative aiming to eliminate preventable blindness by the year 2020. High quality research in eye care is imperative for the initiative to succeed, however, there is a dearth of research in eye care in sub-Saharan Africa in general and specifically in the Eastern, Central, and Southern African (ECSA) region. Identifying the barriers that hamper research in this region is an important step towards the elimination of preventable blindness. METHODS: A structured questionnaire using the SurveyMonkey program was sent to ophthalmologists in the ECSA region and South Africa through their respective regional professional bodies. RESULTS: Lack of funding, inadequate time and poor research knowledge were the main research barriers while the ability to improve eye health care through research was the main incentive for conducting research. The response rate for South Africa was low, restricting comparisons with other ECSA countries. CONCLUSION: The barriers mainly center on financial, human and administrative infrastructure and resources. In spite of the barriers, ophthalmologists in the study region are enthusiastic in research aiming to increase evidence-based knowledge to improve eye health care in line with the goals of "Vision 2020- the Right to Sight" initiative.