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Editorial: Clinical trials in ANCA associated vasculitis
Dr Chetan Mukhtyar MB BS, MSc, MD, FRCP (Edin)
[FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0012]


FDG-PET Imaging in Large Vessel Vasculitis and Polymyalgia Rheumatica
Daniel Blockmans
[Abstract] [FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0013]


Systemic Vasculitis: an epidemiological perspective
Richard Watts
[Abstract] [FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0014]


Treatment of Large Vessel Vasculitis
Marco A Alba, Georgina Espígol-Frigolé, Montserrat Butjosa, Sergio Prieto-González, Ana García-Martínez, José Hernández-Rodríguez, Maria C Cid.
[Abstract] [FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0015]


Anti-tumor necrosis factor blocking agents in the treatment of systemic vasculitis
Marzouq Qubti and Philip Seo
[Abstract] [FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0016]


Autoantibodies as biomarkers for ANCA-associated vasculitides
Cees G.M. Kallenberg
[Abstract] [FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0017]


B cell depletion in systemic vasculitis
RM Smith and DRW Jayne
[Abstract] [FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0018]


The need for diagnostic criteria in systemic vasculitis
Ravi Suppiah, Joanna Robson, Neil Basu and Raashid Luqmani
[Abstract] [FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0019]


Virus-Associated Vasculitides
Christian Pagnoux and David Saadoun
[Abstract] [FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0020]


Management of Antineutrophil Cytoplasmic Antibody Associated Vasculitis
Elena Nikiphorou and Chetan Mukhtyar
[Abstract] [FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0021]


Dendritic cells in autoimmune liver diseases
Masanori Abe, Yoichi Hiasa, Morikazu Onji
[Abstract] [FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0022]


Dendritic cell-based immune therapy in liver diseases
Sheikh Mohammad Fazle Akbar, Yoichi Hiasa, Mamun Al-Mahtab, Morikazu Onji
[Abstract] [FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0023]


Dendritic cells in hepatitis virus infection: a legatus within
Tatsuya Kanto
[Abstract] [FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0024]


Ontogenic development and population dynamics of hepatic dendritic cells
Shang-an Shu, Hong-Di Ma and Zhe-Xiong Lian
[Abstract] [FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0025]


Sleep and The Immune System
Cardinali DP and Esquifino AI
[Abstract] [FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0026]


Obesity as a Model of Premature Immunosenescence
De la Fuente M and De Castro NM
[Abstract] [FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0027]


Modulation of Apoptosis in Acute Ischemic Stroke as Treatment Challenges
Jordan J, Moreno-Parrado L, Anton-Martinez D, Jellinger KA and Galindo MF
[Abstract] [FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0028]


New Challenges in CNS Repair: The Immune and Nervous Connection
Lombardi VRM
[Abstract] [FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0029]


Immune Disturbances in Chronic Pain: Cause, Consequence or Both?
Maletic V and Raison CL
[Abstract] [FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0030]


Rituximab Therapy and Autoimmune Disease
Asha Ram Yadav and Nirmala Deo
[Abstract] [FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0031]


Autoimmune diseases and Atherosclerosis: the Inflammatory Connection
Meenakshi Varma, Lakshmi A Mundkur and V.V. Kakkar
[Abstract] [FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0032]



Abstracts



FDG-PET Imaging in Large Vessel Vasculitis and Polymyalgia Rheumatica
Daniel Blockmans
[FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0013]

Positron emission tomography (PET) with the use of 18fluoro-deoxyglucose (FDG) can reveal the existence of large vessel vasculitis. Patients with giant cell arteritis presenting as fever of unknown origin have increased FDG-uptake in their large thoracic vessels. The temporal arteries cannot be visualized by this technique, but thoracic vascular FDG-uptake has a specificity of 98 % for the diagnosis of GCA/PMR. FDG-PET scintigraphy in GCA has taught us that wide-spread large arterial involvement occurs much more frequently than originally thought. FDG uptake correlates well with the halo sign of duplex ultrasound in arteries which can be visualised with both techniques. FDG-PET may have prognostic value for predicting aortic dilatation but not for predicting relapse. Patients with PMR demonstrate an increased FDG-uptake in the shoulders, hips, and the spinous processes of the cervical and lumbar vertebrae. FDG-uptake in the aorta and its branches in some patients with so-called PMR is probably due to sub-clinical vasculitis. FDG-PET scintigraphy has a role in the diagnosis of Takayasu arteritis, even at an early stage, before stenoses are visible on angiography. In patients with Takayasu arteritis some vascular FDG-uptake may remain visible for years due to either ongoing low-grade inflammation or vascular remodelling. There is no association between intensity of FDG-uptake and acute-phase reactants, or magnetic resonance imaging data. We await the results of an ongoing prospective study to confirm or deny the utility of PET as a tool for the assessment of disease activity and for monitoring.
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Systemic Vasculitis: an epidemiological perspective
Richard Watts
[FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0014]

The descriptive epidemiology of the systemic vasculitides is increasingly well understood and this is beginning to provide insights into potential risk factors. The contribution of age, ethnicity, genetics, infections, drugs, occupation and other environmental factors is discussed in this paper. Age has considerable influence on the expression of vasculitis Kawasaki disease and Henoch Schönlein purpura occurring in children and giant cell arteritis and ANCA-associated vasculitides (AAV) peaking in the age range 65-75 years. From the available data, major differences between populations are clear. Giant cell arteritis is commoner in people of Scandinavian descent. Takayasu arteritis may occur more frequently in Asian populations. The AAV have mainly been described in white populations from both the Northern and Southern hemispheres in which the incidence seems to be fairly constant, but with a possible latitudinal differentiation of the sub-type of AAV. Renal AAV in Japan is solely due to MPA, but In Europe only 50% is MPA, the remainder being WG or CSS. Renal vasculitis in Japan is exclusively associated with pANCA-MPO, whereas in Europe pANCA-MPO is present in only 55% of patients with renal vasculitis. The familial heritability of WG has been shown to be similar to that seen in RA, but in general the genetic basis of vasculitis is not well understood. The strongest HLA allele association for AAV is with HLA DPB1*0401. Hepatitis B infection has been firmly associated with polyarteritis nodosa and Hepatitis C has a strong association with essential mixed cryoglobulinaemia. Many other infections have been associated with vasculitis but a direct pathogenic effect has not been demonstrated. Kawasaki disease occurs with pronounced seasonality with winter and spring peaks in most temperate countries and summer peaks in Asian countries. A number of drugs including hydralazine and propylthiouracil have been associated with anti-MPO AAV. Leucotriene inhibitors and Omalizumab have been linked with CSS. A potential association with silica has been extensively investigated. Systemic vasculitis has been associated with exposure to particulate silica, farming, inhaled fumes and particulates and pesticides.
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Treatment of Large Vessel Vasculitis
Marco A Alba, Georgina Espígol-Frigolé, Montserrat Butjosa, Sergio Prieto-González, Ana García-Martínez, José Hernández-Rodríguez, Maria C Cid.
[FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0015]

Primary large vessel vasculitides are granulomatous disorders and include two closely related but distinct entities: giant-cell arteritis (GCA) and Takayasu arteritis Both conditions were considered self-limiting in the pre-steroid era albeit with the potential for major discomfort and severe vascular complications The introduction of glucocorticoid therapy in the 1950’s provided substantial relief in affected patients as well as prevention of vascular complications and glucocorticoids remain the cornerstone of treatment. In patients with GCA, glucocorticoid treatment is invariably followed by a remarkable improvement of symptoms, and reduction of the risk of visual impairment. The optimal initial glucocorticoid dose has not been established but commonly ranges from 40 to 60 mg oral prednisone or equivalent per day. Initial pulsed intravenous methylprednisolone has been used in patients with visual symptoms. Methotrexate (10-15 mg/week) has a modest effect in lowering relapse rate and cumulative glucocorticoid dose. The role of statins, aspirin and targeted pharmacotherapy in GCA has been discussed in the paper. In patients with Takayasu arteritis, the initial treatment is 0.5 to 1 mg/Kg/day of oral prednisone or equivalent. Cyclophosphamide, methotrexate and azathioprine, mycophenolate mofetil and anti-TNF agents have all been used in open-label studies. TNF α blockade with etanercept or infliximab, seems to be useful in open-label trials. The indications, efficacy and timing of revascularisation procedures are discussed in this paper.
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Anti-tumor necrosis factor blocking agents in the treatment of systemic vasculitis
Marzouq Qubti and Philip Seo
[FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0016]

The primary systemic vasculitides are idiopathic disorders characterized by the inflammatory destruction of blood vessel walls. Many of these disorders are treated with high-dose glucocorticoids and cytotoxic agents which, while effective, are associated with substantial morbidity, particularly for patients who experience recurrent flares requiring chronic therapy. Therefore, attention has turned towards biologic therapies that abrogate specific elements in the inflammatory cascade. Tumor necrosis factor-α is a cytokine that is central to systemic inflammation in many diseases. This article will review the role played by tumor necrosis factor-α in the pathogenesis of systemic vasculitis, and attempt to define a role for blockade of tumor necrosis factor-α in the treatment of patients with these diseases.
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Autoantibodies as biomarkers for ANCA-associated vasculitides
Cees G.M. Kallenberg
[FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0017]

Both PR3-ANCA and MPO-ANCA are highly sensitive and specific markers for the ANCA-associated vasculitides (AAV), in particular Wegener’s Granulomatosis and microscopic polyangiitis. This close association suggests a pathogenic role of the autoantibodies. In vitro and in vivo experimental data strongly support such a role, particularly for MPO-ANCA. As pathogenic autoantibodies ANCA could serve as biomarkers for AAV. Longitudinal observations indeed prove that MPO-ANCA could serve as a biomarker for AAV although being not perfect. For PR3-ANCA, data are less convincing as some studies found a fair correlation between changes in levels of PR3-ANCA and disease activity of the AAV, but others found not. This could be due to methodological shortcomings but also to inherent differences in pathogenicity between MPO-ANCA and PR3-ANCA. More studies are needed to solve this question.
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B cell depletion in systemic vasculitis
RM Smith and DRW Jayne
[FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0018]

The important role of B cells in the pathogenesis of systemic vasculitis has become increasingly clear over recent years. B cell directed therapies offer an exciting new approach to the treatment of these conditions, in which there has been little change in the options available to managing clinicians since the advent of traditional immunosuppressive therapy. The introduction of conventional immunosuppression has transformed survival in systemic vasculitis, particularly ANCA-associated vasculitis, but at the expense of significant toxicity, and with suboptimal efficacy. B cell therapies offer the possibility of targeted, individually tailored immunotherapy, which by improving efficacy, and reducing toxicity will improve clinical outcomes in systemic vasculitis. However, the heterogeneity of vasculitic syndromes suggests that one agent is unlikely to be effective in all situations. The precise indications and optimal combination of B cell directed with other therapies will need to be determined.
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The need for diagnostic criteria in systemic vasculitis
Ravi Suppiah, Joanna Robson, Neil Basu and Raashid Luqmani
[FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0019]

There are currently no diagnostic criteria for the systemic vasculitides. Due to the heterogeneous and non specific manner that vasculitis can present there is often a delay in diagnosis which translates to increased morbidity and mortality. The current disease definitions and classification criteria are often misapplied as diagnostic criteria, but evaluation of this has shown that they do not perform satisfactorily for this purpose. We discuss the CHCC definitions, the ACR classification criteria and the EMEA algorithm which is needed to bridge the inconsistency between the two. We also evaluate the proposals for criteria of polyarteritis nodosa and Behcet’s disease. We provide a brief summary of how a diagnosis of vasculitis is currently made, describe how increased understanding of disease mechanisms has identified biomarkers which aid diagnosis, and describe how clinically applicable diagnostic criteria could be developed.
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Virus-Associated Vasculitides
Christian Pagnoux and David Saadoun
[FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0020]

Several viruses have been suspected of causing or triggering vasculitis, with hepatitis B virus-related polyarteritis nodosa (HBV–PAN) and hepatitis C virus-related mixed cryoglobulinemic vasculitis (HCV–MCV) having the best demonstrated and confident proof for a causal link with viruses. Human immunodeficiency virus, erythrovirus B19, cytomegalovirus, varicella-zoster virus or human T-cell lymphotropic virus-1 can also induce mainly localized vasculitis. Conversely, no strong evidence indicates that viruses are implicated in the pathogenesis of other primary systemic vasculitides, like Kawasaki or Behçet’s diseases, or Wegener’s granulomatosis. Treatment for all these virus-associated vasculitides should be two-pronged: one to control and clear the viral infection, using antiviral drugs; the other to rapidly control the clinical manifestations of vasculitis. Management of this second concomitant therapy is more delicate. It can rely on plasma exchange to clear immune complexes in HBV–PAN or rituximab in HCV–MCV, but sometimes it must include short durations of corticosteroids, and cytotoxic agents for most severe cases, both of which are potentially deleterious because they can hamper virus clearance and delay seroconversion.
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Management of Antineutrophil Cytoplasmic Antibody Associated Vasculitis
Elena Nikiphorou and Chetan Mukhtyar
[FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0021]

Wegener’s granulomatosis (WG), microscopic polyangiitis (MPA) and Churg-Strauss syndrome (CSS) are grouped together under the term ‘Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis’ (AAV). Recently, the British Society for Rheumatology and the European League Against Rheumatism have individually published recommendations on the management of AAV. This paper reviews the two recommendations, and the recent advances in the management of AAV. Pattern recognition and clinical suspicion remains the cornerstone for an early diagnosis. The combination of cyclophosphamide and glucocorticoid is the standard of therapy for remission induction. Patients with less severe disease can be treated effectively with less toxic therapies. There is almost no reason to routinely continue using cyclophosphamide beyond 6 months. Long-term remission maintenance is possible with a variety of immunomodulating agents. With increasing survival, the recognition and management of complications like cardiovascular disease, renal failure, malignancy requires long-term follow up and regular screening.
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Dendritic cells in autoimmune liver diseases
Masanori Abe, Yoichi Hiasa, Morikazu Onji
[FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0022]

Dendritic cells (DC) are professional antigen presenting cells that maintain immune tolerance to self-antigens by controlling the pathogenicity of autoreactive T cells, and a lack of immune tolerance against self-antigens results in autoimmune diseases. Therefore, DCs play an essential role in the induction and/or maintenance of autoimmunity. In the present review, we focus on the role of DCs in the pathogenesis of autoimmune liver diseases. In addition, recent developments in DC-based immunotherapy using regulatory (tolerogenic) DCs in autoimmune diseases will be discussed.
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Dendritic cell-based immune therapy in liver diseases
Sheikh Mohammad Fazle Akbar, Yoichi Hiasa, Mamun Al-Mahtab, Morikazu Onji
[FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0023]

The field of immune therapy is currently undergoing a shift in focus, from non antigen-specific immune modulator-based immune therapy to antigen-based vaccine therapy to more sophisticated cell-based vaccine applications. Dendritic cells (DCs) are rare leukocytes that are uniquely potent in their ability to capture, process and present antigens to T cells. By culturing DCs with viral antigens or tumor-associated antigens or different cellular products, immunogenic or tolerogenic DCs can be produced. When antigen-pulsed DCs are administered, an increase in the functional capacities of cells of innate immune system is observed. Also, patients administered with antigen-loaded DCs exhibit an augmentation of helper T cells, cytotoxic T cells, and plasma cells activities. Patients with liver diseases exhibit distorted immune responses to invading pathogens or cancer cells or autoantigens. On the other hand, recovery from liver diseases is usually associated with restoration of host immunity. In this review, we would discuss about rationale and strategies of immune therapy including DC-based therapy in liver diseases. 
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Dendritic cells in hepatitis virus infection: a legatus within
Tatsuya Kanto
[FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0024]

Hepatitis B or C virus (HBV or HCV) causes chronic liver diseases that eventually progress to liver cancer. Both viruses are armed with multiple machineries for modulating immune responses in infected hosts. Mild and pervasive immune cell dysfunction, but not fully compromised, is a hallmark of chronic HBV or HCV infection, of which fundamental mechanisms are yet to be clarified. Dendritic cells (DC) as immune sentinels sense virus via toll-like receptors (TLR) or retinoic acid inducible gene-I (RIG-I) and evoke a cascade of immune reactions by secreting cytokines or by interacting other lymphocytes. Reduced and disabled DC potentially give negative impact on adjacent cells, such as NK cells, NKT cells and T cells. However, lack of evidence for active viral replication in DC or blood cells imply the presence of undisclosed contrivances that are independent of infection. Successful treatment of chronically infected patients with anti-viral agents is accompanied with numerical and/or functional restoration of DC, suggesting that DC could serve as potential therapeutic targets. Further studies are warranted for the establishment of therapeutic DC vaccine in order to gain more vigorous and sustained virus-specific immune responses. Cross talk between DC and lymphocytes are thus critical in shaping innate and subsequent adaptive immune responses against hepatitis virus, either spontaneously or therapeutically.
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Ontogenic development and population dynamics of hepatic dendritic cells
Shang-an Shu, Hong-Di Ma and Zhe-Xiong Lian
[FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0025]

Dendritic cells (DCs) are rare, bone marrow-derived antigen-presenting cells (APCs) characterized by a unique capacity to stimulate naïve T cells and initiate primary immune responses.  The special immunological microenvironment in the liver is associated with the induction of tolerance to dietary food antigens, and yet, it maintains the capacity to sustain effective responses against pathogens.  Recent studies have provided data to elucidate the critical roles that DCs play in the induction of central and peripheral immunological tolerance, in regulating the types of T cell immune responses, and functioning as sentinels in innate immunity against microbes in the liver.  The diverse functions of hepatic DCs in immune regulation depend on the heterogeneity of DC subsets and their functional plasticity.  Here, we review recent progress in our understanding of the ontogenic development, the population dynamics, and the functional plasticity of DCs in the liver.
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Sleep and The Immune System
Cardinali DP and Esquifino AI
[FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0026]

From a physiological perspective the sleep-wake cycle can be envisioned as a sequence of three physiological states, identified by a particular homeostatic patent: wakefulness, non-rapid eye movement (NREM) or slow sleep, and REM sleep. These three physiological states are defined by a particular neuroendocrine-immune profile that regulates the immune system response. This review discusses the physiological basis of such a control of the immune system at different sleep stages, as well as the manner in which humoral signals (cytokines) produced by immunocompetent cells modify the mechanisms of sleep.
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Obesity as a Model of Premature Immunosenescence
De la Fuente M and De Castro NM
[FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0027]

With aging the neuroendocrine-immune communication suffers an impairment, which explains the altered homeostasis and the resulting increase of morbidity and mortality. Since the aging process is very heterogeneous, the biological age determines the level of aging experienced by each individual and therefore his/her life expectancy. We have proposed several immune functions as markers of biological age and predictors of longevity, as well as the key involvement of the immune system in the rate of aging modulating oxi-inflamm-aging. This has been confirmed in several murine models of premature aging of neuroimmunomodulation such as poor response to stress, anxiety, depression or loss of estrogens. In the present article we summarise knowledge of the obesity and immune system and suggest that obese subjects, compared to non-obese of the same chronological age, are prematurely aged. Thus, we show some data supporting the hypothesis that obesity is a model of premature immunosenescence.
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Modulation of Apoptosis in Acute Ischemic Stroke as Treatment Challenges
Jordan J, Moreno-Parrado L, Anton-Martinez D, Jellinger KA and Galindo MF
[FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0028]

Stroke is a major cause of death and disability throughout the world. Its pathophysiology is complex and includes excitotoxity, inflammatory pathways, oxidative damage, ionic imbalances, apoptosis and other cell death mechanisms, angiogenesis, and neuroprotection. The ultimate result of the complex ischemic cascade is neuronal death with irreversible loss of neuronal functions. New developments in stroke pathophysiology have induced significant advances in acute stroke management. Among the extracellular signals, inflammation, microglia and cytokines as major consequences of hypoxia may be targets for future therapies. Among the intracellular signals, calcium-induced cell death and oxidative stress as most important factors of ischemic cell death and for dysfunctions of the blood-brain barrier are important goals for neuroprotective agents. Third messengers, like p53, peroxisome proliferator-activated receptors and nuclear factor kappa-B (NF-kB) also play important roles in the pathogenesis of ischemic cell death, and may be further important targets of modern neuroprotective agents. The final stage of ischemic cell death via apopotosis and other cell death cascades, mainly influenced by energy deficiency and mitochondrial dysfunction may be influenced by antiapoptotic and other strategies as potential new targets for designing newer and more successful therapeutic modalities of acute ischemic stroke.
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New Challenges in CNS Repair: The Immune and Nervous Connection
Lombardi VRM
[FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0029]

The Central Nervous System (CNS) is the organ with the least capacity for repair in mammals. Diseases of the CNS may follow developmental deficits, inappropriate environmental factors and acquired damages after maturation. The latter damages may consist of neuronal cell death, like Alzheimer's disease and/or to a lesion of the axon, like in the paraplegic patients. Hopes of obtaining a functional recovery after trauma or neurodegeneration, are very low and clinicians have very low possibilities for therapeutic interventions. The causes of the regenerative block in the adult CNS are only partially attributable to the neural component. Direct or indirect interactions with glial cells, the resident CNS immune cells, and with the extracellular matrix play a crucial role in determining the relative inability of adult CNS connections to be modified: adult neurites find themselves within an environment rich in molecules strongly inhibitory for regrowth and sprouting. A further complication arises from the fact that regenerative processes are always accompanied by an inflammatory reaction with the consequent activation of astrocytes and microglia; this activation alters the properties of the extracellular milieu. Thus, research on post lesional plasticity must not only study the molecular mechanisms active in neurons but also consider the role of glial cells and the extracellular environment.
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Immune Disturbances in Chronic Pain: Cause, Consequence or Both?
Maletic V and Raison CL
[FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0030]

This review discusses the role of aberrant neuroimmune functioning in chronic pain disorders. Like other negatively-valenced emotions, pain activates a complex adaptive response that includes endocrine, autonomic and immune components. When appropriate, this response re-establishes homeostasis. However, in the context of chronic pain dysregulated immune, autonomic and endocrine responses contribute to peripheral and central sensitization, a phenomena emblematic of chronic pain. Excessive neuroimmune interactions in the vicinity of nociceptors and in dorsal root ganglia augment peripheral pain-related transmission. These amplified peripheral signals are associated with increased immune/inflammatory signaling in the dorsal horn and supraspinal pain-processing circuitry, the so-called “pain maitrix”. We focus on the neuron-glia-immune cell junction as the principal processing unit of pain signals in the CNS. Neuroimmune disturbances not only have functional consequences, such as amplified pain signaling, but also contribute to structural alterations in pain-processing brain areas. Lastly, aberrant immune activation also participates in dysfunctional descending pain regulation. The role of the immune system as a meta-homeostatic entity that coordinates interactions of emotion- and stress-modulating brain circuitry with endocrine and autonomic systems is discussed in some detail. We emphasize the importance of neuroimmune mechanisms not only in the genesis but also in treatment of chronic pain.
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Rituximab Therapy and Autoimmune Disease
Asha Ram Yadav and Nirmala Deo
[FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0031]

In recent years, advances in our understanding of the regulation of the immune system have enabled the identification of cellular and molecular targets that could affect the pathogenesis of many autoimmune diseases. B-cells play pivotal role in autoantigen presentation and in autoantibody production. Thus, rituximab (RTX), a chimeric monoclonal antibody specific for human CD20, which targets B lymphocytes, could be a potential new biological treatment for autoimmune diseases. The aim of this mini review is to discuss the potential use of RTX in the management of autoimmune disorders.  Results from early phase clinical trials indicates that RTX therapy may provide clinical benefit in systemic lupus erythematosus , Sjogren’ syndrome, thrombocytopenic purpura, hemolytic anemia, rheumatoid arthritis and myasthenia gravis. So, it is concluded that RTX therapy alone/ or in combinations with corticosteroids, is likely to provide an important new treatment option for a number of difficult to treat autoimmune diseases.
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Autoimmune diseases and Atherosclerosis: the Inflammatory Connection
Meenakshi Varma, Lakshmi A Mundkur and V.V. Kakkar
[FULL-TEXT INQUIRY] [BSP/CIR/E-Pub/0032]

Atherosclerosis is a chronic inflammatory disease that contributes to majority of cardiovascular morbidity and mortality in the world. Immune system is involved in atherogenesis and disease pathogenesis. Several studies have suggested a pivotal role for immune response to autoantigens, particularly oxidized lipoproteins and heat shock proteins, in the development of the disease. Several autoimmune disorders such as inflammatory bowel disease (IBD), rheumatoid arthritis, psoriasis, diabetes type1, multiple sclerosis, chronic obstructive pulmonary disease (COPD) and systemic lupus erythematosus (SLE) have an increased association with atherosclerosis leading to higher cardiovascular mortality rates. Inflammation is a crucial link in the development of atherosclerosis and autoimmune disorders. Immune dysregulation in autoimmune diseases could contribute to the increased risk of atherosclerosis in these patients. Thus, immune modulation and anti-inflammatory treatments may help control the development of atherosclerosis in autoimmune disorders.
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