Autoantibodies from patients with complex regional pain syndrome induce pro-inflammatory effects and functional disturbances on endothelial cells in vitro.

Complex regional pain syndrome (CRPS) is an inadequate local response after a limb trauma, which leads to severe pain and autonomic and trophic changes of the affected limb. Autoantibodies directed against human β2 adrenergic and muscarinic M2 receptors (hβ2AR and hM2R) have been described in CRPS patients previously. We analyzed sera from CRPS patients for autoantibodies against hβ2AR, hM2R, and endothelial cells and investigated the functional effects of purified IgG, derived from 13 patients with CRPS, on endothelial cells.

Pathogenesis, diagnosis and treatment of paraneoplastic neurologic syndromes.

: Paraneoplastic neurological syndromes (PNS) are a rare heterogeneous group of neurological diseases associated with tumors. These syndromes are the result of a cross-reactive immune response against antigens shared by the tumor and the nervous system. The discovery of an increasing number of autoantigens and the identification of tumoral factors leading to a substantial antitumoral immune response makes this topic highly innovative.

NK Cell-mediated Neuroblastoma Cell Lysis is Enhanced by IgG From Patients With Pediatric Opsoclonus-Myoclonus Syndrome.

Pediatric opsoclonus-myoclonussyndrome (OMS) is a rare autoimmune disorder of which 50% are associated with neuroblastoma (NB). We investigated whether surface-binding autoantibodies in OMS can enhance natural killer (NK) cell-mediated cytotoxicity in these patients. OMS immunoglobulin G (IgG) bound to NB cell lines and NK cell-mediated cytotoxicity to NB cells was enhanced after preincubation with OMS-IgG, but not IgG from NB without OMS or healthy controls.

BAFF serum and CSF levels in patients with multiple sclerosis and infectious nervous system diseases.

Purpose: Multiple sclerosis (MS) is the most common immune-mediated CNS disease, characterised by demyelination and progressive neurological disability. The B-cell activating factor BAFF has been described as one important factor in the pathophysiology of different autoimmune diseases.

Methods: We measured BAFF levels in the serum and cerebrospinal fluid (CSF) in 50 consecutive patients with MS and 35 patients with infectious CNS disease (ID).

No evidence for humoral autoimmunity against cardiomyocytes, adrenergic or muscarinic receptors in patients with Tako-Tsubo cardiomyopathy.

Background: An association between Tako-Tsubo cardiomyopathy (TTC) and underlying malignancies has been observed, suggesting that TTC might be the consequence of paraneoplastic phenomena. This study investigates the presence of autoantibodies against cardiomyocytes as well as adrenergic (β, β) and muscarinic (M2) receptors in patients with TTC.

Methods And Results: Serum from 20 TTC patients and 20 controls with ischemic heart disease was obtained.

Acetylcholine Receptor Antibody Titers and Clinical Course after Influenza Vaccination in Patients with Myasthenia Gravis: A Double-Blind Randomized Controlled Trial (ProPATIent-Trial).

Background: It is a continuous matter of discussion whether immune activation by vaccination in general and Influenza vaccination in particular increases the risk for clinical deterioration of autoimmune diseases. This prospective study investigated the serological and clinical course of autoimmune Myasthenia gravis (MG) after a seasonal influenza vaccination.

Methods: This randomized, placebo-controlled, double-blind study enrolled MG patients with antibodies against acetylcholine-receptors (AChR-ab).

Cancer and Autoimmunity: Paraneoplastic Neurological Disorders Associated With Neuroblastic Tumors.

Cancer and autoimmunity come together in paraneoplastic syndromes (PNS), which reflect the remote, not direct, effects of cancer. In the pediatric population, a variety of PNS have been described, but the most common of these rare disorders are instigated by neuroblastic tumors, such as neuroblastoma, ganglioneuroblastoma, and ganglioneuroma. The main pediatric-onset neurological PNS are ROHHAD syndrome, anti-ANNA1 (anti-Hu), and opsoclonus-myoclonus syndrome.

Childhood opsoclonus-myoclonus syndrome: diagnosis and treatment.

Opsoclonus-myoclonus syndrome (OMS) is a rare and primarily immune-mediated disease in children and adults. The main symptoms include opsoclonus, myoclonus and ataxia. In children, the symptoms also include irritability, and, over a long-term course, learning and behavioural disturbances.

Autoantibody-mediated cytotoxicity in paediatric opsoclonus-myoclonus syndrome is dependent on ERK-1/2 phophorylation.

Paediatric opsoclonus-myoclonus syndrome (OMS) is in 50% of the cases associated with a neuroblastoma as a paraneoplastic syndrome and is associated with surface-binding antibodies against cerebellar granular neurons (CGN). To evaluate possible pathogenic effects of these autoantibodies on CGN we examined their influence on the MAPKinase enzymes ERK-1/2 and p38 using flow cytometry and phospho-specific antibodies. OMS IgG but not IgG from neuroblastoma without OMS or healthy controls induced phosphorylation of ERK-1/2 in cerebellar granular neurons (p<0.

Aquaporin-4 autoantibodies increase vasogenic edema formation and infarct size in a rat stroke model.

Background: Neuromyelitis optica (NMO) is an autoimmune disorder of the central nervous system, which is characterized by autoantibodies directed against the water channel aquaporin-4 (AQP4). As one of the main water regulators in the central nervous system, APQ4 is supposed to be involved in the dynamics of brain edema. Cerebral edema seriously affects clinical outcome after ischemic stroke; we therefore aimed to investigate whether NMO-antibodies may exert the same functional effects as an AQP4-inhibitor in-vivo in acute ischemic stroke.

Diagnosis and therapeutic options for peripheral vasculitic neuropathy.

Vasculitis can affect the peripheral nervous system alone (nonsystemic vasculitic neuropathy) or can be a part of primary or secondary systemic vasculitis. In cases of pre-existing systemic vasculitis, the diagnosis can easily be made, whereas suspected vasculitic neuropathy as initial or only manifestation of vasculitis requires careful clinical, neurophysiological, laboratory and histopathological workout. The typical clinical syndrome is mononeuropathia multiplex or asymmetric neuropathy, but distal-symmetric neuropathy can frequently be seen.

Longstanding complex regional pain syndrome is associated with activating autoantibodies against alpha-1a adrenoceptors.

Complex regional pain syndrome (CRPS) is a limb-confined posttraumatic pain syndrome with sympathetic features. The cause is unknown, but the results of a randomized crossover trial on low-dose intravenous immunoglobulins (IVIG) treatment point to a possible autoimmune mechanism. We tested purified serum immunoglobulin G (IgG) from patients with longstanding CRPS for evidence of antibodies interacting with autonomic receptors on adult primary cardiomyocytes, comparing with control IgG from healthy and diseased controls, and related the results to the clinical response to treatment with low-dose IVIG.

Neuronal surface and glutamic acid decarboxylase autoantibodies in Nonparaneoplastic stiff person syndrome.

Importance: High titers of autoantibodies to glutamic acid decarboxylase (GAD) are well documented in association with stiff person syndrome (SPS). Glutamic acid decarboxylase is the rate-limiting enzyme in the synthesis of γ-aminobutyric acid (GABA), and impaired function of GABAergic neurons has been implicated in the pathogenesis of SPS. Autoantibodies to GAD might be the causative agent or a disease marker.

Role of BAFF in Opsoclonus-Myoclonus syndrome, a bridge between cancer and autoimmunity.

OMS is a rare paraneoplastic disorder that affects adults and children. Pediatric OMS is often associated with NB, a common, solid tumor of childhood, derived from the sympathetic nervous system. The detection of autoantibodies and lymphocytic infiltration in NB patients led to advance an autoimmune hypothesis for the pathogenesis of OMS-related NB.

Paraneoplastic brain stem encephalitis.

Paraneoplastic brain stem encephalitis can occur as an isolated clinical syndrome or, more often, may be part of a more widespread encephalitis. Different antineuronal autoantibodies, such as anti-Hu, anti-Ri, and anti-Ma2 can be associated with the syndrome, and the most frequent tumors are lung and testicular cancer. Anti-Hu-associated brain stem encephalitis does not normally respond to immunotherapy; the syndrome may stabilize under tumor treatment.

Intravenous immunoglobulin inhibits BAFF production in chronic inflammatory demyelinating polyneuropathy - a new mechanism of action?

Chronic-inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated disease treated with intravenous immunoglobulin (IVIg). The underlying mechanism of action remains incompletely understood. The B-cell activating factor BAFF contributes to B-cell homeostasis and (auto-)antibody production.

Complex regional pain syndrome, prototype of a novel kind of autoimmune disease.

Complex regional pain syndrome (CRPS) is a painful condition, which arises in a limb after trauma. CRPS can profoundly affect patients' quality of life, and there is no cure. CRPS is associated with limb-confined sensory, motor, skin, bone and autonomic abnormalities.

Paraneoplastic neurological syndromes--diagnosis and management.

Paraneoplastic neurological syndromes (PNS) are rare nervous system dysfunctions in cancer patients, which are not due to a local effect of the tumour or its metastases. PNS in adults are mainly associated with lung cancer, especially small cell lung cancer, lymphoma and gynaecological tumours. In some cases an overlapping of different clinical syndromes can be observed.

Biomarkers of inflammation and endothelial dysfunction in stroke with and without sleep apnea.

Objective: Although sleep apnea (SA) is a risk factor for ischemic stroke and an important prognostic factor in affected patients, the exact pathophysiological link between SA and stroke is unknown. We investigated whether the plasma concentration of biomarkers of inflammation and endothelial dysfunction, including soluble tumor necrosis factor receptor-1 and -2 (sTNF-R1 and sTNF-R2), tumor necrosis factor-β (TNF-β), soluble intercellular cell adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) are increased in patients with acute stroke and SA compared with stroke patients without SA.

Design/methods: In total, 76 patients with ischemic stroke admitted to the stroke unit were included in this study.

Autoimmunity against the β2 adrenergic receptor and muscarinic-2 receptor in complex regional pain syndrome.

Complex regional pain syndrome (CRPS) is a painful condition affecting one or more extremities of the body, marked by a wide variety of symptoms and signs that are often difficult to manage because the pathophysiology is incompletely understood. Thus, diverse treatments might be ineffective. A recent report revealed the presence of autoantibodies against differentiated autonomic neurons in CRPS patients.

Paraneoplastic neurological disorders.

The article provides an overview on the diagnosis and pathogenesis of paraneoplastic neurological disorders (PNDs), and subsequently the current therapeutic strategies in these patients. PNDs are nervous system dysfunctions in cancer patients, which are not due to a local effect of the tumor or its metastases. Most of these clinically defined syndromes in adults are associated with lung cancer, especially small-cell lung cancer, lymphoma and gynecological tumors.

Evaluation of methods to predict early long-term neurobehavioral outcome after coronary artery bypass grafting.

Postoperative cognitive decrease (POCD) represents the most frequent complication in modern cardiac surgery. The application of easily assessable surrogate parameters that predict long-term POCD at early time points is tempting. The aim of the present study was to analyze the predictive value of cerebral biomarkers, diffusion-weighted magnetic resonance imaging (DWI), and cognitive bedside testing after coronary artery bypass grafting (CABG).