Our results support the notion that ion channel autoimmunity might at least partially contribute to HaNDL pathogenesis and occurrence of neurological symptoms.

Background/Aims: To better characterize progressive encephalomyelitis with rigidity and myoclonus (PERM) syndrome and identify novel PERM phenotypes. Methods: The clinical features and antibody status of PERM patients were investigated using immunoblots, cell-based assays, RIA, protein macroarray and ELISA. Results: Two patients with supratentorial involvement showed abnormal PET or EEG findings. One patient was discovered to have renal cell carcinoma, and protein macroarray revealed Ma3-antibodies. Another patient with leucine-rich, glioma-inactivated 1 (LGI1) and glutamic acid decarboxylase (GAD) antibodies showed a good response to immunotherapy. Conclusion: The heterogeneity of the immunological features suggests that PERM is caused by diverse pathogenic mechanisms. Seropositivity to well-characterized neuronal cell surface antigens might indicate a good treatment response.

No disease-specific neuronal antibodies have so far been defined in neuro-Behçet's disease (NBD). Immunohistochemistry and immunocytochemistry studies showed antibodies to hippocampal and cerebellar molecular layers and the surface antigens of cultured hippocampal neurons in sera and/or cerebrospinal fluids (CSF) of 13 of 20 NBD and 6 of 20 BD patients but not in multiple sclerosis or headache controls. Screening with a protein macroarray led to identification of stress-induced-phosphoprotein-1 (STIP-1) as an antigenic target. High-titer STIP-1-antibodies were detected in 6 NBD patients' sera but not in controls. These results suggest that neuronal antibodies could be useful as diagnostic biomarkers in NBD.

Intracellular signaling mechanisms in red blood cells (RBCs) involve various protein kinases and phosphatases and enable rapid adaptive responses to hypoxia, metabolic requirements, oxidative stress, or shear stress by regulating the physiological properties of the cell. Protein phosphorylation is a ubiquitous mechanism for intracellular signal transduction, volume regulation, and cytoskeletal organization in RBCs. Spectrin‐based cytoskeleton connects integral membrane proteins, band 3 and glycophorin C to junctional proteins, ankyrin and Protein 4.1. Phosphorylation leads to a conformational change in the protein structure, weakening the interactions between proteins in the cytoskeletal network that confers a more flexible nature for the RBC membrane. The structural organization of the membrane and the cytoskeleton determines RBC deformability that allows cells to change their ability to deform under shear stress to pass through narrow capillaries. The shear stress sensing mechanisms and oxygenation‐deoxygenation transitions regulate cell volume and mechanical properties of the membrane through the activation of ion transporters and specific phosphorylation events mediated by signal transduction. In this review, we summarize the roles of Protein kinase C, cAMP‐Protein kinase A, cGMP‐nitric oxide, RhoGTPase, and MAP/ERK pathways in the modulation of RBC deformability in both healthy and disease states. We emphasize that targeting signaling elements may be a therapeutic strategy for the treatment of hemoglobinopathies or channelopathies. We expect the present review will provide additional insights into RBC responses to shear stress and hypoxia via signaling mechanisms and shed light on the current and novel treatment options for pathophysiological conditions.

In this study, we investigated the effects of peritoneal dialysis on hemorheological and hematological parameters and their relations with oxidant and antioxidant status of uremic patients. Hemorheological parameters (erythrocyte deformability, erythrocyte aggregation, osmotic deformability, blood and plasma viscosity) were measured in patients with renal insufficiency undergoing peritoneal dialysis (PD) and volunteers. Erythrocyte deformability, osmotic deformability and aggregation in both autologous plasma and 3% dextran 70 were measured by laser diffraction ektacytometry. Enzyme activities of glutathione peroxidase, superoxide dismutase and catalase were studied in erythrocytes; lipid peroxidation was studied by measuring the amount of malondialdehyde in both erythrocytes and plasma samples. Blood viscosity at native hematocrit was significantly lower in PD patients at all measured shear rates compared to controls, but it was high in PD patients at corrected (45%) hematocrit. Erythrocyte deformability did not show any difference between the two groups. Osmotic deformability was significantly lower in PD patients compared to controls. Aggregation index values were significantly high in PD patients in plasma Catalase and glutathione peroxidase activities in erythrocytes were decreased in PD patients whereas superoxide dismutase activity was increased compared to controls. Malondialdehyde was significantly increased in erythrocytes and plasma samples of PD patients which also shows correlations with aggregation parameters. It has been concluded that erythrocytes in PD patients are more prone to aggregation and this tendency could be influenced by lipid peroxidation activity in patient’s plasma. These results imply that uremic conditions, loss of plasma proteins and an increased risk of oxidative stress because of decreasing levels of antioxidant enzymes affect erythrocyte rheology during peritoneal dialysis. This level of distortion may have crucial effects, impairing the blood flow dynamics and causing inadequate microcirculatory perfusion.

Detection of SWAP70 antibodies during the attack period might suggest that SWAP70 is involved in MS relapse pathogenesis. Whether serum SWAP70 antibody detection may be utilized as an MS relapse predictor should be tested in prospective studies.

BACKGROUND: Erythrocytes undergo irreversible morphological and biochemical changes during storage. Reduced levels of deformability have been reported for stored erythrocytes. Erythrocyte deformability is essential for healthy microcirculation.OBJECTIVE: The aim of this study is to evaluate shear stress (SS) induced improvements of erythrocyte deformability in stored blood.METHODS: Deformability changes were evaluated by applying physiological levels of SS (5 and 10 Pa) in metabolically depleted blood for 48 hours and stored blood for 35 days with citrate phosphate dextrose adenine-1 (CPDA-1). Laser diffractometry was used to measure erythrocyte deformability before and after application of SS.RESULTS: Erythrocyte deformability, as a response to continuous SS, was significantly improved in metabolically depleted blood, whereas it was significantly impaired in the blood stored for 35 days with CPDA-1 (p≤0.05). The SS-induced improvements of deformability were deteriorated due to storage and relatively impaired according to the storage time. However, deformability of stored blood after exposure to mechanical stress tends to increase at low levels of shear while decreasing at high SS levels.CONCLUSION: Impairment of erythrocyte deformability after storage may contribute to impairments in the recipient’s microcirculation after blood transfusion. The period of the storage should be considered to prevent microcirculatory problems and insufficient oxygen delivery to the tissues.

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