A strategy for cell-based multiplex diagnostics of Myasthenia gravis and autoimmune encephalitis by modifying the subcellular localization of cell membrane autoantigens

2014 ◽  
Vol 58 (1) ◽  
pp. 211-228 ◽  
Author(s):  
S. George ◽  
M. Georgi ◽  
D. Roggenbuck ◽  
K. Conrad ◽  
J.-H. Küpper
1978 ◽  
Vol 176 (1) ◽  
pp. 175-178 ◽  
Author(s):  
D B Iverson ◽  
P Wang-Iverson ◽  
J K Spitznagel ◽  
L R DeChatelet

NADH and NADPH oxidase activities in a homogenate of human neutrophils co-sediment in a linear sucrose density gradient under either velocity or isopycnic conditions of centrifugation. The position of these activities in the gradient does not correspond to any known subcellular granule or to the cell-membrane fraction. These data suggest that the oxidase activities may reside in a unique granule that has previously not been recognized.


2019 ◽  
Author(s):  
Qingyang Luo ◽  
Xianghong Wu ◽  
Wen Huang

Abstract Background: Autoimmune encephalitis (AE) is a newly recognized autoimmune disorders in which the targets are proteins or receptors involved in synaptic transmission and neuronal excitability. α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) is a subtype of glutamate receptor that mediates most of the fast excitatory neurotransmission in the brain. Case presentation: A 50-year-old woman presented with subacute onset of memory loss and behavioral changes. High levels of serum (1:1000) and CSF (1:32) antibodies against the AMPAR GluR2 were detected. A wide range of abnormalities in 6-8 Hz low to middle slow waves was found by electroencephalographs, and high-intensity signals on fluid-attenuated inversion recovery in both the medial temporal lobe and hippocampus were identified on brain magnetic resonance images. This patient presented with myasthenia gravis and type B2 thymoma (World Health Organization Thymoma Classification) at age 48. This case was unique in that the patient initiated with the symptom of myasthenia gravis and thymoma two years prior to encephalitis, and a complete thymectomy was performed before AE onset without recurrence of the thymoma when encephalitis occurred. Conclusions: Thymoma was reported to be associated with paraneoplastic neurological disease. This is the first time a thymectomy has been applied in a myasthenia gravis patient with thymoma two years prior to the onset of anti-AMPAR2 encephalitis. This case highlights the complexity of autoimmune encephalitis associated with thymoma. Keywords: Autoimmune encephalitis, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, thymoma, myasthenia gravis.


2021 ◽  
Vol 11 ◽  
Author(s):  
Inga Koneczny ◽  
Vuslat Yilmaz ◽  
Konstantinos Lazaridis ◽  
John Tzartos ◽  
Tobias L. Lenz ◽  
...  

IgG4 autoimmune diseases (IgG4-AID) are an emerging group of autoimmune diseases that are caused by pathogenic autoantibodies of the IgG4 subclass. It has only recently been appreciated, that members of this group share relevant immunobiological and therapeutic aspects even though different antigens, tissues and organs are affected: glomerulonephritis (kidney), pemphigus vulgaris (skin), thrombotic thrombocytopenic purpura (hematologic system) muscle-specific kinase (MuSK) in myasthenia gravis (peripheral nervous system) and autoimmune encephalitis (central nervous system) to give some examples. In all these diseases, patients’ IgG4 subclass autoantibodies block protein-protein interactions instead of causing complement mediated tissue injury, patients respond favorably to rituximab and share a genetic predisposition: at least five HLA class II genes have been reported in individual studies to be associated with several different IgG4-AID. This suggests a role for the HLA class II region and specifically the DRβ1 chain for aberrant priming of autoreactive T-cells toward a chronic immune response skewed toward the production of IgG4 subclass autoantibodies. The aim of this review is to provide an update on findings arguing for a common pathogenic mechanism in IgG4-AID in general and to provide hypotheses about the role of distinct HLA haplotypes, T-cells and cytokines in IgG4-AID.


1991 ◽  
Vol 70 (12) ◽  
pp. 1508-1515 ◽  
Author(s):  
R.A. Cowman ◽  
S.S. Baron

Intact cells of Streptococcus sanguis ATCC 10556 possessed arylaminopeptidases exhibiting activity toward the nitroanilide (NA) derivatives of leucine, alanine, methionine, arginine, or lysine. Weak hydrolytic activity was observed in assays with the NA derivatives of valine, proline, glycine, or glutamic acid. Subcellular localization studies revealed that arylaminopeptidase activities were located in both the cell membrane and cytoplasm. Arylaminopeptidases exhibiting activity toward the leucine, alanine, or methionine NA substrates appeared to be more predominantly associated with the membrane, whereas enzymes exhibiting activity toward arginyl-NA or lysyl-NA were more prevalently located in the cytoplasm. Several results from this study suggest that the membrane-associated arginyl and lysyl arylaminopeptidases were located in such a way that their expression was restricted in the intact cell. The addition of 0.5 mol/L NaCl to protoplast preparations derived from mutanolysin-treated cells resulted in an almost complete solubilization of membrane-associated arylaminopeptidase activities. These observations support the conclusion that the association of arylaminopeptidases with the cell membrane may involve hydrophobic or electrostatic interactions, or both. S. sanguis ATCC 10556 also possessed at least one caseinolytic endopeptidase activity. This activity is most likely located near the membrane surface, as no association with the cell wall was evident. The location of membrane-associated endopeptidase and arylaminopeptidase activities, together with intracellular peptidases, is suggested to provide an efficient mechanism for the hydrolysis and subsequent utilization of polypeptide and oligopeptide substrates as sources of amino acids for growth by this microorganism.


2010 ◽  
Vol 191 (3) ◽  
pp. 523-535 ◽  
Author(s):  
Fang Yu ◽  
Lu Sun ◽  
Khaled Machaca

The egg’s competency to activate at fertilization and transition to embryogenesis is dependent on its ability to generate a fertilization-specific Ca2+ transient. To endow the egg with this capacity, Ca2+ signals remodel during oocyte maturation, including inactivation of the primary Ca2+ influx pathway store-operated Ca2+ entry (SOCE). SOCE inactivation is coupled to internalization of the SOCE channel, Orai1. In this study, we show that Orai1 internalizes during meiosis through a caveolin (Cav)- and dynamin-dependent endocytic pathway. Cav binds to Orai1, and we map a Cav consensus–binding site in the Orai1 N terminus, which is required for Orai1 internalization. Furthermore, at rest, Orai1 actively recycles between an endosomal compartment and the cell membrane through a Rho-dependent endocytic pathway. A significant percentage of total Orai1 is intracellular at steady state. Store depletion completely shifts endosomal Orai1 to the cell membrane. These results define vesicular trafficking mechanisms in the oocyte that control Orai1 subcellular localization at steady state, during meiosis, and after store depletion.


2003 ◽  
Vol 185 (4) ◽  
pp. 1391-1398 ◽  
Author(s):  
Christiaan van Ooij ◽  
Richard Losick

ABSTRACT SpoVM is an unusually small (26-residue-long) protein that is produced in the mother cell chamber of the sporangium during the process of sporulation in Bacillus subtilis. We investigated the subcellular localization of SpoVM, which is believed to be an amphipathic α-helix, by using a fusion of the sporulation protein to the green fluorescence protein (GFP). We found that SpoVM-GFP is recruited to the polar septum shortly after the sporangium undergoes asymmetric division and that the fusion protein localizes to the mother cell membrane that surrounds the forespore during the subsequent process of engulfment. We identified a patch of three residues near the N terminus of the proposed α-helix that is needed both for proper subcellular localization and for SpoVM function. We also identified a patch of residues on the opposite face of the helix and residues near both ends of the protein that are needed for SpoVM function but not for subcellular localization. Subcellular localization of SpoVM-GFP was found to require an unknown gene(s) under the control of the mother cell transcription factor σE. We propose that the N-terminal patch binds to an unknown anchoring protein that is produced under the control of σE and that other residues important in SpoVM function to recruit an unknown sporulation protein(s) to the mother cell membrane that surrounds the forespore. Our results provide evidence that SpoVM function depends on proper subcellular localization.


2019 ◽  
Author(s):  
Qingyang Luo ◽  
Xianghong Wu ◽  
wen huang

Abstract Background Autoimmune encephalitis (AE) is a newly recognized autoimmune disorders in which the targets are proteins or receptors involved in synaptic transmission and neuronal excitability. α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) is a subtype of glutamate receptor that mediates most of the fast excitatory neurotransmission in the brain. Case presentation A 50-year-old woman presented with subacute onset of memory loss and behavioral changes. High levels of serum (1:1000) and CSF (1:32) antibodies against the AMPAR GluR2 were detected. A wide range of abnormalities in 6-8 Hz low to middle slow waves was found by electroencephalographs, and high-intensity signals on fluid-attenuated inversion recovery in both the medial temporal lobe and hippocampus were identified on brain magnetic resonance images. This patient presented with myasthenia gravis and type B2 thymoma (World Health Organization Thymoma Classification) at age 48. This case was unique in that the patient initiated with the symptom of myasthenia gravis and thymoma two years prior to encephalitis, and a complete thymectomy was performed before AE onset without recurrence of the thymoma when encephalitis occurred. Conclusions Thymoma was reported to be associated with paraneoplastic neurological disease. This is the first time a thymectomy has been applied in a myasthenia gravis patient with thymoma two years prior to the onset of anti-AMPAR2 encephalitis. This case highlights the complexity of autoimmune encephalitis associated with thymoma.


Author(s):  
M. Ashraf ◽  
L. Landa ◽  
L. Nimmo ◽  
C. M. Bloor

Following coronary artery occlusion, the myocardial cells lose intracellular enzymes that appear in the serum 3 hrs later. By this time the cells in the ischemic zone have already undergone irreversible changes, and the cell membrane permeability is variably altered in the ischemic cells. At certain stages or intervals the cell membrane changes, allowing release of cytoplasmic enzymes. To correlate the changes in cell membrane permeability with the enzyme release, we used colloidal lanthanum (La+++) as a histological permeability marker in the isolated perfused hearts. The hearts removed from sprague-Dawley rats were perfused with standard Krebs-Henseleit medium gassed with 95% O2 + 5% CO2. The hypoxic medium contained mannitol instead of dextrose and was bubbled with 95% N2 + 5% CO2. The final osmolarity of the medium was 295 M osmol, pH 7. 4.


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