scholarly journals Enhanced autoantigen expression in regenerating muscle cells in idiopathic inflammatory myopathy

2005 ◽  
Vol 201 (4) ◽  
pp. 591-601 ◽  
Author(s):  
Livia Casciola-Rosen ◽  
Kanneboyina Nagaraju ◽  
Paul Plotz ◽  
Kondi Wang ◽  
Stuart Levine ◽  
...  
Keyword(s):  
Inflammatory Myopathy ◽  
Idiopathic Inflammatory Myopathy ◽  
Antigen Expression ◽  
Muscle Cells ◽  
Autoimmune Response ◽  
Normal Tissues ◽  
Diagnosis And Prognosis ◽  
Autoimmune Myositis ◽  
Low Levels

Unique autoantibody specificities are strongly associated with distinct clinical phenotypes, making autoantibodies useful for diagnosis and prognosis. To investigate the mechanisms underlying this striking association, we examined autoantigen expression in normal muscle and in muscle from patients with autoimmune myositis. Although myositis autoantigens are expressed at very low levels in control muscle, they are found at high levels in myositis muscle. Furthermore, increased autoantigen expression correlates with differentiation state, such that myositis autoantigen expression is increased in cells that have features of regenerating muscle cells. Consistent with this, we found that cultured myoblasts express high levels of autoantigens, which are strikingly down-regulated as cells differentiate into myotubes in vitro. These data strongly implicate regenerating muscle cells rather than mature myotubes as the source of ongoing antigen supply in autoimmune myositis. Myositis autoantigen expression is also markedly increased in several cancers known to be associated with autoimmune myositis, but not in their related normal tissues, demonstrating that tumor cells and undifferentiated myoblasts are antigenically similar. We propose that in cancer-associated myositis, an autoimmune response directed against cancer cross-reacts with regenerating muscle cells, enabling a feed-forward loop of tissue damage and antigen selection. Regulating pathways of antigen expression may provide unrecognized therapeutic opportunities in autoimmune diseases.

The RAV12 Monoclonal Antibody Recognizes the N-Linked Glycotope RAAG12: Expression in Human Normal and Tumor Tissues

2009 ◽  
Vol 133 (9) ◽  
pp. 1403-1412
Author(s):  
Suzanne K. Coberly ◽  
Francine Z. Chen ◽  
Mark P. Armanini ◽  
Yan Chen ◽  
Peter F. Young ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Antigen Expression ◽  
Subcellular Location ◽  
Carbohydrate Antigen ◽  
Cytoplasmic Staining ◽  
Safety Issues ◽  
Normal Tissues ◽  
Tumor Tissues ◽  
Associated Proteins

Abstract Context.—RAAG12 is a primate-restricted N-linked carbohydrate antigen present on multiple membrane-associated proteins. RAAG12 is recognized by the RAV12 monoclonal antibody. RAV12 binds to RAAG12-expressing gastrointestinal adenocarcinomas, modifies growth factor-mediated signaling, induces oncotic cell death in vitro, and has antitumor activity toward gastrointestinal tumor xenografts. Objective.—To determine the expression pattern of RAAG12 in normal and tumor tissue to identify indications for clinical study and potential safety issues. Design.—Immunohistochemistry of 36 normal human tissues and a broad range of tumor tissues to profile RAAG12 expression. Results.—More than 90% of colon, gastric, and pancreatic adenocarcinomas expressed RAAG12, and expression was uniform in most samples. Expression of RAAG12 at lower frequency and/or uniformity was observed in other cancers, including esophageal, ovarian, liver, breast, and prostate carcinomas and adenocarcinomas. Similar RAAG12 expression was observed between primary and metastatic colon adenocarcinomas. No staining was seen on cardiovascular, endocrine, neuromuscular, hematopoietic, or nervous system tissue from non–tumor-bearing individuals. RAAG12 was expressed on mucosal and glandular/ductal epithelium. The gastrointestinal tract mucosa and pancreatic/biliary ducts displayed the most uniform reactivity. RAAG12 exhibited differential subcellular localization in these normal, compared with tumor, tissues. Normal polarized epithelia primarily displayed apical membrane and cytoplasmic staining, whereas tumors exhibited whole membrane staining that increased with decreasing differentiation. Conclusions.—High expression of RAAG12 on tumors of gastrointestinal origin suggests these cancers are appropriate targets for RAV12 therapy. Differential subcellular location of RAAG12 on normal epithelia may limit accessibility of RAV12 to the subset of normal tissues that exhibit antigen expression.

scholarly journals Altered dynamics of lipid metabolism in muscle cells from patients with idiopathic inflammatory myopathy is ameliorated by 6 months of training

2020 ◽  
Vol 599 (1) ◽  
pp. 207-229
Author(s):  
M. Nemec ◽  
L. Vernerová ◽  
N. Laiferová ◽  
M. Balážová ◽  
M. Vokurková ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Inflammatory Myopathy ◽  
Idiopathic Inflammatory Myopathy ◽  
Muscle Cells

scholarly journals Phenotypic Clusters and Survival Analyses in Interstitial Pneumonia with Myositis-Specific Autoantibodies

2020 ◽  
Author(s):  
Yihua Li ◽  
Shiwen Yu ◽  
Yali Fan ◽  
Na Wu ◽  
Yiran Wang ◽  
...  
Keyword(s):  
Cluster Analysis ◽  
Interstitial Pneumonia ◽  
Respiratory Symptoms ◽  
Inflammatory Myopathy ◽  
Usual Interstitial Pneumonia ◽  
Idiopathic Inflammatory Myopathy ◽  
Acute Onset ◽  
Pulmonary Complications ◽  
Diagnosis And Prognosis ◽  
Potential Risk Factors

Abstract Background: Interstitial pneumonia (IP) is one of the common pulmonary complications of idiopathic inflammatory myopathy (IIM), among which myositis-specific autoantibodies (MSA) are specific for IIM diagnosis and prognosis. However, IP patients with MSA (MSA-IP) have not been well described. The study aimed to explore the phenotypic clusters and prognosis of MSA-IP patients.Methods: A total of 124 MSA-IP patients were prospectively enrolled for analysis. Serum MSA were detected using immunoprecipitation. Radiographic patterns of IP were determined according to the classification of idiopathic IPs. The clusters of MSA-IP patients were identified using cluster analysis. Potential risk factors of acute onset and short-term prognosis were also analyzed. Results: There were four clusters of MSA-IP patients. Cluster 1 patients were elders with chronic onset and usual interstitial pneumonia pattern on CT scan. Cluster 2 patients were all positive for anti-aminoacyl-tRNA antibodies, predominantly females and had frequent respiratory symptoms. Patients of cluster 3 showed multi-system involvements with nonspecific interstitial pneumonia pattern. Patients of cluster 4 had severe respiratory symptoms with anti-MDA5. The patients of cluster 3 (OR 6.682, 95% CI 1.560–28.622, P=0.011) or cluster 4 (OR 6.057, 95% CI 1.715–21.388, P=0.005) were susceptible to acute onset. The patients of cluster 4 were prone to disease progression (HR 2.711, 95% CI 1.128–6.519, P=0.034), which was consistent with the Kaplan–Meier curves.Conclusions: Four distinctive clusters were determined by cluster analysis suggesting the characteristics, serological antibodies and prognosis of MSA-IP.

Autoantibodies to Mi-2 alpha and Mi-2 beta in patients with idiopathic inflammatory myopathy

Rheumatology ◽  
2019 ◽  
Vol 58 (9) ◽  
pp. 1655-1661 ◽  
Author(s):  
Michaelin Richards ◽  
Ignacio García-De La Torre ◽  
Yelitza C. González-Bello ◽  
Mónica Vázquez-Del Mercado ◽  
Lilia Andrade-Ortega ◽  
...  
Keyword(s):  
Inflammatory Myopathy ◽  
Area Under The Curve ◽  
Idiopathic Inflammatory Myopathy ◽  
Control Group ◽  
Operating Characteristics ◽  
High Area ◽  
Characteristics Analysis ◽  
Group 3 ◽  
Low Levels ◽  
Good Agreement

Abstract Objectives The objective of this study was to compare the results obtained from different assays for the detection of anti-Mi-2 antibodies, which are important markers in the diagnosis of DM. Methods The study included 82 patients (68 females/14 males), most of whom had DM (n = 57), followed by PM (n = 16) and juvenile DM (n = 9). All samples were tested using a novel particle-based multi-analyte technology (PMAT) (Inova Diagnostics, research use only) in parallel with a line immunoassay (LIA: Euroimmun). To assess clinical specificity for the PMAT assay, a total of 775 disease and healthy controls were tested. Results 29 samples were positive by at least one test for anti-Mi-2 antibodies. Of those, 24 were Mi-2β LIA+, five were Mi-2α LIA+ and 23 Mi-2 PMAT+. The comparison shows varying agreement between the different methods (kappa 0.27–0.77). When LIA results were used as reference for receiver operating characteristics analysis, high area under the curve values were found for both PMAT vs LIA Mi-2α and LIA Mi-2β. When analysing the results in the context of the myositis phenotype, PMAT associated closest with the DM phenotype. In the control group, 3/775 controls (all low levels) were anti-Mi-2+ resulting in a sensitivity and specificity of 28.1% and 99.6%, respectively. Conclusion Overall, good agreement was found between LIA and PMAT for anti-Mi-2 antibodies, which is important for the standardization of autoantibodies. Anti-Mi-2β antibodies measured by PMAT tend be more highly associated with the clinical phenotype of DM.

Enhanced Increases in Cytosolic Ca2+ in ADP-Stimulated Platelets from Patients with Delta-Storage Pool Deficiency – A Possible Indicator of Interactions between Granule-Bound ADP and the Membrane ADP Receptor

1997 ◽  
Vol 77 (02) ◽  
pp. 376-382 ◽  
Author(s):  
Bruce Lages ◽  
Harvey J Weiss
Keyword(s):  
Platelet Rich Plasma ◽  
Limited Range ◽  
Dense Granule ◽  
Receptor Desensitization ◽  
Fura 2 ◽  
Storage Pool ◽  
Low Levels ◽  
The Right

SummaryThe possible involvement of secreted platelet substances in agonist- induced [Ca2+]i increases was investigated by comparing these increases in aspirin-treated, fura-2-loaded normal platelets and platelets from patients with storage pool deficiencies (SPD). In the presence and absence of extracellular calcium, the [Ca2+]i response induced by 10 µM ADP, but not those induced by 0.1 unit/ml thrombin, 3.3 µM U46619, or 20 µM serotonin, was significantly greater in SPD platelets than in normal platelets, and was increased to the greatest extent in SPD patients with Hermansky-Pudlak syndrome (HPS), in whom the dense granule deficiencies are the most severe. Pre-incubation of SPD-HPS and normal platelets with 0.005-5 µM ADP produced a dose-dependent inhibition of the [Ca2+]i response induced by 10 µ M ADP, but did not alter the [Ca2+]i increases induced by thrombin or U46619. Within a limited range of ADP concentrations, the dose-inhibition curve of the [Ca2+]i response to 10 µM ADP was significantly shifted to the right in SPD-HPS platelets, indicating that pre-incubation with greater amounts of ADP were required to achieve the same extent of inhibition as in normal platelets. These results are consistent with a hypothesis that the smaller ADP-induced [Ca2+]i increases seen in normal platelets may result from prior interactions of dense granule ADP, released via leakage or low levels of activation, with membrane ADP receptors, causing receptor desensitization. Addition of apyrase to platelet-rich plasma prior to fura-2 loading increased the ADP-induced [Ca2+]i response in both normal and SPD-HPS platelets, suggesting that some release of ADP derived from both dense granule and non-granular sources occurs during in vitro fura-2 loading and platelet washing procedures. However, this [Ca2+]i response was also greater in SPD-HPS platelets when blood was collected with minimal manipulation directly into anticoagulant containing apyrase, raising the possibility that release of dense granule ADP resulting in receptor desensitization may also occur in vivo. Thus, in addition to enhancing platelet activation, dense granule ADP could also act to limit the ADP-mediated reactivity of platelets exposed in vivo to low levels of stimulation.

Immuno-compatibility of desaminotyrosine and desaminotyrosyl tyrosine functionalized star-shaped oligo(ethylene glycol)s with different molecular weights

2015 ◽  
Vol 1718 ◽  
pp. 97-102 ◽  
Author(s):  
Toralf Roch ◽  
Konstanze K. Julich-Gruner ◽  
Axel T. Neffe ◽  
Nan Ma ◽  
Andreas Lendlein
Keyword(s):  
Aqueous Solution ◽  
Ethylene Glycol ◽  
Average Molecular Weight ◽  
Molecular Weights ◽  
Immunological Effects ◽  
Microbial Products ◽  
Low Levels ◽  
Chain Lengths ◽  
Immunological Evaluation

ABSTRACTPolymer-based therapeutic strategies require biomaterials with properties and functions tailored to the demands of specific applications leading to an increasing number of newly designed polymers. For the evaluation of those new materials, comprehensive biocompatibility studies including cyto-, tissue-, and immunocompatibility are essential. Recently, it could be demonstrated that star-shaped amino oligo(ethylene glycol)s (sOEG) with a number average molecular weight of 5 kDa and functionalized with the phenol-derived moieties desaminotyrosine (DAT) or desaminotyrosyl tyrosine (DATT) behave in aqueous solution like surfactants without inducing a substantial cytotoxicity, which may qualify them as solubilizer for hydrophobic drugs in aqueous solution. However, for biomedical applications the polymer solutions need to be free of immunogenic contaminations, which could result from inadequate laboratory environment or contaminated starting material. Furthermore, the materials should not induce uncontrolled or undesired immunological effects arising from material intrinsic properties. Therefore, a comprehensive immunological evaluation as perquisite for application of each biomaterial batch is required. This study investigated the immunological properties of sOEG-DAT(T) solutions, which were prepared using sOEG with number average molecular weights of 5 kDa, 10 kDa, and 20 kDa allowing analyzing the influence of the sOEG chain lengths on innate immune mechanisms. A macrophage-based assay was used to first demonstrate that all DAT(T)-sOEG solutions are free of endotoxins and other microbial contaminations such as fungal products. In the next step, the capacity of the different DAT(T)-functionalized sOEG solutions to induce cytokine secretion and generation of reactive oxygen species (ROS) was investigated using whole human blood. It was observed that low levels of the pro-inflammatory cytokines interleukin(IL)-1β and IL-6 were detected for all sOEG solutions but only when used at concentrations above 250 µg·mL-1. Furthermore, only the 20 kDa sOEG-DAT induced low amounts of ROS-producing monocytes. Conclusively, the data indicate that the materials were not contaminated with microbial products and do not induce substantial immunological adverse effectsin vitro,which is a prerequisite for future biological applications.

Sign in / Sign up

Export Citation Format

Share Document