The Experts below are selected from a list of 1884 Experts worldwide ranked by ideXlab platform
Alexander Gelbard - One of the best experts on this subject based on the ideXlab platform.
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the proximal airway is a reservoir for adaptive Immunologic memory in idiopathic subglottic stenosis
Laryngoscope, 2020Co-Authors: Alexander Gelbard, Celestine N Wanjalla, Christopher T Wootten, Wonder P Drake, Anne S Lowery, David A Wheeler, Maria F Cardenas, Andrew G Sikora, Ravi Ramesh Pathak, Wyatt J McdonnellAbstract:OBJECTIVES/HYPOTHESIS Characterization of the localized adaptive immune response in the airway scar of patients with idiopathic subglottic stenosis (iSGS). STUDY DESIGN Basic Science. METHODS Utilizing 36 patients with subglottic stenosis (25 idiopathic subglottic stenosis [iSGS], 10 iatrogenic post-intubation stenosis [iLTS], and one granulomatosis with polyangiitis [GPA]) we applied immunohistochemical and Immunologic Techniques coupled with RNA sequencing. RESULTS iSGS, iLTS, and GPA demonstrate a significant immune infiltrate in the subglottic scar consisting of adaptive cell subsets (T cells along with dendritic cells). Interrogation of T cell subtypes showed significantly more CD69+ CD103+ CD8+ tissue resident memory T cells (TRM ) in the iSGS airway scar than iLTS specimens (iSGS vs. iLTS; 50% vs. 28%, P = .0065). Additionally, subglottic CD8+ clones possessed T-cell receptor (TCR) sequences with known antigen specificity for viral and intracellular pathogens. CONCLUSIONS The human subglottis is significantly enriched for CD8+ tissue resident memory T cells in iSGS, which possess TCR sequences proven to recognize viral and intracellular pathogens. These results inform our understanding of iSGS, provide a direction for future discovery, and demonstrate Immunologic function in the human proximal airway. Laryngoscope, 2020.
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idiopathic subglottic stenosis is associated with activation of the inflammatory il 17a il 23 axis
Laryngoscope, 2016Co-Authors: Alexander Gelbard, Nicolas George Katsantonis, Masanobu Mizuta, Dawn C Newcomb, Joseph E Rotsinger, Bernard Rousseau, James J Daniero, Eric S Edell, Dale C Ekbom, Jan L KasperbauerAbstract:Objectives/Hypothesis Idiopathic subglottic stenosis (iSGS) is a rare and devastating extrathoracic obstruction involving the lower laryngeal and upper tracheal airway. It arises without known antecedent injury or associated disease process. Persistent mucosal inflammation and a localized fibrotic response are hallmarks of the disease. Despite the initial clinical description of iSGS more than 40 year ago, there have been no substantive investigations into the pathogenesis of this enigmatic and progressive airway obstruction. In these studies, we present the initial characterization of the molecular pathogenesis underlying the fibrosing phenotype of iSGS. Methods Utilizing 20 human iSGS and healthy control specimens, we applied histologic, immunohistochemical, molecular, and Immunologic Techniques. Results We demonstrate significant activation of the canonical IL-23/IL-17A pathway in the tracheal mucosa of iSGS patients, as well as identify γδ T cells as the primary cellular source of IL-17A. Conclusion Our results suggest that aberrant mucosal immune activation is a component in of the pathogenesis of iSGS. Most critically, our work offers new targets for future therapeutic intervention. Level of Evidence NA Laryngoscope, 126:E356–E361, 2016
Maarten J Titulaer - One of the best experts on this subject based on the ideXlab platform.
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encephalitis and ampa receptor antibodies novel findings in a case series of 22 patients
Neurology, 2015Co-Authors: Romana Hoftberger, Agnes Van Sonderen, Frank Leypoldt, David J Houghton, Michael D Geschwind, Jeffrey M Gelfand, Mercedes F Paredes, Lidia Sabater, Albert Saiz, Maarten J TitulaerAbstract:We report the clinical features, comorbidities, and outcome of 22 newly identified patients with antibodies to the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR).This was a retrospective review of patients diagnosed between May 2009 and March 2014. Immunologic Techniques have been reported previously.Patients' median age was 62 years (range 23-81; 14 female). Four syndromes were identified: 12 (55%) patients presented with distinctive limbic encephalitis (LE), 8 (36%) with limbic dysfunction along with multifocal/diffuse encephalopathy, one with LE preceded by motor deficits, and one with psychosis with bipolar features. Fourteen patients (64%) had a tumor demonstrated pathologically (5 lung, 4 thymoma, 2 breast, 2 ovarian teratoma) or radiologically (1 lung). Additional antibodies occurred in 7 patients (3 onconeuronal, 1 tumor-related, 2 cell surface, and 1 tumor-related and cell surface), all with neurologic symptoms or tumor reflecting the concurrent autoimmunity. Treatment and outcome were available from 21 patients (median follow-up 72 weeks, range 5-266): 5 had good response to immunotherapy and tumor therapy, 10 partial response, and 6 did not improve. Eventually 5 patients died; all had a tumor or additional paraneoplastic symptoms related to onconeuronal antibodies. Coexistence of onconeuronal antibodies predicted a poor outcome (p = 0.009).Anti-AMPAR encephalitis usually manifests as LE, can present with other symptoms or psychosis, and is paraneoplastic in 64% of cases. Complete and impressive neurologic improvement can occur, but most patients have partial recovery. Screening for a tumor and onconeuronal antibodies is important because their detection influences outcome.
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encephalitis and ampa receptor antibodies novel findings in a case series of 22 patients
Neurology, 2015Co-Authors: Romana Hoftberger, Agnes Van Sonderen, Frank Leypoldt, David J Houghton, Michael D Geschwind, Mercedes F Paredes, Lidia Sabater, Albert Saiz, Jeffrey Gelfand, Maarten J TitulaerAbstract:Objective: We report the clinical features, comorbidities, and outcome of 22 newly identified patients with antibodies to the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR). Methods: This was a retrospective review of patients diagnosed between May 2009 and March 2014. Immunologic Techniques have been reported previously. Results: Patients9 median age was 62 years (range 23–81; 14 female). Four syndromes were identified: 12 (55%) patients presented with distinctive limbic encephalitis (LE), 8 (36%) with limbic dysfunction along with multifocal/diffuse encephalopathy, one with LE preceded by motor deficits, and one with psychosis with bipolar features. Fourteen patients (64%) had a tumor demonstrated pathologically (5 lung, 4 thymoma, 2 breast, 2 ovarian teratoma) or radiologically (1 lung). Additional antibodies occurred in 7 patients (3 onconeuronal, 1 tumor-related, 2 cell surface, and 1 tumor-related and cell surface), all with neurologic symptoms or tumor reflecting the concurrent autoimmunity. Treatment and outcome were available from 21 patients (median follow-up 72 weeks, range 5–266): 5 had good response to immunotherapy and tumor therapy, 10 partial response, and 6 did not improve. Eventually 5 patients died; all had a tumor or additional paraneoplastic symptoms related to onconeuronal antibodies. Coexistence of onconeuronal antibodies predicted a poor outcome ( p = 0.009). Conclusion: Anti-AMPAR encephalitis usually manifests as LE, can present with other symptoms or psychosis, and is paraneoplastic in 64% of cases. Complete and impressive neurologic improvement can occur, but most patients have partial recovery. Screening for a tumor and onconeuronal antibodies is important because their detection influences outcome.
Wyatt J Mcdonnell - One of the best experts on this subject based on the ideXlab platform.
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the proximal airway is a reservoir for adaptive Immunologic memory in idiopathic subglottic stenosis
Laryngoscope, 2020Co-Authors: Alexander Gelbard, Celestine N Wanjalla, Christopher T Wootten, Wonder P Drake, Anne S Lowery, David A Wheeler, Maria F Cardenas, Andrew G Sikora, Ravi Ramesh Pathak, Wyatt J McdonnellAbstract:OBJECTIVES/HYPOTHESIS Characterization of the localized adaptive immune response in the airway scar of patients with idiopathic subglottic stenosis (iSGS). STUDY DESIGN Basic Science. METHODS Utilizing 36 patients with subglottic stenosis (25 idiopathic subglottic stenosis [iSGS], 10 iatrogenic post-intubation stenosis [iLTS], and one granulomatosis with polyangiitis [GPA]) we applied immunohistochemical and Immunologic Techniques coupled with RNA sequencing. RESULTS iSGS, iLTS, and GPA demonstrate a significant immune infiltrate in the subglottic scar consisting of adaptive cell subsets (T cells along with dendritic cells). Interrogation of T cell subtypes showed significantly more CD69+ CD103+ CD8+ tissue resident memory T cells (TRM ) in the iSGS airway scar than iLTS specimens (iSGS vs. iLTS; 50% vs. 28%, P = .0065). Additionally, subglottic CD8+ clones possessed T-cell receptor (TCR) sequences with known antigen specificity for viral and intracellular pathogens. CONCLUSIONS The human subglottis is significantly enriched for CD8+ tissue resident memory T cells in iSGS, which possess TCR sequences proven to recognize viral and intracellular pathogens. These results inform our understanding of iSGS, provide a direction for future discovery, and demonstrate Immunologic function in the human proximal airway. Laryngoscope, 2020.
Romana Hoftberger - One of the best experts on this subject based on the ideXlab platform.
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encephalitis and ampa receptor antibodies novel findings in a case series of 22 patients
Neurology, 2015Co-Authors: Romana Hoftberger, Agnes Van Sonderen, Frank Leypoldt, David J Houghton, Michael D Geschwind, Jeffrey M Gelfand, Mercedes F Paredes, Lidia Sabater, Albert Saiz, Maarten J TitulaerAbstract:We report the clinical features, comorbidities, and outcome of 22 newly identified patients with antibodies to the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR).This was a retrospective review of patients diagnosed between May 2009 and March 2014. Immunologic Techniques have been reported previously.Patients' median age was 62 years (range 23-81; 14 female). Four syndromes were identified: 12 (55%) patients presented with distinctive limbic encephalitis (LE), 8 (36%) with limbic dysfunction along with multifocal/diffuse encephalopathy, one with LE preceded by motor deficits, and one with psychosis with bipolar features. Fourteen patients (64%) had a tumor demonstrated pathologically (5 lung, 4 thymoma, 2 breast, 2 ovarian teratoma) or radiologically (1 lung). Additional antibodies occurred in 7 patients (3 onconeuronal, 1 tumor-related, 2 cell surface, and 1 tumor-related and cell surface), all with neurologic symptoms or tumor reflecting the concurrent autoimmunity. Treatment and outcome were available from 21 patients (median follow-up 72 weeks, range 5-266): 5 had good response to immunotherapy and tumor therapy, 10 partial response, and 6 did not improve. Eventually 5 patients died; all had a tumor or additional paraneoplastic symptoms related to onconeuronal antibodies. Coexistence of onconeuronal antibodies predicted a poor outcome (p = 0.009).Anti-AMPAR encephalitis usually manifests as LE, can present with other symptoms or psychosis, and is paraneoplastic in 64% of cases. Complete and impressive neurologic improvement can occur, but most patients have partial recovery. Screening for a tumor and onconeuronal antibodies is important because their detection influences outcome.
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encephalitis and ampa receptor antibodies novel findings in a case series of 22 patients
Neurology, 2015Co-Authors: Romana Hoftberger, Agnes Van Sonderen, Frank Leypoldt, David J Houghton, Michael D Geschwind, Mercedes F Paredes, Lidia Sabater, Albert Saiz, Jeffrey Gelfand, Maarten J TitulaerAbstract:Objective: We report the clinical features, comorbidities, and outcome of 22 newly identified patients with antibodies to the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR). Methods: This was a retrospective review of patients diagnosed between May 2009 and March 2014. Immunologic Techniques have been reported previously. Results: Patients9 median age was 62 years (range 23–81; 14 female). Four syndromes were identified: 12 (55%) patients presented with distinctive limbic encephalitis (LE), 8 (36%) with limbic dysfunction along with multifocal/diffuse encephalopathy, one with LE preceded by motor deficits, and one with psychosis with bipolar features. Fourteen patients (64%) had a tumor demonstrated pathologically (5 lung, 4 thymoma, 2 breast, 2 ovarian teratoma) or radiologically (1 lung). Additional antibodies occurred in 7 patients (3 onconeuronal, 1 tumor-related, 2 cell surface, and 1 tumor-related and cell surface), all with neurologic symptoms or tumor reflecting the concurrent autoimmunity. Treatment and outcome were available from 21 patients (median follow-up 72 weeks, range 5–266): 5 had good response to immunotherapy and tumor therapy, 10 partial response, and 6 did not improve. Eventually 5 patients died; all had a tumor or additional paraneoplastic symptoms related to onconeuronal antibodies. Coexistence of onconeuronal antibodies predicted a poor outcome ( p = 0.009). Conclusion: Anti-AMPAR encephalitis usually manifests as LE, can present with other symptoms or psychosis, and is paraneoplastic in 64% of cases. Complete and impressive neurologic improvement can occur, but most patients have partial recovery. Screening for a tumor and onconeuronal antibodies is important because their detection influences outcome.
Sadamu Nagai - One of the best experts on this subject based on the ideXlab platform.
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protein antigens of mycobacteria studied by quantitative Immunologic Techniques
Clinical Infectious Diseases, 1992Co-Authors: M Harboe, Harald G Wiker, Sadamu NagaiAbstract:Crossed immunoelectrophoresis has great resolving power in the demonstration of immunogenic constituents of mycobacteria. The pattern with multiple precipitate lines is highly reproducible and allows precise identification of components. After the isolation of individual proteins, Immunologic specificity combined with molecular weight determination and N-terminal amino acid sequencing should be used to ensure consistent identification in different laboratories. Simultaneous quantification of individual proteins in sonicates of washed bacilli and culture fluids permits the determination of a localization index, which indicates whether the proteins are cytoplasmic constituents or actively secreted. Several "new," actively secreted proteins have recently been defined, and the role of these proteins in the interaction between the bacilli and the infected host is discussed.
