Human Leukocyte Antigen Genotyping of Idiopathic Subglottic Stenosis

Rohlfing, Matthew L.; Hillel, Alexander T.; Wohler, Elizabeth; Sobreira, Nara; Phillips, Elizabeth; Mallal, S.; Gelbard, Alexander

doi:10.1002/lary.30580

Cited by 4 publications

(3 citation statements)

References 45 publications

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“…The composition of an individual's TCR repertoire is the result of many forces, including age and HLA genotype. Previous work has shown that the HLA genotype of iSGS patients is similar to matched controls 47 . In addition to the role of HLA in driving overlap in TCR responses, data suggest increased age correlates with more shared low frequency TCR clones 48 .…”

Section: Discussionmentioning

confidence: 76%

“…Previous work has shown that the HLA genotype of iSGS patients is similar to matched controls. 47 In addition to the role of HLA in driving overlap in TCR responses, data suggest increased age correlates with more shared low frequency TCR clones. 48 The average age of our iSGS cohort meets immunologic definitions of "increased age" (>40 years) at 54 (+/À 8 years), and yet there was minimal overlap in TCR clones observed.…”

Section: Discussionmentioning

confidence: 99%

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Characterizing the T Cell Repertoire in the Proximal Airway in Health and Disease

Clark,

Talatala,

et al. 2023

The Laryngoscope

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ObjectivesRecent translational scientific efforts in subglottic stenosis (SGS) support a disease model where epithelial alterations facilitate microbiome displacement, dysregulated immune activation, and localized fibrosis. Given the observed immune cell infiltrate in SGS, we sought to test the hypothesis that SGS cases possessed a low diversity (highly clonal) adaptive immune response when compared with healthy controls.MethodsSingle cell RNA sequencing (scRNA‐seq) of subglottic mucosal scar in iSGS (n = 24), iLTS (n = 8), and healthy controls (n = 7) was performed. T cell receptor (TCR) sequences were extracted, analyzed, and used to construct repertoire structure, compare diversity, interrogate overlap, and define antigenic targets using the Immunarch bioinformatics pipeline.ResultsThe proximal airway mucosa in health and disease are equally diverse via Hill framework quantitation (iSGS vs. iLTS vs. Control, p > 0.05). Repertoires do not significantly overlap between individuals (Morisita <0.02). Among iSGS patients, clonality of the TCR repertoire is driven by CD8+ T cells, and iSGS patients possess numerous TCRs targeting viral and intercellular pathogens. High frequency clonotypes do not map to known targets in public datasets.ConclusionSGS cases do not possess a lower diversity adaptive immune infiltrate when compared with healthy controls. Interestingly, the TCR repertoire in both health and disease contains a restricted number of high frequency clonotypes that do not significantly overlap between individuals. The target of the high frequency clonotypes in health and disease remain unresolved.Level of EvidenceLevel NA Laryngoscope, 2023

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Characterizing the T Cell Repertoire in the Proximal Airway in Health and Disease

Clark,

Talatala,

et al. 2023

The Laryngoscope

Self Cite

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“…A potential association between a specific upper airway microbiota, especially members of the Moraxellaceae family, and ISGS has also been discussed (6). In contrast to patients with granulomatosis with polyangiitis a human leucocyte antigen (HLA) association with allele DPB1*04:01 or allele homozygosity was excluded in ISGS (7). Among ISGS patients, clonality of the TCR repertoire is driven by CD8+ T cells, and ISGS patients possess numerous TCRs targeting viral and intercellular pathogens.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional profiling sheds light on the fibrotic aspects of idiopathic subglottic tracheal stenosis

Direder,

Laggner,

Copic

et al. 2024

Preprint

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1AbstractIdiopathic subglottic stenosis (ISGS) is a rare fibrotic disease of the upper trachea with an unknown pathomechanism. It typically affects adult Caucasian female patients, leading to severe airway constrictions caused by progressive scar formation and inflammation with clinical symptoms of dyspnoea, stridor and potential changes to the voice. Endoscopic treatment frequently leads to recurrence, whereas surgical resection and reconstruction provides excellent long-term functional outcome. This study aimed to identify so far unrecognized pathologic aspects of ISGS using single cell RNA sequencing. Our scRNAseq analysis uncovered the cellular composition of the subglottic scar tissue, including the presence of a pathologic, profibrotic fibroblast subtype and the presence of Schwann cells in a profibrotic state. In addition, a pathology-associated increase of plasma cells was identified. Using extended bioinformatics analyses, we decoded pathology-associated changes of factors of the extracellular matrix. Our data identified ongoing fibrotic processes in ISGS and provide novel insights on the contribution of fibroblasts, Schwann cells and plasma cells to the pathogenesis of ISGS. This knowledge could impact the development of novel approaches for diagnosis and therapy of ISGS.

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Idiopathic Subglottic Stenosis in Non‐Caucasian Women

Suk,

Dehom,

Punjabi

et al. 2024

OTO Open

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ObjectiveTo characterize presentation, disease course, and treatment of idiopathic subglottic stenosis (iSGS) in non‐Caucasian women and compare this cohort to the predominantly female, Caucasian patient cohorts identified in the literature.Study DesignRetrospective review. Results are compared to systematic review of demographics.SettingMultiple California institutions from 2008 to 2021.MethodsPatients with intubation within 2 years of disease or who met exclusion criteria listed in prior publications were excluded. A systematic review of iSGS patient demographics was also completed for comparison.ResultsOf 421 patients with iSGS, 58 self‐identified as non‐Caucasian women, with 50 ultimately included. Mean age of onset was 45.1 years old (95% confidence interval [CI], 41.5‐48.8), and mean age at diagnosis was 47.2 years (95% CI, 43.6‐50.7). Mean Charlson comorbidity index was 1.06 (n = 49, 95% CI, 0.69‐1.44). At diagnosis, Cotton‐Meyer severity scores (documented in n = 45) were Cotton‐Myer (CM) I (28.9%), CM II (40%), and CM III (31.1%). Mean age at first endoscopic surgery was 47.7 (95% CI, 44.2‐51.3) years. 64% experienced disease recurrence with a median of 11 months between their first and second surgery. Our systematic review identified 60 studies that reported demographic features in patients with iSGS. 95% of pooled patients were Caucasian, while other demographic features were similar to the current cohort.ConclusionThe non‐Caucasian population, almost 14% of this Californian cohort, does not differ from the majority Caucasian population detailed in contemporary literature. This cohort supports the presence of some racial and ethnic heterogeneity in this disease population.

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Human Leukocyte Antigen Genotyping of Idiopathic Subglottic Stenosis

Cited by 4 publications

References 45 publications

Characterizing the T Cell Repertoire in the Proximal Airway in Health and Disease

Characterizing the T Cell Repertoire in the Proximal Airway in Health and Disease

Transcriptional profiling sheds light on the fibrotic aspects of idiopathic subglottic tracheal stenosis

Idiopathic Subglottic Stenosis in Non‐Caucasian Women

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