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Allergy & Rhinology (1)
American journal of rhinology (1)
International forum of allergy & rhinology (1)
Carter, Cody S. (1)
Church, Christopher A (1)
Conley, David B. (1)
Grammer, Leslie C. (1)
Harris, Kathleen (1)
Herring, Jason (1)
Kern, Robert C. (1)
Paniagua, Mary C. (1)
Schleimer, Robert P. (1)
Seiberling, Kristin (1)
Seiberling, Kristin A (1)
Seiberling, Kristin A. (1)
Sowers, Lawrence (1)
Stewart, Thomas A. (1)
Suh, Lydia A. (1)
Tripathi, Anju (1)
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Epigenetics of Chronic Rhinosinusitis and the Role of the Eosinophil
Church, Christopher A
International forum of allergy & rhinology
One theory for the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) involves aberration in the expression of genes that maintain the sinonasal innate immune system. We propose that the alteration in gene expression seen in CRSwNP is a result of oxidative byproducts of eosinophils. Activated eosinophils and neutrophils may lead to the production of hypobromous acid (HOBr) and hypochlorous acid (HOCL) and the post-translational modification product 5-bromocytosine (5BrC) and 5 chlorocytosine (CIC) respectively. 5BrC and CIC may cause aberrant methylation of cytosine during DNA replication and mimic the endogenous methylation signal associated with gene silencing. We propose to use gas chromatography-mass spectrometry (GC-MS) to identify the presence of 5BrC and CIC in CRSwNP patients.
Patients with CRSwNP undergoing endoscopic sinus surgery were prospectively recruited into this study. Using GC-MS tissue specimens were analyzed for the presence of 5BrC, CIC and methylated cytosine.
Tissue specimens from 14 patients with CRSwNP and 3 normal controls were processed using GC-MS. CRSwNP specimens demonstrate elevated levels of 5BrC and CIC compared to normal controls.
Eosinophils, which are predominantly found in CRSwNP, may lead to DNA modification and gene silencing via 5BrC and aberrant methylation patterns and may help explain the pathogenesis of CRSwNP.
Temporal lobe abscess in a patient with isolated sphenoiditis
Stewart, Thomas A.
Carter, Cody S.
Allergy & Rhinology
A 74-year-old immunocompetent man admitted for severe retro-orbital headache was diagnosed with isolated sphenoiditis. At the time of scheduled surgery, the patient was mildly obtunded, and a head CT revealed a temporal lobe abscess. The patient underwent a left temporal craniectomy and a bilateral endoscopic sphenoid sinusotomy, which revealed gross fungal debris. The patient made a full recovery with resolution of abscess and sinus findings. Suspicion for intracranial infection should be raised in any sinus patient with neurological changes. Early diagnosis with imaging studies is extremely important for surgical drainage before permanent neurological sequelae.
Abcess; allergic sinusitis; fungal infection; headache; sinonasal; sphenoiditis; temporal lobe
Superantigens and chronic rhinosinusitis: Skewing of T-cell receptor Vβ-distributions in polyp-derived CD4+ and CD8+ T cells
Conley, David B.
Schleimer, Robert P.
Suh, Lydia A.
Paniagua, Mary C.
Grammer, Leslie C.
Kern, Robert C.
American journal of rhinology
Recent studies have suggested that Staphylococcus aureus secrete superantigenic toxins that play a role in the etiology of chronic rhinosinusitis with nasal polyposis (CRSwNP). Twenty S. aureus superantigens (SAg’s) have been identified, each of which bind the Vβ-region of the T-cell receptor (TCR) outside the peptide-binding site. Approximately 50 distinct Vβ-domains exist in the human repertoire, and distinct SAg’s will bind only particular domains generating a pattern of Vβ-enrichment in lymphocytes dependent on the binding characteristics of a given toxin. The aim of this study was to analyze the pattern of Vβ-expression in polyp-derived lymphocytes from CRSwNP patients.
Polyps were harvested from 20 patients with CRSwNP and 3 patients with antrochoanal polyps. Flow cytometry was used to analyze the Vβ-repertoire of polyp-derived CD4+ and CD8+ lymphocytes. Data were analyzed in light of the known skewing associated with SAg exposure in vivo and in vitro. Skewing was defined as a percentage of Vβ-expression >2 SD of that seen in normal blood.
Seven of 20 subjects exhibited skewing in Vβ-domains with strong associations with S. aureus SAg’s. The three antrochoanal polyps failed to show any significant Vβ-skewing.
This study establishes evidence of S. aureus SAg–T-cell interactions in polyp lymphocytes of 35% of CRSwNP patients. Although these results are consistent with intranasal exposure of polyp lymphocytes to SAg’s, additional study is necessary to establish the role of these toxins in disease pathogenesis.
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