Heterogeneous inflammatory patterns in chronic rhinosinusitis without nasal polyps in Chicago, Illinois

Tan, Bruce K.; Klingler, Aiko I.; Poposki, Julie A.; Stevens, Whitney W.; Peters, Anju T.; Suh, Lydia; Norton, James E.; Carter, Roderick G.; Hulse, Kathryn E.; Harris, Kathleen E.; Grammer, Leslie C.; Schleimer, Robert P.; Welch, Kevin C.; Smith, Stephanie Shintani; Conley, David B.; Kern, Robert C.; Kato, Atsushi

doi:10.1016/j.jaci.2016.06.063

Cited by 156 publications

(193 citation statements)

References 12 publications

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“…9, 33 On electronic medical records review, clinical features including medication prescriptions were extracted. As shown in Table 1, patients in the high-IgD group more frequently had CRSsNP compared with the low-IgD cohort (75.0% versus 43.7%, respectively, P =.05).…”

Section: Resultsmentioning

confidence: 99%

“…BAFF) and immunoglobulins of every isotype except IgD and class-switched autoreactive antibodies have been elevated in NP tissue of CRSwNP. 12, 17, 29, 33 In contrast to CRSwNP, CRSsNP is both clinically and molecularly more heterogeneous. 44 Thus, given the association of IgD with CRSsNP, we further evaluated the relationships between a variety of locally expressed mediators including CD40L, BAFF, IFN-γ, IL-2, IL-4, IL-10, IL15 and IL-21 and with tissue IgD levels, as these factors had previously been shown to induce differentiation of IgD plasmablasts in vitro.…”

Section: Discussionmentioning

confidence: 99%

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Evidence for altered levels of IgD in the nasal airway mucosa of patients with chronic rhinosinusitis

Min

Nayak

Hulse

et al. 2017

Journal of Allergy and Clinical Immunology

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Background Immunoglobulin D (IgD) is an enigmatic antibody isotype best known when co-expressed with IgM on naïve B cells. However, elevated soluble IgD (sIgD) and increased IgD+IgM− B cell populations have been described in the human upper respiratory mucosa. Objective We assessed whether levels of sIgD and IgD+ B cells are altered in nasal tissue from patients with chronic rhinosinusitis (CRS). We further characterized IgD+ B cell populations and explored clinical and local inflammatory factors associated with tissue sIgD levels. Methods sIgD levels were measured by ELISA in nasal tissues, nasal lavages, serum, and supernatants of dissociated nasal tissues. IgD+ cells were identified by immunofluorescence and flow cytometry. Inflammatory mediator levels in tissues were assessed by real-time PCR and multiplex immunoassay. Bacterial cultures from the middle meatus were performed. Underlying medical history and medicine use were obtained from medical records. Results sIgD levels and the number of IgD+ cells were significantly increased in uncinate tissue (UT) of CRS without nasal polyps (CRSsNP) compared to control (4-fold, P<.05). IgD+ cells were densely scattered in the periglandular regions of CRSsNP UT. We also found that IgD+CD19+CD38bright plasmablasts were significantly elevated in CRSsNP tissues compared to control (P<.05). Among numerous factors tested, IL-2 levels were increased in CRSsNP UT and were positively correlated with tissue IgD levels. Additionally, the supernatants of IL-2-stimulated dissociated CRSsNP tissue had significantly increased sIgD levels compared to IL-2-stimulated dissociated control tissue ex vivo (P<.05). Tissue from CRS patients with preoperative antibiotic use or those with pathogenic bacteria presence showed higher IgD levels compared to tissue from patients absent these variables (P<.05). Conclusion sIgD levels and IgD+CD19+CD38bright plasmablasts were increased in nasal tissue of CRSsNP. IgD levels were associated with increased IL-2 and the presence of pathogenic bacteria. These findings suggest that IgD might contribute to enhance mucosal immunity, inflammation, or respond to bacterial infections in CRS, especially CRSsNP.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Evidence for altered levels of IgD in the nasal airway mucosa of patients with chronic rhinosinusitis

Min

Nayak

Hulse

et al. 2017

Journal of Allergy and Clinical Immunology

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“…28 Nevertheless, the coexistence or absence of type 1, type 2 and type 3 immune responses can also be found in some CRS patients. 26,27,29 Currently, studies on how the intermingling of different types of inflammatory pathways impacts the downstream clinical behavior of CRS are limited. However, it seems that patients with high levels of type 2 inflammatory mediators combined with high levels of type 1, type 3 and/or neutrophilic inflammatory markers, have the worst prognosis or the most severe inflammation load.…”

Section: Immune Polarization In Crsmentioning

confidence: 99%

Pathophysiologic mechanisms of chronic rhinosinusitis and their roles in emerging disease endotypes

Cao

Wang

Schleimer

et al. 2019

Annals of Allergy, Asthma & Immunology

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102

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Objective: Chronic rhinosinusitis (CRS) is a heterogeneous disorder with distinct pathophysiologic mechanisms. Based on the transcription factor expression and cytokine production patterns in different types of innate lymphoid cells (ILCs), in parallel with those of adaptive CD4+ T helper (Th) cells and CD8+ cytotoxic T (Tc) cells, new perspectives on endotypes of patients are emerging around the immune response deviation into type 1 (orchestrated by ILC1s, Tc1 and Th1 cells), type 2 (characterized by ILC2s, Tc2 and Th2 cells), and type 3 (mediated by ILC3s, Tc17 and Th17 cells) responses. Additionally, cluster analysis has been applied to the endotyping of CRS in recent years, which has provided additional novel insights into the CRS pathogenesis. This article aims to review pathological mechanisms of CRS on the basis of type 1, type 2, and type 3 immune responses and how they inform us to begin to understand CRS endotypes. This article also reviews the recent cluster analysis studies of CRS endotypes. Finally, the impact of endotype on therapeutic management of CRS is summarized. Data Sources: Review of published literature. Study Selections: Relevant literature concerning CRS endotypes and the possible underlying mechanisms were obtained from a PubMed search and summarized here. Results and Conclusion: Both CRSwNP and CRSsNP are comprised of distinct endotypes with distinct deviated immune responses, pathogenic mechanisms, and different responses to medical and surgical treatment. An endotype of CRS with prominent type 2 immune responses is the most well studied endotype, and generally can benefit from treatment with steroids and specific type 2 disrupting biologics.

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“…CRS subgroups have classically been phenotypically classified based on the presence (CRSwNP) or absence (CRSsNP) of nasal polyps, with each being associated with unique etiologies and inflammatory mediators. While CRSwNP and CRSsNP have historically been linked with Th2- and Th1-associated inflammation, respectively, these distinctions have more recently come into question, with a mixed Th1/Th2 picture being identified in many cases, regardless of polyp status 2-4 . The CRSwNP phenotype is frequently linked with tissue eosinophilia, a characteristic strongly associated with greater disease severity, poorer outcomes, and increased rates of polyp recurrence 5-8 .…”

Section: Introductionmentioning

confidence: 99%

Mucus T helper 2 biomarkers predict chronic rhinosinusitis disease severity and prior surgical intervention

Turner

Chandra

2018

Int Forum Allergy Rhinol

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Heterogeneous inflammatory patterns in chronic rhinosinusitis without nasal polyps in Chicago, Illinois

Cited by 156 publications

References 12 publications

Evidence for altered levels of IgD in the nasal airway mucosa of patients with chronic rhinosinusitis

Evidence for altered levels of IgD in the nasal airway mucosa of patients with chronic rhinosinusitis

Pathophysiologic mechanisms of chronic rhinosinusitis and their roles in emerging disease endotypes

Mucus T helper 2 biomarkers predict chronic rhinosinusitis disease severity and prior surgical intervention

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