xRead - Nasal Obstruction (September 2024) Full Articles

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Orlandi et al.

of superantigen-induced Th1 cell recruitment, and favors mucosal type 2 immune responses. 1437 SEs also downregulate the anti-inflammatory prostaglandin PGE4 in CRSwNP fibroblasts, and induce growth factors and chemokines in nasal epithelial cells. 1438,1439 In CRSwNP, evidence for local IgE synthesis and class switch recombination was also provided; 1440 recombination activating genes RAG1 and RAG2 mRNA concentrations were increased in polyps and correlated with the magnitude of inflammation and the presence of SE-specific IgE in the NP mucosa, pointing to a very active local Ig production in SE-IgE positive polyps. 1441 The locally formed IgE is polyclonal, with IgE antibodies against several 100 or more allergens, and functional, even in the absence of systemic IgE antibodies or a positive skin prick test. 1442,1443 ISE-IgE were associated with significantly higher concentrations of antagonizing IgG antibodies in NPs. 1444 CRSwNP showed a significantly higher S. aureus culture-positivity, a higher detection rate of S. aureus superantigens and of specific SE-IgE in a recent meta-analysis 1445 confirming that superantigens may be a risk factor for CRSwNP, and the presence of superantigen also was related to disease severity. Recent work focused on further SA released serine protease-like (spl) proteins, which stimulate the release IL-33 from the epithelium, activating ILC2s to produce type 2 cytokines. 1446–1448 This finding could explain how the S. aureus bacteria initiate type 2 immune reactions even from the mucosal surface. Once a severe type 2 immune reaction is established, tissue eosinophilia is a typical feature. Activated eosinophils migrate toward the epithelium and, upon stimulation with SA, release extra cellular traps containing DNA, MBP and galectin 10 to immobilize and kill the bacteria. 1449 Galectin 10 then forms Charcot-Leyden-Crystals (CLCs) at the epithelial layer, which further damage the epithelium and induce severe neutrophilic inflammation. 1449,1450 As CLCs stay intact for many months, this mechanisms may be relevant for the persistence of CRSwNP disease. In a cluster analysis, SE-IgE in the NP tissue was the best categorical value to predict comorbid asthma in CRSwNP patients; 178 other positive determinants were total IgE, eosinophilic cationic protein (ECP) and IL-5 in the con tinuous model, all representing Th2-associated markers. Whereas SE-IgE in CRSwNP patients often is undetectable inserum, 1451 it is associated with asthma in a Europe-wide epidemiological study 1452 and associated with severe, often non-atopic late-onset asthma. 1453 Staphylococcal entero toxin IgE antibodies, but not IgE against inhalant aller gens, were found to be risk factors for severe asthma, hospi talization and oral corticosteroid use as well as limitations in lung function. 1454 Furthermore, serum SE-IgE positiv ity was recently demonstrated to predict severe asthma and

CRSwNP have lower 25VD 3 than CRSsNP. 25VD 3 is inversely correlated

with polyp grade severity.

Serum 25VD3 is lower in pediatric CRSwNP and

AFRS. Low serum 25VD3

correlates with increased dendritic cells. Ozkara 1416 2012 4 Case-Control 40 Control (healthy volunteers) Serum 1,25VD 3

CRSwNP and AFRS. Low 25VD3 correlates with increased circulating dendritic cells.

CRSwNP with AR have lower serum 1,25VD3 than control. CRSwNP with AR have Th2 cytokine profile.

Study Year LOE Study Design Study Groups Clinical Endpoint Conclusions Wang 720 2013 4 Case-Control 25CRSwNP 20CRSsNP Serum25VD 3 Polyp grade

Serum 25VD3 is lower in

Number of CD209 +

Dendritic cells in nasal tissue

Serum IL-4, IL-10, IFNɣ level

percentage of total peripheral blood

mononuclear cells

Lund-Mackay Score Serum total IgE

Serum 25VD3 level

Serum 25VD3 level Dendritic cells as

14 control patients) 17CRSsNP 5CRSwNP 14AFRS

14 Control (CSF Leak) 20CRSsNP 9CRSwNP 14AFRS

30 CRSwNP and AR 30CRSwNP

Case-Control

Case-Control

Mulligan 717 2012 4 Retrospective

Mulligan 718 2011 4 Retrospective

TABLE X-8 (Continued)