Predictive significance of Charcot‐Leyden crystal structures for nasal polyp recurrence

Abstract

Background: Charcot-Leyden crystals (CLCs) are recognized to be classic hallmarks of eosinophilic inflammation.Both protein and mRNA levels of CLC in nasal secretions and nasal brushing samples have been associated with nasal polyp recurrence. However, whether the crystalline CLC structures in nasal tissue could serve as an effective biomarker to predict polyp recurrence remains unclear.Methods: A total of 110 patients with chronic rhinosinusitis with nasal polyps (CRSwNP) completing the postoperative follow-up over a period of 24 months were recruited. Hematoxylin and eosin staining was employed for CLCs identification. The predictive factors for polyp recurrence were determined by binary logistic regression analysis.Results: Thirty three (30.00%) patients developed recurrence during a 24-month postoperative follow-up, in which 84.85% (28/33) patients had crystalline CLC structures. Logistic regression analysis showed that crystalline CLC structure in nasal tissues is predictive of polyp recurrence. Youden index demonstrated crystalline CLC structure higher than 1 per high power field can predict postoperative polyp recurrence with 84.80% sensitivity and 98.70% specificity. Conclusions:The crystalline CLC structures in nasal tissues may serve as an easy-counting and promising biomarker to predict CRSwNP recurrence.To the editor, Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous and challenging inflammatory airway disease involving noneosinophilic and eosinophilic endotypes. In fact, 98.5% eosinophilic CRSwNP (Eos CRSwNP) patients were recurrent after undergone endoscopic sinus surgery (ESS). 1 Therefore, the identification of predictors of recurrence for Eos CRSwNP is crucial for better disease control. The local tissue eosinophilia has been proven to be the most important predictor. 2 However, there are no standard methods for evaluating tissue eosinophilia due to uneven distribution and diversity in geographic conditions. 2,3 Thus, there are limitations to the predict recurrence of CRSwNP based only on tissue eosinophilia.Charcot-Leyden crystals (CLCs), composed by Galectin-10 (Gal-10), were first proposed in the late 1800s by Charcot and Leyden.The typical CLCs are structures identified as needle-shaped bipyramidal Gal-10 crystals detected by morphological methods. Gal-10 protein have three distinct forms including crystalline CLC/Gal-10 crystal structures (CLCs), extracellular vesicles, and extracellular soluble Gal-10. 4 Recent studies have indicated that CLC mRNA and protein levels in nasal brushing/secretions/tissues detected by ELISA and PCR were used as predictive indicators for recurrent CRSwNP and glucocorticoid sensitivity. [5][6][7] Since only crystalline CLCs, but not soluble CLC/Gal-10 protein, drive type 2 immunity, allergy and neutrophilic inflammation, 8,9 the predictive value of functional CLCs for nasal polyp (NP) relapse should be evaluated. However, little is known regarding whether crystalline CLC structures can be utilized to predict NP recurrence.This was a retrospecti...

Lactose and Galactose Promote the Crystallization of Human Galectin-10

“…Logistic regression analysis showed that crystalline CLCs in nasal tissues are predictive of nasal polyp recurrence. The occurrence of crystalline CLCs at a rate of more than one per high-power field could predict postoperative polyp recurrence with 84.80% sensitivity and 98.70% specificity [ 44 ]. At the intracellular level, CLCs are mostly stored in the peripheral cytoplasm of human eosinophils, being accumulated within an area about 250 nm wide underneath the plasma membrane but not within specific (secretory) granules.…”

Charcot‐Leyden crystals in tissues

“…We read with interest the paper by Chen et al. entitled “Predictive significance of Charcot‐Leyden crystal (CLC) structures for nasal polyp recurrence” 1 . CLCs are formed when galectin‐10 crystallizes intracellularly or extracellularly through eosinophil ETosis, an active cell death process involving the disruption of the cell nucleus and plasma membrane to release web‐like chromatin structures 2,3 .…”

Interaction of eosinophilic and neutrophilic inflammation in patients with chronic rhinosinusitis

“…Eosinophils can further damage tissues by the formation of eosinophil extracellular traps (EETs), which is actively mediated by the production of reactive oxygen species (ROS) depending on the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase pathway [51]. The process of EETs formation can lead to the deposition of Charcot-Leyden crystals (CLCs), which are the crystalline form of galectin- Observing CLC structures at a rate higher than 1/HPF in nasal tissue was suggested as a promising biomarker to predict the recurrence of CRSwNP (with 84.80% sensitivity and 98.70% specificity) by Chen [58]. Wu et al [59] reported that a CLC concentration higher than 34.24 ng/ml could predict the postoperative recurrence of CRSwNP with 92.6% sensitivity and 87.5% specificity.…”

“…CLCs can upregulate the gene expression of GM-CSF further enhancing eosinophilic inflammation [57 ▪ ]. Observing CLC structures at a rate higher than 1/HPF in nasal tissue was suggested as a promising biomarker to predict the recurrence of CRSwNP (with 84.80% sensitivity and 98.70% specificity) by Chen [58]. Wu et al [59] reported that a CLC concentration higher than 34.24 ng/ml could predict the postoperative recurrence of CRSwNP with 92.6% sensitivity and 87.5% specificity.…”