Charcot-Leyden Crystals Research Articles

Primary Radical Extended Sinus Surgery for Management of Extensive Allergic Fungal Rhinosinusitis

Introduction: Allergic fungal rhinosinusitis (AFRS), a subset of sinusitis secondary to hypersensitivity, is clinically similar to chronic rhinosinusitis with nasal polyp but histologically different with rich eosinophils and Charcot Leyden crystals. Since the primary pathology in AFRS is immune mediated, the recurrence rates are high. In this study, we describe the application of radical extended sinus surgery (RESS) as the surgical technique with the usage of postoperative high-volume steroidal nasal irrigation and short-term oral steroid therapy – a threefold strategy – for the prevention of recurrence of this disease. Materials and Methods: A retrospective surgical chart audit of patients diagnosed with AFRS and treated between January 2012 and December 2019 was done. The clinical findings and postoperative outcomes performed by a single senior surgeon in a tertiary referral institution were extracted and analyzed. Results: Of the 17 patients, 88% of patients were immunocompetent and Lund Mackay (LM) of 24, 16 patients had Grade 3 nasal polyps, except one with Grade 1 nasal polyps and an LM score of 8. All patients underwent RESS and received postoperative high-volume topical steroid irrigation with oral steroids in the immediate postoperative period and on follow-up, if recurrence was noted, none required revision surgery. Conclusions: A three-fold strategy is beneficial in the management of AFRS-RESS followed by oral steroids during the immediate postoperative period along with long-term topical high-volume steroid nasal irrigation.

The Role of Galectins in Asthma Pathophysiology: A Comprehensive Review.

Galectins are a group of β-galactoside-binding proteins with several roles in immune response, cellular adhesion, and inflammation development. Current evidence suggest that these proteins could play a crucial role in many respiratory diseases such as pulmonary fibrosis, lung cancer, and respiratory infections. From this standpoint, an increasing body of evidence have recognized galectins as potential biomarkers involved in several aspects of asthma pathophysiology. Among them, galectin-3 (Gal-3), galectin-9 (Gal-9), and galectin-10 (Gal-10) are the most extensively studied in human and animal asthma models. These galectins can affect T helper 2 (Th2) and non-Th2 inflammation, mucus production, airway responsiveness, and bronchial remodeling. Nevertheless, while higher Gal-3 and Gal-9 concentrations are associated with a stronger degree of Th-2 phlogosis, Gal-10, which forms Charcot-Leyden Crystals (CLCs), correlates with sputum eosinophilic count, interleukin-5 (IL-5) production, and immunoglobulin E (IgE) secretion. Finally, several galectins have shown potential in clinical response monitoring after inhaled corticosteroids (ICS) and biologic therapies, confirming their potential role as reliable biomarkers in patients with asthma.

Langerhans Cell Histiocytosis With Unusual Hexagonal Crystals in Addition to Usual Charcot-Leyden Crystals. Report of a Patient With Possible Process of Crystal Formation and Clinical Significance of a "Necrotic" Change.

Langerhans cell histiocytosis is a rare neoplastic disorder characterized by the proliferation of Langerhans cells and often accompanied by eosinophil infiltration. Charcot-Leyden crystals, composed of galectin 10, are occasionally observed in Langerhans cell histiocytosis; however, histological images are rarely reported. We herein present a patient with Langerhans cell histiocytosis with Charcot-Leyden crystals and hexagonal crystals by describing the histologic and immunohistochemical features of a lymph node. A unique distribution of Charcot-Leyden crystals and hexagonal crystals was observed in this patient, shedding light on their possible formation process of the latter. We discuss the biological significance of eosinophilic abscesses in Langerhans cell histiocytosis and propose that these crystals may be linked to extracellular trap-cell death (ETosis). This example challenges the conventional characterization of "necrosis" in Langerhans cell histiocytosis and underscores the importance of recognizing ETosis as a potential mechanism involved in the pathogenesis of Langerhans cell histiocytosis. Further studies are underway to validate significance of these findings in a larger cohort of Langerhans cell histiocytosis patients.

Eosinophil extracellular traps in eosinophilic chronic rhinosinusitis induce Charcot-Leyden crystal formation and eosinophil recruitment.

Eosinophil extracellular traps (EETs) are implicated in various eosinophil-associated diseases; however, their role in chronic rhinosinusitis (CRS) remains unclear. In the present study, 57 CRS patients were enrolled, and immunofluorescence was used to analyze EETs in eosinophilic (eCRS) and non-eosinophilic (Non-eCRS) tissues. MSD was used to examine IL-4, IL-5, and IL-13 concentrations in tissue homogenates. Charcot-Leyden crystals (CLCs) protein expression was detected in PMA, PMA+DNase I, and blank control eosinophils using ELISA. Eotaxin-3 mRNA and protein levels were measured in human nasal epithelial cells (HNECs) cultured with EETs, EETs+DNase I, DNase I, and unstimulated eosinophils using PCR and ELISA. EETs were significantly increased in eCRS tissues compared with Non-eCRS (P<0.001), and correlated with VAS and Lund-Mackay CT scores. IL-5 expression was related to EETs formation (r = 0.738, P<0.001). PMA-stimulated eosinophils exhibited higher CLCs protein levels (P<0.01). Co-culturing HNECs with EETs significantly increased eotaxin-3 mRNA and protein levels (P<0.0001, P<0.001) compared with other groups. The study suggests EETs formation is elevated in eCRS patients and is involved in CLCs formation and chemokine secretion, promoting eosinophilic inflammation.

Validation and shortcomings of the most common mouse model of chronic rhinosinusitis with nasal polyps.

Chronic rhinosinusitis (CRS) is a highly prevalent airway disease worldwide. Whereas eosinophilic CRS with nasal polyps (eCRSwNP) represents its most severe phenotype, pathogenic mechanisms remain poorly understood despite a wide spectrum of in vitro and in vivo experimental models. A mouse model of experimental ovalbumin (OVA)-induced airway allergy with coadministration of Staphylococcus aureus enterotoxin B (SEB) has been widely used to study eosinophilic eCRSwNP. This study revisits the features of this model and its suitability for studying eCRS. We implemented the most used eCRSwNP mouse model based on OVA+SEB intranasal challenges. Readouts including inflammatory features by (immuno)histology of the sinonasal epithelium (NP formation, eosinophils, epithelial and basement membrane thickness, fibrosis, goblet cells, Charcot-Leyden crystals (CLC)-like, tight junctions) and IgE production by enzyme-linked immunosorbent assay (ELISA), were compared to features of the corresponding human disease. The OVA+SEB model induced eosinophilic inflammation of upper and lower airways, with epithelial and basement membrane thickening, goblet cell hyperplasia and subepithelial fibrosis in the sinuses, along increased IgE production. Except local IgE in nasal lavage (NL), which was only increased in OVA+SEB group, all other features did not differ between OVA and OVA+SEB groups. Macro- or microscopic NP were not detected. With the notable exception of local IgE production, the addition of SEB did not induce additional inflammatory or structural change in the sinuses from mice exposed to and challenged with OVA. This model might represent a model for severe upper airway allergy rather than a specific model of human eCRSwNP.

Pneumoascariasis: Ascaris Worm Infestation in the Lungs

Pneumoascariasis is an infestation from one of the most common worms or helminths found on earth in the respiratory system. The worm is called Ascaris lumbricoides, which penetrates and infests the human body through the fecal-oral process. The fertilized Ascaris ova, or simply egg, would develop into larvae, which then move to the liver and lungs through the portal vein system. These larvae will soon develop into mature worms in the human respiratory system, inside the lungs, particularly in the bronchioles. These Ascaris larvae trigger common symptoms such as persistent cough, shortness of breath, and wheezing. To diagnose this condition, supplementary examinations are necessary since it is difficult to diagnose only by history taking and some physical exams. Additional exams include chest X-rays that, at one point, display lung infiltration. The chest computed tomography (CT) scan shows ground-glass opacity and a classic inflammation marker called Charcot-Leyden crystals that are most likely present. Pneumoascariasis is often misinterpreted and misdiagnosed. Therefore, this literature review was made to further understand about pneumoascariasis.

Ym1 protein crystals promote type 2 immunity

Spontaneous protein crystallization is a rare event, yet protein crystals are frequently found in eosinophil-rich inflammation. In humans, Charcot-Leyden crystals (CLCs) are made from galectin-10 (Gal10) protein, an abundant protein in eosinophils. Although mice do not encode Gal10 in their genome, they do form pseudo-CLCs, made from the chitinase-like proteins Ym1 and/or Ym2, encoded by Chil3 and Chil4 and made by myeloid and epithelial cells respectively. Here, we investigated the biological effects of pseudo-CLCs since their function is currently unknown. We produced recombinant Ym1 crystals which were shown to have identical crystal packing and structure by X-ray crystallography as in vivo native crystals derived from murine lung. When administered to the airways of mice, crystalline but not soluble Ym1 stimulated innate and adaptive immunity and acted as a type 2 immune adjuvant for eosinophilic inflammation via triggering of dendritic cells (DCs). Murine Ym1 protein crystals found at sites of eosinophilic inflammation reinforce type 2 immunity and could serve as a surrogate model for studying the biology of human CLCs.

Ym1 protein crystals promote type 2 immunity.

Spontaneous protein crystallization is a rare event, yet protein crystals are frequently found in eosinophil-rich inflammation. In humans, Charcot-Leyden crystals (CLCs) are made from galectin-10 (Gal10) protein, an abundant protein in eosinophils. Although mice do not encode Gal10 in their genome, they do form pseudo-CLCs, made from the chitinase-like proteins Ym1 and/or Ym2, encoded by Chil3 and Chil4 and made by myeloid and epithelial cells respectively. Here, we investigated the biological effects of pseudo-CLCs since their function is currently unknown. We produced recombinant Ym1 crystals which were shown to have identical crystal packing and structure by X-ray crystallography as in vivo native crystals derived from murine lung. When administered to the airways of mice, crystalline but not soluble Ym1 stimulated innate and adaptive immunity and acted as a type 2 immune adjuvant for eosinophilic inflammation via triggering of dendritic cells (DCs). Murine Ym1 protein crystals found at sites of eosinophilic inflammation reinforce type 2 immunity and could serve as a surrogate model for studying the biology of human CLCs.

Histopathology of Allergic Fungal Rhinosinusitis Versus Chronic Rhinosinusitis with Nasal Polyps.

Structured histopathology (SHP) is a method of analyzing sinonasal tissue to characterize endotypes of chronic rhinosinusitis with nasal polyps (CRSwNP). Allergic fungal rhinosinusitis (AFRS) shares several features with certain endotypes of CRSwNP. Our objective was to compare the histopathology of AFRS and eosinophilic CRSwNP to further understand whether they are separate endotypes or disease entities altogether. A retrospective review of AFRS and CRSwNP patients undergoing endoscopic sinus surgery was performed. Data were collected on demographics, comorbidities, subjective and objective severity scores, and 13-variable SHP reports. CRSwNP patients with >10 eosinophils per high-power field (eCRSwNP) were included. Chi-squared and t-tests were used for statistical analysis. A total of 29 AFRS and 108 eCRSwNP patients were identified. AFRS patients were younger and more often Black. Symptom severity scores (SNOT-22, Lund-MacKay, and Lund-Kennedy) were uniform between groups. AFRS patients had a higher rate of Charcot-Leyden crystals (41.4% vs. 10.2%; p < 0.001). Severe degree of inflammation, eosinophilic inflammatory predominance, eosinophil aggregates, subepithelial edema, and basement membrane thickening were common in both groups, and their rates were not statistically significantly different between groups. Metaplasia, ulceration, fibrosis, and hyperplastic/papillary change rates were low (<30%) and similar between groups. The SHP of eCRSwNP and AFRS are highly consistent, which suggests AFRS is a severe subtype of CRSwNP overall rather than a separate disease entity. This also lends credence to AFRS belonging on the endotypic spectrum of CRSwNP. 3 Laryngoscope, 134:2617-2621, 2024.

Frequency of strongyloidiasis and associated factors: Analysis of 13 years of laboratory results in a tertiary referral hospital in Honduras, 2010-2022.

The frequency of detected strongyloidiasis is affected by the selected laboratory method in the studied population. Considering that Honduras has few community-based studies, the analysis of the laboratory record data can provide information helping to understand this parasitosis. To estimate the frequency and to identify the factors associated with strongyloidiasis, analyzing the laboratory records of the Servicio de Parasitología at Hospital Escuela in Tegucigalpa (Honduras) between 2010 and 2022. We carried out a descriptive, cross-sectional, analytical study. The laboratory diagnosis consisted of stool samples' examination by direct smear and modified Baermann technique. We estimated frequencies and percentages. The statistical association was calculated with prevalence ratios and a 95% confidence interval. Software R, version 4.2.0, and epiR package, version 2.0.46, were used to perform the analysis. The frequency of strongyloidiasis was 0.29% (112/38,085). It was higher with the modified Baermann technique (0.87%; 40/4,575) among male patients (0.44%; 70/15,758). Regarding the age, strongyloidiasis was higher in the 20-40 years old group (0.41%; 28/6,886) with direct smear and 41-61 years old (1.14%; 14/1,232) group with the modified Baermann technique. Among the factors associated with strongyloidiasis were age between 20 and 61 years old (PR=2.26, CI 95%=1.53-3.31), male patients (PR=2.34, CI 95%=1.60‑3.44), mucus (PR=1.86, CI 95%=1.22-2.83) and Charcot-Leyden crystals in stool (PR=8.47, CI 95%=5.14-13.96); watery stool (PR=2.39, CI 95%=1.55-3.68), and other helminthiases (PR=6.73, CI 95%=3.98-11.38). Associated factors to cases detected with the modified Baermann technique were outpatient consultation (PR=4.21, CI 95%=1.91-9.28) and formed stools (PR=3.99, CI 95%=1.94-8.19). The modified Baermann technique increased the detection of strongyloidiasis almost four times. Most cases were distributed among male adults. The cases diagnosed exclusively with the modified Baermann technique have differences from those with observed larvae in the direct smear. It is necessary to develop community-based population studies.

Myocarditis as a cause of neonate’s circulatory failure during delivery - case study

&#x0D; Myocarditis (MCI) is a heart pathology characterized by its rare occurrence and a possible fatal course. In the natural history of the disease inflammatory cell infiltrates are present. There are subtypes of MCI depending on the predominant cell type in the biopsy sampls. One of them is eosinophilic myocarditis. In eosinophilic myocarditis more that 50% of the cells are eosinophils. In the later phases of the disease the myocardium is infiltrated by fibrous tissue and the heart vessels are often affected by thrombosis. Cardiomyopathy is a common long-term complication of the MCI.&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; Reported case presents a death of a male neonate. The neonate was delivered by vaginal delivery. Both prenatal development and all the prenatal tests indicated proper development of the fetus. At the delivery the neonate weight was 3900 grams and was evaluated with only 1 point on the Apgar score. Moreover, the neonate presented a complete acute cardiorespiratory failure at birth. Despite the 2 hour-long cardio-pulmonary resuscitation no return of spontaneous circulation was observed. The neonate’s remains were pathologically as well as histologically examined. The microscopic examination of the neonate’s heart samples contained many inflammatory cell infiltrations. Microabscesses with Charcot-Leyden crystals inside were also observed. Furthermore, the presence of atypical, polynuclear cells was noted. On the basis of the morphological image, it was recognized as an eosinophilic MCI.&#x0D;

A Rare Case of Charcot-Leyden Crystals In liver biopsy in a 14-Year-Old Boy with Persistent Fever and Miliary Infiltrates

The presence of Charcot-Leyden Crystals in liver biopsy is rare. A report case of a 14-year-old boy who presented with persistent fever and respiratory symptoms. Chest X-ray and CT thorax showed miliary infiltrates. The Mantoux test was positive and sputum for acid-fast bacilli (AFB) was negative. The patient started antitubercular therapy (ATT). There was no response and the patient still had fever. Further evaluation with an ultrasound of the abdomen revealed multiple small liver abscesses with septic emboli in the spleen. Since the patient was non-responsive to antibiotics, biopsy from the lesion in the liver was suggested. Biopsy report revealed Charcot-Leyden crystals with no granulomas. The Patient was diagnosed as a case of systemic parasitic infestation. Albendazole under steroid cover was prescribed and the patient was afebrile on follow-up. It was concluded that the presence of CLCs in a biopsy specimen is rare but may be a cause of an underlying parasitic infestation. Early diagnosis and treatment with antiparasitic drugs can lead to a favorable outcome.

Endotyping Difficult-to-Treat Chronic Rhinosinusitis with Nasal Polyps by Structured Histopathology

Introduction: This study aimed to identify the histopathologic characteristics associated with difficult-to-treat chronic rhinosinusitis with nasal polyps (CRSwNPs), enabling physicians to predict the risk of poor outcome after endoscopic sinus surgery (ESS). Methods: A prospective cohort study performed at the First Affiliated Hospital of Sun Yat-sen University between January 2015 and December 2018 with CRSwNP patients who underwent ESS. Polyp specimens were collected during surgery and were subjected to structured histopathological evaluation. Difficult-to-treat CRSwNPs were determined at 12–15 months post-operation according to the European Position Paper. Multiple logistic regression model was used to assess the association between histopathological parameters and the difficult-to-treat CRSwNP. Results: Among 174 subjects included in the analysis, 49 (28.2%) were classified with difficult-to-treat CRSwNP, which had higher numbers of total inflammatory cells, tissue eosinophils, and percentages of eosinophil aggregates and Charcot-Leyden crystals (CLC) formation but a lower number of interstitial glands than the nondifficult-to-treat CRSwNP. Inflammatory cell infiltration (adjusted OR: 1.017), tissue eosinophilia (adjusted OR: 1.005), eosinophil aggregation (adjusted OR: 3.536), and CLC formation (adjusted OR: 6.972) were independently associated with the difficult-to-treat outcome. Furthermore, patients with tissue eosinophil aggregation and CLC formation had an increasingly higher likelihood of uncontrolled disease versus those with tissue eosinophilia. Conclusion: The difficult-to-treat CRSwNP appears to be characterized by increased total inflammatory infiltrates, tissue eosinophilia, eosinophil aggregation, and CLC formation in structured histopathology.

Glutathione disrupts galectin-10 Charcot-Leyden crystal formation to possibly ameliorate eosinophil-based diseases such as asthma.

Charcot-Leyden crystals (CLCs) are the hallmark of many eosinophilic-based diseases, such as asthma. Here, we report that reduced glutathione (GSH) disrupts CLCs and inhibits crystallization of human galectin-10 (Gal-10). GSH has no effect on CLCs from monkeys ( Macaca fascicularis or M. mulatta), even though monkey Gal-10s contain Cys29 and Cys32. Interestingly, human Gal-10 contains another cysteine residue (Cys57). Because GSH cannot disrupt CLCs formed by the human Gal-10 variant C57A or inhibit its crystallization, the effects of GSH on human Gal-10 or CLCs most likely occur by chemical modification of Cys57. We further report the crystal structures of Gal-10 from M. fascicularis and M. mulatta, along with their ability to bind to lactose and inhibit erythrocyte agglutination. Structural comparison with human Gal-10 shows that Cys57 and Gln75 within the ligand binding site are responsible for the loss of lactose binding. Pull-down experiments and mass spectrometry show that human Gal-10 interacts with tubulin α-1B, with GSH, GTP and Mg 2+ stabilizing this interaction and colchicine inhibiting it. Overall, this study enhances our understanding of Gal-10 function and CLC formation and suggests that GSH may be used as a pharmaceutical agent to ameliorate CLC-induced diseases.

Latent class analysis of structured histopathology in prognosticating surgical outcomes of chronic rhinosinusitis with nasal polyps in Singapore.

Structured histopathology profiling is recommended when reporting chronic rhinosinusitis with nasal polyp (CRSwNP) tissue. The objective of this study is to identify features in structured histopathology that predict outcome after functional endoscopic sinus surgery (FESS) in a cohort of CRSwNP patients from Singapore. Latent class analysis was performed on structured histopathology reports of 126 CRSwNP patients who had undergone FESS. Outcome measures were polyp recurrence, need for systemic corticosteroids, revision surgery or biologics, and disease control at 2 years post-FESS. Three classes were identified. Class 1 was characterised by mild, predominantly lymphoplasmacytic inflammation. Class 2 comprised of 100 eosinophils/HPF, hyperplastic seromucinous glands, mucosal ulceration and mucin containing eosinophil aggregates and Charcot-Leyden crystals. Classes 2 and 3 were significantly associated with uncontrolled disease at 2 years post-FESS. Class 3 was additionally associated with the need for systemic corticosteroids. Eosinophil count, degree of inflammation, predominant inflammatory type, hyperplastic seromucinous glands, mucosal ulceration and mucin containing eosinophil aggregates and Charcot-Leyden crystals predicted need for systemic corticosteroids and uncontrolled disease at 2 years post-FESS. The presence of &gt;100 eosinophils/HPF should be reported, as this subset of tissue eosinophilia was associated with less favourable outcomes after FESS.

Charcot-Leyden crystals: An ancient but never so current discovery

From the first description of Charcot-Leyden crystals (CLCs) to the present, many steps have been taken to understand the mechanisms underlying their formation. In particular, to date not only eosinophils but also mast cells are known to be responsible for the production of CLCs, which represent the crystallized form of Galectin-10. Due to their characteristics, CLCs typically induce a crystallopathy and are responsible for an exacerbation of inflammation. Nasal cytology (NC) has allowed to better understand the correlation between the severity of several rhinopaties and the presence of CLCs in NC samples, which is strictly correlated with an eosinophiles and mast cells infiltration. As a matter of fact, rhinopaties with a mixed eosinophilic-mast cell inflammatory infiltrate, characterized by the presence of abundant CLCs, show a worse prognosis and a higher risk of relapse. This could have important therapeutic implications, since the treatments available today could be exploited to target both eosinophils and mast cells, to reduce the damage induced by CLCs.

Lactose and Galactose Promote the Crystallization of Human Galectin-10.

Galectin-10 (Gal-10) forms Charcot-Leyden crystals (CLCs), which play a key role in the symptoms of asthma and allergies and some other diseases. Gal-10 has a carbohydrate-binding site; however, neither the Gal-10 dimer nor the CLCs can bind sugars. To investigate the monomer-dimer equilibrium of Gal-10, high-performance size-exclusion chromatography (SEC) was employed to separate serial dilutions of Gal-10 with and without carbohydrates. We found that both the dimerization and crystallization of Gal-10 were promoted by lactose/galactose binding. A peak position shift for the monomer was observed after treatment with either lactose or galactose, implying that the polarity of the monomer was reduced by lactose/galactose binding. Further experiments indicated that alkaline conditions of pH 8.8 mimicked the lactose/galactose-binding environment, and the time interval between monomers and dimers in the chromatogram decreased from 0.8 min to 0.4 min. Subsequently, the electrostatic potential of the Gal-10 monomers was computed. After lactose/galactose binding, the top side of the monomer shifted from negatively charged to electrically neutral, allowing it to interact with the carbohydrate-binding site of the opposing subunit during dimerization. Since lactose/galactose promotes the crystallization of Gal-10, our findings implied that dairy-free diets (free of lactose/galactose) might be beneficial to patients with CLC-related diseases.

Murine model for chronic rhinosinusitis: an interventional study

BackgroundChronic rhinosinusitis (CRS) is a complex inflammatory disease of the sinonasal tract. To understand this disease entity and develop targeted treatments, a reproducible animal model is paramount.Aims/objectivesTo optimize a murine model of eosinophilic CRS by establishing benchmark histological markers and validate its fidelity in evaluating intranasal treatments.Material and methodsForty-five Balb/c mice were included in the 7-week protocol. Experimental animals (n = 20) were induced a CRS disease state upon receiving intraperitoneal sensitization with ovalbumin (OVA), followed by intranasal OVA with Aspergillus oryzae protease. Analysis of complete blood count with differential, peripheral blood smear, and histological markers from the nasal cavity mucosa were performed. CRS mice were additionally treated with intranasal saline (n = 5) or mometasone (n = 10) and compared with control groups of untreated CRS (n = 5) and healthy (n = 5) mice after week 7.ResultsHistological analysis of experimental animal nasal mucosa revealed significantly higher levels of eosinophilic tissue infiltration/degranulation, hyaline droplets, Charcot–Leyden crystals, and respiratory epithelial thickness compared to healthy controls. Treatment with mometasone significantly reversed the histopathological changes observed in CRS mice.Conclusion and significanceThis murine model induced substantial local eosinophilic inflammation within sinonasal mucosa, that was reversible with mometasone. This model may be used to evaluate the efficacy of therapeutics designed to target CRS.

Presence of eosinophil extracellular trap cell death in the affected skin of eosinophilic granulomatosis with polyangiitis.

Eosinophil activation in tissue might be associated with disease severity. Eosinophil cytolysis, a process of active cell death, has been referred to as eosinophil extracellular trap cell death (EETosis). In the present study, the authors investigated EETosis in the affected skin of four patients with eosinophilic granulomatosis with polyangiitis (EGPA) using an immunofluorescence staining method. Immunofluorescence staining for myelin basic protein, galectin-10, and DNA revealed various degrees of EETosis and Charcot-Leyden crystals in skin tissue, suggesting the different degree of eosinophil activation status. The histopathological characteristic features may help physicians establish an earlier diagnosis of intractable eosinophilic-related disease including EGPA. Furthermore, ETotic eosinophil infiltration in perineurium of skin tissue might play a primary role in peripheral neuropathy of this disorder.

Galectin-10 as a Potential Biomarker for Eosinophilic Diseases.

Galectin-10 is a member of the lectin family and one of the most abundant cytoplasmic proteins in human eosinophils. Except for some myeloid leukemia cells, basophils, and minor T cell populations, galectin-10 is exclusively present in eosinophils in the human body. Galectin-10 forms Charcot–Leyden crystals, which are observed in various eosinophilic diseases. Accumulating studies have indicated that galectin-10 acts as a new biomarker for disease activity, diagnosis, and treatment effectiveness in asthma, eosinophilic esophagitis, rhinitis, sinusitis, atopic dermatitis, and eosinophilic granulomatosis with polyangiitis. The extracellular release of galectin-10 is not mediated through conventional secretory processes (piecemeal degranulation or exocytosis), but rather by extracellular trap cell death (ETosis), which is an active cell death program. Eosinophils undergoing ETosis rapidly disintegrate their plasma membranes to release the majority of galectin-10. Therefore, elevated galectin-10 levels in serum and tissue suggest a high degree of eosinophil ETosis. To date, several studies have shown that galectin-10/Charcot–Leyden crystals are more than just markers for eosinophilic inflammation, but play functional roles in immunity. In this review, we focus on the close relationship between eosinophils and galectin-10, highlighting this protein as a potential new biomarker in eosinophilic diseases.