Number Of Eosinophils Research Articles

Plain Language Summary of principles for improving the care of people with eosinophil-associated diseases.

Eosinophil-associated diseases (EADs) are a group of conditions in which eosinophils (a type of white blood cell) are thought to play a key role in the disease and how it develops. Some EADs are common, such as atopic dermatitis (also called eczema) and a subtype of asthma called eosinophilic asthma, while others are rare, such as hypereosinophilic syndrome (a condition in which a person has a very high number of eosinophils in both the blood and one or more organs). People with EADs face many problems related to their conditions. Symptoms such as severe abdominal pain, itch, or shortness of breath impact both the patient as well as their friends and family. Patients with EADs also experience delays to diagnosis and treatment as well as financial barriers. Healthcare professionals sometimes fail to recognize the complex set of symptoms that characterize an EAD, and this may cause delays in reaching a correct diagnosis. As a result, it may take longer for a patient to get the best care and the most effective treatments, which may contribute to poor health. The goal of this charter is to describe the key elements of good quality care, which all people with EADs deserve, as well as to present an action plan to improve health and overall well-being for people with EADs. Proposed use of this patient charter: The principles described in this charter (a written guide to achieve an outcome) show the core elements of quality care that people with EADs must receive. They also describe clear steps to reduce the burden on patients and their caregivers and to improve patient health outcomes. We urge healthcare professionals, hospitals, and policymakers around the world to adopt these principles quickly. By doing this, people with EADs will be more likely to receive an accurate and timely diagnosis and have access to quality care and treatment in the right setting.

Diagnostic role of fractional exhaled nitric oxide in pediatric eosinophilic esophagitis, relationship with gastric and duodenal eosinophils

Eosinophilic esophagitis (EoE) is an eosinophilic-predominant inflammation of the esophagus diagnosed by upper endoscopy and biopsies. A non-invasive and cost-effective alternative for management of EoE is being researched. Previous studies assessing utility of fractional exhaled nitric oxide (FeNO) in EoE were low powered. None investigated the contribution of eosinophilic inflammation of the stomach and duodenum to FeNO. To assess the utility of FeNO as a non-invasive biomarker of esophageal eosinophilic inflammation for monitoring disease activity. Patients aged 6-21 years undergoing scheduled upper endoscopy with biopsy for suspected EoE were recruited in our observational study. Patients on steroids and with persistent asthma requiring daily controller medication were excluded. FeNO measurements were obtained in duplicate using a chemiluminescence nitric oxide analyzer (NIOX MINO, Aerocrine, Inc.; Stockholm, Sweden) prior to endoscopy. Based on the esophageal peak eosinophil count (PEC)/high power field on biopsy, patients were classified as EoE (PEC ≥ 15) or control (PEC ≤ 14). Mean FeNO levels were correlated with presence or absence of EoE, eosinophil counts on esophageal biopsy, and abnormal downstream eosinophilia in the stomach (PEC ≥ 10) and duodenum (PEC ≥ 20). Wilcoxon rank-sum test, Spearman correlation, and logistic regression were used for analysis. P value < 0.05 was considered significant. We recruited a total of 134 patients, of which 45 were diagnosed with EoE by histopathology. The median interquartile range FeNO level was 17 parts per billion (11-37, range: 7-81) in the EoE group and 12 parts per billion (8-19, range: 5-71) in the control group. After adjusting for atopic diseases, EoE patients had significantly higher FeNO levels as compared to patients without EoE (Z = 3.33, P < 0.001). A weak yet statistically significant positive association was found between the number of esophageal eosinophils and FeNO levels (r = 0.30, P < 0.005). On subgroup analysis within the EoE cohort, higher FeNO levels were noted in patients with abnormal gastric (n = 23, 18 vs 15) and duodenal eosinophilia (n = 28, 21 vs 14); however, the difference was not statistically significant. After ruling out atopy as possible confounder, we found significantly higher FeNO levels in the EoE cohort than in the control group.

Long-term mepolizumab treatment reduces relapse rates in super-responders with eosinophilic granulomatosis with polyangiitis

BackgroundThe mainstay of treatment for eosinophilic granulomatosis with polyangiitis (EGPA) is systemic corticosteroid therapy; some patients also receive intravenous immunoglobulins, other immunosuppressive agents, and biologics. Mepolizumab, an anti-interleukin-5 monoclonal antibody, induces remission and decreases the daily corticosteroid dose; however, the clinical efficacy of mepolizumab in EGPA and the prognosis with long-term treatment with this drug are unknown.MethodsSeventy-one EGPA patients were treated at Hiratsuka City Hospital, Japan, between April 2018 and March 2022. We administered mepolizumab for a mean of 2.8 ± 1.7 years to 43 patients in whom remission could not be induced by conventional treatment. After excluding 18 patients who had received mepolizumab for less than 3 years, we classified 15 patients into a “super-responder group” (the daily dose of corticosteroids or other immunosuppressant could be decreased, or the interval between IVIG treatments could be prolonged) and 10 patients into a “responder group” (neither of these changes was achievable). Eosinophil numbers, serum IgG levels, daily doses of corticosteroids and other immunosuppressants, Birmingham Vasculitis Activity Score (BVAS), and relapse frequency before and after mepolizumab initiation were determined.ResultsBlood eosinophil count at diagnosis and the lowest serum IgG level before mepolizumab treatment were significantly higher in super-responders than in responders (p < 0.05). In super-responders, the prednisolone dose at last visit on mepolizumab treatment was lower than that before treatment (p < 0.01) and lower than that at last visit in the responders (p < 0.01). In both groups, peripheral blood eosinophil numbers and BVAS were lower after starting mepolizumab than before (p < 0.01). BVAS before mepolizumab (p < 0.05) and at last visit (p < 0.01) were lower in super-responders than in responders. Relapse rates every year after the start of mepolizumab were lower in super-responders than in responder groups (p < 0.01). In super-responders, relapse rates were lower during the 3 years following mepolizumab initiation (p < 0.01) and at last visit (p < 0.01) were significantly lower than after 1 year of treatment.ConclusionMepolizumab treatment of super-responders sustainably reduced the relapse rate.

IL-21 induces pyroptosis of Treg cells via Akt–mTOR–NLRP3–caspase 1 axis in eosinophilic chronic rhinosinusitis

Regulatory T (Treg) cells, which prevent inflammation-induced eosinophil infiltration, are deficient in nasal polyps (NPs) in patients with eosinophilic chronic rhinosinusitis (ECRS). It is concomitant with loss of Foxp3 after certain inflammatory stimuli. We sought to determine the inflammatory cytokines involved in inducing the loss of Treg cells in NPs. The abundance of cytokines in ECRS patients or mice were tested using ELISA, immunochemistry, immunofluorescence, quantitative reverse transcription PCR (qPCR), and/or flow cytometry. Expression of eosinophil cationic protein (ECP), CD4+ T cells, IL-4, and IL-17A and eosinophils in nasal mucosa of mouse model was investigated by immunochemistry, immunofluorescence, and hematoxylin and eosin staining. The percentage and death of induced Treg (iTreg) cells, source of IL-21 in NPs from ECRS and non-ECRS patients, and abundance of different systemic phenotypes of CD4+ T cells in a mouse model were studied by flow cytometry. Western blot analysis, scanning, and transmission electronic microscopy were used to detect pyroptosis of iTreg cells. IL-21 was highly expressed in nasal mucosa of ECRS patients and mice, causing pyroptosis and preventing development of iTreg cells invitro. The elevated IL-21 in NPs from ECRS patients was mainly produced by CD3+ T cells, including T follicular helper, T peripheral helper, TH2, and TH17 cells and CD3+CD4- T cells. T peripheral helper cells and CD3+CD4- T cells were the predominant source of IL-21 in NPs from non-ECRS patients. Blocking IL-21/IL-21R signaling significantly reduced the number of eosinophils and CD4+ T cells along with ECP, IL-4, and IL-17A expression in the nasal mucosa of ECRS mice. It also increased Treg cell percentage and systemically decreased TH2 and TH17 ratios. Akt-mTOR inhibition prevented IL-21-induced pyroptosis in human and mouse iTreg cells. Elevated IL-21 drives pyroptosis and prevents Treg cell development in ECRS patients. IL-21 induced pyroptosis via activating Akt-mTOR-NLRP3-caspase 1 signaling.

Eosinophils from A to Z.

Eosinophils are bone marrow-derived granulocytes and are found in low numbers in the peripheral blood of healthy subjects. In type 2 inflammatory diseases, eosinopoiesis in the bone marrow is increased, resulting in a rise in the number of mature eosinophils released in the circulation. From the blood, eosinophils can migrate in multiple tissues and organs under both physiological and pathological conditions. Eosinophils exert their various functions through the synthesis and release of a variety of granule proteins and pro-inflammatory mediators. Despite being present in all species of vertebrates, the functional role of eosinophils is still a matter of debate. Eosinophils may play a role in host defense against various pathogens. In addition, eosinophils have been reported to be involved in tissue homeostasis and exhibit immunomodulatory activities. In this review, we aim to provide a broad overview of eosinophil biology and eosinophilic diseases in a lexicon-style format using keywords starting from A until Z with cross-references to other chapters indicated in italics in the text or specified in parentheses.

Effect of Locally Administered Estradiol on Wound Healing in a Nasal Septal Perforation Animal Model.

We aimed to investigate the effect of estradiol on wound healing in an experimental nasal septal perforation (NSP) model created in rats. Twenty-two Sprague Dawley healthy male rats were separated into two groups. NSP, approximately 2 mm in diameter, was created in each animal. The 0.1 mL 0.12% estradiol (12 g/L) (study group) and 0.1 mL 0.9% saline (9 g/L) (control group) were applied topically once a day for 14 days. The rats were sacrificed on the 14th day and the cartilage nasal septum of each animal was excised for histopathological examination. The nasal mucosal epithelial regeneration and degeneration, acute inflammatory cell count, fibroblast number, vascularization, granulation tissue formation, giant cell number, eosinophil number, degeneration and regeneration of the nasal cartilage, and collagen density were examined. The macroscopic closure rate of the perforations and histopathological parameters were evaluated statistically. In this study, the epithelial regeneration, the fibroblast count, the granulation tissue formation, and the amount of collagen were significantly higher in the study group than in the saline group (p < 0.05). The acute inflammatory activity was lower in the estradiol group than in the saline group (p < 0.05). There was no statistically significant difference in the closure rate of perforation between the two groups (p = 0.163). No significant difference was found in other comparisons (p > 0.05). The locally administered estradiol may improve wound healing of the nasal septum in an experimental NSP animal model. LEVEL OF EVIDENCE: Not applicable.

TSLP acts on Tregs to limit effector Th2 cell generation during type 2 immune responses

Abstract Thymic stromal lymphopoietin (TSLP) is a type 2 alarmin secreted by epithelial cells to promote type 2 inflammation. After antigen recognition, naïve CD4 T cells differentiate into effector T (Teff) cells, whereas regulatory T (Tregs) cells suppress the immune response to prevent adverse effects caused by inflammation. Therefore, a delicate balance between Teff and Treg activity is required for the homeostasis of immune responses. Here we generated a TSLPR conditional KO mice (Crlf2fl/fl) to investigate the functional role(s) of TSLP on Teff and Tregs. Conditional deletion of TSLPR on T cells (Cd4CreCrlf2fl/fl) resulted in lower numbers of eosinophils and Th2 cells with OVA-induced airway inflammation. In contrast, conditional deletion of TSLPR on Tregs (Foxp3CreCrlf2fl/fl) resulted in elevated numbers of eosinophils and increased IL-5- and IL-13-secreting effector Th2 cells. Furthermore, phenotypic analysis of Foxp3 +Tregs during type 2 immune responses shows that Tregs from Foxp3CreCrlf2fl/flmice have upregulated levels of GATA3 and secrete IL-13. Together, these data indicate that TSLP not only promotes suppressive activity by Tregs in the generation of Th2 cell-mediated responses but that it also restrains GATA3 production and IL-13 secretion by the Treg cells, indicating a key role for TSLP in shaping an immunosuppressive environment during type 2 immune responses. This research was supported by the Intramural Research Programs of NHLBI, NIH.

Maternal stress increases risk of allergic lung inflammation in adult mice

BackgroundAllergies are increasing worldwide. The presence of atopic diseases in the mother propagates the onset of allergic diseases in the offspring with a considerably stronger penetrance than atopic diseases of the father. Such observation challenges genetic predispositions as the sole cause of allergic diseases. Epidemiological studies suggest that caregiver stress in the perinatal period may predispose offspring to asthma. Only one group has studied the link between prenatal stress and neonatal asthma susceptibility in a murine model. ObjectivesWe aimed to study if the neonatal increased risk of developing allergic lung inflammation persists after puberty and if there are sex differences in susceptibility. MethodsPregnant BALB/c mice were subjected to a single restraint stress exposure at day 15 of gestation. Pups were separated by gender and subjected to a well-known sub-optimal asthma model after puberty. ResultsAdult mice born to stressed dams were more susceptible to developing allergic pulmonary inflammation since an increase in the number of eosinophils in bronchoalveolar lavage (BAL), a greater peribronchial and perivascular infiltrate, a higher proportion of mucus-producing cells, and increased IL-4 and IL-5 levels in BAL were detected compared to control mice. These effects were more profound in females than males. Moreover, only females from stressed dams showed an increase in IgE levels. ConclusionsIncreased litter susceptibility to develop allergic lung inflammation induced by maternal stress persists after puberty and is more potent in females than in male mice.

NOX2-Deficient Pulmonary Neutrophils and Macrophages Have Lower PD-L1 Expression and May Aggravate Allergic Lung Inflammation through Affecting ILC Populations

Abstract Redox balance plays an important role in the pathogenesis of allergic asthma. We previously reported that NADPH oxidase 2 (NOX2)-derived ROS may modulate tissue inflammation through affecting neutrophil programmed cell death 1 ligand 1 (PD-L1) expression. To reveal the role of NOX2 in regulating PD-L1 expressions on pulmonary neutrophils and macrophages and in ILC differentiation, we established an allergic asthma model using NOX2-deficient (Cybb−/−)mice stimulated with the Dermatophagoides pteronyssinus(Der p) extract along with LPS. We first found that NOX2 deficiency led to increased group 2 innate lymphoid cell (ILC2) in Der p extract induced lung inflammation. The cell numbers of neutrophil, eosinophil and alveolar macrophage (AM) also increased in the stimulated Cybb−/−mice when compared with WT mice. The AM in Cybb−/−mice expressed higher levels of CD11b and the M2 marker CD163 and produced more TNF-α. Moreover, the Cybb−/−neutrophils and AMs had low PD-L1 expressions while ILC2s had significant levels of programmed cell death 1 (PD-1) expression in the inflammatory lungs. Altogether, these results indicated that NOX2 deficiency may lead to downregulation of PD-L1 expression on neutrophils and AMs while eliciting the M2 phenotype and inducing higher amounts of pro-inflammatory cytokine production. Our results suggested that the lowered PDL1 on NOX2-deficient neutrophils and AMs may aggravate allergic Inflammation through affecting ILC populations in the lung.

Inflammation à éosinophiles du tube digestif

Eosinophilic inflammation of the digestive tract is an inflammatory disease characterized by extensive infiltration of eosinophils into the gastrointestinal tract. It can be either a primary disorder of the digestive tract or be secondary to another cause of tissue eosinophilia. Primary disorders include eosinophilic esophagitis (OE) and eosinophilic gastroenteritis (GEEo). These are 2 rare pathologies considered to be diseases related to a Th2-mediated food allergy. The role of the pathologist is twofold: (1) he must make the diagnosis of tissue esosinophilia and propose the various causes, knowing that a secondary cause is the most frequently observed; (2) identify the abnormal number of polymorphonuclear eosinophils, which implies knowing the normal distribution of eosinophils in the different digestive segments. To carry the diagnosis of EO, the threshold of polymorphonuclear eosinophils must be≥15/fields×400. There is no predefined threshold concerning the other segments of the digestive tract to carry the diagnosis of GEEO. In addition, to make the diagnosis of primary digestive tissue eosinophilia, the patient must be symptomatic with histological evidence of eosinophilia and have ruled out all secondary causes. The main differential diagnosis of OE is gastroesophageal reflux disease. The differential diagnoses of GEEo are multiple, including primarily drugs and parasitic infections.

Oral exposure to Escherichia colitoxin protects against lung allergen-induced inflammation

Abstract Recent studies suggest that the intestinal microenvironment regulate lung immune cells. Conversely, changes in the lung can modulate the gut immune system. Yet, mucosal-associated immune responses have been studied in a compartmentalized manner, as if there is no communication between different organs. Thus, the role of the gut-lung axis in mucosal immune responses is poorly understood. Using enterotoxigenic Escherichia coli (ETEC), we established a model of intestine-localized infection without translocation to any other tissue. In response to ETEC, type 2 innate lymphoid cells (ILC2s) and eosinophils accumulated in the intestinal lamina propria, even after bacterial clearance. In addition, oral ETEC transiently increased the numbers of ILC2 and eosinophils in the lung parenchyma. To test if oral ETEC promote lung immune responses to allergen, we exposed mice that recently cleared ETEC to intranasal papain/ovalbumin allergy induction model. Unexpectedly, ETEC-exposed mice were significantly resistant to allergen-induced lung inflammation, with reduced number of ILC2, Type 2 effector CD4 +T cells (Th2) and eosinophils. Paradoxically, oral ETEC-induced protection against lung allergen exposure was dependent on IL-33: IL-33KO mice developed partial lung inflammation in this model, and no protection induced by ETEC exposure was observed. Importantly, protection from allergy was achieved with ETEC heat-labile toxin (LT) oral exposure; we also found that the toxicity domain of LT is needed for this protection. Our results indicate that gastrointestinal bacterial infection mediators (toxins) negatively regulate the onset of allergic inflammation and may provide a novel immunological basis for the “hygiene hypothesis”. R01AI170649 FAPESP 2021/15185-2

IgG4 related disease: a novel association with hypertrophic osteoarthropathy

IgG4 related disease (IgG4-RD) is a recently recognized disease that has several associated clinical phenotypes including autoimmune pancreatitis, sclerosing cholangitis, major salivary gland enlargement (Mikulicz disease), orbital pseudotumor, retroperitoneal fibrosis, and inflammatory vascular disease manifesting as aortitis or coronary artery calcification. Histopathology of affected organs shows lymphoplasmacytic infiltrations with a predominance of IgG4-positive plasma cells in the affected tissue and an increased number of eosinophils. Serum IgG4 levels are elevated in two-thirds of patients, and IgE is also often elevated. We report here the first known associated case of presumed IgG4-RD with hypertrophic osteoarthropathy. Hypertrophic osteoarthropathy (HOA) is frequently a paraneoplastic disease of bone, but HOA can be associated with chronic infection, chronic pulmonary disease, cardiac shunts, and cirrhosis. HOA is a clinical diagnosis consisting of arthralgia, digital clubbing, and periostosis of tubular bones seen on imaging with or without synovial effusion. Our 35 yo male LatinX patient presented with typical clinical symptoms of HOA that were confirmed on imaging. During the negative work up for malignancy, disproportionate-for-age coronary artery calcification was identified, which prompted an evaluation for IgG4-RD. The patient also had lung disease (peribronchial thickening), atopic dermatitis, subtle clubbing, elevated IgE, elevated IgG4 (9× normal), and eosinophilia. The patient's symptoms and inflammatory markers improved on prednisone and methotrexate, but a decision to treat with rituximab was made after having to discontinue methotrexate for transaminitis. Rituximab has been used in patients with IgG4-RD with some success, and our patient continues to improve in his skin, respiratory, and bone symptoms with reduction in IgG4, inflammatory markers, and bone turnover markers (alkaline phosphatase).

Potential role for a Nematode Pan Allergen (NPA) in Tropical Pulmonary Eosinophilia (TPE)

Abstract Tropical Pulmonary Eosinophilia (TPE) is an asthma-like hyper-responsive syndrome characterized by accumulation of a high number of eosinophils in the lungs leading to severe respiratory morbidity in patients infected with lymphatic filariasis (LF), a helminth parasitic infection that affects 51 million people in 47 different countries worldwide. Subjects showing TPE also have circulating microfilariae (larval stages of LF) and a high titer of parasite-specific IgE in their blood. IgE and eosinophils are thought to play a major role in TPE pathology. However, specific antigens that are released from microfilariae responsible for generating the IgE antibodies in TPE are not known. Therefore, in this study, we screened a phage displayed cDNA expression library of Wuchereria bancrofti microfilaria with human monoclonal IgE antibodies generated from B cells isolated from TPE patients. The iterative screening identified WbNPA (Nematode Pan Allergen) and WbTCTP (Translationally Controlled Tumor Protein) as IgE antibody binding antigens. Subsequent analysis showed that rWbNPA and rWbTCTP can result in the release of histamine from mast cells in an IgE-dependent and independent manner. rWbNPA can induce accumulation of eosinophils in the peritoneal cavity of mice and can trigger the secretion of IL-2 and TNF-α from alveolar macrophages. These results suggest that WbNPA and WbTCTP have a potential role in the pathology of TPE in LF infections.

Characterization of a group of children with eosinophilic esophagitis in Cali, Colombia.

Eosinophilic esophagitis (EoE) is an immunologically mediated chronic disease of the gastrointestinal tract. The objective of this study was to clinically and demographically describe a child population with EoE diagnosed in a high-complexity hospital in Cali, Colombia. A retrospective study was carried out. The clinical histories of patients between 0 and 18 years with clinical suspicion and a histological diagnosis of EoE were analyzed. All patients underwent an allergy study, either by measurement of specific immunoglobulin (Ig) E and/or an intraepidermal skin-prick test. Thirty-five patients were included in the study, of which 21 (60%) women. The median age was 8 years (interquartile range [IQR] 5-12), and the age of onset of symptoms was 5 years (IQR 2-10). Thirty patients (85.7%) reported a history of allergic disease, with rhinitis being the most frequent (n = 25, 71.4%). Only one patient reported with food allergy mediated by IgE. The main symptoms in patients included abdominal pain (17 [48.6%]), refractory gastroesophageal reflux (16 [45.7%]), and choking (9 [25.7%]). Upper gastrointestinal endoscopy was normal in 10 patients (38.5%). The median number of eosinophils in the biopsy was 42 (IQR 31-92). Allergenic sensitization was verified in 25 of 35 patients (71.4%). Of these, dust mite allergy was positive in 21 patients (84%), while the most frequent food allergy was toward cow's milk, in five patients (31.3%). The majority of patients with EoE were females. The most frequent symptom was abdominal pain. Endoscopic abnormalities were also observed frequently, and the prevalence of other allergic diseases (especially rhinitis) and allergenic sensitization (especially to mites) was high.

Evaluation and Treatment of a Severe Case of Pediatric Idiopathic Hypereosinophilic Syndrome

BackgroundHypereosinophilic syndromes (HES) are a group of rare disorders characterized by marked peripheral eosinophilia resulting in end organ damage. When evaluating a patient with persistent hypereosinophilia, it is important to screen for the more common secondary causes of eosinophilia and assess for primary, myeloid HES. When no clear etiology is determined, a diagnosis of idiopathic HES is made. While this evaluation can be clinically challenging, making an accurate diagnosis can help guide effective treatment. CaseA 3-year-old Caucasian female with profound peripheral eosinophilia (70,100 cells/mL) and lymphocytosis (24,900 cells/mL) presented for immunologic evaluation following a two year history of persistent eosinophilia (1,450–27,700 cells/mL), presumably secondary to recurrent toxocariasis. The patient had been treated with albendazole three times for Toxocara after having positive serology and imaging consistent with visceral larva migrans in the context of an otherwise negative extensive infectious evaluation. Intermittent oral steroids and daily medium-dose inhaled steroids had also been started for wheezing. A bone marrow biopsy (BMbx) demonstrated increased numbers of eosinophils with cytoplasmic vacuoles, areas of hypogranulation, and subtle segmentation abnormalities, but genetic rearrangements for PDGFRA, PDGFRB, FIP1L1, and JAK2 were negative. An abnormal population of lymphocytes (CD3-CD4+) making up 1.7% of total lymphocytes was noted; however, this was not reproducible on repeat BMbx. Positron emission tomography redemonstrated bilateral pulmonary nodules and mild hilar lymphadenopathy, and bronchoalveolar lavage was normal other than an eosinophilia. The remainder of her immunologic evaluation was normal other than a pan-hypergammaglobulinemia without evidence ofT or B cell clonality. A 429 gene primary immunodeficiency panel was not felt to be clinically significant.Given the patient's persistent eosinophilia, oral steroids at 2 mg/kg were started with only a partial response (2,600 eosinophils/mL). Ultimately, mepolizumab 100 mg injected subcutaneously every 4 weeks was started as steroid sparing therapy with an excellent clinical response (780 eosinophils/mL) even after weaning off of oral steroids. ConclusionThis unique case illustrates the importance of a thorough evaluation of patients with persistent eosinophilia and the efficacy of mepolizumab in a child with marked idiopathic HES.

Morphological features of skin changes in the undetermined clinical picture of psoriasis and atopic dermatitis in children

Absrtact Introduction The literature describes atypical clinical forms of psoriasis and atopic dermatitis in children that combine features of both diseases. In such cases, dermatologists resort to biopsy of plaque skin elements in the complex diagnosis. However, the histological picture in these biopsy specimens is uncertain and does not allow to make an unequivocal judgment about the correspondence of changes to one or another disease. The purpose of work was to compare pathomorphological changes in biopsy specimens of plaque skin elements in children with undetermined clinical picture of the disease with changes in typical forms of psoriasis and atopic dermatitis. Materials and methods A morphometric study of 10 plaque skin biopsy specimens from children (mean age 9.2±1.11 years) with an indeterminate clinical picture of the disease was performed. The obtained data were compared with two control groups of adult patients with typical clinical pictures of psoriasis (n=20; mean age 34.35±3.58 years) and atopic dermatitis (n=10; mean age 41.33±7.35 years). Results A comparative morphometric analysis of skin biopsy specimens revealed the fewest differences between the analyzed parameters of the squamous epithelium of the patients in the study group and the group with psoriasis. In all three groups, the main mass of the inflammatory infiltrate in the dermis was composed of lymphocytes and macrophages whose numerical density differed in psoriasis and atopic dermatitis at different levels of the dermis, while in the study group it had intermediate values. The number of neutrophils and eosinophils in the study group had minimal values. Discussion Morphological changes in the epidermis of the study group were closest to those in psoriasis, while the cellular composition of the inflammatory infiltrate of the dermis did not correspond to any of the control groups and had either intermediate values (in terms of lymphocytes and macrophages) or minimal values (in terms of eosinophils and neutrophils).

Leukocyte Differentiation Mice (Mus Musculus) Infected with Plasmodium Berghei after Therapy With Sargassum Duplicatum Extract

Leukocytes are white blood cells produced by hematopoietic tissue that serves to help the body fight various infectious diseases as part of the immune system. Sargassum duplicatum contains steroid, alkaloid, phenol, flavonoid, saponin, and tannin compounds that can be immunomodulatory. The purpose of this research is to know the effect of methane extract of brown algae Sargassum duplicatum on the differentiation of leukocyte mice (Mus musculus) infected with Plasmodium berghei. Mice weighing 20-30 grams in Plasmodium berghei infection as much as 0.1 ml per head and left to the percentage of parasitemia reaches 1-5%. Then the mice (Mus musculus) were given brown algae methanol extract (Sargassum duplicatum) at doses 10, 100, and 200 mg / g BW for 4 consecutive days. From day 0 to 6 also made a blood smear to calculate the number of leukocytes. Data analysis will be done using ANOVA. The results showed that the administration of brown algae extracts of Sargassum duplicatum influenced in increasing the number of neutrophils, monocytes, and basophils and decreased the number of eosinophils and lymphocytes of mice infected with Plasmodium berghei to near normal range. Dose 200 mg/kg BB methanol extract of brown alga Sargassum duplicatum is a dose that can affect the number of neutrophils, eosinophils, lymphocytes, and monocytes of mice infected with Plasmodium berghei most closely to normal range.

An Inflammatory Myopathy in the Dutch Kooiker Dog.

The Dutch Kooiker dog (het Nederlandse Kooikerhondje) is one of nine Dutch dog breeds. As of 1960, a number of heritable diseases have been noted in this breed. One is an inflammatory myopathy that emerged in 1972, with numbers of affected dogs gradually increasing during the last few decades. The objective of this paper is to describe clinical signs, laboratory results, electromyography and histopathology of the muscle biopsies of the affected dogs. Method: Both retrospectively as well as prospectively affected Kooiker dogs were identified and categorized using a Tiered level of Confidence. Results: In total, 160 Kooiker dogs-40 Tier I, 33 Tier II and 87 Tier III-were included. Clinical signs were (1) locomotory problems, such as inability to walk long distances, difficulty getting up, stiff gait, walking on eggshells; (2) dysphagia signs such as drooling, difficulty eating and/or drinking; or (3) combinations of locomotory and dysphagia signs. CK activities were elevated in all except for one dog. Histopathology revealed a predominant lymphohistiocytic myositis with a usually low and variable number of eosinophils, neutrophils and plasma cells. It is concluded that, within this breed, a most likely heritable inflammatory myopathy occurs. Further studies are needed to classify this inflammatory myopathy, discuss its treatment, and unravel the genetic cause of this disease to eradicate it from this population.

Expanded ILC2s in human infant intestines promote tissue growth

Early life is characterized by extraordinary challenges, including rapid tissue growth and immune adaptation to foreign antigens after birth. During this developmental stage, infants have an increased risk to immune-mediated diseases. Here, we demonstrate that tissue-resident, IL-13 and IL-4-producing ILC2s are enriched in human infant intestines compared to adult intestines. Organoid systems were employed to assess the role of infant intestinal ILC2s in intestinal development and showed that IL-13 and IL-4 increased epithelial cell proliferation and skewed cell differentiation towards secretory cells. IL-13 furthermore upregulated the production of mediators of type-2 immunity by infant intestinal epithelial cells, including VEGF-A and IL-26, a chemoattractant for eosinophils. In line with these in vitro findings increased numbers of eosinophils were detected in vivo in infant intestines. Taken together, ILC2s are enriched in infant intestines and can support intestinal development, while inducing an epithelial secretory response associated with type 2 immune-mediated diseases.

Status Jumlah Leukosit pada Petani Garam di Desa Romokalisari Kecamatan Benowo Kota Surabaya

White blood cells or leukocytes are an important component that acts as an immune system in the blood. Salt farmers work under hot sun exposure and lack the understanding to wear personal protective equipment, which causes the body's resistance to decrease so that the number of leukocyte cells also decreases. The number of leukocytes is reduced, making the body susceptible to infection. Immunity is resistance to several diseases, namely against infectious diseases. This study aims to describe the results of examining leukocyte cell counts in salt farmers in Romokalisari Village. This study uses a descriptive method conducted by observation. The sample in the study was all salt farmers, as many as 25 people. The results showed that the salt farmers examined did not experience abnormalities in the number of leukocytes. However, there was an increase in the number of eosinophils from the normal value of 6 out of 25 samples with a percentage of 24%. The conclusion from the samples examined obtained the results of 84% normal leukocytes, and 16% got abnormal leukocyte results, so salt farmers can be said to be healthy.