Eosinophilic Infiltration Research Articles

Serum Periostin is Able to Stratify Type 2-Dominant Ulcerative Colitis.

Ulcerative colitis (UC) is a heterogeneous disease composed of different endotypes. It is important to develop useful biomarkers for endotyping UC; however, available biomarkers are insufficient. We have already established that periostin is a surrogate biomarker of type 2 inflammation. In this study, we examined the usefulness of periostin as a biomarker of UC and the role of periostin in its pathogenesis. We examined periostin expression in the colons of UC patients. We next investigated serum periostin in UC patients and its correlation with eosinophilic infiltration in their colons. We then examined whether serum periostin could predict the efficacy of oral prednisolone. Finally, we investigated the role of periostin in UC pathogenesis by creating its genetic deficiency using dextran sulfate sodium (DSS)-treated mice. Periostin expression and serum periostin were significantly high in UC patients compared to healthy controls; however, both were diverse, showing heterogeneity of the underlying mechanism of UC. Both serum periostin and tissue periostin expression, but not blood eosinophils, were significantly associated with eosinophil infiltration. Type 2-dominant UC patients as defined by serum periostin showed significantly higher clinical remission rates for the treatment with oral prednisolone. Genetic deficiency in periostin improved colonic inflammation in a DSS-treated mouse model. Periostin can be a useful biomarker to stratify type 2-dominant UC patients, thereby predicting the efficacy of oral prednisolone. Moreover, periostin plays an important role in the setting of type 2-dominant UC.

Prolonged Vancomycin‐Induced Linear IgA Disease in a Patient With Renal Failure

ABSTRACTA 64‐year‐old man with pneumococcal septic shock and subsequent renal failure underwent treatments with antibiotics including intravenous vancomycin (VCM). Blistering skin lesions appeared 10 days after the initiation of VCM. When the patient was transferred to us 5 months later, blisters with erythema were still observed on the abdomen and thighs. Histopathological examination revealed subepidermal blister with infiltration of eosinophils and neutrophils, and direct immunofluorescence revealed linear IgA deposition at the basement membrane zone. The diagnosis of linear IgA disease (LAD)was made, and drug‐induced LAD by VCM was suspected, because of the episode of the blister development 10 days after the first VCM administration. Although the results of various sero‐immunological tests were negative, IgA reactivity with type Ⅶ collagen was detected by VCM‐treated ELISA, which further suggested the diagnosis of VCM‐induced LAD. The possible mechanism for the prolonged disease course was speculated.

Adalimumab induced psoriasis in Crohn’s disease and treatment with ustekinumab: case report and special histopathological findings

This case report presents an instance of Tumor Necrosis Factor-α Inhibitor-induced psoriasis (TNFiIP), also known as paradoxical psoriasis, in a 30-year-old male with fistulizing Crohn’s disease. The patient developed extensive erythematous and scaly lesions on the palms, lower limbs, ankles, and soles after 4 months of adalimumab monotherapy. Histopathological analysis revealed a pattern of psoriasiform dermatitis with notable dermal neutrophil and eosinophil infiltration, distinguishing TNFiIP from idiopathic psoriasis. The patient’s condition significantly improved following the transition from adalimumab to ustekinumab, which highlights the importance of alternative therapeutic strategies for patients who exhibit paradoxical reactions to TNF-α inhibitors.

The Innate Immune Sensor Zbp1 Mediates Central Nervous System Inflammation Induced by Angiostrongylus Cantonensis by Promoting Macrophage Inflammatory Phenotypes.

Angiostrongylus cantonensis (AC) is the leading cause of eosinophilic meningoencephalitis worldwide. The neuroimmune interactions between peripheral and central immune systems in angiostrongyliasis remain unclear. In this study, significant infiltration of eosinophils, myeloid cells, macrophages, neutrophils, and Ly6C monocytes is observed in the brains of AC-infected mice, with macrophages being the most abundant. RNA-seq and SMART-seq analysis of pattern recognition receptor (PRR) and DNA sensor gene sets revealed a marked increase in Z-DNA binding protein 1 (Zbp1) expression in infected mice. Confocal microscopy, RT-qPCR, western blotting, and immunohistochemistry further confirmed that Zbp1 is specifically upregulated in macrophages and microglia. Using Zbp1-knockout mice and flow cytometry, it is found that knockout of Zbp1 enhanced lymphocyte infiltration and natural killer cell cytotoxicity, modulating the immune microenvironment in the central nervous system(CNS) during AC infection. Mechanistically, it is revealed that in macrophage Zbp1 directly binds to receptor-interacting protein 3 (RIP3) to promote its phosphorylation, subsequently facilitating the phosphorylation of mixed lineage kinase domain-like protein (Mlkl). The activated Zbp1-pRIP3-pMlkl axis leads to necroptosis and upregulates pro-inflammatory cytokines including TNF-α, IL-1α, CXCL9, CXCL10 in macrophages, which recruits and activates immune cells. These findings offer new insights into the pathogenic mechanisms of angiostrongyliasis and suggest potential therapeutic strategies.

18F-FDG PET/CT Versus 18F-FAPI PET/CT in Eosinophilic Liver Infiltration.

A 48-year-old man presented with upper abdominal discomfort for 10 days. Abdominal contrast-enhanced CT showed multiple abnormal enhanced masses in liver, suggesting a probability of malignancies. The patient was then enrolled in a clinical trial of comparison of 18F-FDG and 18F-FAPI PET/CT in hepatic lesions. Compared with 18F-FDG PET/CT, 18F-FAPI PET/CT showed higher tracer uptake, more lesions in liver. Meanwhile, peripheral blood eosinophils increased remarkably. The hepatic lesions were highly suspected as eosinophilic liver infiltration. Finally, pathologic analysis confirmed the diagnosis of eosinophilic liver infiltration.

Acute therapeutic effects and pathophysiology of eosinophilic granulomatosis with polyangiitis neuropathy

ObjectiveThis study investigated the effects of early treatment and pathophysiology on eosinophilic granulomatosis with polyangiitis neuropathy (EGPA-N).MethodsTwenty-six consecutive patients with EGPA-N were diagnosed and treated within a day of admission...

Comparison of Imaging Findings between Granulomatosis with Polyangiitis and Eosinophilic Granulomatosis with Polyangiitis on Sinus CT: Importance of High-Density Opacification of the Paranasal Sinuses.

Granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (EGPA) are the most common causes of chronic sinusitis from systemic granulomatous diseases. While both are small- to medium-sized vasculitis with necrotizing granulomas, they have different clinical courses and prognoses. High-density sinus opacification has been reported in allergic fungal sinusitis with eosinophilic infiltrates. Given that EGPA also has eosinophilic tissue infiltrates, we evaluated the differences in sinus CT findings, focusing on the sinus secretion attenuation between patients with GPA and EGPA, along with other previously described findings. This study included 31 patients with GPA and 22 patients with EGPA who underwent sinus CT. The attenuation of secretions within the paranasal sinuses was visually assessed, and the Hounsfield unit (HU) of the highest-density portions within each sinus was measured. Lund-Mackay scores (LMS), bony destruction, sclerotic wall changes, adjacent organ involvement, and nasal polyps were evaluated and compared between patients with GPA and EGPA. Multiple logistic regression analyses were conducted to determine which factors independently discriminated GPA from EGPA, and the diagnostic ability to differentiate between these 2 diseases was evaluated by using a receiver operating characteristic curve analysis. More patients in the GPA group showed bony destructions, bone sclerosis, and involvement of organs adjacent to paranasal sinuses than in the EGPA group (P = .006, 0.048, and 0.035, respectively). The EGPA group had higher LMS and more nasal polyps than the GPA group (P = .078 and 0.333, respectively). More patients in the EGPA group showed internal high-density opacification than in the GPA group, and patients with EGPA had higher mean HUs (both P < .0001). The presence of high-density opacification or mean HUs independently distinguished GPA from EGPA (OR, 53.67 and 1.07; 95% CI, 4.07-708.03 and 1.02-1.13, respectively) and showed a greater ability to discriminate between these diseases compared with other findings. Patients with EGPA had more high-density sinus opacification and higher mean HU on sinus CT than the patients with GPA. In addition to the previously reported CT findings, such as bony destruction, bone sclerosis, and adjacent organ involvement, evaluating secretion attenuation can assist in distinguishing between GPA and EGPA.

Eosinophilic Esophagitis and Cow's Milk: Mechanisms, Challenges, and Treatment Perspectives.

Eosinophilic esophagitis is a chronic, antigen-driven, immune-mediated disease characterized by esophageal dysfunction and significant eosinophilic infiltration. Its rising incidence and prevalence over recent decades reflect both increased clinical awareness and the influence of environmental factors such as dietary patterns and allergen exposure. Among food allergens, cow's milk proteins are the most commonly implicated triggers, contributing to esophageal inflammation through complex immunological pathways involving both IgE-mediated and non-IgE-mediated mechanisms. Dietary elimination of cow's milk has been shown to induce histologic remission in over 60% of pediatric patients, underscoring its pivotal role in eosinophilic esophagitis management. Despite these promising results, challenges persist, including variability in individual responses, the burden of adherence to restrictive diets, and gaps in understanding the molecular mechanisms driving cow's milk-induced esophageal inflammation. This review examines the complex relationship between eosinophilic esophagitis and cow's milk, focusing on its role in disease pathogenesis and management, offering insights into its therapeutic implications. Understanding the interplay between eosinophilic esophagitis and dietary allergens, particularly cow's milk, may inform the development of targeted interventions and improve clinical outcomes for affected patients.

Anti-C1q antibodies in IgG4-related disease are common and associated with renal involvement and cutaneous small-vessel vasculitis.

To evaluate the prevalence and clinical associations of anti-C1q antibodies in IgG4-related disease (IgG4-RD), focusing on renal involvement and cutaneous small-vessel vasculitis (CSVV). We enrolled patients who met the revised 2020 Comprehensive Diagnostic Criteria and/or the 2019 ACR/EULAR Classification Criteria for IgG4-RD. Variables included demographics, organ involvement, clinical phenotypes, disease activity, serum biomarkers, follow-up duration, remission, and relapses. Anti-C1q antibodies were measured using a quantitative enzyme-linked immunosorbent assay (cut-off <10 U/ml). Seventy patients with a mean age of 52.1 years were included. 34 (48.6%) were male. Anti-C1q antibodies were positive in 74.3%, with a median level of 19.8 U/ml. Patients with active disease had higher anti-C1q antibody levels than inactive patients (p= 0.03). Renal involvement was more frequent in anti-C1q positive patients (p= 0.01). Six patients (8.6%) had CSVV, and all had positive anti-C1q levels. All exhibited palpable purpura and one patient had urticarial-like lesions. These patients had multi-organ involvement, and most had high IgG, IgG1, IgG4, and hypocomplementemia. Skin biopsies in three patients showed leukocytoclastic vasculitis with lymphocytic and eosinophilic infiltrates. Anti-C1q antibody levels correlated negatively with levels of C3 and C4, and positively with levels of IgG1, IgG4, and serum free light chains. Anti-C1q positivity did not predict relapse-free survival. This study is the first to evaluate anti-C1q antibodies in IgG4-RD, finding a high prevalence, particularly in patients with renal involvement and CSVV. The results support the hypothesis that immune complex-mediated complement activation contributes to IgG4-RD pathogenesis.

Eosinophilic esophagitis

Eosinophilic esophagitis (EoE) was first described in the early 1990s. Initially ararity, it is now the most common cause of dysphagia for solid foods in young adults. Its prevalence is estimated to be 1:2000. Mechanistically, EoE is characterized by a chronic type‑2 T‑helper cell (Th2) inflammation of the esophagus which is triggered by food allergens. It often occurs in association with other Th2-mediated diseases, such as asthma, atopic dermatitis, and chronic rhinosinusitis with nasal polyps. EoE is diagnosed based on an esophagogastroduodenoscopy with biopsies of the esophageal epithelium. The diagnosis can be established when both symptoms of esophageal dysfunction (usually dysphagia) and an eosinophilic infiltration of at least 15 eosinophils per high-power field (HPF) are present. EoE can be treated with drugs, diet, and endoscopic dilatation. In terms of diet, milk elimination appears most reasonable, particularly as first choice. Drug treatment includes proton pump inhibitors (PPI), topical steroids, and the biologic agent dupilumab. Endoscopic dilatation is effective but does not treat the underlying inflammation. Therefore, it should never be used alone, but rather as an add-on therapy. In cases where clinical suspicion of EoE is strong but no or only few eosinophils are detected in esophageal biopsies, the diagnosis of an EoE variant should be considered. This review article provides adetailed discussion of the epidemiology, clinical features, diagnosis, treatment, and variants of EoE.

Gαi1/3 signaling mediates IL-5-induced eosinophil activation and type 2 inflammation in eosinophilic chronic rhinosinusitis.

Uncontrolled severe eosinophilic chronic rhinosinusitis (eCRS) is associated with elevated levels of Th2 cells and raised immunoglobulin concentrations in nasal polyp tissue. eCRS is characterized by high eosinophilic infiltration and type 2 inflammation. Gαi1/3 proteins participate in allergic inflammation by regulating immune cells. Whether Gαi1/3 proteins have a role in the development of eCRS remains unknown. To investigate the association between Gαi1/3 expression levels and CRS and the underlying mechanisms. Western blotting and immunohistology were used to detect Gαi1/3 expression. Correlations between Gαi1/3 and immune cells and clinical parameters were analyzed. Signaling pathway activation in IL-5-induced Gαi1/3-knockout or knockdown mouse embryonic fibroblasts (MEFs) and eosinophils (EoL-1 cells) was detected by western blotting. EdU/DAPI was used to evaluate the proliferation of EoL-1 cells. A CRS model was established using Gαi1/3-knockout mice, and histological analysis and inflammatory cytokine measurements were performed. Compared with the non-eCRS subset, the eCRS subset showed significantly increased Gαi1/3 expression levels. High nasal tissue Gαi1/3 levels were linked to high tissue eosinophil infiltration, and high disease severity and allergic conditions in CRS patients. Gαi1/3 were required for IL-5-induced Akt-mTOR and Erk activation in MEFs. In EoL-1 cells, Gαi1/3 was associated with IL-5-activated IL-5Rα, promoting IL-5Rα endocytosis and transducing downstream signaling. IL-5-induced EoL-1 cell proliferation and degranulation were suppressed after Gαi1/3 silencing. In a CRS murine model, immune cell infiltration and type 2 inflammation were largely impaired in Gαi1/3-double-knockout mice. Increased Gαi1/3 expression levels in nasal tissue are linked to eosinophil infiltration and increased disease severity in CRS patients. Gαi1/3 contributes to eosinophil activation and participates in regulating allergic inflammation in CRS patients.

Neochlorogenic acid ameliorates allergic airway inflammation by suppressing type 2 immunity and upregulating HO-1 expression.

Neochlorogenic acid is a natural compound isolated from various fruits and vegetables that has anti-inflammation and anti-oxidative effects in macrophages. Inflammatory immune cells and tracheal epithelial cells can stimulate airway hyperresponsiveness, inflammation, and reactive oxygen species. In this study, we investigated the effect of neochlorogenic acid in ameliorating inflammatory and oxidative responses in asthmatic mice. We used an ovalbumin (OVA)-induced mouse model, treating mice with neochlorogenic acid by intraperitoneal injection. We also treated inflammatory human tracheal epithelial (BEAS-2B) cells with neochlorogenic acid to evaluate inflammatory cytokine levels and oxidative responses. The results demonstrate that neochlorogenic acid attenuated airway hyperresponsiveness, eosinophil infiltration, and goblet cell hyperplasia in the lungs of asthmatic mice. Neochlorogenic acid also reduced type 2 cytokine expression in bronchoalveolar lavage fluid and improved oxidative stress in the lung. Neochlorogenic acid effectively blocked monocyte attachment to adherent BEAS-2B cells, and reduced pro-inflammatory cytokine and reactive oxygen species production in inflammatory BEAS-2B cells. These findings suggest that neochlorogenic acid is a potential immunomodulator that can ameliorate airway hyperresponsiveness and airway inflammation in asthmatic mice.

Prognostic value and clinical significance of IL-33 expression in patients with uterine corpus endometrial carcinoma.

Uterine corpus endometrial carcinoma (UCEC) is one of the most common malignant tumours of the female genital tract. In the occurrence, progression and prognosis of UCEC, chronic inflammation plays an important role, making it pivotal to identify inflammatory response-related endometrial diseases. The cytokine interleukin-33 (IL-33) plays significant roles in immune responses, and has been associated with inappropriate allergic reactions, autoimmune diseases, and cancer pathology. In the past decade, studies have begun to uncover the pivotal roles of IL-33 in shaping tumour microenvironment (TME), where it may promote or inhibit tumorigenesis and development depending on the specific tumour types. However, the association between IL-33 expression and UCEC remains unclear. Here we investigated the expression profiles of IL-33 in pan-cancer based on TCGA database. Then, differential gene expression analysis and correlation analysis of IL-33 was investigated in UCEC. In addition, functional enrichment analysis and Kaplan-Meier survival analysis were performed to predict the potential function of IL-33 and its role in the prognosis of UCEC patients. Also, a nomogram model was constructed to predict the prognosis of UCEC. The expression of the inflammatory factor NF-κB p65 and the IL-33, along with its receptor ST2, was analyzed in UCEC tumour tissues and normal tissues of clinical specimens through immunohistochemical staining. Meanwhile, we used toluidine blue staining and methanol Congo red staining to observe the infiltration of mast cells and eosinophils in the endometrial tissue. The results of Kaplan-Meier plotter data indicated that patients with lower IL-33 expression had poorer progression-free interval than those with higher expression. Based on the results of multifactor Cox regression, a nomogram was generated to predict UCEC occurrence risk and prognosis. Clinical specimen characteristics also confirmed a negative correlation between IL-33 expression and UCEC staging and grading. This comprehensive analysis of IL-33, based on bioinformatics and immunohistochemistry, revealed that IL-33 has the function of inhibiting UCEC occurrence and progression and can be served as a beneficial prognostic marker in the clinic.

CCL4 Affects Eosinophil Survival via the Shedding of the MUC1 N-Terminal Domain in Airway Inflammation.

Eosinophilic chronic rhinosinusitis (ECRS), a CRS with nasal polyps (CRSwNP), is characterized by eosinophilic infiltration with type 2 inflammation and is highly associated with bronchial asthma. Intractable ECRS with poorly controlled asthma is recognized as a difficult-to-treat eosinophilic airway inflammation. Although eosinophils are activated and coincubation with airway epithelial cells prolongs their survival, the interaction mechanism between eosinophils and epithelial cells is unclear. This study examined the effect of eosinophils on mucin glycoprotein 1 (MUC1), a member of membrane-bound mucin, in the airway epithelial cells, to elucidate the mechanisms of the eosinophil-airway epithelial cell interaction. Nasal polyp samples from patients with CRSwNP and BEAS-2B airway epithelial cells, coincubated with purified eosinophils, were stained with two MUC1 antibodies. To confirm the involvement of CCL4, an anti-CCL4 neutralizing antibody or recombinant CCL4 was used as needed. The immunofluorescence results revealed a negative correlation between the expression of full-length MUC1 and eosinophil count in nasal polyps. In BEAS-2B coincubated with eosinophils, full-length MUC1, but not the C-terminal domain, was reduced, and eosinophil survival was prolonged, which was concomitant with CCL4 increase, whereas the anti-CCL4 neutralizing antibody decreased these reactions. The survival of eosinophils that contacted recombinant MUC1 without the N-terminal domain was prolonged, and recombinant CCL4 increased the expression of metalloproteases. Increased CCL4 induces the contact between eosinophils and airway epithelial cells by shedding the MUC1 N-terminal domain and enhances eosinophil survival in eosinophilic airway inflammation. This novel mechanism may be a therapeutic target for difficult-to-treat eosinophilic airway inflammation.

Literature review and case study of recurrent EPGA with elevated IgG4 and positive HBsAg successfully treated with rituximab

Background Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of autoimmune vasculitis. The involvement of IgG4 and HBsAg in EGPA is less common but can occur and may present unique challenges in management. Case presentation: We present a case study of a 70-year-old female diagnosed with EGPA confirmed via renal biopsy. She initially presented with recurrent purpura, diarrhea and progressive numbness in the hands and feet, accompanied by general weakness. Complete remission was achieved with a one-year course of prednisone acetate and cyclophosphamide treatment. However, upon discontinuation of self-medication, the disease relapsed, manifesting as a generalized rash and weakness in the extremities. Skin biopsy revealed eosinophil infiltration, with inflammatory cells predominantly surrounding blood vessels. Notably, during treatment, the patient’s hepatitis B markers transitioned from negative to positive for HBsAg. Subsequent administration of entecavir, along with monitoring for a decrease in HBV DNA levels, preceded the initiation of steroids and rituximab to attain remission once more. Among the remaining 15 patients analyzed, all exhibited elevated serum IgG4 levels, with none testing positive for hepatitis B. Notably, only one patient was diagnosed with immunoglobulin G4-related disease (IgG4-RD), suggesting that elevated IgG4 levels alone may not necessarily indicate IgG4-RD. Conclusions Our case report highlights the first instance of recurrent EGPA accompanied by elevated IgG4 and positivity for hepatitis B, which was successfully treated with rituximab. In cases of concurrent hepatitis B, rituximab treatment may be considered once viral replication is under control. However, emphasis on maintenance therapy is crucial following the induction of disease remission.

Effects of Repeated Cisplatin and Monosodium Glutamate on Visceral Sensitivity in Rats.

Cisplatin, a chemotherapeutic drug, is known for causing gastrointestinal disorders and neuropathic pain, but its impact on visceral sensitivity is unclear. Monosodium glutamate (MSG) has been shown to improve gastrointestinal dysmotility and neuropathic pain induced by cisplatin in rats. This study aimed to determine if repeated cisplatin treatment alters visceral sensitivity and whether dietary MSG can prevent these changes. Male Wistar HAN rats were treated with saline or cisplatin (2 mg/kg/week, ip) for 5 weeks, and visceral sensitivity to intracolonic mechanical stimulation was recorded after the final cisplatin administration (week 5) and one-week post-treatment (week 6). In a second cohort, rats treated with cisplatin or saline also received MSG (4 g/L) in their drinking water, and visceral sensitivity was evaluated on week 6. Finally, the untouched distal colon was obtained from a third cohort of animals one week after treatment to assess immunocyte infiltration. Cisplatin significantly increased colonic mechanical sensitivity on week 6 but not on week 5. MSG did not prevent cisplatin-induced visceral hypersensitivity on week 6 and even exacerbated it. On week 6, compared with the control, cisplatin (with or without MSG) did not modify the colonic infiltration of eosinophils, macrophages, neutrophils, or mast cells. Although MSG seems to be useful in ameliorating some of the adverse effects of cisplatin, such as gastrointestinal motility disturbances or neuropathic pain, it does not alleviate visceral pain.

Ameliorative Effect of Melittin Encoded DNA Plasmid in an Ovalbumin-induced Murine Model of Allergy

Melittin is a natural toxin used in traditional medicine as an anti-inflammatory drug. It seems that the anti-inflammatory properties of melittin are caused by suppressing the expression of inflammatory genes and inhibiting signaling pathways. However, the use of melittin is limited due to instability, rapid degradation, and impurity. The aim of this study was to investigate the intranasal administration of a melittin-encoded plasmid as a new melittin delivery method for allergic diseases. After the induction of a mouse model of allergic rhinitis, mice received intranasal melittin plasmid. After the final challenge with allergen and allergic symptom assessment, the required samples were collected, and transforming growth factor-beta (TGF-β), interferon-gamma (IFN-γ), and interleukin-4 (IL-4) cytokine levels, serum levels of ovalbumin-specific immunoglobulin (Ig) E and histopathological changes were assessed. In addition to investigating the immune response, the effect of melittin on the expression level of genes involved in apoptosis was also investigated. The melittin plasmid significantly improved nasal symptoms and decreased eosinophil infiltration into the nasal mucosa. Moreover, melittin decreased the expression levels of IL-4 and TGF-β in nasal lavage fluid, while IFN-γ expression was increased. Regarding the expression level of genes involved in apoptosis, melittin led to an increase in BAX mRNA expression. These results suggest intranasal administration of a plasmid encoding melittin can suppress nasal symptoms, eosinophil infiltration, and immunomodulation of the immune response, which can be considered a promising approach in the treatment of inflammatory diseases.

Vectorized Human Antibody-Mediated Anti-Eosinophil Gene Therapy.

Chronic hypereosinophilia, defined as persistent elevated blood levels of eosinophils ≥1,500/μL, is associated with tissue infiltration of eosinophils and consequent organ damage by eosinophil release of toxic mediators. The current therapies for chronic hypereosinophilia have limited success, require repetitive administration, and are associated with a variety of adverse effects. As a novel approach to treat chronic hypereosinophilia, we hypothesized that adeno-associated virus (AAV)-mediated delivery of an anti-human eosinophil antibody would provide one-time therapy that would mediate persistent suppression of blood eosinophil levels. To assess this hypothesis, we first generated a human monoclonal antibody (mAb) directed against Siglec8, a sialic-acid binding immunoglobulin-like lectin, expressed at high levels on the cell surface of human eosinophils. Transgenic mice with a human immunoglobulin repertoire were immunized with human Siglec8 protein or DNA encoding human Siglec8. Based on target binding assessments, the 08C07 mAb was chosen for further study. The human variable regions of 08C07 were joined to the human Ig constant region, creating H08C07 (hAntiEos), a fully human anti-human eosinophil mAb. Using the gene sequence of hAntiEos, we created AAVrh.10hAntiEos, an AAVrh.10-based vector expressing the heavy and light chains of H08C07. Intravenous administration of AAVrh.10hAntiEos (1011 genome copies or gc) to C57Bl/6 mice resulted in persistent elevated serum levels of hAntiEos. In vivo gene therapy generated hAntiEos bound to recombinant human Siglec8 protein in a dose-dependent manner and to human eosinophils, mediated apoptosis of human eosinophils, and antibody-dependent cellular cytotoxicity activity against human eosinophils. Consistent with these data, administration of AAVrh.10hAntiEos to human CD34+ transplanted NSG-SGM3 immunodeficient mice suppressed levels of human eosinophils invivo. AAVrh.10hAntiEos holds the potential to offer therapeutic benefit to patients with chronic hypereosinophilia.

Epidermal spongiotic Langerhans cell collections, but not eosinophils, are a clue to the diagnosis of allergic contact dermatitis: A series of 170 clinically- and patch test-confirmed cases.

Allergic contact dermatitis cannot be reliably differentiated from other forms of spongiotic/eczematous dermatitis by histology alone. Textbooks and recent studies have variably supported the specificity of dermal eosinophils, eosinophilic spongiosis, and Langerhans cell collections, among other features. To assess which histopathologic features favor a diagnosis of allergic contact dermatitis. In this case control study with prospective validation, patients were evaluated by patch testing and skin biopsy. Lesional histopathologic features were independently assessed. 170 cases fulfilled inclusion criteria. Langerhans cell collections were more likely to be found in allergic contact dermatitis (29/111, 26%)(p = 0.03). Heavy dermal eosinophilic infiltration was associated with diagnoses other than allergic contact dermatitis. No significant differences were found for any other predictor variables. Mostly retrospective study with small validation sample. This largest study to date is the first to independently confirm Langerhans cell collections as the single histopathologic feature most closely associated with allergic contact dermatitis.

Effect of different doses of cyclobenzaprine-HCl on the reproductive health of female Wistar rats

Background Women often experience significant burdens both at home and in their professional lives, which can lead to physical and mental strain. To manage these challenges, medications such as cyclobenzaprine-HCl, originally developed as a tricyclic antidepressant but reintroduced as a muscle relaxant, are sometimes used. Its effectiveness in treating muscle spasms, localized pain, and limited range of motion in acute musculoskeletal conditions has been well documented. Objective The objective of this study was to explore the potential consequences of cyclobenzaprine-HCl on reproductive health by assessing its influence on female Wistar rats. Materials and methods The study was conducted on 18 adult female Wistar rats, divided into three groups: a control group receiving distilled water and two treated groups with two doses − a low-dose group receiving 1.5 mg/kg of cyclobenzaprine-HCl and a high-dose group receiving 3 mg/kg, administered orally for 30 days. We assessed the impact of cyclobenzaprine-HCl on serum hormonal levels (progesterone, estradiol, luteinizing hormone, follicle-stimulating hormone), oxidative stress markers (glutathione, superoxide dismutase, catalase, malondialdehyde), histopathological changes in ovaries and uteri, and DNA stability using the comet assay. Results and conclusion The study revealed that cyclobenzaprine-HCl caused hormonal imbalances distinguished by significant increase in estradiol and follicle-stimulating hormone levels, and significant decreases in progesterone and luteinizing hormone levels. Dissruptions in oxidative stress markers were characterized by elevated malondialdehyde and reduced glutathione levels. Histopathological abnormalities included degeneration, deformed follicles, congested blood vessels, and necrosis in the ovarian tissue. In addition, diffused eosinophil infiltration, pyknotic nuclei, glandular hyperplasia, necrosis, and hypercellularity in the uterine tissue. DNA instability was observed in both dosage groups as evidenced by fragmented DNA in the shape of comets. These findings underscore the potential reproductive toxicity of cyclobenzaprine-HCl in female rats, suggesting a need for caution in its use considering its possible adverse effects on reproductive health.