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1.
Allergol Int ; 71(2): 185-192, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35236619

RESUMO

Non-HIV immune reconstitution inflammatory syndrome (non-HIV IRIS) is associated with the recovery from an immunocompromised condition. It is defined as inflammatory disorders caused by antigens, including drugs or pathogenic microorganisms present prior to immune recovery, or by the exacerbation of an inflammatory disorder that was already present. Drug-induced hypersensitivity syndrome is a prototype of IRIS, and the pathophysiology of non-HIV IRIS can be recognized in several disorders treated with corticosteroids, immunosuppressants, molecular-targeted drugs, TNF-α antibody drugs, immune checkpoint inhibitors, and dipeptidyl peptidase-4 inhibitors. This review focuses on the relationship between the immune mechanism of non-HIV IRIS and drug allergies, especially severe drug eruption. The antigen recognition mechanism in drug allergy varies depending on the clinical type and the causative drug. The p-i concept is the main mechanism in severe drug eruption such as Stevens-Johnson syndrome/toxic epidermal necrolysis, and drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms. Lymphocytes activated by an antigen other than a drug, such as a virus, can also develop drug allergy by the loose binding of drugs with immune receptors of T cells or human leukocyte antigen. Therefore, fluctuations in the immune environment affect the onset of severe drug eruption. Novel agents that cause major changes in immunity have been marketed mainly for autoimmune diseases and malignant tumors; therefore, it is necessary to consider their effects when treating severe drug eruptions. Moreover, although a list of diagnostic criteria for this syndrome has been drafted, predictive and diagnostic biomarkers for this syndrome needs to be urgently developed.


Assuntos
Síndrome de Hipersensibilidade a Medicamentos , Eosinofilia , Síndrome Inflamatória da Reconstituição Imune , Síndrome de Stevens-Johnson , Corticosteroides/uso terapêutico , Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Eosinofilia/tratamento farmacológico , Humanos , Síndrome Inflamatória da Reconstituição Imune/complicações , Síndrome Inflamatória da Reconstituição Imune/diagnóstico , Síndrome de Stevens-Johnson/diagnóstico
2.
Rinsho Shinkeigaku ; 62(6): 481-486, 2022 Jun 24.
Artigo em Japonês | MEDLINE | ID: mdl-35644584

RESUMO

A 60-year-old man with a history of bronchial asthma and nasal polyp presented with loss of vision in the right eye. His visual loss progressed within a single day, and he presented to our hospital 5 days after the onset of the symptom. Fundoscopy showed swelling and hemorrhage of the right optic disc. Blood tests revealed increased eosinophils, C-reactive protein, and perinuclear anti-neutrophil cytoplasmic antibody. Cerebrospinal fluid was normal. Cranial MRI showed local enhancement of the right optic disc and posterior ciliary arteries. He was diagnosed with arteritic anterior ischemic optic neuropathy caused by eosinophilic granulomatosis with polyangiitis (EGPA). High dose intravenous methylprednisolone was started on presentation, but the patient showed no improvement in visual function. Although a rare complication, ischemic optic neuropathy associated with EGPA should be noted, as this is an emergent condition and requires prompt diagnosis and treatment.


Assuntos
Síndrome de Churg-Strauss , Eosinofilia , Granulomatose com Poliangiite , Neuropatia Óptica Isquêmica , Anticorpos Anticitoplasma de Neutrófilos , Síndrome de Churg-Strauss/complicações , Síndrome de Churg-Strauss/diagnóstico , Síndrome de Churg-Strauss/tratamento farmacológico , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Neuropatia Óptica Isquêmica/etiologia
3.
Cutis ; 109(3): E29-E32, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35659145

RESUMO

Angioimmunoblastic T-cell lymphoma (AITL) is a rare and aggressive lymphoma arising from follicular T-helper cells. Cutaneous findings and nonspecific systemic symptoms often associated with this malignancy can closely resemble those of more common entities, such as a viral exanthem or drug eruption, depending on the history and context. These similarities in presentation to more common entities can cause a delay in the diagnosis of AITL and subsequent initiation of treatment, which has considerable implications for morbidity and mortality. We present the case of a patient whose clinical features resembled drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) and who was found to have AITL after extensive workup. This atypical case highlights the importance of maintaining a flexible differential diagnosis in patients with suspected DRESS syndrome whose condition does not improve with appropriate drug withdrawal and therapy.


Assuntos
Síndrome de Hipersensibilidade a Medicamentos , Eosinofilia , Exantema , Linfadenopatia Imunoblástica , Linfoma de Células T , Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Eosinofilia/patologia , Exantema/diagnóstico , Exantema/etiologia , Humanos , Linfadenopatia Imunoblástica/diagnóstico , Linfoma de Células T/diagnóstico
4.
Curr Opin Gastroenterol ; 38(4): 395-401, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35762699

RESUMO

PURPOSE OF REVIEW: Management for patients with refractory eosinophilic esophagitis (EoE) remains a clinical challenge. This review aims to define refractory EoE, explore rates and reasons for nonresponse, and discuss the evidence that informs the approach to these patients. RECENT FINDINGS: Many patients will fail first-line therapies for EoE. Longer duration of therapy can increase response rates, and initial nonresponders may respond to alternative first-line therapies. There are ongoing clinical trials evaluating novel therapeutics that hold promise for the future of EoE management. Increasingly, there is recognition of the contribution of oesophageal hypervigilance, symptom-specific anxiety, abnormal motility and oesophageal remodelling to ongoing clinical symptoms in patients with EoE. SUMMARY: For refractory EoE, clinicians should first assess for adherence to treatment, adequate dosing and correct administration. Extending initial trials of therapy or switching to an alternative first-line therapy can increase rates of remission. Patients who are refractory to first-line therapy can consider elemental diets, combination therapy or clinical trials of new therapeutic agents. Patients with histologic remission but ongoing symptoms should be evaluated for fibrostenotic disease with EGD, barium esophagram or the functional luminal imaging probe (FLIP) and should be assessed for the possibility of oesophageal hypervigilance.


Assuntos
Esofagite Eosinofílica , Dieta , Enterite , Eosinofilia , Esofagite Eosinofílica/diagnóstico , Gastrite , Humanos , Inibidores da Bomba de Prótons/uso terapêutico , Esteroides/uso terapêutico
5.
J Investig Med High Impact Case Rep ; 10: 23247096221104465, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35723281

RESUMO

A healthy 11-year-old girl presents with epigastric abdominal pain, fever, weight loss, and decreased appetite for 1 month. On physical examination, she appears ill, dehydrated, and cachectic. Her abdominal examination is significant for large ascites with a fluid wave and is nontender to palpation. Her labs show leukocytosis with an eosinophilic-predominant granulocytosis and an absolute eosinophil count of 6800/mm3. She has elevated serum inflammatory markers, hypoalbuminemia, and lipase is 5000 U/L. Magnetic resonance cholangiopancreatography (MRCP) shows an irregular and dilated pancreatic duct, so she had an endoscopic retrograde cholangiopancreatography with pancreatic stent placement, paracentesis, and colonoscopy. Her peritoneal fluid was significant for an eosinophilic-predominant granulocytosis with no evidence of malignancy on flow cytometry. All other studies and cultures did not reveal an etiology. She initially showed improvement, 18 days later she developed a fever, night sweats, tachycardia, and abdominal distention. Empiric antibiotics were initiated due to concern for infected pancreatic necrosis versus spontaneous bacterial peritonitis. Repeat MRCP showed interval development of 2 peripancreatic fluid collections and re-accumulation of ascites. She continued to have daily fever ranging from 39°C to 40°C. Repeat paracentesis and evaluation of her peritoneal fluid showed resolution of eosinophilia with an elevated neutrophil count, negative Gram stain, and no growth on culture. She completed a 10-day course of antibiotics, however, remained febrile with elevated inflammatory markers and leukocytosis throughout her hospitalization. A genetic panel to evaluate for a hereditary cause of chronic pancreatitis was sent and returned positive for a mutation of the serine protease inhibitor Kazal type 1.


Assuntos
Eosinofilia , Pancreatite , Antibacterianos , Ascite/etiologia , Criança , Feminino , Humanos , Leucocitose , Pancreatite/diagnóstico
6.
Front Immunol ; 13: 893844, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35711456

RESUMO

Acetylcholine (ACh) from neuronal and non-neuronal sources plays an important role in the regulation of immune responses and is associated with the development of several disease pathologies. We have previously demonstrated that group 2 innate lymphoid cell (ILC2)-derived ACh is required for optimal type 2 responses to parasitic infection and therefore sought to determine whether this also plays a role in allergic inflammation. Rora Cre+ Chat LoxP mice (in which ILC2s cannot synthesize ACh) were exposed to an allergenic extract of the fungus Alternaria alternata, and immune responses in the airways and lung tissues were analyzed. Airway neutrophilia and expression of the neutrophil chemoattractants CXCL1 and CXCL2 were enhanced 24 h after exposure, suggesting that ILC2-derived ACh plays a role in limiting excessive pulmonary neutrophilic inflammation. The effect of non-selective depletion of ACh was examined by intranasal administration of a stable parasite-secreted acetylcholinesterase. Depletion of airway ACh in this manner resulted in a more profound enhancement of neutrophilia and chemokine expression, suggesting multiple cellular sources for the release of ACh. In contrast, depletion of ACh inhibited Alternaria-induced activation of ILC2s, suppressing the expression of IL-5, IL-13, and subsequent eosinophilia. Depletion of ACh reduced macrophages with an alternatively activated M2 phenotype and an increase in M1 macrophage marker expression. These data suggest that ACh regulates allergic airway inflammation in several ways, enhancing ILC2-driven eosinophilia but suppressing neutrophilia through reduced chemokine expression.


Assuntos
Eosinofilia , Pneumonia , Acetilcolina/farmacologia , Acetilcolinesterase/metabolismo , Animais , Imunidade Inata , Inflamação/metabolismo , Interleucina-33/metabolismo , Pulmão , Linfócitos , Camundongos
7.
Int J Immunopathol Pharmacol ; 36: 3946320221109529, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35726645

RESUMO

Eosinophilic chronic rhinosinusitis (ECRS) is a chronic inflammatory disease characterized by prominent eosinophilic infiltration along with a T-helper-2 (Th2) response. It has been well documented that signal transducer and activator of transcription 6 (STAT6) is a nuclear transcription factor that mediates Th2-type immunity and is implicatory of STAT1 and STAT3 in the pathogenesis of allergic airway diseases. However, little is known about the association between STATs and ECRS. Here, we explored the relationship between STAT1, STAT3, and/or STAT6 and eosinophilic inflammation accompanied by Th2-type immunity in a mouse model of ECRS. An ovalbumin (OVA)-staphylococcal enterotoxin B (SEB)-induced ECRS murine model was first established. The mucosal histological alterations were determined using hematoxylin and eosin staining. The number of eosinophils in peripheral blood was measured using a blood cell analyzer. The cytokine (IL-4, IL-5, IL17 A and IFN-γ) expression levels in the sinonasal mucosa and total and OVA-specific IgE from serum were measured using ELISA. Then, the protein levels of STAT1, STAT3, STAT6, phosphorylated STAT1 (p-STAT1), p-STAT3, p-STAT6, T-box expressed in T-cells (T-bet), GATA binding protein 3 (GATA-3), and retinoic acid receptor-related orphan receptor γ (RORγt) in the sinonasal mucosa were examined by immunohistochemical staining or Western blotting. Local administration of OVA combined with SEB (OVA + SEB) induced multiple polyp-like lesions, accompanied by prominent eosinophilic infiltration in the sinonasal mucosa. The OVA- and OVA+SEB-treated groups showed significantly higher eosinophil counts from peripheral blood and total and OVA-specific IgE levels from serum than those in the PBS- and SEB-treated groups. The levels of p-STAT6 were markedly increased by OVA + SEB exposure, as well as GATA-3, IL-4, and IL-5, but did not affect STAT6, p-STAT1, p-STAT3, T-bet, RORγt, IFN-γ, or IL-17A. Furthermore, an eosinophil count in the sinonasal mucosa showed a positive correlation with the level of p-STAT6 in the ECRS mouse model. Signal transducer and activator of transcription 6 signaling could be activated in the OVA+SEB-induced ECRS model and might be a crucial signal transducer in the development of Th2-skewed ECRS.


Assuntos
Eosinofilia , Rinite , Fator de Transcrição STAT6 , Sinusite , Alérgenos , Animais , Modelos Animais de Doenças , Eosinofilia/patologia , Imunoglobulina E , Interleucina-4/metabolismo , Interleucina-5/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Ovalbumina , Rinite/patologia , Fator de Transcrição STAT6/metabolismo , Sinusite/patologia
9.
J Immunol Res ; 2022: 2273121, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35747690

RESUMO

The pathogenesis of CRSwNP is complex and unclear. CRSwNP is subdivided into two types based on the infiltration of EOSs: eCRSwNP and noeCRSwNP. This study was designed to seek the role of autophagy, mitophagy, and Akt/mTOR pathway in these two subtypes of CRSwNP. This study included 29 patients with CRSwNP and 9 controls. The levels of autophagy, mitophagy, and Akt/mTOR pathway-related proteins in nasal tissues were quantified using western blot analysis. Levels of eosinophilic inflammation-related cytokines in nasal tissues were quantified by enzyme-linked immunosorbent assay. Immunohistochemistry was also used to evaluate autophagy, mitophagy, and Akt/mTOR pathway-related protein expression and distribution in nasal polyps and control tissues. Transmission electron microscopy was used to detect the formation of autophagosomes and mitochondrial autophagosomes. Masson's trichrome and periodic acid-Schiff Alcian blue staining were used to evaluate the severity of tissue remodeling. The expression of p-Akt/Akt and p-mTOR/mTOR was upregulated in patients with eCRSwNP or noeCRSwNP. Beclin 1, PINK1, BNIP3, and FUNDC1 levels were significantly reduced in the nasal polyps of patients with eCRSwNP or noeCRSwNP. Autophagosomes and mitochondrial autophagosomes formed less frequently in the nasal polyps of patients with eCRSwNP or noeCRSwNP. Levels of IL-4, IL-5, IL-13, and ECP and the eotaxins CCL11, CCL24, and CCL26 were elevated in the nasal polyps of patients with eCRSwNP or noeCRSwNP. Tissue remodeling is enhanced in patients with eCRSwNP or noeCRSwNP. The Akt/mTOR pathway, eosinophilic inflammation, and tissue remodeling are activated in the nasal polyps of patients with eCRSwNP or noeCRSwNP. The downregulation of autophagy and mitophagy is also observed in eosinophilic and noneosinophilic nasal polyps. The targeting of mitophagy may provide new therapeutic options for different endotypes of CRSwNP.


Assuntos
Eosinofilia , Pólipos Nasais , Rinite , Sinusite , Autofagia , Doença Crônica , Humanos , Inflamação/complicações , Mitofagia , Pólipos Nasais/complicações , Proteínas Proto-Oncogênicas c-akt , Rinite/metabolismo , Sinusite/patologia , Serina-Treonina Quinases TOR
10.
Medicine (Baltimore) ; 101(22): e29274, 2022 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-35665730

RESUMO

RATIONALE: Pituitary apoplexy occurs in about 8% of those with nonfunctioning pituitary adenoma. Subsequent hormone deficiency, especially corticotropic deficiency, is the most common finding. We describe the unusual manifestations of adrenal insufficiency that are usually overlooked in such cases, with the aim of raising awareness of this disease. PATIENT CONCERNS: A 53-year-old male with a history of hyponatremia came to our hospital with intermittent fever and generalized pruritic skin rash. He also reported general weakness, abdominal pain, poor appetite, and severe retroorbital headache. DIAGNOSES: Laboratory data revealed hypereosinophilia, hypotonic hyponatremia, and hypopituitarism, including secondary adrenal insufficiency. Sellar magnetic resonance imaging revealed a pituitary macroadenoma, 2 cm in height, with mild displacement of the optic chiasm. Pathologic report and immunohistochemical stains of surgical specimen showed pituitary gonadotropic adenoma with apoplexy. INTERVENTIONS: Transsphenoidal removal of the pituitary adenoma was performed. The patient received intravenous hydrocortisone then oral form cortisone acetate regularly. OUTCOMES: His symptoms and laboratory data recovered after the operation and medical treatment. LESSONS: This case highlights that eosinophilia, pruritic skin rash and fever can be manifestations of adrenal insufficiency, and that they may initially be regarded as cellulitis.


Assuntos
Adenoma , Insuficiência Adrenal , Eosinofilia , Exantema , Hiponatremia , Hipopituitarismo , Neoplasias Hipofisárias , Acidente Vascular Cerebral , Adenoma/complicações , Adenoma/diagnóstico , Adenoma/cirurgia , Insuficiência Adrenal/complicações , Celulite (Flegmão)/complicações , Eosinofilia/complicações , Exantema/complicações , Humanos , Hiponatremia/complicações , Hipopituitarismo/complicações , Hipopituitarismo/etiologia , Imageamento por Ressonância Magnética/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/cirurgia , Prurido , Acidente Vascular Cerebral/complicações
11.
Front Immunol ; 13: 915906, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35720347

RESUMO

The alarmin cytokine interleukin (IL)-33 plays an important proinflammatory role in type 2 immunity and can act on type 2 innate lymphoid cells (ILC2s) and type 2 T helper (TH2) cells in eosinophilic inflammation and asthma. The mechanistic target of rapamycin (mTOR) signaling pathway drives immune responses in several inflammatory diseases, but its role in regulating bone marrow responses to IL-33 is unclear. The aim of this study was to determine the role of the mTORC1 signaling pathway in IL-33-induced bone marrow ILC2 responses and its impact on IL-33-induced eosinophilia. Wild-type mice were intranasally exposed to IL-33 only or in combination with the mTORC1 inhibitor, rapamycin, intraperitoneally. Four groups were included in the study: saline-treated (PBS)+PBS, rapamycin+PBS, PBS+IL-33 and rapamycin+IL-33. Bronchoalveolar lavage fluid (BALF), serum and bone marrow cells were collected and analyzed by differential cell count, enzyme-linked immunosorbent assay and flow cytometry. IL-33 induced phosphorylation of the mTORC1 protein rpS6 in bone marrow ILC2s both ex vivo and in vivo. The observed mTOR signal was reduced by rapamycin treatment, indicating the sensitivity of bone marrow ILC2s to mTORC1 inhibition. IL-5 production by ILC2s was reduced in cultures treated with rapamycin before stimulation with IL-33 compared to IL-33 only. Bone marrow and airway eosinophils were reduced in mice given rapamycin before IL-33-exposure compared to mice given IL-33 only. Bone marrow ILC2s responded to IL-33 in vivo with increased mTORC1 activity and rapamycin treatment successfully decreased IL-33-induced eosinophilic inflammation, possibly by inhibition of IL-5-producing bone marrow ILC2s. These findings highlight the importance of investigating specific cells and proinflammatory pathways as potential drivers of inflammatory diseases, including asthma.


Assuntos
Asma , Eosinofilia , Animais , Asma/induzido quimicamente , Asma/tratamento farmacológico , Medula Óssea , Eosinofilia/tratamento farmacológico , Imunidade Inata , Inflamação/tratamento farmacológico , Interleucina-33 , Interleucina-5 , Pulmão , Linfócitos , Alvo Mecanístico do Complexo 1 de Rapamicina , Camundongos , Camundongos Knockout , Sirolimo/farmacologia , Serina-Treonina Quinases TOR
12.
Proc Natl Acad Sci U S A ; 119(23): e2204557119, 2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35653568

RESUMO

SignificanceEosinophils contribute to type 2 immunity against helminths and allergens. The small intestine harbors eosinophils with incompletely understood pathophysiological roles. Here, we show that intestinal eosinophils include two subsets. One expresses the inhibitory receptor Clec4a4 and the inhibitory ligand PD-L1 and is unique to the small intestine; the other manifests a proinflammatory phenotype. Both subsets are blood derived. Remarkably, Clec4a4+ eosinophils were instructed by the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor that imprints many gut immune cells. Selective AHR deletion in eosinophils depleted Clec4a4+ eosinophils, augmented innate lymphocytes producing type 2 cytokines, and enhanced helminth clearance. We conclude that Clec4a4+ eosinophils have immunomodulatory functions, which could be harnessed for the therapy of food allergies and eosinophilic gastrointestinal disorders.


Assuntos
Eosinófilos , Receptores de Hidrocarboneto Arílico , Receptores de Superfície Celular , Eosinofilia/terapia , Hipersensibilidade Alimentar/terapia , Imunomodulação , Intestino Delgado , Contagem de Leucócitos , Ligantes , Receptores de Hidrocarboneto Arílico/genética
14.
Artigo em Inglês | MEDLINE | ID: mdl-35751537

RESUMO

Strongyloides stercoralis causes chronic, mostly asymptomatic infections but hyperinfection syndrome may occur in immunosuppressed patients, especially in those receiving corticosteroids. We report a case of S. stercoralis hyperinfection syndrome in a solid organ transplant recipient that occurred approximately 2.5 months after heart transplantation. The patient presented to the intensive care unit with acute respiratory distress, bacteremia, and petechial rash on abdomen and toe. Microbiology testing of respiratory samples excluded infection with Pneumocystis jirovecii, respiratory viruses, pathogenic bacteria and fungi. No eosinophilia was found. Histopathological examination of the skin biopsy of the petechial rash provided the first indication of the diagnosis, revealing the presence of isolated filariform S. stercoralis larvae in the dermis. Subsequent microbiology testing confirmed the diagnosis. This case highlights the role of histopathological examination of a skin rash in diagnosing patients with atypical clinical presentation of Strongyloides hyperinfection syndrome.


Assuntos
Eosinofilia , Exantema , Strongyloides stercoralis , Estrongiloidíase , Animais , Eosinofilia/diagnóstico , Eosinofilia/etiologia , Humanos , Hospedeiro Imunocomprometido , Estrongiloidíase/complicações , Estrongiloidíase/diagnóstico , Síndrome
15.
PLoS One ; 17(6): e0268651, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35759448

RESUMO

The prevalence of allergic diseases is on the rise, yet the environmental factors that contribute to this increase are still being elucidated. Laundry detergent (LD) that contains cytotoxic ingredients including microbial enzymes continuously comes into contact with the skin starting in infancy. An impaired skin barrier has been suggested as a route of allergic sensitization. We hypothesized that exposure of skin to LD damages the skin barrier resulting in systemic sensitization to allergens that enter through the impaired skin barrier. Mouse skin samples exposed in vitro to microbial proteases or LD exhibited physical damage, which was more pronounced in neonatal skin as compared to adult skin. Exposure of the skin to microbial proteases in vitro resulted in an increase in the levels of interleukin (IL)-33 and thymic stromal lymphopoietin (TSLP). BALB/c wild type mice epicutaneously exposed to LD and ovalbumin (OVA) showed an increase in levels of transepidermal water loss, serum OVA-specific immunoglobulin (Ig) G1 and IgE antibodies, and a local increase of Il33, Tslp, Il4 and Il13 compared with LD or OVA alone. Following intranasal challenge with OVA, mice epicutaneously exposed to LD showed an increase in allergen-induced esophageal eosinophilia compared with LD or OVA alone. Collectively, these results suggest that LD may be an important factor that impairs the skin barrier and leads to allergen sensitization in early life, and therefore may have a role in the increase in allergic disease.


Assuntos
Dermatite Atópica , Eosinofilia , Hipersensibilidade , Alérgenos , Animais , Dermatite Atópica/induzido quimicamente , Detergentes/toxicidade , Eosinofilia/induzido quimicamente , Inflamação , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina , Peptídeo Hidrolases
16.
BMC Immunol ; 23(1): 33, 2022 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-35752781

RESUMO

BACKGROUND: Chronic rhinosinusitis (CRS) is a group of heterogeneous diseases characterized by epithelial inflammation and tissue eosinophilic infiltration. IL-5, POSTN, and IL-33 are important factors that act as chemoattractants for eosinophils, and a tissue-remodeling protein positively correlated with eosinophils in blood and mediators of eosinophilic infiltration. The aim of the study was to determine the expression of IL-5, POSTN and IL-33, at the gene and protein levels, in eosinophilic CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP), and to correlate this expression with clinical severity. MATERIALS AND METHODS: The study included 40 CRSwNP patients and 53 CRSsNP patients and 40 control subjects. The expression of IL-5, POSTN and IL-33 mRNA was determined in sinonasal mucosal samples and in nasal polyp tissue by real-time PCR. Protein levels in the serum of CRSwNP patients were measured by ELISA. Computed tomography was evaluated according to Lund-Mackay scores, and visual analog scale scores were assessed. RESULTS: NP tissue demonstrated significantly higher IL-5 and POSTN mRNA expression than the sinonasal tissue in the CRSsNP and CRSwNP groups. CRS groups demonstrated elevated IL-33 mRNA expression in comparison to controls irrespective of the presence of NP. No correlation was found between IL-5, POSTN and IL-33 mRNA expression and disease severity. CRSwNP group demonstrated significantly higher serum IL-5, POSTN and IL-33 protein levels than controls, and this corresponds to disease severity. CONCLUSION: Serum IL-5, POSTN and IL-33 levels may be important markers for classification of eosinophilic CRSwNP patients, along with disease severity.


Assuntos
Eosinofilia , Interleucina-33/sangue , Interleucina-5/sangue , Pólipos Nasais , Rinite , Sinusite , Moléculas de Adesão Celular , Doença Crônica , Humanos , Interleucina-33/genética , Pólipos Nasais/genética , Pólipos Nasais/metabolismo , RNA Mensageiro/genética , Rinite/metabolismo , Sinusite/metabolismo
17.
Front Immunol ; 13: 841141, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35720294

RESUMO

Background & Aims: Eosinophils are the main inflammatory effector cells that damage gastrointestinal tissue in eosinophilic gastrointestinal diseases (EGIDs). Activation of the OX40 pathway aggravates allergic diseases, such as asthma, but it is not clear whether OX40 is expressed in eosinophils to regulate inflammation in EGIDs. In this study, we assessed the expression and effect of OX40 on eosinophils in WT and Ox40-/- eosinophilic gastroenteritis (EGE) mice. Methods: Eosinophil infiltration, ovalbumin (OVA)-specific Ig production, OX40 expression and inflammatory factor levels in the intestine and bone marrow (BM) were investigated to evaluate inflammation. Results: We confirmed that OVA-challenged mice produced high levels of Ox40, Mbp, Ccl11, Il5, Il4, Il13, and Il6 mRNA and a low level of Ifng mRNA in the intestine. Increased eosinophils were observed in intestinal and lymph tissues, accompanied by significantly upregulated OX40 and Type 2 cytokine production in eosinophils of EGE mice. Ox40 deficiency ameliorated OVA-induced inflammation, eosinophil infiltration, and cytokine production in the intestine. Consistently, Ox40-/ - eosinophils exhibited decreased proliferation and proinflammatory function. The stimulation of the agonistic anti-OX40 antibody, OX86, promoted the effect of OX40 on eosinophils. The present study also showed that Ox40 deficiency dampened the Traf2/6-related NF-κB signaling pathway in eosinophils. Conclusions: OX40 may play a critical role in the progress of OVA-induced EGE by promoting the maturation and function of eosinophils via the Traf2/6-related NF-κB signaling pathway.


Assuntos
Eosinófilos , NF-kappa B , Animais , Enterite , Eosinofilia , Gastrite , Inflamação/metabolismo , Camundongos , NF-kappa B/metabolismo , Ovalbumina , RNA Mensageiro/metabolismo , Receptores OX40 , Fator 2 Associado a Receptor de TNF/metabolismo
18.
Aliment Pharmacol Ther ; 56(2): 330-331, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35748829
20.
Eur Neuropsychopharmacol ; 60: 25-37, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35635994

RESUMO

Clozapine-related drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare adverse reaction. We aimed to screen a large pharmacovigilance database to identify clozapine-related DRESS cases, even if otherwise reported and provide a clinical overview. We screened spontaneous reports of clozapine-related DRESS syndrome in EudraVigilance database applying the European Registry on Severe Cutaneous Adverse Drug Reactions (RegiSCAR) criteria and scores to identify probable/definite DRESS syndrome cases. Clinical and demographic characteristics of included cases were provided and associations between RegiSCAR scores, and time to develop/recover DRESS were assessed. In a total of 262,146 adverse drug reactions reports for 75,190 clozapine-treated patients, 596 cases fulfilled RegiSCAR criteria; ultimately, 51 cases were rated as probable/definite DRESS according to RegiSCAR scores, of which 4 were previously published as case reports. The mean age of patients was 41.06 years (43.1% females), with 13 patients (25.5%) receiving reported co-medication with other DRESS culprit drugs. Median time between clozapine initiation and DRESS symptoms was 25 days. Clozapine dose was associated with days to develop symptoms (Spearman's ρ 0.40, p = 0.03). Organ involvement was reported in all cases followed by fever (n = 49; 96.1%) and eosinophilia (n = 47; 92.2%). Treatment involved clozapine discontinuation for 37 patients (72.5%), while 3.9% (n = 2) of cases ended fatally. Clozapine rechallenge was undertaken in 25 patients (49.0%). The screening of the EudraVigilance database revealed 47 novel clozapine-related DRESS cases, and only one was originally reported as DRESS. Clozapine-related DRESS may occur with clozapine monotherapy not only during dose titration, but also during maintenance treatment.


Assuntos
Clozapina , Síndrome de Hipersensibilidade a Medicamentos , Eosinofilia , Adulto , Clozapina/efeitos adversos , Bases de Dados Factuais , Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Síndrome de Hipersensibilidade a Medicamentos/epidemiologia , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Eosinofilia/induzido quimicamente , Eosinofilia/complicações , Eosinofilia/epidemiologia , Feminino , Humanos , Masculino , Farmacovigilância
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