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Platelets in Kawasaki disease:Is this only a numbers game or something beyond?

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Genes & Diseases 2020年第1期7卷 62-66页

作者： Kanika Arora Sandesh Guleria Ankur Kumar Jindal Amit Rawat Surjit Singh allergy Immunology Unit Department of PediatricsAdvanced Pediatrics CentrePostgraduate Institute of Medical Education and ResearchChandigarhIndia

Kawasaki disease(KD)is a medium vessel vasculitis with predilection to cause coronary artery *** is now the most common cause of acquired heart disease in developed *** is consistently found in patients with KD,usually in 2nd to 3rd week of *** has occasionally been reported in the acute phase of *** increase or decrease in platelet number in patients with KD was initially considered to be a benign ***,recent literature on platelet biology in KD has suggested that platelets are not only increasing but are rather *** phenomenon has been found to increase the risk of thrombosis in these *** a fall in platelet counts during acute stage of KD has also been found to be associated with increased severity of *** this review,we update on the current best understanding about pathogenic role of platelets in patients with KD.

关键词： Aspirin CD40 ligand Kawasaki disease Platelet derived microparticles Platelets Thrombosis

Psychiatric comorbidities in children and adolescents with chronic urticaria

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World Journal of Pediatrics 2023年第4期19卷 315-322页

作者： George N.Konstantinou Gerasimos N.Konstantinou department of allergy and Clinical Immunology 424 General Military Training HospitalThessaloníkiGreece department of Psychiatry University of TorontoTorontoONCanada Center for Addiction and Mental Health(CAMH) TorontoONCanada

Background Chronic urticaria(CU)has been shown to impact patients'quality of life negatively and may coexist with psychiatric *** systematically reviewed the published evidence of comorbid psychiatric disorders in children and adolescents with *** A systematic review of studies published until February 2022 in PubMed,Google Scholar,and Scopus was *** a priori set of inclusion criteria was predefined for the studies to be included:(1)clear distinction between urticaria and other allergies;(2)precise distinction between acute and CU;(3)participants younger than 18 years old,exclusively;(4)use of appropriate standardized questionnaires,psychometric tools,and standard diagnostic nomenclature for the mental health and behavioral disorders diagnosis;and(5)manuscripts written or published in the English *** Our search identified 582 potentially relevant *** eight of them satisfied the inclusion ***-tive meta-analysis was not deemed appropriate,given the lack of relevant randomized control trials,the small number of relevant shortlisted,the small sample size of the patients included in each study,and the remarkable heterogeneity of the studies'*** The included studies suggest an increased incidence of psychopathology among children and adolescents with CU as opposed to healthy age-matched individuals,but the data are *** research is required to clarify whether psychopathology is just a comorbid entity,the cause,or the consequence of *** an interdisciplinary collaboration between allergists/dermatologists and psychiatrists is expected to substantially minimize CU burden and improve patients'quality of life.

关键词： Adolescents Children Chronic urticaria Psychiatry Psychopathology Quality of life

Possible therapeutic role of Ig E blockade in irritable bowel syndrome

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World Journal of Gastroenterology 2016年第43期22卷 9451-9456页

作者： Eli Magen Tinatin Chikovani Medicine C department Allergy and Clinical Immunology Unit Barzilai Medical Center Ben Gurion University of Negev department of Microbiology and Im-munology Tbilisi State Medical University

Omalizumab is a humanized monoclonal antibody that binds to the high-affinity type-I Ig E Fc receptors on mast cells(MCs) and basophils, inhibiting the Ig E immune pathway. Irritable bowel syndrome(IBS) is the most common functional gastrointestinal disorder, and dysregulation of the immune system likely contributes to its etiology and/or symptomatology. Colonic biopsies from patients with IBS demonstrate considerable increase in the number of degranulating MCs releasing histamine in proximity to nerves, and this event may underlie the common IBS symptom of abdominal pain. Pharmacologic control of MC activation and mediator release is a current area of active interest in the field of IBS research. Recently, we and Pearson et al described 2 cases of patients with IBS with diarrhea(IBS-D) showing positive clinical response to omalizumab. In both cases, the female patients had severe, long-lasting IBS-D and achieved an almost complete resolution of IBS symptoms. Both patients were also able to discontinue all IBS medications after commencing the anti-Ig E therapy. For both patients, the omalizumab treatment showed a relatively rapid onset of action, resembling the efficacy observed in and previously reported for patients with chronic spontaneous urticaria. In this Editorial, we discuss the possible biological mechanisms that may underlie the clinical efficacy of omalizumab in IBS. We suggest that there is a need for a well-designed prospective study to investigate the therapeutic effects of anti-Ig E in IBS.

关键词： IgE Omalizumab Irritable bowel syndrome Anti-inflammatory Irritable bowel syndrome with diarrhea

TNF-α and IL-8 of the Patients with Allergic Asthma

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2005年第3期25卷 274-275,309页

作者：刘光辉祝戎飞李宝珠 department of allergy Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

The levels of serum TNF-α and IL-8 in the patients with allergic asthma during acute attack period and remission period, and the effects of glucocorticoid (GC) on them were investigated. By using ELISA, the levels of TNF-α and IL-8 were detected in the healthy volunteers (group C, n=40), the patients with allergic asthma (n=40) during acute attack period (group A) and remission period (group B) and those taking GC for a week (n=28). The results were compared among them. It was found that the levels of TNF-α and IL-8 in group A were higher than in group B and group C. In the patients subject to GC therapy, the levels of TNF-α and IL-8 were decreased as compared with those in group A. In group B, the level of TNF-α was higher than in group C, but there was no significant difference in the level of IL-8 between group B and group C. It was concluded that the inflammatory cytokines, TNF-α and IL-8, played important roles in the bronchus allergic inflammation. GC could reduce the levels of serum TNF-α and IL-8 to exert the anti-inflammatory effects.

关键词： allergic asthma TNF-α IL-8

Interleukin- 13 interferes with activation-induced t-ce apoptosis by repressing p53 expression

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Cellular & Molecular Immunology 2016年第5期13卷 669-677页

作者： Li Yang Ling-Zhi Xu Zhi-Qiang Liu Gui Yang Xiao-Rui Geng Li-Hua Mo Zhi-Gang Liu Peng-Yuan Zheng Ping-Chang Yang department of Gastroenterology the Zhengzhou People's Hospital Zhengzhou China department of Gastroenterology the Fifth Affiliated Hospital of Zhengzhou University Zhengzhou China Shenzhen Key Laboratory of allergy and Immunology Shenzhen University School of Medicine and State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University Shenzhen China ENT Institute of Shenzhen University Longgang Central Hospital Shenzhen China

The etiology and the underlying mechanism of CD4＋ T-cell polarization are unclear. This study sought to investigate the mechanism by which interleukin （IL）-13 prevents the activation-induced apoptosis of CD4＋ T cells. Here we report that CD4＋ T cells expressed IL-13 receptor a2 in the intestine of sensitized mice. IL-13 suppressed both the activation-induced apoptosis of CD4＋ T cells and the expression of p53 and FasL. Exposure to recombinant IL-13 inhibited activation-induced cell death （AICD） along with the expression of p53, caspase 3, and tumor necrosis factor-a in CD4＋ T cells. Administration of an anti-lL-13 antibody enhanced the effect of specific immunotherapy on allergic inflammation in the mouse intestine, enforced the expression of p53 in intestinal CD4＋ T cells, and enhanced the frequency of CD4＋ T-cell apoptosis upon challenge with specific antigens. In summary, blocking IL-13 enhances the therapeutic effect of antigen-specific immunotheraov by regulating aDoptosis and thereby enforcing AICD in CD4＋ T cells.

关键词： activation-induced cell death apoptosis interleukin 13 T lymphocytes Th2 polarization

Three novel homozygous ITGB2 mutations among two patients with leukocyte adhesion defect type-1:Two case reports

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World Journal of Clinical Pediatrics 2022年第5期11卷 429-436页

作者： Yiwa Suksawat Punchama Pacharn Nunthana Siripipattanamongkol Boonchai Boonyawat Division of allergy and Immunology Department of PediatricsPhramongkutklao Hospital and Phramongkutklao College of MedicineBangkok 10400Thailand Division of allergy and Immunology Department of PediatricsSiriraj HospitalMahidol UniversityBangkok 10700Thailand Division of allergy and Immunology Department of PediatricsChiangrai Prachanukroh Regional HospitalChiangrai 57000Thailand Division of Medical Genetics Department of PediatricsPhramongkutklao Hospital and Phramongkutklao College of MedicineBangkok 10400Thailand

BACKGROUND A leukocyte adhesion defect(LAD) is a rare primary immunodeficiency disorder. LAD type 1(LAD-1) is the most common, which is caused by ITGB2 mutation resulting in dysfunction of β2 integrin, which impairs leukocyte adherence to the *** SUMMARY The first two cases of LAD-1 in Thailand presented with recurrent omphalitis, soft tissue infection, marked leukocytosis, and neutrophilia. One patient experienced delayed umbilical cord separation. Mutation analysis was performed by direct DNA sequencing of the ITGB2 gene. The results revealed two novel homozygous missense mutations, c.920C>T(***307Pro) in exon 8 and c.758G>A(***-253His) in exon 7, and one novel homozygous nonsense mutation, c.262C>T(***88Ter) in exon 4, in the genomic DNA of the first and second patients, respectively. Heterozygous mutations were identified in the parents of both patients, suggesting a carrier status. The patients were administered intravenous antibiotics for infections with good clinical responses. Hematopoietic stem cell transplantation could not be performed due to the unavailability of matched donors. However, a significant decline in infections was observed after antibiotic prophylaxis. Several follow-up visits were conducted for both patients. They are currently 6 years *** Molecular analysis is essential for definitive diagnosis, early treatment implementation, and prevention of LAD-1 in future pregnancy.

关键词： Leukocyte adhesion defect ITGB2 Omphalitis Bacterial soft tissue infection Molecular investigation Case report

Empyema and mediastinal abscess in pyriform sinus f istula: A case report

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World Journal of Emergency Medicine 2019年第4期10卷 244-247页

作者： Hai-jiang Zhou Wen-peng Yin Tian-fei Lan Shu-bin Guo department of Emergency Medicine Beijing Chao-yang HospitalCapital Medical UniversityBeijing 100020China department of allergy Beijing Shijitan HospitalCapital Medical UniversityBeijing 100038China

Dear editor,Though notorious for its tendency to induce recurrent neck abscess,pyriform sinus fistula is of importance despite its *** usually presents diagnostic and therapeutic *** of post-infectious fi brosis,the embryologic origin of pyriform sinus fi stula is diffi cult to appreciate in certain *** we present a case with empyema and mediastinal abscess caused by pyriform sinus fi stula and share our experience in the treatment of this patient.

关键词： Empyema mediastinal abscess pyriform sinus fistula

Juvenile dermatomyositis:advances in clinical presentation,myositis-specific antibodies and treatment

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World Journal of Pediatrics 2020年第1期16卷 31-43页

作者： Jian-Qiang Wu Mei-Ping Lu Ann M.Reed department of Rheumatology Immunology and allergy Children's HospitalZhejiang University School of MedicineHangzhou 310052China department of Pediatrics Division of Pediatric RheumatologyDuke University School of MedicineDurham 27710USA

Background Juvenile dermatomyositis(JDM)is a chronic autoimmune disease characteristic by inflammation of small vessels within the skin,muscle and vital *** the clinical features and treatment of JDM have not been fully *** sources Databases underwent through PubMed for articles about the clinical features,myositis-specific antibodiesof JDM and its treatment,and we selected publications written in English which were relevant to the topic of this *** Clinical features and myositis-specific antibodies may predict the severity and prognosis of *** the mortality rate has been lower with traditional treatments,such as corticosteroid,intravenous immunoglobulin,and diseasemodifying anti-rheumatic drugs such as methotrexate,their usages are *** biological therapies seem to be effective for refractory JDM patients,but more clinical trials are *** JDM is a sever disease of *** need to better understand recent advances of JDM in the context of clinical features including skin manifestations,muscle weakness and organ damage,myositis-specific antibodies and their associated outcomes and the treatment of disease.

关键词： Biologic agents Extramuscular manifestations Juvenile dermatomyositis Myositis autoantibodies

Discrimination of membrane antigen affinity by B cells requires dominance of kinetic proofreading over serial engagement

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Cellular & Molecular Immunology 2012年第1期9卷 62-74页

作者： Philippos K Tsourkas Wanli Liu Somkanya C Das Susan K Pierce Subhadip Raychaudhuri department of Biomedical Engineering University of CaliforniaDavisCAUSA Laboratory of Immunogenetics National Institute of Allergy and Infectious DiseasesNational Institutes of HealthRockvilleMDUSA

B-cell receptor signaling in response to membrane-bound antigen increases with antigen affinity,a process known as affinity *** use computational modeling to show that B-cell affinity discrimination requires that kinetic proofreading predominate over serial *** find that if B-cell receptors become signaling-capable immediately upon antigen binding,which results in decreasing serial engagement as affinity increases,then increasing affinity can lead to weaker ***,antigen must stay bound to B-cell receptors for a threshold time of several seconds before becoming signaling-capable,a process similar to kinetic *** process overcomes the loss in serial engagement due to increasing antigen affinity,and replicates the monotonic increase in B-cell signaling with increasing affinity that has been observed in B-cell activation *** finding matches well with the experimentally observed time(,20 s)required for the B-cell receptor signaling domains to undergo antigen and lipid raft-mediated conformational changes that lead to Src-family kinase *** hypothesize that the physical basis for a threshold time of antigen binding might lie in the formation timescale of B-cell receptor *** time required for dimer formation decreases with increasing antigen affinity,thereby resulting in shorter threshold antigen binding times as affinity *** an affinity-dependent kinetic proofreading requirement results in affinity discrimination very similar to that observed in biological experiments.B-cell affinity discrimination is critical to the process of affinity maturation and the production of high-affinity antibodies,and thus our results have important implications in applications such as vaccine design.

关键词： computational modeling Monte Carlo lymphocyte signaling Lyn Syk