RESUMO
Food allergy to seeds is increasingly more common, with sesame being the most prevalent. Allergy to other seeds, including sunflower, pumpkin, poppy, mustard, and flaxseed, have been reported. Diagnosing a seed allergy is challenging, with many seeds being hidden additives in processed foods and cross-reactive testing. Food labels in the United States are now required to indicate the presence of sesame but other seeds are not required. Oral immunotherapy (OIT) protocols for peanut, milk, and egg are clinically being extrapolated to other foods, including sesame and sunflower seed. This article highlights a case of a patient in whom sunflower seed OIT was administered in a clinical setting.
Assuntos
Helianthus , Hipersensibilidade , Humanos , Sementes , Arachis , ImunoterapiaRESUMO
OBJECTIVE: To assess the safety of, and subsequent allergy documentation associated with, an antimicrobial stewardship intervention consisting of test-dose challenge procedures prompted by an electronic guideline for hospitalized patients with reported ß-lactam allergies. DESIGN: Retrospective cohort study. SETTING: Large healthcare system consisting of 2 academic and 3 community acute-care hospitals between April 2016 and December 2017. METHODS: We evaluated ß-lactam antibiotic test-dose outcomes, including adverse drug reactions (ADRs), hypersensitivity reactions (HSRs), and electronic health record (EHR) allergy record updates. HSR predictors were examined using a multivariable logistic regression model. Modification of the EHR allergy record after test doses considered relevant allergy entries added, deleted, and/or specified. RESULTS: We identified 1,046 test-doses: 809 (77%) to cephalosporins, 148 (14%) to penicillins, and 89 (9%) to carbapenems. Overall, 78 patients (7.5%; 95% confidence interval [CI], 5.9%-9.2%) had signs or symptoms of an ADR, and 40 (3.8%; 95% CI, 2.8%-5.2%) had confirmed HSRs. Most HSRs occurred at the second (ie, full-dose) step (68%) and required no treatment beyond drug discontinuation (58%); 3 HSR patients were treated with intramuscular epinephrine. Reported cephalosporin allergy history was associated with an increased odds of HSR (odds ratio [OR], 2.96; 95% CI, 1.34-6.58). Allergies were updated for 474 patients (45%), with records specified (82%), deleted (16%), and added (8%). CONCLUSION: This antimicrobial stewardship intervention using ß-lactam test-dose procedures was safe. Overall, 3.8% of patients with ß-lactam allergy histories had an HSR; cephalosporin allergy histories conferred a 3-fold increased risk. Encouraging EHR documentation might improve this safe, effective, and practical acute-care antibiotic stewardship tool.
Assuntos
Antibacterianos/efeitos adversos , Gestão de Antimicrobianos/métodos , Hipersensibilidade a Drogas/epidemiologia , beta-Lactamas/administração & dosagem , beta-Lactamas/efeitos adversos , Adulto , Idoso , Antibacterianos/administração & dosagem , Cefalosporinas/administração & dosagem , Cefalosporinas/efeitos adversos , Sistemas de Apoio a Decisões Clínicas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Penicilinas/administração & dosagem , Penicilinas/efeitos adversos , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Addressing inaccurate penicillin allergies is encouraged as part of antibiotic stewardship in the inpatient setting. However, implementing interventions targeted at the 10% to 15% of inpatients reporting a previous penicillin allergy can pose substantial logistic challenges. We implemented a computerized guideline for patients with reported beta-lactam allergy at 5 hospitals within a single health care system in the Boston area. In this article, we describe our implementation roadmap, including both successes achieved and challenges faced. We explain key implementation steps, including assembling a team, stakeholder engagement, developing or selecting an approach, spreading the change, establishing measures, and measuring impact. The objective was to detail the lessons learned while empowering others to be part of this important, multidisciplinary work to improve the care of patients with reported beta-lactam allergies.
Assuntos
Hipersensibilidade a Drogas/diagnóstico , beta-Lactamas/efeitos adversos , Boston , Humanos , Pacientes Internados , Guias de Prática Clínica como Assunto , Testes Cutâneos , beta-Lactamas/uso terapêuticoRESUMO
The American Academy of Allergy, Asthma & Immunology (AAAAI) and the American College of Allergy, Asthma & Immunology (ACAAI) have jointly accepted responsibility for establishing the "Practice parameter for the diagnosis and management of primary immunodeficiency." This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma & Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion.
Assuntos
Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/terapia , Comitês Consultivos , Animais , Ensaios Clínicos como Assunto , Gerenciamento Clínico , Medicina Baseada em Evidências , HumanosRESUMO
Chronic granulomatous disease (CGD) is typically characterized by recurrent infections, granulomatous disease, and an increased susceptibility to autoimmune disease. We report a novel homozygous mutation in NCF2 that permits residual expression of an alternatively spliced variant in a patient with duodenitis and systemic lupus erythematosus (SLE), followed by a late-onset, single pulmonary infection in the setting of immunosuppressive medications. This report highlights the importance of considering CGD in patients who present initially exclusively with autoimmune disease.
Assuntos
Doenças Autoimunes/genética , Mutação/genética , NADPH Oxidases/genética , Criança , Feminino , Doença Granulomatosa Crônica/genética , Homozigoto , Humanos , Pneumopatias/genética , Lúpus Eritematoso Sistêmico/genéticaRESUMO
BACKGROUND: A number of heritable immune dysregulatory diseases result from defects affecting regulatory T (Treg) cell development, function, or both. They include immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, which is caused by mutations in forkhead box P3 (FOXP3), and IPEX-like disorders caused by mutations in IL-2 receptor α (IL2RA), signal transducer and activator of transcription 5b (STAT5b), and signal transducer and activator of transcription 1 (STAT1). However, the genetic defects underlying many cases of IPEX-like disorders remain unknown. OBJECTIVE: We sought to identify the genetic abnormalities in patients with idiopathic IPEX-like disorders. METHODS: We performed whole-exome and targeted gene sequencing and phenotypic and functional analyses of Treg cells. RESULTS: A child who presented with an IPEX-like syndrome and severe Treg cell deficiency was found to harbor a nonsense mutation in the gene encoding LPS-responsive beige-like anchor (LRBA), which was previously implicated as a cause of common variable immunodeficiency with autoimmunity. Analysis of subjects with LRBA deficiency revealed marked Treg cell depletion; profoundly decreased expression of canonical Treg cell markers, including FOXP3, CD25, Helios, and cytotoxic T lymphocyte-associated antigen 4; and impaired Treg cell-mediated suppression. There was skewing in favor of memory T cells and intense autoantibody production, with marked expansion of T follicular helper and contraction of T follicular regulatory cells. Whereas the frequency of recent thymic emigrants and the differentiation of induced Treg cells were normal, LRBA-deficient T cells exhibited increased apoptosis and reduced activities of the metabolic sensors mammalian target of rapamycin complexes 1 and 2. CONCLUSION: LRBA deficiency is a novel cause of IPEX-like syndrome and Treg cell deficiency associated with metabolic dysfunction and increased apoptosis of Treg cells.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/deficiência , Proteínas Adaptadoras de Transdução de Sinal/genética , Linfócitos T Reguladores/imunologia , Adolescente , Autoanticorpos/imunologia , Pré-Escolar , Diabetes Mellitus Tipo 1/congênito , Diarreia , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/imunologia , Humanos , Doenças do Sistema Imunitário/congênito , Interleucina-10/imunologia , Masculino , MutaçãoRESUMO
BACKGROUND: The prevalence of peanut (PN) and tree nut (TN) allergy in children has tripled in the past decade. Prenatal exposures, including maternal diet and medications, may account for some of this increase. In the United States, progesterone for luteal support in assisted reproduction is commonly formulated in PN or sesame seed (SS) oil. OBJECTIVE: To determine whether prenatal exposure to PN or SS oil as progesterone in oil increases the child's odds of PN, TN, or SS allergy. METHODS: Parents of 1,272 children evaluated by allergists from May 2005 through October 2009 completed questionnaires on conception, prenatal exposures, dietary history, and allergic history, with review of the child's medical record and skin prick and specific IgE test results. Odds ratios and 95% confidence intervals were calculated using multivariable adjusted logistic regression models. RESULTS: Children of mothers with a history of infertility, in vitro fertilization, or use of progesterone in oil did not have increased odds of PN, TN, and/or SS sensitization. Maternal consumption of TNs during first 2 trimesters was associated with 60% higher odds of having a PN/TN/SS-sensitized child (95% confidence interval 1.01-2.51), with similarly increased odds with maternal SS ingestion. Odds of PN/TN/SS sensitization were doubled in children with asthma or environmental allergies. CONCLUSION: Neither maternal infertility nor exposure to PN or SS oils through progesterone support during assisted reproduction treatment was associated with increased odds of PN/TN/SS sensitization in the child. However, maternal ingestion of TNs and SS during pregnancy was associated with increased odds of PN/TN/SS sensitization in the child.
Assuntos
Hipersensibilidade a Noz/imunologia , Hipersensibilidade a Amendoim/imunologia , Efeitos Tardios da Exposição Pré-Natal , Sesamum/imunologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Fenômenos Fisiológicos da Nutrição , Gravidez , Progesterona , Testes Cutâneos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Studies of asthma have been limited by a poor understanding of how nonallergic environmental exposures, such as air pollution and infection, are translated in the lung into inflammation and wheezing. OBJECTIVE: Our goal was to understand the mechanism of nonallergic asthma that leads to airway hyperreactivity (AHR), a cardinal feature of asthma independent of adaptive immunity. METHOD: We examined mouse models of experimental asthma in which AHR was induced by respiratory syncytial virus infection or ozone exposure using mice deficient in T-cell immunoglobulin and mucin domain 1 (TIM1/HAVCR1), an important asthma susceptibility gene. RESULTS: TIM1(-/-) mice did not have airways disease when infected with RSV or when repeatedly exposed to ozone, a major component of air pollution. On the other hand, the TIM1(-/-) mice had allergen-induced experimental asthma, as previously shown. The RSV- and ozone-induced pathways were blocked by treatment with caspase inhibitors, indicating an absolute requirement for programmed cell death and apoptosis. TIM-1-expressing, but not TIM-1-deficient, natural killer T cells responded to apoptotic airway epithelial cells by secreting cytokines, which mediated the development of AHR. CONCLUSION: We defined a novel pathway in which TIM-1, a receptor for phosphatidylserine expressed by apoptotic cells, drives the development of asthma by sensing and responding to injured and apoptotic airway epithelial cells.
Assuntos
Apoptose/imunologia , Asma/fisiopatologia , Brônquios/imunologia , Hiper-Reatividade Brônquica/imunologia , Proteínas de Membrana/genética , Animais , Asma/genética , Asma/imunologia , Asma/metabolismo , Brônquios/citologia , Brônquios/metabolismo , Hiper-Reatividade Brônquica/genética , Hiper-Reatividade Brônquica/metabolismo , Células Epiteliais/citologia , Células Epiteliais/imunologia , Receptor Celular 1 do Vírus da Hepatite A , Proteínas de Membrana/deficiência , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Células T Matadoras Naturais/imunologia , Ozônio/efeitos adversos , Infecções por Vírus Respiratório Sincicial/imunologiaRESUMO
BACKGROUND CONTEXT: The use of topical hemostatic agents is widespread and has been shown to reduce bleeding during a wide variety of surgical procedures. Nonetheless, as biologically active agents, there is potential for allergic reactions to these products. PURPOSE: This is a report of intraoperative anaphylaxis to gelatin associated with the use of two topical hemostatic agents. STUDY DESIGN: Case report. There is no outside funding or potential conflict of interest. PATIENT SAMPLE: A patient with anaphylaxis during anterior spinal fusion. OUTCOME MEASURES: Laboratory assays for tryptase, gelatin-specific immunoglobulin E (IgE), and total IgE. METHODS: A 14-year-old male with myelomeningocele and scoliosis was treated with anterior spinal fusion from T12 to L3. Gelfoam sponges were applied during the preparation of the disc spaces. Approximately 1 hour later, Floseal hemostatic matrix was applied to a briskly bleeding screw hole in the L3 vertebral body, and the patient experienced an abrupt onset of hypotension and ventilatory difficulty. Epinephrine, dexamethasone, and blood products were administered for hemodynamic support while the surgical site was closed. Removal of the drapes revealed a widespread erythematous rash, and the patient was then transferred to the intensive care unit. When stable 3 days later, he returned to the operating room for completion of the spinal fusion. RESULTS: Postoperative laboratory assays were sent that revealed elevated levels of tryptase, total IgE, porcine, and bovine gelatin-specific IgE. The patient was counseled to avoid gelatin-containing products. At 6-month follow-up, his instrumented spine was radiographically fused and he reported no further allergic issues. CONCLUSIONS: Anaphylaxis may occur because of animal gelatin components of topical hemostatic agents. Previous reports have focused on the thrombin components. Care should be taken in the administration of these products, particularly in the atopic individual.
Assuntos
Anafilaxia/etiologia , Gelatina/efeitos adversos , Hemostáticos/efeitos adversos , Meningomielocele/cirurgia , Escoliose/cirurgia , Fusão Vertebral , Adolescente , Anafilaxia/terapia , Perda Sanguínea Cirúrgica/prevenção & controle , Esponja de Gelatina Absorvível/efeitos adversos , Humanos , MasculinoRESUMO
The Sir2 histone deacetylase functions as a chromatin silencer to regulate recombination, genomic stability, and aging in budding yeast. Seven mammalian Sir2 homologs have been identified (SIRT1-SIRT7), and it has been speculated that some may have similar functions to Sir2. Here, we demonstrate that SIRT6 is a nuclear, chromatin-associated protein that promotes resistance to DNA damage and suppresses genomic instability in mouse cells, in association with a role in base excision repair (BER). SIRT6-deficient mice are small and at 2-3 weeks of age develop abnormalities that include profound lymphopenia, loss of subcutaneous fat, lordokyphosis, and severe metabolic defects, eventually dying at about 4 weeks. We conclude that one function of SIRT6 is to promote normal DNA repair, and that SIRT6 loss leads to abnormalities in mice that overlap with aging-associated degenerative processes.
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Envelhecimento/metabolismo , Doenças Genéticas Inatas/genética , Instabilidade Genômica , Sirtuínas/genética , Sirtuínas/fisiologia , Animais , Proliferação de Células , Cromatina/metabolismo , Dano ao DNA , Reparo do DNA , Doenças Genéticas Inatas/patologia , Humanos , Antígeno Ki-1/metabolismo , Linfócitos/imunologia , Camundongos , Camundongos Knockout , Fenótipo , Tolerância a Radiação , Transdução de Sinais , Sirtuínas/deficiênciaRESUMO
The FcRH4 transmembrane molecule, a member of the Fc receptor homologue family, can potently inhibit B cell receptor (BCR) signaling. We show that cell surface expression of this immunoregulatory molecule is restricted to a subpopulation of memory B cells, most of which lack the classical CD27 marker for memory B cells in humans. The FcRH4+ and FcRH4- memory B cells have undergone comparable levels of immunoglobulin isotype switching and somatic hypermutation, while neither subpopulation expresses the transcription factors involved in plasma cell differentiation. The FcRH4+ memory cells are morphologically distinctive large lymphocytes that express the CD69, CD80, and CD86 cell activation markers. They are also shown to be poised to secrete high levels of immunoglobulins in response to stimulation with T cell cytokines, but they fail to proliferate in response either to BCR ligation or Staphylococcus aureus stimulation. A heightened expression of the CCR1 and CCR5 chemokine receptors may facilitate their preferential localization in lymphoid tissues near epithelial surfaces. Cell surface FcRH4 expression thus marks a unique population of memory B cells with distinctive morphology, functional capabilities, and tissue localization.
Assuntos
Subpopulações de Linfócitos B/imunologia , Memória Imunológica , Receptores Fc/biossíntese , Receptores Fc/genética , Anticorpos Monoclonais/biossíntese , Subpopulações de Linfócitos B/metabolismo , Células Cultivadas , Humanos , Região Variável de Imunoglobulina/genética , Memória Imunológica/genética , Ativação Linfocitária/imunologia , Receptores de Superfície Celular , Receptores de Quimiocinas/metabolismo , Receptores Fc/imunologia , Hipermutação Somática de ImunoglobulinaRESUMO
Fc receptor homolog 4 (FcRH4) is a B cell-specific member of the recently identified family of FcRHs whose intracellular domain contains three potential immunoreceptor tyrosine-based inhibitory motifs (ITIMs). The signaling potential of this receptor, shown here to be preferentially expressed by memory B cells, was compared with the inhibitory receptor FcgammaRIIb in B cells expressing either WT FcgammaRIIb or chimeric proteins in which the intracellular domain of FcRH4 was fused to the transmembrane and extracellular domains of FcgammaRIIb. Coligation of the FcgammaRIIb/FcRH4 chimeric protein with the B cell receptor (BCR) led to tyrosine phosphorylation of the two membrane-distal tyrosines and profound inhibition of BCR-mediated calcium mobilization, whole cell tyrosine phosphorylation, and mitogen-activated protein (MAP)-kinase activation. Mutational analysis of the FcRH4 cytoplasmic region indicated that the two membrane-distal ITIMs are essential for this inhibitory potential. Phosphopeptides corresponding to these ITIMs could bind the Src homology 2 (SH2) domain-containing tyrosine phosphatases SHP-1 and SHP-2, which associated with the WT FcRH4 and with mutants having inhibitory capability. These findings indicate the potential for FcRH4 to abort B cell receptor signaling by recruiting SHP-1 and SHP-2 to its two membrane distal ITIMs.