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1.
Clin Exp Allergy ; 47(7): 856-889, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-30239057

RESUMO

This is an updated guideline for the diagnosis and management of allergic and non-allergic rhinitis, first published in 2007. It was produced by the Standards of Care Committee of the British Society of Allergy and Clinical Immunology, using accredited methods. Allergic rhinitis is common and affects 10-15% of children and 26% of adults in the UK, it affects quality of life, school and work attendance, and is a risk factor for development of asthma. Allergic rhinitis is diagnosed by history and examination, supported by specific allergy tests. Topical nasal corticosteroids are the treatment of choice for moderate to severe disease. Combination therapy with intranasal corticosteroid plus intranasal antihistamine is more effective than either alone and provides second line treatment for those with rhinitis poorly controlled on monotherapy. Immunotherapy is highly effective when the specific allergen is the responsible driver for the symptoms. Treatment of rhinitis is associated with benefits for asthma. Non-allergic rhinitis also is a risk factor for the development of asthma and may be eosinophilic and steroid-responsive or neurogenic and non- inflammatory. Non-allergic rhinitis may be a presenting complaint for systemic disorders such as granulomatous or eosinophilic polyangiitis, and sarcoidoisis. Infective rhinitis can be caused by viruses, and less commonly by bacteria, fungi and protozoa.


Assuntos
Rinite Alérgica/diagnóstico , Rinite Alérgica/terapia , Rinite/diagnóstico , Rinite/terapia , Gerenciamento Clínico , Humanos , Rinite/epidemiologia , Rinite/etiologia , Rinite Alérgica/epidemiologia , Rinite Alérgica/etiologia
2.
Clin Exp Allergy ; 45(2): 300-27, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25623506

RESUMO

The Standards of Care Committee of the British Society for Allergy and Clinical Immunology (BSACI) and an expert panel have prepared this guidance for the management of immediate and non-immediate allergic reactions to penicillins and other beta-lactams. The guideline is intended for UK specialists in both adult and paediatric allergy and for other clinicians practising allergy in secondary and tertiary care. The recommendations are evidence based, but where evidence is lacking, the panel reached consensus. During the development of the guideline, all BSACI members were consulted using a Web-based process and all comments carefully considered. Included in the guideline are epidemiology of allergic reactions to beta-lactams, molecular structure, formulations available in the UK and a description of known beta-lactam antigenic determinants. Sections on the value and limitations of clinical history, skin testing and laboratory investigations for both penicillins and cephalosporins are included. Cross-reactivity between penicillins and cephalosporins is discussed in detail. Recommendations on oral provocation and desensitization procedures have been made. Guidance for beta-lactam allergy in children is given in a separate section. An algorithm to help the clinician in the diagnosis of patients with a history of penicillin allergy has also been included.


Assuntos
Antibacterianos/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/terapia , Penicilinas/efeitos adversos , beta-Lactamas/efeitos adversos , Fatores Etários , Gerenciamento Clínico , Hipersensibilidade a Drogas/epidemiologia , Humanos
3.
Clin Exp Allergy ; 43(8): 874-80, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23889241

RESUMO

BACKGROUND: Aspirin-exacerbated respiratory disease is under-diagnosed and therefore effective and inexpensive therapy with aspirin desensitization is rarely performed. METHODS: We present an audit of 150 patients with difficult to treat nasal polyposis, 132 of whom also had asthma, 131 of whom underwent challenge with the only soluble form of aspirin, lysine aspirin (LAS), to confirm or exclude the diagnosis of aspirin-exacerbated respiratory disease (AERD). RESULTS: One hundred patients proved positive on nasal challenge, 31 who were negative went onto oral LAS challenge and a further 14 gave positive results, leaving 17 who were negative to a dose equivalent to over 375 mg of aspirin. Nineteen were not challenged because of contraindications. With the exception of one patient who developed facial angioedema and two patients with > 20% drop in FEV1 (following nasal plus oral challenge) no other severe adverse events occurred. No hospitalization was required for these three patients. Nasal inspiratory peak flow monitoring was less sensitive to obstruction caused by aspirin than was acoustic rhinometry - which should be employed when aspirin challenge is an outpatient procedure. CONCLUSIONS: Provided patients are carefully chosen and monitored LAS challenge is suitable for ENT day case practice where respiratory physician help with asthma is available and should reduce the under-diagnosis of this condition.


Assuntos
Aspirina/análogos & derivados , Aspirina/efeitos adversos , Asma Induzida por Aspirina/diagnóstico , Lisina/análogos & derivados , Rinite/induzido quimicamente , Rinite/diagnóstico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Provocação Nasal , Reprodutibilidade dos Testes
4.
Clin Exp Allergy ; 40(1): 15-31, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20205694

RESUMO

Investigation of anaphylaxis during general anaesthesia requires an accurate record of events including information on timing of drug administration provided by the anaesthetist, as well as timed acute tryptase measurements. Referrals should be made to a centre with the experience and ability to investigate reactions to a range of drug classes/substances including neuromuscular blocking agents (NMBAs) intravenous (i.v.) anaesthetics, antibiotics, opioid analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), local anaesthetics, colloids, latex and other agents. About a third of cases are due to allergy to NMBAs. Therefore, investigation should be carried out in a dedicated drug allergy clinic to allow seamless investigation of all suspected drug classes as a single day-case. This will often require skin prick tests, intra-dermal testing and/or drug challenge. Investigation must cover the agents administered, but should also include most other commonly used NMBAs and i.v. anaesthetics. The outcome should be to identify the cause and a range of drugs/agents likely to be safe for future use. The allergist is responsible for a detailed report to the referring anaesthetist and to the patient's GP as well as the surgeon/obstetrician. A shorter report should be provided to the patient, adding an allergy alert to the case notes and providing an application form for an alert-bracelet indicating the wording to be inscribed. The MHRA should be notified. Investigation of anaphylaxis during general anaesthesia should be focussed in major allergy centres with a high throughput of cases and with experience and ability as described above. We suggest this focus since there is a distinct lack of validated data for testing, thus requiring experience in interpreting tests and because of the serious consequences of diagnostic error.


Assuntos
Anafilaxia/diagnóstico , Anestesia Geral/efeitos adversos , Anestésicos/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Anafilaxia/prevenção & controle , Antibacterianos/efeitos adversos , Hipersensibilidade a Drogas/prevenção & controle , Inglaterra , Humanos , Látex/efeitos adversos , Bloqueadores Neuromusculares/efeitos adversos , Fatores de Risco , Testes Cutâneos/métodos , Triptases/sangue
6.
Clin Exp Allergy ; 39(1): 43-61, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19128352

RESUMO

These guidelines have been prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI) and are intended for allergists and others with a special interest in allergy. As routine or validated tests are not available for the majority of drugs, considerable experience is required for the investigation of allergic drug reactions and to undertake specific drug challenge. A missed or incorrect diagnosis of drug allergy can have serious consequences. Therefore, investigation and management of drug allergy is best carried out in specialist centres with large patient numbers and adequate competence and resources to manage complex cases. The recommendations are evidence-based but where evidence was lacking consensus was reached by the panel of specialists on the committee. The document encompasses epidemiology, risk factors, clinical patterns of drug allergy, diagnosis and treatment procedures. In order to achieve a correct diagnosis we have placed particular emphasis on obtaining an accurate clinical history and on the physical examination, as these are critical to the choice of skin tests and subsequent drug provocation. After the diagnosis of drug allergy has been established, communication of results and patient education are vital components of overall patient management.


Assuntos
Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/tratamento farmacológico , Adulto , Idoso , Criança , Hipersensibilidade a Drogas/epidemiologia , Hipersensibilidade a Drogas/etiologia , Medicina Baseada em Evidências , Feminino , Humanos , Lactente , Masculino , Anamnese , Exame Físico , Fatores de Risco , Testes Cutâneos , Adulto Jovem
7.
Clin Exp Allergy ; 38(2): 260-75, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18167126

RESUMO

This guidance for the management of patients with rhinosinusitis and nasal polyposis has been prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI). The recommendations are based on evidence and expert opinion and are evidence graded. These guidelines are for the benefit of both adult physicians and paediatricians treating allergic conditions. Rhinosinusitis implies inflammation of the nose and sinuses which may or may not have an infective component and includes nasal polyposis. Acute rhinosinusitis lasts up to 12 weeks and resolves completely. Chronic rhinosinusitis persists over 12 weeks and may involve acute exacerbations. Rhinosinusitis is common, affecting around 15% of the population and causes significant reduction in quality of life. The diagnosis is based largely on symptoms with confirmation by nasendoscopy. Computerized tomography scans and magnetic resonance imaging are abnormal in approximately one third of the population so are not recommended for routine diagnosis but should be reserved for those with acute complications, diagnostic uncertainty or failed medical therapy. Underlying conditions such as immune deficiency, Wegener's granulomatosis, Churg-Strauss syndrome, aspirin hypersensitivity and allergic fungal sinusitis may present as rhinosinusitis. There are few good quality trials in this area but the available evidence suggests that treatment is primarily medical, involving douching, corticosteroids, antibiotics, anti-leukotrienes, and anti-histamines. Endoscopic sinus surgery should be considered for complications, anatomical variations causing local obstruction, allergic fungal disease or patients who remain very symptomatic despite medical treatment. Further well conducted trials in clearly defined patient groups are needed to improve management.


Assuntos
Pólipos Nasais/diagnóstico , Pólipos Nasais/tratamento farmacológico , Rinite/diagnóstico , Rinite/tratamento farmacológico , Sinusite/diagnóstico , Sinusite/tratamento farmacológico , Aspirina/efeitos adversos , Aspirina/imunologia , Criança , Síndrome de Churg-Strauss/diagnóstico , Síndrome de Churg-Strauss/tratamento farmacológico , Síndrome de Churg-Strauss/etiologia , Feminino , Humanos , Masculino , Pólipos Nasais/etiologia , Rinite/etiologia , Sinusite/etiologia
8.
Clin Exp Allergy ; 38(1): 19-42, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18081563

RESUMO

This guidance for the management of patients with allergic and non-allergic rhinitis has been prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI). The guideline is based on evidence as well as on expert opinion and is for use by both adult physicians and paediatricians practicing in allergy. The recommendations are evidence graded. During the development of these guidelines, all BSACI members were included in the consultation process using a web-based system. Their comments and suggestions were carefully considered by the SOCC. Where evidence was lacking, consensus was reached by the experts on the committee. Included in this guideline are clinical classification of rhinitis, aetiology, diagnosis, investigations and management including subcutaneous and sublingual immunotherapy. There are also special sections for children, co-morbid associations and pregnancy. Finally, we have made recommendations for potential areas of future research.


Assuntos
Hipersensibilidade/imunologia , Hipersensibilidade/terapia , Rinite/imunologia , Rinite/terapia , Sociedades Médicas/normas , Alérgenos/imunologia , Animais , Inglaterra , Humanos , Hipersensibilidade/classificação , Hipersensibilidade/diagnóstico , Rinite/classificação , Rinite/diagnóstico
9.
Clin Exp Allergy ; 37(5): 631-50, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17456211

RESUMO

This guidance for the management of patients with chronic urticaria and angio-oedema has been prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI). The guideline is based on evidence as well as on expert opinion and is aimed at both adult physicians and paediatricians practising in allergy. The recommendations are evidence graded. During the development of these guidelines, all BSACI members were included in the consultation process using a web-based system. Their comments and suggestions were carefully considered by the SOCC. Where evidence was lacking a consensus was reached by the experts on the committee. Included in this guideline are clinical classification, aetiology, diagnosis, investigations, treatment guidance with special sections on children with urticaria, and the use of antihistamines in women who are pregnant or breastfeeding. Finally, we have made recommendations for potential areas of future research.


Assuntos
Urticária/terapia , Adulto , Algoritmos , Angioedema/diagnóstico , Angioedema/etiologia , Angioedema/terapia , Aleitamento Materno , Criança , Doença Crônica , Medicina Baseada em Evidências , Feminino , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Humanos , Masculino , Gravidez , Complicações na Gravidez/terapia , Prognóstico , Urticária/diagnóstico , Urticária/etiologia
10.
Diabet Med ; 23(2): 204-6, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16433720

RESUMO

BACKGROUND: Patients with poor control of Type 2 diabetes on maximum oral hypoglycaemic therapy invariably need insulin therapy. Insulin allergy is uncommon, particularly in patients with Type 2 diabetes. Management of the condition can be difficult, and here we report the case of a patient with Type 2 diabetes and insulin allergy successfully managed with a continuous subcutaneous insulin infusion (CSII). CASE REPORT: A 60-year-old man was referred with insulin allergy. He had poorly controlled Type 2 diabetes (glycated haemoglobin 10.4%), on maximum doses of sulphonylurea and metformin, with osmotic symptoms. He was compliant with diet and tablets. His diabetes was complicated by retinopathy, nephropathy, coronary heart disease, obstructive sleep apnoea, obesity, depression and hypertension. He commenced on twice daily mixed insulin and, shortly after, developed pain, itching and erythema at the injection sites. The sites became indurated and tender, and he had constitutional symptoms. The insulin was changed to other preparations, including short- and long-acting analogues, with similar responses. Triple therapy with rosiglitazone was tried, with no improvement in control. Skin-prick testing confirmed allergy to insulin rather than additives. The patient was reluctant to undergo desensitization. He was commenced on an insulin pump in addition to his oral hypoglycaemics, and achieved fair control (glycated haemoglobin 8.3%) on 88 units of lispro per day, with little or no skin or systemic reaction. CONCLUSION: This is the first case report of insulin allergy in Type 2 diabetes being successfully managed by CSII.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Hipersensibilidade a Drogas/complicações , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/imunologia , Hipersensibilidade a Drogas/imunologia , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/imunologia , Insulina/administração & dosagem , Insulina/imunologia , Sistemas de Infusão de Insulina , Masculino , Pessoa de Meia-Idade , Pele/imunologia , Resultado do Tratamento
11.
Int J STD AIDS ; 15(4): 275-6, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15075025

RESUMO

A case of persistent Trichomonas vaginalis (TV) in a pregnant, metronidazole-allergic woman is described. This case posed a management dilemma as untreated TV has been associated with adverse pregnancy outcomes but antibiotic desensitization is potentially dangerous during pregnancy.


Assuntos
Antitricômonas/efeitos adversos , Hipersensibilidade a Drogas/complicações , Metronidazol/efeitos adversos , Complicações Parasitárias na Gravidez/tratamento farmacológico , Vaginite por Trichomonas/tratamento farmacológico , Adulto , Animais , Anti-Infecciosos Locais/uso terapêutico , Clotrimazol/uso terapêutico , Feminino , Humanos , Pessários , Gravidez
13.
Clin Exp Immunol ; 130(3): 484-8, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12452839

RESUMO

Hereditary periodic fever syndromes comprise a group of distinct disease entities linked by the defining feature of recurrent febrile episodes. Hyper IgD with periodic fever syndrome (HIDS) is caused by mutations in the mevalonate kinase (MVK) gene. The mechanisms by which defects in the MVK gene cause febrile episodes are unclear and there is no uniformly effective treatment. Mutations of the TNFRSF1A gene may also cause periodic fever syndrome (TRAPS). Treatment with the TNFR-Fc fusion protein, etanercept, is effective in some patients with TRAPS, but its clinical usefulness in HIDS has not been reported. We describe a 3-year-old boy in whom genetic screening revealed a rare combination of two MVK mutations producing clinical HIDS as well as a TNFRSF1A P46L variant present in about 1% of the population. In vitro functional assays demonstrated reduced receptor shedding in proband's monocytes. The proband therefore appears to have a novel clinical entity combining Hyper IgD syndrome with defective TNFRSF1A homeostasis, which is partially responsive to etanercept.


Assuntos
Antígenos CD/genética , Febre Familiar do Mediterrâneo/tratamento farmacológico , Imunoglobulina G/uso terapêutico , Leucócitos Mononucleares/metabolismo , Mutação , Receptores do Fator de Necrose Tumoral/antagonistas & inibidores , Receptores do Fator de Necrose Tumoral/genética , Receptores do Fator de Necrose Tumoral/uso terapêutico , Antígenos CD/sangue , Pré-Escolar , Análise Mutacional de DNA , Etanercepte , Febre Familiar do Mediterrâneo/genética , Febre Familiar do Mediterrâneo/metabolismo , Humanos , Masculino , Ácido Mevalônico/urina , Linhagem , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Receptores do Fator de Necrose Tumoral/sangue , Receptores Tipo I de Fatores de Necrose Tumoral
14.
J Immunol Methods ; 265(1-2): 161-75, 2002 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-12072186

RESUMO

Over the last few years, the importance of apoptosis in determining the fate of thyrocytes in autoimmune thyroid disease has been the topic of intense investigation. It is now clear that thyrocytes from patients with Hashimoto's thyroiditis are destroyed as a result of an apoptotic process. However, there is no general consensus on whether the intrathyroidal lymphocytes or the thyrocytes themselves are responsible for their death. The use of a wide range of techniques has contributed to the assessment of this process both in situ on thyroid sections and in vitro on thyroid cell preparations. The apoptosis field of research is rapidly evolving and as the pathways to cell death become unravelled, novel methods will emerge. As each technique offers some advantage, it is critical to know the most suitable method for a specific study. Equally, each method also has intrinsic limitations. Thus, to achieve reliable results, it is necessary to use more than one technique per study. In addition, techniques related to the measurement of the expression of pro-apoptotic and anti-apoptotic genes have been contributing to the study of the susceptibility of the cells to apoptosis and/or to their ability to kill themselves or neighbouring cells. In this review we will focus on the most relevant techniques.


Assuntos
Apoptose , Glândula Tireoide/patologia , Tireoidite Autoimune/patologia , Animais , Anexina A5/metabolismo , Apoptose/genética , DNA/análise , Proteína Ligante Fas , Citometria de Fluxo , Humanos , Immunoblotting , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Glicoproteínas de Membrana/análise , Microscopia Eletrônica , Glândula Tireoide/ultraestrutura , Receptor fas/análise
15.
Thyroid ; 11(10): 919-27, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11716038

RESUMO

In Hashimoto's thyroiditis, thyrocytes die by apoptosis. Whether this is the result of impaired antiapoptotic gene expression or hyperexpression of proapoptotic signals or other mechanisms is not fully established. Following the suggestion that thyrocytes from Hashimoto's glands die by a fratricidal killing mediated by Fas/Fas ligand, we have investigated whether thyroid cells from different clinical conditions are able to kill Fas-expressing target cells. We have studied whether this effector ability was mediated by Fas/Fas ligand, perforin or other death receptors/ligands, i.e., tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/tumor necrosis factor-related apoptosis-inducing ligand receptor (TRAIL-R). We have confirmed that thyroid preparations can kill Fas-expressing HUT78 targets through apoptosis. Cell death was only partially dependent on Fas/Fas ligand but it was trypsin-sensitive. Blocking perforin did not affect Fas-expressing target killing while caspase inhibitors had a consistent although limited effect. Thyroid cells were not sensitive to TRAIL/TRAIL-R. We have also found that both thyrocytes and lymphocytes from Graves' disease thyroids were effective at killing autologous and heterologous Fas-expressing targets. Conversely, killing of these targets could be shown only with lymphocytes (but not with thyrocytes) from Hashimoto's glands. In Hashimoto's thyroiditis, thyrocytes were poorly functional while lymphocytes were able to operate as effectors. It is envisaged that thyrocyte death in Hashimoto's would result from autologous thyrocyte killing perpetrated by lymphocytes. Death receptors/ligands would appear to play a role. However, a caspase-independent mechanism may also coexist and contribute to cell death in Hashimoto's thyroiditis.


Assuntos
Autoimunidade , Glândula Tireoide/imunologia , Anticorpos Bloqueadores/farmacologia , Anticorpos Monoclonais/farmacologia , Apoptose/imunologia , Proteínas Reguladoras de Apoptose , Inibidores de Caspase , Citotoxicidade Imunológica , DNA/metabolismo , Proteína Ligante Fas , Bócio Nodular/imunologia , Bócio Nodular/metabolismo , Bócio Nodular/patologia , Doença de Graves/imunologia , Doença de Graves/metabolismo , Doença de Graves/patologia , Humanos , Técnicas In Vitro , Glicoproteínas de Membrana/imunologia , Glicoproteínas de Membrana/metabolismo , Receptores do Fator de Necrose Tumoral/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Tireoidite Autoimune/imunologia , Tireoidite Autoimune/metabolismo , Tireoidite Autoimune/patologia , Fator de Necrose Tumoral alfa/imunologia , Receptor fas/metabolismo
17.
Thyroid ; 10(7): 561-72, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10958308

RESUMO

Programmed cell death or apoptosis is central both in physiology during development and in disease. The mechanism of apoptosis is under the control of antiapoptotic survival genes of the Bcl-2 family and proapoptotic death receptors of the TNF superfamily (Fas, TNFR, TRAILR). Following death signal, the death receptor binds to its own receptor and initiates, through binding of adaptors, a cascade of events mediated by the autoproteolytic activation of specific enzymes called caspases. This enzyme activation is ultimately responsible for the dissembly of basic nuclear and cytoplasmic cell structures leading to cell death. In certain cell systems, antiapoptotic genes of the Bcl-2 family prevent the proapoptotic pathway. One of their roles is to maintain mitochondrial function integrity. In autoimmune destructive thyroiditis high levels of apoptosis have been demonstrated particularly within the destructed follicles near the infiltrated areas in comparison to Graves' disease and non autoimmune glands. In Hashimoto's thyroiditis Fas expression has been found increased on thyrocytes and in vitro can be modulated by proinflammatory cytokines. FasL expression on thyrocytes remains controversial. Thyroid cells from Graves' disease and multinodular glands are known to kill Fas expressing target cells although Hashimoto's thyrocytes are not efficient effector cells. Intrathyroidal lymphocytes from Hashimoto's thyroids maintain functional killer activity. These findings would suggest that intrathyroidal lymphocytes could be responsible for thyrocyte death in vivo. Whether this mechanism is Fas/FasL, TRAIL/TRAILR dependent can not be confirmed as specific blocking reagents were not able to inhibit cell induced death. In Hashimoto's thyroiditis an impairment of Bcl-2 and Bcl-X anitapoptotic genes on thyrocytes has also been detected. Bcl-X expression can be down-regulated in vitro by incubation with cytokines. These findings suggest that thyrocyte death may not exclusively be the result of specific interactions between death receptor and their ligands but it may involve simultaneous impairment of protective genes of the Bcl-2 family. Whether the impairment of the Bcl-2 family is a direct consequence of environmental stimuli or is the result of an intrinsic thyrocyte (mitochondrial?) alteration is as yet not known.


Assuntos
Apoptose , Doenças Autoimunes/patologia , Doenças da Glândula Tireoide/imunologia , Glândula Tireoide/imunologia , Glândula Tireoide/patologia , Animais , Apoptose/genética , Caspases/fisiologia , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/fisiologia , Doenças da Glândula Tireoide/genética , Receptor fas/fisiologia
18.
Int Immunol ; 12(4): 405-13, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10744641

RESUMO

MHC class II molecules are heterodimeric, polymorphic transmembrane glycoproteins physiologically expressed on cells of the immune system and pathologically expressed on the affected target cells of autoimmunity. Their function is to present processed peptides to antigen-specific CD4(+) T cells. To understand the molecular mechanism of the regulation of class II genes in autoimmune target cell thyrocytes, we investigated the transcriptional regulation of DRA on untransformed, differentiated human thyroid cells following IFN-gamma stimulation, which is potentially relevant to the inappropriate class II expression found in Graves' disease. Data from this study show that IFN-gamma enhances a promoter Y box binding protein and induces an X box binding protein in untransformed thyrocytes, but not in SV-40-transfected thyrocytes. Initial characterization of the proteins has indicated that the Y box binding protein is approximately 132 kDa in size while the X box binding protein binds to the X2 region and is approximately 116 kDa. The X box binding protein may correspond to poly(ADP-ribose) polymerase, a recently described component of the X2 box binding protein, X2BP. In addition, the signal transducer and activator of transcription 1alpha protein (STAT1alpha) is also induced by IFN-gamma in these cells. These results further suggest that there are differences in class II gene regulation between differentiated cells and transformed cell lines.


Assuntos
Regulação da Expressão Gênica/imunologia , Genes MHC da Classe II , Antígenos HLA-DR/genética , Glândula Tireoide/imunologia , Glândula Tireoide/metabolismo , Sequência de Bases , Sítios de Ligação/genética , Sítios de Ligação/imunologia , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Linhagem Celular , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/imunologia , Proteínas de Ligação a DNA/metabolismo , Antígenos HLA-DR/biossíntese , Antígenos HLA-DR/metabolismo , Cadeias alfa de HLA-DR , Humanos , Fator Gênico 3 Estimulado por Interferon , Dados de Sequência Molecular , Peso Molecular , Regiões Promotoras Genéticas/imunologia , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Glândula Tireoide/citologia , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
19.
Lancet ; 354(9178): 568, 1999 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-10470707

RESUMO

Tryptophan hydroxylase antibodies, associated with gastrointestinal disease in autoimmune polyendocrine syndrome type 1, are specific for this disease and not present in patients with other bowel disorders or healthy controls.


Assuntos
Autoanticorpos/sangue , Enteropatias/etiologia , Poliendocrinopatias Autoimunes/enzimologia , Poliendocrinopatias Autoimunes/imunologia , Triptofano Hidroxilase/imunologia , Humanos , Enteropatias/sangue , Enteropatias/enzimologia , Enteropatias/imunologia , Poliendocrinopatias Autoimunes/sangue , Poliendocrinopatias Autoimunes/complicações , Triptofano Hidroxilase/sangue
20.
J Autoimmun ; 12(4): 305-14, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10330302

RESUMO

Microbial superantigens have been implicated in the pathogenesis of human autoimmune diseases. In autoimmune glands, thyrocytes inappropriately express HLA-DR molecules and these cells may function as antigen presenting cells (APC) We studied the effect in vitro of staphylococcal enterotoxin B (SEB) on HLA molecule expression on thyrocytes obtained from autoimmune and non-autoimmune glands by immunofluorescence. HLA class I and class II upregulation could be detected by FACS analysis on thyrocytes. Anti-IFN-gamma neutralizing antibodies markedly affect both class I and class II upregulation on thyrocytes. FRTL5 cells were not responsive to SEB. Similarly, a human thyroid cell strain maintained in culture in a conditioned medium was not induced to express HLA products by SEB stimulation. The addition of autologous intrathyroidal lymphocytes caused reestablishment of the SEB effect.


Assuntos
Enterotoxinas/farmacologia , Antígenos de Histocompatibilidade Classe II/biossíntese , Antígenos de Histocompatibilidade Classe I/biossíntese , Staphylococcus aureus/imunologia , Superantígenos/farmacologia , Glândula Tireoide/efeitos dos fármacos , Células Cultivadas , Citometria de Fluxo , Humanos , Interferon gama/metabolismo , Interferon gama/farmacologia , Glândula Tireoide/citologia , Glândula Tireoide/imunologia , Regulação para Cima
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