RESUMEN
BACKGROUND: The International Consensus on Antinuclear Antibody (ANA) Patterns (ICAP) has recently proposed nomenclature in order to harmonize ANA indirect immunofluorescence (IIF) pattern reporting. ICAP distinguishes competent-level from expert-level patterns. A survey was organized to evaluate reporting, familiarity, and considered clinical value of ANA IIF patterns. METHODS: Two surveys were distributed by European Autoimmunity Standardization Initiative (EASI) working groups, the International Consensus on ANA Patterns (ICAP) and UK NEQAS to laboratory professionals and clinicians. RESULTS: 438 laboratory professionals and 248 clinicians from 67 countries responded. Except for dense fine speckled (DFS), the nuclear competent patterns were reported by > 85% of the laboratories. Except for rods and rings, the cytoplasmic competent patterns were reported by > 72% of laboratories. Cytoplasmic IIF staining was considered ANA positive by 55% of clinicians and 62% of laboratory professionals, with geographical and expertise-related differences. Quantification of fluorescence intensity was considered clinically relevant for nuclear patterns, but less so for cytoplasmic and mitotic patterns. Combining IIF with specific extractable nuclear antigens (ENA)/dsDNA antibody testing was considered most informative. Of the nuclear competent patterns, the centromere and homogeneous pattern obtained the highest scores for clinical relevance and the DFS pattern the lowest. Of the cytoplasmic patterns, the reticular/mitochondria-like pattern obtained the highest scores for clinical relevance and the polar/Golgi-like and rods and rings patterns the lowest. CONCLUSION: This survey confirms that the major nuclear and cytoplasmic ANA IIF patterns are considered clinically important. There is no unanimity on classifying DFS, rods and rings and polar/Golgi-like as a competent pattern and on reporting cytoplasmic patterns as ANA IIF positive.
RESUMEN
IL-6 excess is central to the pathogenesis of multiple inflammatory conditions and is targeted in clinical practice by immunotherapy that blocks the IL-6 receptor encoded by IL6R We describe two patients with homozygous mutations in IL6R who presented with recurrent infections, abnormal acute-phase responses, elevated IgE, eczema, and eosinophilia. This study identifies a novel primary immunodeficiency, clarifying the contribution of IL-6 to the phenotype of patients with mutations in IL6ST, STAT3, and ZNF341, genes encoding different components of the IL-6 signaling pathway, and alerts us to the potential toxicity of drugs targeting the IL-6R.
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Síndromes de Inmunodeficiencia/patología , Inflamación/patología , Receptores de Interleucina-6/deficiencia , Adolescente , Adulto , Niño , Preescolar , Femenino , Células HEK293 , Humanos , Recién Nacido , Masculino , Receptores de Interleucina-6/metabolismoRESUMEN
BACKGROUND: Flucloxacillin is a narrow-spectrum, beta-lactamase-resistant penicillin. Type I (IgE-mediated) and type IV (T-cell-mediated) reactions are less frequently reported than with other penicillins. OBJECTIVE: To undertake a detailed clinical characterization of a cohort of patients referred with suspected flucloxacillin hypersensitivity. METHODS: We retrospectively analyzed demographic characteristics, presentation, investigation, and management of 108 patients presenting to 4 UK centers. Patients underwent skin prick and intradermal testing with flucloxacillin, major (benzylpenicilloyl poly-l-lysine) and minor determinants, amoxicillin, and benzylpenicillin with immediate and, where appropriate, delayed reading of the test. In the immediate group, a further 14 patients were tested to ampicillin and 16 to Augmentin (co-amoxiclav-combination of clavulanic acid and amoxicillin). Skin test-negative patients underwent oral drug provocation. A multistep protocol was used, depending on risk assessment. RESULTS: Forty of 108 (37%) patients were diagnosed with hypersensitivity to flucloxacillin, of whom 33 (82.5%) showed immediate and 7 (17.5%) nonimmediate hypersensitivity, respectively. In the immediate group, most reactions were severe: 19 of 33 (58%). Intradermal testing had a higher negative predictive value (86%) in the immediate group than in the nonimmediate group (67%). Only a minority of patients (6 of 17 [35%]) with IgE-mediated allergy were cross-sensitized on intradermal testing with other penicillins, compared with 3 of 4 (75%) in the delayed group. CONCLUSIONS: Immediate hypersensitivity reactions to flucloxacillin are more common than delayed. Cross-sensitization to other penicillins appears higher in delayed reactions than in immediate. The negative predictive value of intradermal testing is higher in the immediate group than in the nonimmediate group. Drug provocation testing remains the diagnostic criterion standard.
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Antibacterianos/efectos adversos , Hipersensibilidad a las Drogas/diagnóstico , Floxacilina/efectos adversos , Hipersensibilidad Tardía/diagnóstico , Hipersensibilidad Inmediata/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Amoxicilina , Combinación Amoxicilina-Clavulanato de Potasio , Reacciones Cruzadas , Erupciones por Medicamentos/diagnóstico , Erupciones por Medicamentos/etiología , Hipersensibilidad a las Drogas/etiología , Hipersensibilidad a las Drogas/metabolismo , Síndrome de Hipersensibilidad a Medicamentos/diagnóstico , Síndrome de Hipersensibilidad a Medicamentos/etiología , Femenino , Humanos , Hipersensibilidad Tardía/inducido químicamente , Hipersensibilidad Tardía/metabolismo , Hipersensibilidad Inmediata/inducido químicamente , Hipersensibilidad Inmediata/metabolismo , Inmunoglobulina E/metabolismo , Pruebas Intradérmicas , Masculino , Persona de Mediana Edad , Penicilina G , Valor Predictivo de las Pruebas , Derivación y Consulta , Estudios Retrospectivos , Pruebas Cutáneas , Triptasas/metabolismo , Adulto JovenAsunto(s)
Proteínas de Unión al ADN/deficiencia , Proteínas de Homeodominio/genética , Síndromes de Inmunodeficiencia/genética , Síndromes de Inmunodeficiencia/inmunología , Proteínas Nucleares/deficiencia , Adulto , Proteínas de Unión al ADN/genética , Humanos , Síndromes de Inmunodeficiencia/fisiopatología , Proteínas Nucleares/genética , PrevalenciaAsunto(s)
Anticuerpos Anticitoplasma de Neutrófilos/análisis , Técnica del Anticuerpo Fluorescente Indirecta/métodos , Algoritmos , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Europa (Continente) , Técnica del Anticuerpo Fluorescente Indirecta/normas , Humanos , Laboratorios , Mieloblastina , Peroxidasa/inmunología , Sociedades Científicas , Encuestas y CuestionariosRESUMEN
A proportion of people living with common variable immunodeficiency disorders develop granulomatous-lymphocytic interstitial lung disease (GLILD). We aimed to develop a consensus statement on the definition, diagnosis, and management of GLILD. All UK specialist centers were contacted and relevant physicians were invited to take part in a 3-round online Delphi process. Responses were graded as Strongly Agree, Tend to Agree, Neither Agree nor Disagree, Tend to Disagree, and Strongly Disagree, scored +1, +0.5, 0, -0.5, and -1, respectively. Agreement was defined as greater than or equal to 80% consensus. Scores are reported as mean ± SD. There was 100% agreement (score, 0.92 ± 0.19) for the following definition: "GLILD is a distinct clinico-radio-pathological ILD occurring in patients with [common variable immunodeficiency disorders], associated with a lymphocytic infiltrate and/or granuloma in the lung, and in whom other conditions have been considered and where possible excluded." There was consensus that the workup of suspected GLILD requires chest computed tomography (CT) (0.98 ± 0.01), lung function tests (eg, gas transfer, 0.94 ± 0.17), bronchoscopy to exclude infection (0.63 ± 0.50), and lung biopsy (0.58 ± 0.40). There was no consensus on whether expectant management following optimization of immunoglobulin therapy was acceptable: 67% agreed, 25% disagreed, score 0.38 ± 0.59; 90% agreed that when treatment was required, first-line treatment should be with corticosteroids alone (score, 0.55 ± 0.51).
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Inmunodeficiencia Variable Común , Granuloma , Enfermedades Pulmonares Intersticiales , Organizaciones de Beneficencia , Inmunodeficiencia Variable Común/diagnóstico , Inmunodeficiencia Variable Común/diagnóstico por imagen , Inmunodeficiencia Variable Común/tratamiento farmacológico , Inmunodeficiencia Variable Común/patología , Consenso , Granuloma/diagnóstico , Granuloma/diagnóstico por imagen , Granuloma/tratamiento farmacológico , Granuloma/patología , Humanos , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/patología , Sociedades Médicas , Reino UnidoRESUMEN
BACKGROUND: Sheffield National Adverse Reactions Consultancy Service (NARCOS) investigates and triages suspected perioperative anaesthetic reactions to allergy clinics, using serial tryptase samples, urinary methylhistamine and clinical information on a pro forma request. OBJECTIVE: To determine if current UK guidelines on serial tryptase samples are achieved and describe the patterns of tryptase release. METHOD: A retrospective review of 3455 NARCOS cases. Tryptase and clinical details were analysed. 1746 had sufficient clinical information to grade the reactions according to the Ring and Messmer scale. RESULTS: 98% provided two or more acute samples, but only 60% supplied clinical information. 308 patients never dropped within the reference range over three samples. CONCLUSIONS: Good compliance with UK guidelines for tryptase measurements is achievable in this long-term cohort, but obtaining clinical details at referral remains a challenge. Sample sequence labelling and apparent timing may be misleading. Baseline tryptase may frequently need to be rechecked in allergy clinics to estimate true peak-to-trough changes.
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Anafilaxia/inmunología , Adhesión a Directriz , Mastocitos/metabolismo , Triptasas/análisis , Femenino , Humanos , Masculino , Mastocitos/inmunología , Estudios Retrospectivos , Manejo de Especímenes , Reino UnidoRESUMEN
BACKGROUND: In cerebrospinal fluid (CSF) spectrophotometry, if the net bilirubin absorbance (NBA) and net oxyhaemoglobin absorbance (NOA) are both raised with a visible oxyhaemoglobin peak, the revised national guidelines for analysis of CSF bilirubin advise interpreting the results as 'Consistent with subarachnoid haemorrhage (SAH)' regardless of the CSF total protein concentration of the specimen. We wanted to study the range of CSF total protein concentrations found in confirmed SAH to establish if the CSF total protein value can give further guidance on the likelihood of SAH. METHODS: Consecutive cases from five different hospital sites were included if the CSF NBA was greater than 0.007 AU and the NOA was greater than 0.02 AU with a visible oxyhaemoglobin peak. For the cases identified, the laboratory information management system and patient records were interrogated to identify the total protein concentration of the CSF specimen and whether SAH had ultimately been confirmed or excluded by other methods and supporting evidence. RESULTS: Results from 132 patients were included. The CSF total protein range in confirmed SAH was 0.23-3.08 g/L with a median concentration of 0.7 g/L (n = 51). In the SAH excluded group, the CSF total protein range was 0.43-29 g/L with a median concentration of 1.9 g/L (n = 81). CONCLUSIONS: Although confirmed SAH was not associated with the very highest concentrations of CSF total protein, a definite CSF protein cut-off concentration above which SAH could reliably be excluded cannot be recommended.
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Bilirrubina/líquido cefalorraquídeo , Proteínas del Líquido Cefalorraquídeo/análisis , Oxihemoglobinas/líquido cefalorraquídeo , Hemorragia Subaracnoidea/líquido cefalorraquídeo , Hemorragia Subaracnoidea/diagnóstico , Humanos , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: The measurement of serum IgE aids in the diagnosis and management of atopic allergic disease and hyper-IgE immunodeficiency syndromes. The 2nd World Health Organization (WHO) International Reference Reagent (IRR) for serum IgE (75/502; 5000 IU/ampoule), is widely used to calibrate assays for serum IgE. Exhaustion of stocks of the 2nd IRR necessitated the production of a replacement preparation and its evaluation in an international collaborative study to determine its suitability to serve as the 3rd International Standard (IS) for serum IgE. METHODS: Sera and defibrinated plasma with elevated IgE levels were pooled and lyophilised in ampoules. This preparation, coded 11/234, was assayed by 18 laboratories in 11 countries using commercial assay methodology for IgE, along with the 2nd IRR, 75/502, and two lyophilised serum samples. RESULTS: Overall, there were no consistent differences in the way that the candidate IS (11/234), the IRR (75/502), and the two serum samples behaved in the assays with respect to linearity and parallelism. The mean IgE value of the candidate IS, 11/234, relative to the IRR, 75/502, was 13,411 IU/mL based on parallel line analysis of raw assay data at NIBSC, and 13,551 IU/mL based on the laboratories' own estimates after correcting for the values obtained for 75/502. CONCLUSIONS: The use of 11/234 will ensure that assays for serum IgE continue to be well standardised. The preparation was established by the WHO Expert Committee on Biological Standardization as the 3rd IS for serum IgE with an assigned value of 13,500 IU/mL, corresponding to 6750 IU/ampoule.
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Análisis Químico de la Sangre/normas , Inmunoensayo/normas , Inmunoglobulina E/sangre , Análisis de Varianza , Análisis Químico de la Sangre/estadística & datos numéricos , Liofilización , Humanos , Inmunoensayo/estadística & datos numéricos , Inmunoglobulina E/aislamiento & purificación , Indicadores y Reactivos/normas , Laboratorios , Proteolisis , Estándares de Referencia , Organización Mundial de la SaludRESUMEN
The updated ESPGHAN guidance on coeliac disease recommends the use of common multiples of the upper limit of normal (ULN) for IgA tissue transglutaminase antibodies (TG2) when deciding which diagnostic pathway to follow. The current lack of standardisation between assays makes it difficult to harmonise results between centres as different performance characteristics are observed with each assay. This variability is shown in data from external quality assessment distributions. As a result, the updated guidance is too generalised for use with all the commercial TG2 kits and is therefore not translatable for use in all centres.
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Enfermedad Celíaca/diagnóstico , Duodeno/patología , Antígenos HLA-DQ/sangre , Inmunoglobulina A/sangre , Transglutaminasas/inmunología , HumanosRESUMEN
OBJECTIVE: To determine the prevalence, prognostic value, and response to thyroxine therapy of thyroid peroxidase antibody (TPOAb) in women with unexplained recurrent miscarriage (RM). DESIGN: Observational, cohort study. The index cases included women with unexplained RM who tested positive for thyroid peroxidase antibody, and control cases included women with unexplained RM who tested negative for the antibodies; a second age-matched control group included women with RM who had a known cause for the repeated pregnancy loss. SETTING: Tertiary referral center for RM. PATIENT(S): A total of 496 women with unexplained RM and 220 women with known diagnoses of RM who had a TPOAb test. INTERVENTION(S): Thyroxine replacement (50 µg daily during pregnancy) was begun in some patients who tested positive for thyroid peroxidase antibody, irrespective of TSH level. MAIN OUTCOME MEASURE(S): Miscarriage and live birth rates of a subsequent pregnancy. RESULT(S): A total of 496 women with unexplained RM who had a TPOAb test were included in the study. Of these, 10.7% of subjects tested positive for TPOAb. The prevalence of TPOAb in control subjects who had a known cause for RM was 11.8%. The live birth rate of the first pregnancies after referral was 64%, 53%, and 58% in TPOAb-negative, TPOAb-positive with thyroxine treatment, and TPOAb-positive without treatment subjects; there was no significant difference in the outcome between any two or three groups, or between those who tested positive or negative for TPOAb. Among women who tested positive for TPOAb, there was no difference in the antibody titer between women with unexplained RM and those with a known cause for the pregnancy loss. Women who tested positive for TPOAb were significantly more likely to have TSH levels above the normal range (≥4.2 mIU/L). CONCLUSION(S): The prevalence of TPOAb-positive results in women with unexplained RM is not higher than in the general population, TPOAb-positive status does not have a prognostic value regarding the outcome of a subsequent pregnancy, and empirical thyroxine therapy in those who tested positive did not seem to improve outcome.
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Aborto Habitual/epidemiología , Aborto Habitual/inmunología , Autoanticuerpos/biosíntesis , Yoduro Peroxidasa/inmunología , Tiroxina/uso terapéutico , Aborto Habitual/tratamiento farmacológico , Adulto , Biomarcadores/sangre , Estudios de Cohortes , Femenino , Humanos , Embarazo , Resultado del Embarazo/epidemiología , Prevalencia , Pronóstico , Resultado del TratamientoRESUMEN
We describe the programme of an established External Quality Assurance (EQA) provider and a Specialist Advisory Group (SAG) to develop a successful EQA scheme for cerebrospinal fluid (CSF) haem pigments as an example of a professionally led, unfunded initiative with the real potential to benefit patients. Within three years, we had assured sample stability, stoichiometry, and published best practice guidelines, enabling both analytical results and interpretation to be assessed and reported with an educative summary of the desired responses. Misclassification scoring of analysis and interpretation was introduced. Following audit, guidelines were modified and republished. The outcomes were as follows: Participant numbers increased from 63 at inception to 150 10 years later; The percentage of participants using visual inspection, a poor practice indicator, decreased from 27% to less than 1%; In all, 94-100% of participants consistently detected minor increases in bilirubin over the last four years of the scheme; More than 93% of participants were able to interpret analytical results linked to straightforward clinical scenarios; Misclassification scoring demonstrated that more complex scenarios repeatedly posed problems and is the next challenge to address. Scheme success is attributed to the experience of the operator and the formation of a voluntary expert advisory group, with both concerned to advance science and patient safety and thus contribute unpaid time and effort in order to succeed. In times of fiscal constraint, such resource may not be so readily available, yet is a vital part of continuous quality improvement for the benefit of patients.
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Bilirrubina/líquido cefalorraquídeo , Garantía de la Calidad de Atención de Salud , Mejoramiento de la Calidad , Hemorragia Subaracnoidea/diagnóstico , Humanos , Guías de Práctica Clínica como Asunto , Estándares de Referencia , Sensibilidad y Especificidad , Manejo de Especímenes , Espectrofotometría/normas , Hemorragia Subaracnoidea/líquido cefalorraquídeoRESUMEN
Cryoglobulins are serum immunoglobulins that precipitate at temperatures below 37 degrees C and re-dissolve on warming. Cryoglobulinaemia leads to variable symptoms including characteristic purpura, ischaemia of extremities, renal failure, peripheral neuropathy, abdominal pain secondary to intestinal ischaemia and arthralgias. Cryoglobulin testing is underutilized in clinical practice. It has been neglected in clinical laboratories and by clinicians due to several factors, such as the length of time it takes for serum cryoglobulin analysis to be performed in the laboratory, the perceived difficulty in getting optimal sampling conditions and a failure to appreciate that even apparently low levels of cryoglobulin can be associated with severe symptoms in some patients. The most important variable confounding standardization of cryoglobulin testing is improper sample handling. A recent report critically appraising the current practice of cryoglobulin evaluation in 137 laboratories in Europe by United Kingdom National External Quality Assurance Scheme (UKNEQAS) illustrated the wide variability in practice. Although many clinical laboratories perform cryoglobulin evaluation, there are widespread differences in the methodology used and the care with which this is carried out and this leads to considerable intralaboratory and interlaboratory variability. The most common sources of error are false-negative results due to loss of cryoprecipitate during transport and storage. Better standardization is needed to avoid missed diagnoses and improve the comparability of results. Laboratories should ensure that sample temperature is maintained at 37 degrees C until the serum is separated. In this article, we briefly review the classification and clinical features of cryoglobulins and suggest best practice guidelines for laboratory detection and identification of cryoglobulins.
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Técnicas de Laboratorio Clínico , Crioglobulinemia/diagnóstico , Crioglobulinas/análisis , Guías de Práctica Clínica como Asunto , Algoritmos , Recolección de Muestras de Sangre/métodos , Recolección de Muestras de Sangre/normas , Técnicas de Laboratorio Clínico/normas , Crioglobulinemia/sangre , Crioglobulinemia/virología , Hepacivirus/fisiología , Humanos , Valores de Referencia , Síndrome de Sjögren/sangre , Síndrome de Sjögren/diagnósticoRESUMEN
Patients with autoimmune polyendocrine syndrome type 1 (APS-1) suffer from multiple organ-specific autoimmunity with autoantibodies against target tissue-specific autoantigens. Endocrine and nonendocrine organs such as skin, hair follicles, and liver are targeted by the immune system. Despite sporadic observations of pulmonary symptoms among APS-1 patients, an autoimmune mechanism for pulmonary involvement has not been elucidated. We report here on a subset of APS-1 patients with respiratory symptoms. Eight patients with pulmonary involvement were identified. Severe airway obstruction was found in 4 patients, leading to death in 2. Immunoscreening of a cDNA library using serum samples from a patient with APS-1 and obstructive respiratory symptoms identified a putative potassium channel regulator (KCNRG) as a pulmonary autoantigen. Reactivity to recombinant KCNRG was assessed in 110 APS-1 patients by using immunoprecipitation. Autoantibodies to KCNRG were present in 7 of the 8 patients with respiratory symptoms, but in only 1 of 102 APS-1 patients without respiratory symptoms. Expression of KCNRG messenger RNA and protein was found to be predominantly restricted to the epithelial cells of terminal bronchioles. Autoantibodies to KCNRG, a protein mainly expressed in bronchial epithelium, are strongly associated with pulmonary involvement in APS-1. These findings may facilitate the recognition, diagnosis, characterization, and understanding of the pulmonary manifestations of APS-1.
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Autoantígenos/inmunología , Autoinmunidad/inmunología , Bronquios/inmunología , Enfermedades Pulmonares/inmunología , Poliendocrinopatías Autoinmunes/complicaciones , Poliendocrinopatías Autoinmunes/inmunología , Canales de Potasio/inmunología , Obstrucción de las Vías Aéreas , Autoanticuerpos/análisis , Bronquiolos/inmunología , Bronquiolos/patología , Causas de Muerte , Células Epiteliales/inmunología , Biblioteca de Genes , Humanos , Inmunoprecipitación , Enfermedades Pulmonares/etiología , Canales de Potasio/análisis , Canales de Potasio/genética , Enfermedad Pulmonar Obstructiva Crónica/inmunología , ARN Mensajero/análisis , Proteínas Recombinantes/inmunologíaRESUMEN
It is crucially important to detect subarachnoid haemorrhage (SAH) in all patients in whom it has occurred to select patients for angiography and preventative surgery. A computerized tomography (CT) scan is positive in up to 98% of patients with SAH presenting within 12 h, but is positive in only 50% of those presenting within one week. Cerebrospinal fluid (CSF) bilirubin spectrophotometry can be used to determine the need for angiography in those few CT-negative patients in whom clinical suspicion of SAH remains high; it may remain positive up to two weeks after the event. A lumbar puncture (LP) should only be performed >12 h after the onset of presenting symptoms. Whenever possible collect sequential specimens. Always ensure that the least blood-stained CSF sample taken (usually the last) is sent for bilirubin analysis. Protect the CSF from light and avoid vacuum tube transport systems, if possible. Always use spectrophotometry in preference to visual inspection. All CSF specimens are precious and should always be analysed unless insufficient sample is received. Centrifuge the specimen at >2000 rpm for 5 min as soon as possible after receipt in the laboratory. Store the supernatant at 4 degrees C in the dark until analysis. An increase in CSF bilirubin is the key finding, which supports the occurrence of SAH but is not specific for this. In most positive cases, bilirubin will occur with oxyhaemoglobin.
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Bilirrubina/líquido cefalorraquídeo , Hemorragia Subaracnoidea/líquido cefalorraquídeo , Hemorragia Subaracnoidea/diagnóstico , Bilirrubina/sangre , Bilirrubina/metabolismo , Árboles de Decisión , Humanos , Metahemoglobina/metabolismo , Guías de Práctica Clínica como Asunto , Control de Calidad , Reino UnidoRESUMEN
BACKGROUND & AIMS: The optimal serologic tests for the detection of celiac disease and follow-up assessment remains controversial. Our aim was to evaluate all current immunologic assays for diagnosing celiac disease using the gold standard of duodenal biopsy. We also assessed whether tissue transglutaminase (tTG) antibody is a quantitative marker for histologic severity. METHODS: Consecutive adult patients referred for gastroscopy without a previous known diagnosis of celiac disease were recruited (group 1). Concurrently, patients with a known diagnosis of celiac disease on a gluten-free diet for more than 1 year undergoing repeat duodenal biopsy were identified (group 2). All patients had duodenal biopsies and serologic analysis performed for immunoglobulin(Ig) A and antibodies to human immunoglobulin (Ig)A-tTG, IgA-gliadin, IgG-gliadin, and IgA-endomysial antibody. RESULTS: Two thousand patients were recruited in the first group. Seventy-seven (3.9%) patients were diagnosed with new celiac disease. The sensitivity, specificity, positive predictive value, and negative predictive value for IgA tTG were 90.9%, 90.9%, 28.6%, and 99.6%. When adopting a 2-step approach using tTG first and then EMA the sensitivity, specificity, positive predictive value, and negative predictive value was 85.7%, 98.6%, 71.7%, and 99.7%, respectively. The use of nondeamidated IgA/IgG gliadin antibodies conferred no additional diagnostic benefit when considering the detection of adult celiac disease. In the second group 48 patients with celiac disease on a gluten-free diet were identified. Sixteen of 48 of these patients had persisting villous atrophy, but 7 of 16 (44%) had a normal tTG level. CONCLUSIONS: IgA tTG alone is a sensitive marker for celiac disease. A normal tTG level does not predict recovery of villous atrophy in patients with celiac disease on a gluten-free diet.
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Anticuerpos Antiidiotipos/análisis , Biopsia/economía , Enfermedad Celíaca/diagnóstico , Duodeno/patología , Inmunoglobulinas/inmunología , Pruebas Serológicas/economía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia/métodos , Enfermedad Celíaca/economía , Enfermedad Celíaca/inmunología , Costos y Análisis de Costo , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Pruebas Serológicas/métodos , Índice de Severidad de la EnfermedadRESUMEN
To assess current practice in the detection, analysis, and reporting of cryoglobulins, a questionnaire was sent to 140 laboratories. Only 36% of laboratories used standard procedures (tube preheating, transport in container, and sedimentation and/or centrifugation at 37 degrees C) to ensure that the temperature did not drop below 37 degrees C until after serum separation. Time periods allowed for cryoprecipitation at 4 degrees C varied from 12 h to 9 days, with 30% of laboratories allowing precipitation for <3 days. After cryoprecipitation, 81% of laboratories resolubilized the cryoprecipitate at 37 degrees C, and 77% further immunotyped the cryoprecipitate. After analysis, 5% referred the sample for confirmation, 58% provided a nonquantitative report, and 37% reported the cryoglobulin concentration in the cryoprecipitate as cryocrit, total protein concentration, and/or immunoglobulin concentration. Only 3 laboratories (2%) provided cryoprecipitate-specific reference values for total protein content, and none provided reference values for immunoglobulins. We believe standardization is needed for cryoglobulin detection to avoid missed diagnoses and improve the comparability of results. Laboratories should ensure that sample temperature does not drop below 37 degrees C until after serum separation. The serum should cryoprecipitate at 4 degrees C for at least 3 (preferably 7) days. The cryoprecipitate should be washed and resolubilized at 37 degrees C for further analysis.