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The recombination-activating genes (RAG) 1 and 2 are indispensable for diversifying the primary B cell receptor repertoire and pruning self-reactive clones via receptor editing in the bone marrow; however, the impact of RAG1/RAG2 on peripheral tolerance is unknown. Partial RAG deficiency (pRD) manifesting with late-onset immune dysregulation represents an 'experiment of nature' to explore this conundrum. By studying B cell development and subset-specific repertoires in pRD, we demonstrate that reduced RAG activity impinges on peripheral tolerance through the generation of a restricted primary B cell repertoire, persistent antigenic stimulation and an inflammatory milieu with elevated B cell-activating factor. This unique environment gradually provokes profound B cell dysregulation with widespread activation, remarkable extrafollicular maturation and persistence, expansion and somatic diversification of self-reactive clones. Through the model of pRD, we reveal a RAG-dependent 'domino effect' that impacts stringency of tolerance and B cell fate in the periphery.
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Linfócitos B , Proteínas de Ligação a DNA , Proteínas de Homeodomínio , Proteínas Nucleares , Diferenciação Celular , Proteínas de Ligação a DNA/deficiência , Proteínas de Ligação a DNA/genética , Proteínas de Homeodomínio/genética , Humanos , Tolerância Imunológica , Contagem de Linfócitos , Proteínas Nucleares/deficiênciaRESUMO
Primary immunodeficiency (PID) is characterized by recurrent and often life-threatening infections, autoimmunity and cancer, and it poses major diagnostic and therapeutic challenges. Although the most severe forms of PID are identified in early childhood, most patients present in adulthood, typically with no apparent family history and a variable clinical phenotype of widespread immune dysregulation: about 25% of patients have autoimmune disease, allergy is prevalent and up to 10% develop lymphoid malignancies1-3. Consequently, in sporadic (or non-familial) PID genetic diagnosis is difficult and the role of genetics is not well defined. Here we address these challenges by performing whole-genome sequencing in a large PID cohort of 1,318 participants. An analysis of the coding regions of the genome in 886 index cases of PID found that disease-causing mutations in known genes that are implicated in monogenic PID occurred in 10.3% of these patients, and a Bayesian approach (BeviMed4) identified multiple new candidate PID-associated genes, including IVNS1ABP. We also examined the noncoding genome, and found deletions in regulatory regions that contribute to disease causation. In addition, we used a genome-wide association study to identify loci that are associated with PID, and found evidence for the colocalization of-and interplay between-novel high-penetrance monogenic variants and common variants (at the PTPN2 and SOCS1 loci). This begins to explain the contribution of common variants to the variable penetrance and phenotypic complexity that are observed in PID. Thus, using a cohort-based whole-genome-sequencing approach in the diagnosis of PID can increase diagnostic yield and further our understanding of the key pathways that influence immune responsiveness in humans.
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Doenças da Imunodeficiência Primária/genética , Sequenciamento Completo do Genoma , Complexo 2-3 de Proteínas Relacionadas à Actina/genética , Teorema de Bayes , Estudos de Coortes , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Doenças da Imunodeficiência Primária/diagnóstico , Doenças da Imunodeficiência Primária/imunologia , Proteína Tirosina Fosfatase não Receptora Tipo 2/genética , Proteínas de Ligação a RNA/genética , Sequências Reguladoras de Ácido Nucleico/genética , Proteína 1 Supressora da Sinalização de Citocina/genética , Fatores de Transcrição/genéticaRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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BACKGROUND: The fecal immunochemical test (FIT) is recommended for triaging primary care patients in England with low-risk symptoms of colorectal cancer (CRC). The evidence underpinning recommendations by the National Institute for Health and Care Excellence had limitations, with a paucity of primary care evidence. This study examines the diagnostic accuracy of FIT in a defined low-risk symptom primary care population. PATIENTS AND METHODS: Consecutive symptomatic adult patients referred for a FIT between October and December 2019 were included. Patients were derived from 225 primary care practices in England. Serious colorectal diseases (CRC, high-risk polyps, and inflammatory bowel disease [IBD]) were identified through patient follow-up over 18 months, using both primary and secondary healthcare records. Performance characteristics of FIT are reported according to differing thresholds, including the currently recommended threshold of ≥10 µg hemoglobin per gram of feces (µg/g). RESULTS: A total of 3,506 patients were included in the final analysis. Of these, 708 had a positive FIT result (≥10 µg/g). The prevalence of CRC was 1.3%. FIT positivity declined from 20.2% to 5.8% and 4.5% at cutoffs of 10, 80, and 120 µg/g, respectively. The sensitivity of FIT at ≥10 µg/g to detect CRC was 91.1% (95% CI, 77.9%-97.1%); its specificity was 80.7% (95% CI, 79.3%-82.0%); the positive predictive value (PPV) was 5.8% (95% CI, 4.2%-7.8%); and the negative predictive value (NPV) was 99.9% (95% CI, 99.6%-99.95%). The area under the receiver operating characteristic curve was 0.93 (0.91-0.96). PPV and specificity increased, whereas sensitivity and NPV decreased when serious colorectal diseases (CRC, high-risk polyps, and IBD) were combined. Age, sex, socioeconomic deprivation, and anemia did not significantly influence FIT sensitivity on subgroup analysis. CONCLUSIONS: Utilization of FIT at a threshold ≥10 µg/g can safely triage patients with low-risk symptoms in primary care, with negative results effectively ruling out CRC.
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Neoplasias Colorretais , Doenças Inflamatórias Intestinais , Adulto , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Detecção Precoce de Câncer/métodos , Fezes/química , Hemoglobinas/análise , Humanos , Sangue Oculto , Sensibilidade e EspecificidadeRESUMO
We describe scalable and cost-efficient production of full length, His-tagged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein trimer by Chinese hamster ovary (CHO) cells that can be used to detect SARS-CoV-2 antibodies in patient sera at high specificity and sensitivity. Transient production of spike in both human embryonic kidney (HEK) and CHO cells mediated by polyethyleneimine was increased significantly (up to 10.9-fold) by a reduction in culture temperature to 32°C to permit extended duration cultures. Based on these data GS-CHO pools stably producing spike trimer under the control of a strong synthetic promoter were cultured in hypothermic conditions with combinations of bioactive small molecules to increase yield of purified spike product 4.9-fold to 53 mg/L. Purification of recombinant spike by Ni-chelate affinity chromatography initially yielded a variety of co-eluting protein impurities identified as host cell derived by mass spectrometry, which were separated from spike trimer using a modified imidazole gradient elution. Purified CHO spike trimer antigen was used in enzyme-linked immunosorbent assay format to detect immunoglobulin G antibodies against SARS-CoV-2 in sera from patient cohorts previously tested for viral infection by polymerase chain reaction, including those who had displayed coronavirus disease 2019 (COVID-19) symptoms. The antibody assay, validated to ISO 15189 Medical Laboratories standards, exhibited a specificity of 100% and sensitivity of 92.3%. Our data show that CHO cells are a suitable host for the production of larger quantities of recombinant SARS-CoV-2 trimer which can be used as antigen for mass serological testing.
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Teste para COVID-19/métodos , COVID-19/diagnóstico , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/biossíntese , Animais , Células CHO , COVID-19/virologia , Cricetinae , Cricetulus , Humanos , Proteínas Recombinantes/biossíntese , Testes Sorológicos/métodosAssuntos
Asma Ocupacional/etiologia , Caseínas/imunologia , Dermatite de Contato/etiologia , Hipersensibilidade a Leite/etiologia , Rinite/etiologia , Asma Ocupacional/patologia , Dermatite de Contato/patologia , Humanos , Masculino , Hipersensibilidade a Leite/patologia , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Rinite/patologia , Adulto JovemAssuntos
Proteínas de Ligação a DNA/deficiência , Proteínas de Homeodomínio/genética , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/imunologia , Proteínas Nucleares/deficiência , Adulto , Proteínas de Ligação a DNA/genética , Humanos , Síndromes de Imunodeficiência/fisiopatologia , Proteínas Nucleares/genética , PrevalênciaRESUMO
INTRODUCTION/OBJECTIVES: The fecal immunochemical test (FIT) helps triage primary care patients at risk of colorectal cancer (CRC). Improving FIT returns has received recent attention, however uncertainty exists regarding the accurate completion of samples provided for laboratory analysis. This study aims to identify the rejection rate of returned FIT samples and determine rejection causes. METHODS: FIT samples from symptomatic patients within South Yorkshire, Bassetlaw, and North Derbyshire are processed at a central laboratory. Tests requests are made from 225 GP practices, which serve an estimated 2 million population. This study describes a retrospective review of FIT samples received in the central laboratory between 01/09/19 and 31/12/22. Locally held data was interrogated in March 2023 to determine the number of FIT samples received and rejected during the study period. Documented reasons for rejection were explored to identify common themes. RESULTS: Total FIT specimens received during the study period was 126 422. Of these, 5190 (4.1%) were rejected. Monthly rejection rates fell from 17.4% in September 2019 to 1.3% in December 2022 (P < .001). Sampling errors were the most frequent cause for FIT rejection (2151/5190), with other causes including: expired specimen; no sample collection date/ time, no request form, incomplete patient information and illegible handwriting. CONCLUSIONS: This is the first study exploring FIT rejection rates in symptomatic primary care patients, which shows improvements in rejection rates over time. Targeted interventions could improve rejection rates further, thereby reducing NHS resource use and costs and diagnostic delays.
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Neoplasias Colorretais , Humanos , Estudos de Coortes , Neoplasias Colorretais/diagnóstico , Sangue Oculto , Estudos Retrospectivos , Detecção Precoce de Câncer , Colonoscopia , FezesRESUMO
Background: Robust preanalytical and analytical processes are critical for the detection of cryoproteins. There is significant variation in practice in the detection, analysis and reporting. Results: A survey in 2018 of 137 laboratories participating in the UK National External Quality Assessment Service (UK NEQAS) (6) quality control program showed significant variation in the laboratory processes which highlighted the need for standardisation of the detection, analysis and reporting of cryoglobulins.Conclusion: The first available EQA scheme aiming to harmonise practice for cryoprotein testing has been developed by UK NEQAS and laboratories should participate in an appropriate EQA scheme to fulfil requirements for ISO accreditation.
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BACKGROUND: Detailed demographic data on people with hereditary angioedema (HAE) and acquired C1 inhibitor deficiency in the United Kingdom are relatively limited. Better demographic data would be beneficial in planning service provision, identifying areas of improvement, and improving care. OBJECTIVE: To obtain more accurate data on the demographics of HAE and acquired C1 inhibitor deficiency in the United Kingdom, including treatment modalities and services available to patients. METHODS: A survey was distributed to all centers in the United Kingdom that look after patients with HAE and acquired C1 inhibitor deficiency to collect these data. RESULTS: The survey identified 1152 patients with HAE-1/2 (58% female and 92% type 1), 22 patients with HAE with normal C1 inhibitor, and 91 patients with acquired C1 inhibitor deficiency. Data were provided by 37 centers across the United Kingdom. This gives a minimum prevalence of 1:59,000 for HAE-1/2 and 1:734,000 for acquired C1 inhibitor deficiency in the United Kingdom. A total of 45% of patients with HAE were on long-term prophylaxis (LTP) with the most used medication being danazol (55% of all patients on LTP). Eighty-two percent of patients with HAE had a home supply of acute treatment with C1 inhibitor or icatibant. A total of 45% of patients had a supply of icatibant and 56% had a supply of C1 inhibitor at home. CONCLUSIONS: Data obtained from the survey provide useful information about the demographics and treatment modalities used in HAE and acquired C1 inhibitor deficiency in the United Kingdom. These data are useful for planning service provision and improving services for these patients.
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Angioedemas Hereditários , Humanos , Feminino , Masculino , Angioedemas Hereditários/epidemiologia , Angioedemas Hereditários/tratamento farmacológico , Proteína Inibidora do Complemento C1/uso terapêutico , Danazol/uso terapêutico , Reino Unido/epidemiologia , Inquéritos e QuestionáriosRESUMO
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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Doença Celíaca/diagnóstico , Duodeno/patologia , Antígenos HLA-DQ/sangue , Imunoglobulina A/sangue , Transglutaminases/imunologia , HumanosRESUMO
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/imunologia , Autoimunidade/imunologia , Brônquios/imunologia , Pneumopatias/imunologia , Poliendocrinopatias Autoimunes/complicações , Poliendocrinopatias Autoimunes/imunologia , Canais de Potássio/imunologia , Obstrução das Vias Respiratórias , Autoanticorpos/análise , Bronquíolos/imunologia , Bronquíolos/patologia , Causas de Morte , Células Epiteliais/imunologia , Biblioteca Gênica , Humanos , Imunoprecipitação , Pneumopatias/etiologia , Canais de Potássio/análise , Canais de Potássio/genética , Doença Pulmonar Obstrutiva Crônica/imunologia , RNA Mensageiro/análise , Proteínas Recombinantes/imunologiaRESUMO
BACKGROUND: Infliximab dose escalation (DE) can be used in inflammatory bowel disease patient; however, the long-term benefit remains unclear, especially in those with antibodies to infliximab (ATI). The aim was to assess the effect of DE in patients with ATI on drug level, clinical response and ATI status. METHODS: All patients undergoing infliximab DE (a reduction in dose interval between infusions <8 weeks ± an increase in dose up to 10 mg/kg) at a referral centre between April 2016 and August 2019 were included. RESULTS: Ninety-two patients were DE: 51 were men, 50 had CD and 63 were receiving immunosuppression. A total of 87 people received DE for a median of 44 weeks (range 4-176). Five stopped infliximab after 1 dose of DE: 2 for loss of response and 3 for infusion reaction. In patients with ATI ≤10 vs. >10 AU/mL, DE significantly increased drug levels: median infliximab levels of 1.4 and 0.9 at baseline, respectively, to 3.2 and 3.5 at week 24. After DE, 21/35 ATI-positive patients had a fall in ATI ≤10 AU/mL. At week 24 following DE 62/92 patients were in clinical remission. Duration of clinical remission was shorter in those with ATI >10 AU/mL (median 24 weeks, range 0-88) than in those with transient/ATI ≤10 AU/mL (median 36 weeks, range 0-126, P = 0.06). CONCLUSIONS: A strategy of DE for selected patients receiving infliximab is associated with an increase in drug levels and reduced ATI positivity. This is associated with clinical remission in approximately 70% of patients at 6 months.
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Doenças Inflamatórias Intestinais , Infliximab , Anticorpos , Feminino , Fármacos Gastrointestinais/administração & dosagem , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/administração & dosagem , MasculinoRESUMO
BACKGROUND: The coronavirus disease 2019 pandemic imposed multiple restrictions on health care services. OBJECTIVE: To investigate the impact of the pandemic on Allergy & Immunology (A&I) services in the United Kingdom. METHODS: A national survey of all A&I services registered with the Royal College of Physicians and/or the British Society for Allergy and Clinical Immunology was carried out. The survey covered staffing, facilities, personal protective equipment, appointments & patient review, investigations, treatments, and research activity. Weeks commencing February 3, 2020 (pre-coronavirus disease), April 6, 2020, and May 8, 2020, were used as reference points for the data set. RESULTS: A total of 99 services participated. There was a reduction in nursing, medical, administrative, and allied health professional staff during the pandemic; 86% and 92% of A&I services continued to accept nonurgent and urgent referrals, respectively, during the pandemic. There were changes in immunoglobulin dose and infusion regimen in 67% and 14% of adult and pediatric services, respectively; 30% discontinued immunoglobulin replacement in some patients. There was a significant (all variables, P ≤ .0001) reduction in the following: face-to-face consultations (increase in telephone consultations), initiation of venom immunotherapy, sublingual and subcutaneous injection immunotherapy, anesthetic allergy testing, and hospital procedures (food challenges, immunoglobulin and omalizumab administration); and a significant increase (P ≤ .0001) in home therapy for immunoglobulin and omalizumab. Adverse clinical outcomes were reported, but none were serious. CONCLUSIONS: The pandemic had a significant impact on A&I services, leading to multiple unplanned pragmatic amendments in service delivery. There is an urgent need for prospective audits and strategic planning in the medium and long-term to achieve equitable, safe, and standardized health care.
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Alergia e Imunologia/organização & administração , COVID-19/epidemiologia , Atenção à Saúde , Pandemias , Pediatria/organização & administração , SARS-CoV-2 , Adulto , COVID-19/diagnóstico , Criança , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/terapia , Medicina Estatal , Inquéritos e Questionários , Reino UnidoRESUMO
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/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Floxacilina/efeitos adversos , Hipersensibilidade Tardia/diagnóstico , Hipersensibilidade Imediata/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Amoxicilina , Combinação Amoxicilina e Clavulanato de Potássio , Reações Cruzadas , Toxidermias/diagnóstico , Toxidermias/etiologia , Hipersensibilidade a Drogas/etiologia , Hipersensibilidade a Drogas/metabolismo , Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Feminino , Humanos , Hipersensibilidade Tardia/induzido quimicamente , Hipersensibilidade Tardia/metabolismo , Hipersensibilidade Imediata/induzido quimicamente , Hipersensibilidade Imediata/metabolismo , Imunoglobulina E/metabolismo , Testes Intradérmicos , Masculino , Pessoa de Meia-Idade , Penicilina G , Valor Preditivo dos Testes , Encaminhamento e Consulta , Estudos Retrospectivos , Testes Cutâneos , Triptases/metabolismo , Adulto JovemRESUMO
Autoimmunity is becoming an increasingly recognized complication in patients with primary immunodeficiencies (PIDs), including a variety of combined immune deficiencies such as Recombination Activating Gene (RAG) defects. The approach to treating autoimmunity in PID patients is complex, requiring a balance between immunosuppression and susceptibility to infection. Inflammatory arthritis is a feature of immune dysregulation in many PIDs, and the optimal treatment may differ from first line therapies that usually consist of disease-modifying anti rheumatic drugs (DMARDs). An example of mechanism-based therapy of arthritis in PID uses blockade of IL-6 signaling with tocilizumab for patients with STAT 3 gain-of-function (GOF) mutation and augmented IL-6 pathway. Herein, we describe two PID cases with arthritis who were found to have defects in RAG. One patient with refractory inflammatory arthritis experienced remarkable improvement in symptoms with tocilizumab therapy. Arthritis can be a clinical feature of immune dysregulation in RAG deficiency, and tocilizumab therapy has been suggested to have utility in treatment of arthritis in RAG deficiency.
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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 Imunodeficiência/patologia , Inflamação/patologia , Receptores de Interleucina-6/deficiência , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Células HEK293 , Humanos , Recém-Nascido , Masculino , Receptores de Interleucina-6/metabolismoRESUMO
BACKGROUND: Faecal calprotectin (FC) measurement distinguishes patients with inflammatory bowel disease (IBD) from those with irritable bowel syndrome but evidence of its performance in primary care is limited. AIMS: To assess the yield of IBD from FC testing in primary care. METHODS: Retrospective review of hospital records to assess the outcome following FC testing in primary care. Investigations for all patients undergoing FC testing in a single laboratory for 6 months from 1 October 2013 to 28 February 2014 were reviewed. RESULTS: 410 patients (162 male; median age 42; range 16-91) were included. FC>50 µg/g was considered positive (FC+). 148/410 (36.1%; median age 44 (17-91)) were FC+ (median FC 116.5 µg/g (51-1770)). 122/148 FC-positive patients (82.4%) underwent further investigation. 97 (65.5%) underwent lower gastrointestinal endoscopy (LGIE), of which 7 (7.2%) had IBD. 49/262 (18.7%) FC-negative (FC-) patients (FC ≤50 µg/g) (median age 47 (19-76)) also underwent LGIE, of whom 3 (6.1%) had IBD.IBD was diagnosed in 11/410 (2.7%; 4 ulcerative colitis, 3 Crohn's disease, 4 microscopic colitis). 8/11 were FC+ (range 67-1170) and 3 FC-. At a 50 µg/g threshold, sensitivity for detecting IBD was 72.7%, specificity 64.9%, positive predictive value (PPV) 5.41% and negative predictive value 98.9%. Increasing the threshold to 100 µg/g reduced the sensitivity of the test for detecting IBD to 54.6%. CONCLUSIONS: FC testing in primary care has low sensitivity and specificity with poor PPV for diagnosing IBD. Its use needs to be directed to those with a higher pretest probability of disease. Local services and laboratories should advise general practitioners accordingly.