RESUMEN
BACKGROUND: Gut microbiota play an important role in human health. However, the application of gut microbiome in regular clinical practice is limited by interindividual variations and complexity of test results. HYPOTHESIS: It is possible to address interindividual variation by using large data-based exploratory-pattern analysis. METHODS: The current study was conducted using a large data set (n = 173,221) of nonselective incoming patients' test results from a stool test. The data set included assays for the detection of 24 selected commensal microorganisms and multiple biomarkers in feces. Patients were grouped based on their levels of inflammation biomarkers such as calprotectin, eosinophil protein X, and IgA. Group mean values of biomarkers and commensal microbes were used in an exploratory-pattern analysis for association from which an index score for intestinal inflammation-associated dysbiosis (IAD) was developed. The IAD score was evaluated in one questionnaire-based study (n = 7263) and one prospective case series study (n = 122) with patients of inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and celiac disease. RESULTS: We identified a microbial profile strongly associated with fecal inflammation biomarkers. Developed on the pattern of the microbial profile, the IAD score demonstrated a strong association with fecal inflammation biomarkers and was significantly different between patients with IBD and those with IBS or celiac disease. CONCLUSION: Using real-world data, we have developed a method to predict gut dysbiosis associated with different GI disease conditions. It may help clinicians simplify the process of interpreting gut microbial status and provide gut health assessment and treatment evaluation.
Asunto(s)
Disbiosis/diagnóstico , Disbiosis/microbiología , Heces/microbiología , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/microbiología , Índice de Severidad de la Enfermedad , Adolescente , Adulto , Anciano , Niño , Preescolar , Estudios de Cohortes , Heces/química , Femenino , Microbioma Gastrointestinal/fisiología , Humanos , Inflamación/diagnóstico , Inflamación/microbiología , Complejo de Antígeno L1 de Leucocito/análisis , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
Detection and specificity of autoantibodies against extractable nuclear antigens (ENA) play a critical role in the diagnosis and management of autoimmune disease. Historically, the detection of these antibodies has employed double immunodiffusion (DID). Autoantibody specificity was correlated with diagnoses by this technique. Enzyme immunoassays have been developed by multiple manufacturers to detect and identify the specificity ENA autoantibodies. To address the relationship of ENA detection by DID and enzyme immunoassay, the performances of five immunoassays were compared. These included two DID and three enzyme-linked immunoassays (ELISA) (both screening and individual antigen profile kits). The sample set included 83 ENA-positive, antinuclear-antibody (ANA)-positive specimens, 77 ENA-negative, ANA-positive specimens, and 20 ENA- and ANA-negative specimens. Sensitivity and specificity were calculated by two methods: first, by using the in-house DID result as the reference standard, and second, by using latent class analysis, which evaluates each kit result independently. Overall, the results showed that the ELISA methods were more sensitive for detection of ENA autoantibodies than DID techniques, but presence and/or specific type of ENA autoantibody did not always correlate with the patient's clinical presentation. Regardless of the testing strategy an individual laboratory uses, clear communication with the clinical staff regarding the significance of a positive result is imperative. The laboratory and the clinician must both be aware of the sensitivity and specificity of each testing method in use in the clinical laboratory.
Asunto(s)
Especificidad de Anticuerpos , Antígenos Nucleares/inmunología , Autoanticuerpos/inmunología , Enfermedades Autoinmunes/diagnóstico , Ensayo de Inmunoadsorción Enzimática , Autoanticuerpos/análisis , Enfermedades Autoinmunes/inmunología , Epítopos , Humanos , Juego de Reactivos para Diagnóstico , Sensibilidad y EspecificidadRESUMEN
CONTEXT: Acute human immunodeficiency virus (HIV) infection cannot be diagnosed by routine antibody tests and is rarely diagnosed in clinical practice. However, HIV nucleic acid-based testing is widely used to screen for antibody-negative acute infection among low-risk blood donors. OBJECTIVE: To assess the feasibility of screening in high-volume laboratories for acute and long-term HIV infection in a routine HIV testing population, in which HIV infection prevalence is low, using specimen pooling and HIV RNA reverse transcriptase-polymerase chain reaction (RT-PCR) tests. DESIGN AND SETTING: Clinical diagnostic performance evaluation at a state-funded public health virology and serology laboratory. PARTICIPANTS: A total of 8505 consecutive individuals presenting for routine HIV counseling and testing during a total of 20 business days to simulate a month of testing in August and December 2001 at 110 publicly funded testing sites in North Carolina. MAIN OUTCOME MEASURES: Prevalence of acute and long-term HIV infection. Serum specimens negative by HIV enzyme immunoassay (EIA) were screened in pools by an ultrasensitive HIV RNA RT-PCR test. Results for individual HIV RNA-positive specimens were reclassified as true or false according to results of confirmatory testing. RESULTS: Of the 8505 individuals screened, 8194 had not previously tested HIV positive and had sufficient serum to complete the testing protocol. Of those, 39 had long-term HIV infection (prevalence, 47.6 per 10,000 at-risk persons [95% confidence interval, 33.8-65.0 per 10,000]). Of the 8155 at-risk individuals whose antibody tests were negative, 5 were HIV RNA positive. Four of those had true-positive acute infection (prevalence, 4.9 per 10,000 [95% confidence interval, 1.3-12.5 per 10,000]). All 4 were women; 2 developed symptoms consistent with an acute retroviral syndrome in the week after testing. Screening all specimens required 147 HIV RNA tests. Overall specificity of the strategy was 0.9999. CONCLUSIONS: These findings suggest the widespread diagnosis of acute HIV infections in a routine testing population is not only possible but feasible using specimen pooling and nucleic acid testing. These additional procedures may increase diagnostic yield by approximately 10% compared with conventional HIV antibody testing.