自身免疫性肝病患者自身抗体的分析

目的了解自身免疫性肝病患者可能出现的各种自身抗体阳性率.方法分别应用间接免疫荧光法和免疫印迹法检测200例健康人和178例自身免疫性肝病患者(分为自身免疫性肝炎组、原发性胆汁性肝硬化组及未明原因肝损组)血清中多种自身抗体,分析各组自身抗体出现的阳性率.结果自身免疫性肝炎组可按所出现的自身抗体的类型的不同分为Ⅰ、Ⅱ、Ⅲ型,各型所占比例分别为75%、8.3%、16.7%.原发性胆汁性肝硬化组抗线粒体抗体(AMA)100%阳性,其中M2型AMA的阳性率高达95.5%.未明原因肝损患者自身抗体的出现率达80.0%,有20%未出现自身抗体,4.5%患者出现未知自身抗体.结论大多数自身免疫性肝病伴有特征性自身抗体的出现;注重自身抗体的检测对于明确诊断自身免疫性肝病和分类有重要的临床意义.     

自身免疫性肝病患者自身抗体的分析

目的：了解自身免疫性肝病患者可能出现的各种自身抗体阳性率。方法：分别应有应用间接免疫荧光法和免疫印迹法检测200例健康人和178例自身免疫性肝病患者（分为自身免疫性肝炎组，原发性胆汁性肝硬化组及未明原因肝损组）血清中多种自身抗体，分析各组自身抗体出现的阳性率。结果：自身免疫性肝炎组可按所出现的自身抗体的类型的不同分为Ⅰ、Ⅱ、Ⅲ型，各型所占比例分别为75％、8．3％、16．7％，原发性胆汁性肝硬化组抗线粒体抗体（AMA）100％阳性，其中M2型AMA的阳性率高达95．5％，未明原因肝损患者自身抗体的出现率达80．0％，有20％未出现自身抗体，4．5％患者出现未知自身抗体。结论：大多数自身免疫性肝病伴有特征性自身抗体的出现；注重自身抗体的检测对于明确诊断自身免疫性肝病和分类有重要的临床意义。     

Early efficacy trial of anakinra in corticosteroid-resistant autoimmune inner ear disease

BACKGROUND. Autoimmune inner ear disease (AIED) is a rare disease that results in progressive sensorineural hearing loss. Patients with AIED initially respond to corticosteroids; however, many patients become unresponsive to this treatment over time, and there is no effective alternative therapy for these individuals.METHODS. We performed a phase I/II open-label, single-arm clinical trial of the IL-1 receptor antagonist anakinra in corticosteroid-resistant AIED patients. Given that the etiology of corticosteroid resistance is likely heterogeneous, we used a Simon 2-stage design to distinguish between an unacceptable (≤10%) and an acceptable (≥30%) response rate to anakinra therapy. Subjects received 100 mg anakinra by subcutaneous injection for 84 days, followed by a 180-day observational period.RESULTS. Based on patient responses, the Simon 2-stage rule permitted premature termination of the trial after 10 subjects completed the 84-day drug period, as the target efficacy for the entire trial had been achieved. Of these 10 patients, 7 demonstrated audiometric improvement, as assessed by pure tone average (PTA) and word recognition score (WRS). In these 7 responders, reduced IL-1β plasma levels correlated with clinical response. Upon discontinuation of treatment, 3 subjects relapsed, which correlated with increased IL-1β plasma levels.CONCLUSION. We demonstrated that IL-1β inhibition in corticosteroid-resistant AIED patients was effective in a small cohort of patients and that IL-1β plasma levels associated with both clinical hearing response and disease relapse. These results suggest that a larger phase II randomized clinical trial of IL-1β inhibition is warranted.TRIAL REGISTRATION. ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01267994","term_id":"NCT01267994"}}NCT01267994.FUNDING. NIH, Merrill & Phoebe Goodman Otology Research Center, and Long Island Hearing & Speech Society.     

Multimodal hyperspectral fluorescence and spatial frequency domain imaging for tissue health diagnostics of the oral cavity

A multimodal, hyperspectral imaging system was built for diagnostics of oral tissues. The system, termed Hyperspectral-Fluorescence-Spatial Frequency Domain Imaging (Hy-F-SFDI), combines the principles of spatial frequency domain imaging, quantitative light fluorescence, and CIELAB color measurement. Hy-F-SFDI employs a compact LED projector, excitation LED, and a 16 channel hyperspectral camera mounted on a custom platform for tissue imaging. A two layer Monte Carlo approach was used to generate a reference table for quick tissue analysis. To demonstrate the clinical capabilities of Hy-F-SFDI, we used the system to quantify gingival tissue hemoglobin volume fraction, detect caries, bacterial activity, and measure tooth color of a volunteer at different time points. Hy-F-SFDI was able to measure quantitative changes in tissue parameters.     

Transforming growth factor-β1, Th1 responses, and autoimmune liver disease

Transforming growth factor-β1 (TGF-β1) is released during the storage of blood components, particularly platelet concentrates, and transfusion recipients are exposed to high levels of TGF-β1. Because TGF-β1 is one of the most potent immunosuppressive cytokines known, understanding the immunobiologic functions of TGF-β1 may be relevant for understanding the immunobiologic effects of transfusion. Our laboratory studies the biologic effects of TGF-β1 in the immune system. Mice deficient in TGF-β1 spontaneously develop autoimmunity, confirming the important role of this cytokinean an immune regulator. A few years ago, my laboratory made the observation that genetic background strongly affects the phenotype of TGF-β1–/– mice. TGF-β1–/– mice on the BALB/c background rapidly develop an aggressive T-cell–mediated hepatitis, whereas TGF-β1–/– mice on the 129/CF-1 background do not. In this review, I summarize findings published or in press from our laboratory on disease pathogenesis in TGF-β1–/– mice and then discuss some of the exciting (as-yet-unpublished) directions our laboratory is currently taking.     

Ischemic renal disease: clinico-pathogenetic features, diagnostics, treatment

Ischemic renal disease (IRD) is one of leading causes of terminal renal insufficiency, characterized by very high risk of cardiovascular complications. Approaches to IRD diagnostics and treatment, use of preventive and invasive strategies are considered in the article.     

Autoantibodies, sheep cell agglutinins and anti-albumin antibodies in alcoholic liver disease

The frequency of serum autoantibodies including anti-albumin antibodies was investigated for patients with various categories of alcoholic liver disease (ALD). The 95 patients were grouped into 3 categories: fatty liver (25 cases), alcoholic hepatitis (29 cases), and alcoholic cirrhosis (41 cases), and each group was matched with healthy controls by age, sex, ethnic origin and socio-economic status. For all patients with ALD, there was a 5-fold greater frequency over the controls of positive tests for antinuclear antibody (ANA), but titres were low; the pattern of ANA reactions was speckled in 50% of the cases. For patients with alcoholic cirrhosis, there was an 8-fold increase in frequency over the controls in anti-smooth muscle antibody (ASMA), but titres were low, pointing to a possibility that autoimmunity might be one of several determinants of progression of alcoholic hepatitis to cirrhosis. For none of the groups was there an increase over the controls in the mean titre of sheep red cell agglutinins, nor were there increased haemagglutinin titres of antibody to bovine serum albumin or to human albumin, arguing against a general increase in antibody production in ALD. Greater knowledge of the frequency, significance and pathogenicity of reactive autoantibodies which occur in response to various types of tissue damage is required for interpretation of the increase in ANA and ASMA in alcoholic liver disease.     

Celiac disease and autoimmune thyroid disease

Celiac disease (CD) or gluten sensitive enteropathy is relatively common in western populations with prevalence around 1%. With the recent availability of sensitive and specific serological testing, many patients who are either asymptomatic or have subtle symptoms can be shown to have CD. Patients with CD have modest increases in risks of malignancy and mortality compared to controls. The mortality among CD patients who comply poorly with a gluten-free diet is greater than in compliant patients. The pattern of presentation of CD has altered over the past three decades. Many cases are now detected in adulthood during investigation of problems as diverse as anemia, osteoporosis, autoimmune disorders, unexplained neurological syndromes, infertility and chronic hypertransaminasemia of uncertain cause. Among autoimmune disorders, increased prevalence of CD has been found in patients with autoimmune thyroid disease, type 1 diabetes mellitus, autoimmune liver diseases and inflammatory bowel disease. Prevalence of CD was noted to be 1% to 19% in patients with type 1 diabetes mellitus, 2% to 5% in autoimmune thyroid disorders and 3% to 7% in primary biliary cirrhosis in prospective studies. Conversely, there is also an increased prevalence of immune based disorders among patients with CD. The pathogenesis of co-existent autoimmune thyroid disease and CD is not known, but these conditions share similar HLA haplotypes and are associated with the gene encoding cytotoxic T-lymphocyte-associated antigen-4. Screening high risk patients for CD, such as those with autoimmune diseases, is a reasonable strategy given the increased prevalence. Treatment of CD with a gluten-free diet should reduce the recognized complications of this disease and provide benefits in both general health and perhaps life expectancy. It also improves glycemic control in patients with type 1 diabetes mellitus and enhances the absorption of medications for associated hypothyroidism and osteoporosis. It probably does not change the natural history of associated autoimmune disorders.     

Diatom biosilica in plasmonics: applications in sensing, diagnostics and therapeutics [Invited]

Several living organisms are able to synthesize complex nanostructures provided with peculiar physical and chemical properties by means of finely-tuned, genetically controlled biomineralization processes. Frustules, in particular, are micro- and nano-structured silica shells produced by ubiquitous diatom microalgae, whose optical properties have been recently exploited in photonics, solar energy harvesting, and biosensing. Metallization of diatom biosilica, both in the shape of intact frustules or diatomite particles, can trigger plasmonic effects that in turn can find application in high-sensitive detection platforms, allowing to obtain effective nanosensors at low cost and on a large scale. The aim of the present review article is to provide a wide, complete overview on the main metallization techniques applied to diatom biosilica and on the principal applications of diatom-based plasmonic devices mainly but not exclusively in the fields of biochemical sensing, diagnostics and therapeutics.     

Application of metagenomic next-generation sequencing for bronchoalveolar lavage diagnostics in patients with lower respiratory tract infections

ObjectiveMetagenomic next-generation sequencing (mNGS) has the potential to overcome the shortcomings of traditional culture methods. This study aimed to assess the diagnostic value of mNGS in patients with lower respiratory tract infections (LRTIs).MethodsThis retrospective observational study sequentially enrolled 47 patients with LRTIs admitted to Shenzhen Hospital of Southern Medical University between February 2019 and November 2020. Pathogens in bronchoalveolar lavage fluid (BALF) samples were investigated to compare diagnoses by mNGS with culture methods.ResultsCompared with culture methods, mNGS had a diagnostic sensitivity of 80% and a specificity of 35.13% with an agreement rate of 44.68% between these two methods. mNGS significantly increased the pathogen detection rate.ConclusionsmNGS may show some advantages in identifying a wide range of LRTI pathogens, improving the sensitivity for viruses and atypical pathogens. The clinical application of NGS technology is worth looking forward to.     

Identification of candidate biomarkers of liver hydatid disease via microarray profiling,bioinformatics analysis,and machine learning

ObjectivesLiver echinococcosis is a severe zoonotic disease caused by Echinococcus (tapeworm) infection, which is epidemic in the Qinghai region of China. Here, we aimed to explore biomarkers and establish a predictive model for the diagnosis of liver echinococcosis.MethodsMicroarray profiling followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis was performed in liver tissue from patients with liver hydatid disease and from healthy controls from the Qinghai region of China. A protein–protein interaction (PPI) network and random forest model were established to identify potential biomarkers and predict the occurrence of liver echinococcosis, respectively.ResultsMicroarray profiling identified 1152 differentially expressed genes (DEGs), including 936 upregulated genes and 216 downregulated genes. Several previously unreported biological processes and signaling pathways were identified. The FCGR2B and CTLA4 proteins were identified by the PPI networks and random forest model. The random forest model based on FCGR2B and CTLA4 reliably predicted the occurrence of liver hydatid disease, with an area under the receiver operator characteristic curve of 0.921.ConclusionOur findings give new insight into gene expression in patients with liver echinococcosis from the Qinghai region of China, improving our understanding of hepatic hydatid disease.     

Autoantibodies to intracellular autoantigens and their B-cell epitopes: molecular probes to study the autoimmune response

A common laboratory finding in systemic autoimmune diseases is the presence of autoantibodies against intracellular autoantigens. Although their pathogenesis is not fully understood, autoantibodies are important tools for establishing diagnosis, classification, and prognosis of autoimmune diseases. Autoantibodies mainly target multicomponent complexes containing both protein antigens and (ribo)-nucleic acid(s), such as the spliceosome or Ro/La RNPs. In this review, we address the main characteristics and the clinical value of the main autoantibody types with respect to their disease association, and we describe the corresponding autoantigens, their biologic function, and their B-cell antigenic determinants (epitopes). The structural characteristics and clinical associations of these epitopes, and their utility as tools to investigate the autoimmune response, are discussed in detail. New insights into the pathogenetic role of epitopes in systemic autoimmunity are also examined. In this regard, using the defined structures of the B-cell antigenic epitopes, complementary epitopes can be designed according to the "molecular recognition" theory. These complementary epitopes can be used as probes to study pathogenetic and immunoregulatory aspects of the anti-idiotypic response. The origin of humoral autoimmunity and the spreading of the epitopes in systemic lupus erythematosus are also discussed. Finally, the ability of post-translational modifications to induce autoreactive immune attack via the generation of neo-epitopes is summarized.