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A middle-aged male patient initially appeared scattered erythema with pruritus all over the body without obvious cause. According to the skin manifestations of the patient, combined with pathological diagnosis, direct immunofluorescence examination, and different serum autoantibody spectrum, the diagnosis and differential diagnosis of the patient was made by clinicians. The diagnosis of dermatitis herpetiformis was confirmed by the use of autoantibodies in the absence of any apparent history of pasta discomfort. With targeted treatment, the patient′s symptoms and laboratory indicators improved significantly.
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As the research on autoimmune diseases has been more developed and supplemented, the related markers started to play an important role in clinical prediction, disease diagnosis, concomitant diagnosis, treatment evaluation, and prognosis determination. Biomarkers such as neurological autoimmune disease indicators, special proteins, lymphocyte subpopulation, reproduction related autoantibodies are in urgent need of translation from laboratory studies to clinical precise diagnosis and treatment.
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The Idiopathic inflammatory myopathy (IIM), which collectively referred to as myositis, has been considered as a series of heterogeneous diseases characterized by the proximal symmetrical muscle weakness and involvement of multiple organs (such as skin, joints, lungs, gastrointestinal tract, and heart). IIM mainly includes the polymyositis, dermatomyositis, inclusion body myositis and other clinical subtypes. Although the pathogenesis of IIM is not clear, but myositis autoantibodies have been considered to play a certain role in the development and diagnosis of the disease. Myositis autoantibodies can be divided into myositis-specific autoantibodies or myositis-associated autoantibodies. This review provides a comprehensive summary of the progress in the related field of myositis autoantibodies in recent years, hoping to further demonstrate the clinical value of myositis autoantibodies and promote the clinical application of myositis autoantibodies.
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As specific serological markers for autoimmune diseases, autoantibodies are significantly related to diseases or their clinical phenotypes with exclusiveness. Therefore, autoantibodies can not only favor clinical comprehension of different pathophysiological processes of autoimmune diseases, but also contribute to the early screening or diagnosis, severity evaluation, prognosis prediction and the decision-making process for treatment. An increasing number of international clinical practice guidelines have included autoantibodies for disease classification indicators, which further promoted the laboratory utility of them. However, there still exists many problems in the quality management of the determination and clinical application of autoantibodies in China. Thus, attentions should be paid to the standardized detection of autoantibodies and the promotion of new clinical applications.
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BackgroundTo investigate the significance of IgM and IgG in the progress of COVID-19. MethodA multicenter cross-sectional study conducted in suspected and confirmed patients from four hospitals of China and a cohort study to identify the change pattern and significance in the process of COVID-19 disease. ResultsA total of 571 patients were enrolled in the cross-sectional study, including 235 confirmed SARS-CoV-2 infection with 91.9% patients IgG positive and 92.3% IgM positive. 30 patients diagnosed with SARS-CoV-2 infection were enrolled in the cohort study for flowing-up in 20 days. The peak of IgM and IgG reached in 10th and 20 th day separately after symptom onset. The relationship between clinical classification and serological antibodies were analysed. The positive rate of COVID-19 IgG and IgM increased along with the clinical classification and the delay of treatment time. ConclusionWe demonstrated the kinetics of IgM and IgG SARS-CoV-2 antibody in COVID-19 patients, which may contribute to explain the results of IgM and IgG SARS-CoV-2 antibody test and predict the prognosis of COVID-19.
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Coronavirus disease 2019 (COVID-19) is a highly contagious infection and threating the human lives in the world. The elevation of cytokines in blood is crucial to induce cytokine storm and immunosuppression in the transition of severity in COVID-19 patients. However, the comprehensive changes of serum proteins in COVID-19 patients throughout the SARS-CoV-2 infection is unknown. In this work, we developed a high-density antibody microarray and performed an in-depth proteomics analysis of serum samples collected from early COVID-19 (n=15) and influenza (n=13) patients. We identified a large set of differentially expressed proteins (n=125) that participate in a landscape of inflammation and immune signaling related to the SARS-CoV-2 infection. Furthermore, the significant correlations of neutrophil and lymphocyte with the CCL2 and CXCL10 mediated cytokine signaling pathways was identified. These information are valuable for the understanding of COVID-19 pathogenesis, identification of biomarkers and development of the optimal anti-inflammation therapy.
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Rapid and accurate tests that detect IgM and IgG antibodies to SARS-CoV-2 proteins are essential in slowing the spread of COVID-19 by identifying patients who are infected with COVID-19. Using a SARS-CoV-2 proteome microarray developed in our lab, we comprehensively profiled both IgM and IgG antibodies in forty patients with early-stage COVID-19, influenza, or non-influenza who had similar symptoms. The results revealed that the SARS-CoV-2 N protein is not an ideal biomarker for COVID-19 diagnosis because of its low immunogenicity, thus tests that rely on this marker alone will have a high false negative rate. Our data further suggest that the S protein subunit 1 receptor binding domain (S1-RBD) might be the optimal antigen for IgM antibody detection, while the S protein extracellular domain (S1+S2ECD) would be the optimal antigen for both IgM and IgG antibody detection. Notably, the combination of all IgM and IgG biomarkers can identify 87% and 73.3% COVID-19 patients, respectively. Finally, the COVID-19-specific antibodies are significantly correlated with the clinical indices of viral infection and acute myocardial injury (p[≤]0.05). Our data may help understand the function of anti-SARS-CoV-2 antibodies and improve serology tests for rapid COVID-19 screening.
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COVID-19 has quickly become a worldwide pandemic, which has significantly impacted the economy, education, and social interactions. Understanding the humoral antibody response to SARS-CoV-2 proteins may help identify biomarkers that can be used to detect and treat COVID-19 infection. However, no immuno-proteomics platform exists that can perform such proteome-wide analysis. To address this need, we created a SARS-CoV-2 proteome microarray to analyze antibody interactions at amino acid resolution by spotting peptides 15 amino acids long with 5-amino acid offsets representing full-length SARS-CoV-2 proteins. Moreover, the array processing time is short (1.5 hours), the dynamic range is ~2 orders of magnitude, and the lowest limit of detection is 94 pg/mL. Here, the SARS-CoV-2 proteome array reveals that antibodies commercially available for SARS-CoV-1 proteins can also target SARS-CoV-2 proteins. These readily available reagents could be used immediately in COVID-19 research. Second, IgM and IgG immunogenic epitopes of SARS-CoV-2 proteins were profiled in the serum of ten COVID-19 patients. Such epitope biomarkers provide insight into the immune response to COVID-19 and are potential targets for COVID-19 diagnosis and vaccine development. Finally, serological antibodies that may neutralize viral entry into host cells via the ACE2 receptor were identified. Further investigation into whether these antibodies can inhibit the propagation of SARS-CoV-2 is warranted. Antibody and epitope profiling in response to COVID-19 is possible with our peptide-based SARS-COV-2 proteome microarray. The data gleaned from the array could provide invaluable information to the scientific community to understand, detect, and treat COVID-19.
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Systemic lupus erythematosus (SLE), commonly seen in clinical cases, is a systemic inflammatory disease of connective tissue, which involves multiple systems and organs. It is mainly characterized by a wide range of clinical complications, such as lupus nephritis, neuropsychiatric lupus, and SLE-related cardiovascular events, however, the pathogenesis of SLE has not yet been elucidated. Early diagnosis is of great significance in estimating the severity of SLE, disease activity, predicting relevant progression, supervising therapeutic effects, as well as, improving prognosis. This review will mainly focus on the research advances in clinical application of auto-antibodies and biomarkers previously and recently discovered in patients who has been suffered from SLE.
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Objective:To establish autoverification rules for coagulation tests in multicenter cooperative units, in order to reduce workload for manual review of suspected results and shorten turnaround time (TAT) of test reports, while ensure the accuracy of results.Methods:A total of 14 394 blood samples were collected from fourteen hospitals during December 2019 to March 2020. These samples included: Rules Establishment Group 11 230 cases, including 1 182 cases for Delta check rules; Rules Validation Group 3 164 cases, including 487cases for Delta check; Clinical Application Trial Group 77 269 cases. Samples were analyzed for coagulation tests using Sysmex CS series automatic coagulation analyzers, and the clinical information, instrument parameters, test results, clinical diagnosis, medication history of anticoagulant and other relative results such as HCT, TG, TBIL, DBIL were summarized; on the basis of historical data, the 2.5 and 97.5 percentile of all data arranged from low to high were initially accumulated; on the basis of clinical suggestions, critical values and specific drug use as well as relative guidelines, autoverification rules and limits were established.The rules were then input into middleware, in which Stage I/Stage II validation was done. Positive coincidence, negative coincidence, false negative, false positive, autoverification pass rate, passing accuracy (coincidence of autoverification and manual verification) were calculated. Autoverification rules underwent trial application in coagulation results reports.Results:(1) The autoverification algorisms involve 33 rules regarding PT/INR, APTT, FBG, D-dimer, FDP,Delta check, reaction curve and sample abnormalities; (2)Autoverification Establishment Group showed autoverification pass rate was 68.42% (7 684/11 230), the false negative rate was 0%(0/11230), coincidence of autoverification and manual verification was 98.51%(11 063/11 230), in which positive coincidence and negative coincidence were respectively 30.09% (3 379/11 230) and 68.42%(7 684/11 230); Autoverification Validation Group showed autoverification pass rate was 60.37%(1 910/3 164), the false negative rate was 0%(0/11 230), coincidence of autoverification and manual verification was 97.79%(3 094/3 164), in which positive coincidence and negative coincidence were respectively 37.42%(1 184/3 164) and 60.37%(1 910/3 164); (3) Trialed implementation of these autoverification rules on 77 269 coagulation samples showed that the average TAT shortened by 8.5 min-83.1 min.Conclusions:This study established 33 autoverification rules in coagulation tests. Validation showedthese rules could ensure test quality while shortening TAT and lighten manual workload.
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Objective To explore the influence of prozone effect on anti-nuclear antibodies (ANA) testing by indirect immunofluorescence assay (IIFA).Methods The samples with high titer of ANA (≥1∶1 000) were selected from 880fresh serum samples, and were subsequently diluted in 1∶100, 1∶1 000and 1∶10 000ratio.Prozone effect was defined as fluorescence intensity from 1∶1 000dilution was stronger than that from1∶100dilution.The samples with prozone effect were determined manually or by Sprinter XL and EUROPattern.The samples with prozone effect were further characterized by combinations of fluorescence patterns, fluorescence intensities and autoantibody specificities.Results A total of 880samples were tested.Importantly, 34samples displayed prozone effect (3.86％in total and 29.57％in samples with ANA≥1∶1 000).Interestingly, prozone effect was identified by manual detection as well as by Sprinter XL with similar fluorescence patterns and fluorescence intensities.Notably, EUROPattern can only select the central area for identification.Among all samples with prozone effect, 74.42％samples exhibited fluorescence intensities of≥1∶10 000.Speckled pattern was the most prevalent fluorescence patterns in samples with prozone effect (46.51％).In addition, anti-RNP antibodies (62.79％) were the most popular autoantibodies in samples with prozone effect, followed by anti-dsDNA antibodies (51.16％) and anti-SSA antibodies (51.16％).Conclusion Prozone effect was present in ANA testing, especially in samples with high titers, resulting in underestimating the titers.The study highlighted that special attention should be paid to the prozone effect in clinical practice.
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Objective@#To analyze the changes of peripheral blood leukocyte in patients with Behçet uveitis (BU) at different stages.@*Methods@#Case control study was performed.Twenty active stage BU patients and 21 quiet stage BU patients were enrolled from July to November 2015 in Peking Union Medical College Hospital.Ten active stage BU patients treated with glucocorticoid and/or immunosuppressive agents were served as improvement stage BU patients.Meanwhile, 82 healthy controls were collected from the physical examination center.Peripheral blood was obtained and then analyzed by using Hematoflow method.The percentages of leukocytes in peripheral blood of different stage BU patients were compared.This study was approved by the Ethics Committee of Peking Union Medical College Hospital (ZS-1341) and all participants signed informed consent.@*Results@#The percentage of mature neutrophils, eosinophils, basophils, B lymphocytes, non-cytotoxic T and NK lymphocytes, granular T and NK lymphocytes, T blasts, B blasts and immature granulocytes were all significantly different among active stage BU group, quiet stage BU group and healthy control group (F=42.324, 10.220, 8.660, 11.254, 29.795, 31.305, 23.742, 27.738 and 34.638, all at P<0.001). The percentage of mature neutrophils in active stage BU group and quiet stage BU group were (73.10±10.21)% and (62.40±12.09)%, which were significantly higher than (54.95±6.07)% in healthy control group.The percentage of mature neutrophils in active stage BU group was significantly higher than that in quiet stage BU group (P<0.05). The percentages of non-cytotoxic T, NK lymphocytes, granular T and NK lymphocytes in active stage BU group and quiet stage BU group were significantly lower than that in healthy control group, the percentage of non-cytotoxic T, NK lymphocytes and granular T, NK lymphocytes in active stage BU group were significantly lower than those in quiet stage BU group (all at P<0.05). The percentage of immature granulocytes after treatment was significantly higher than that before treatment in improvement stage BU group (t=-2.469, P=0.036).@*Conclusions@#Increase of peripheral blood mature neutrophil was observed in BU patients, which may help to monitor the inflammatory activity of BU.
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Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease of unclear pathogenesis that is manifested by a progressive and destructive poly-arthritis. The early diagnosis of RA is critical to determine the severity of the disease, which may have an impact on improving the prognosis and life quality of patients with RA. A variety of autoantibodies and protein biomarkers have been reported in the serum of RA patients. Herein will be reviewed updates in the field of serum autoantibodies and biomarkers of RA, as well as their application in diagnosis, prognosis, and potential future directions for study.
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Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease of unclear pathogenesis that is manifested by a progressive and destructive poly-arthritis. The early diagnosis of RA is critical to determine the severity of the disease, which may have an impact on improving the prognosis and life quality of patients with RA. A variety of autoantibodies and protein biomarkers have been reported in the serum of RA patients. Herein will be reviewed updates in the field of serum autoantibodies and biomarkers of RA, as well as their application in diagnosis, prognosis, and potential future directions for study.
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Objective To investigate the expression of programmed death receptor-1 (PD-1) in CD8+ T cells and FoxP3+CD4+ cells in patients with primary biliary cholangitis (PBC).Methods The peripheral blood and clinical data of 69 PBC patients in Peking Union Medical College Hospital and 58 health controls (HC) were collected.They were divided into initial treatment group and follow-up group according to whether they were treated or not.Patients in the treatment group were further divided into the refractory group and stable group according to treatment response.Flow cytometry was used to detect the expression of PD-1 in CDS+T cells and FoxP3+CD4+ cells.T-test and Person correlation analysis were used for data analysis.Results The PD-1 expression in peripheral blood mononuclear cells (PBMCs) of 69 PBC patients (12±9)％ was lower than that of HC (20±12)％ (t=-3.687,P＜0.01).The percentage of PD-1+ in FoxP3+ CD4+T cells was significantly increased in PBC (5.6±3.7)％ than HC (7.4±2.4)％ (t=2.048,P＜0.01).The proportion of CD8+T cells,PD-1 expression in CD8+T cells and the proportion of FoxP3+CD4+ cells weren't correlated with clinical parameters (P＞0.05).There was a negative correlation between the expression of PD-1 cells in FoxP3+CD4+ cells and GLOBE score (r=-0.307,P＜0.05).Conclusion The expression of PD-1 in peripheral CD8+T lymphocytes of PBC patients is lower than that of HC,and decreases more significantly in the refractory group.The expression of PD-1 on FoxP3+CD4+T cells is higher than that in HC,and is negatively correlated with the prognostic GLOBE score.It suggests that PD-1/PD-L1 pathway participates in the immune mechanism of PBC.
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Objective To investigate the health related quality of life score [primary biliary cholangitis (PBC)-40] in patients with PBC,and the relationship between PBC-40 and clinical presentations.Methods The PBC-40 score and clinical presentations in PBC patients (n=65) were adapted in this study.Patients were divided into the untreated group and the treated group,and the treated group was further divided into ursodesoxycholic acid (UDCA) response group and UDCA non-response group.PBC-40 scores of different groups were analyzed by t-test and the relationship between PBC-40 and clinical presentations were analyzed with Pearson's test.Results Dimensions of PBC-40 scores of this group of patients were as follows:symptoms were (15.8±4.1) points,itch was (4.9±2.8) points,atigue was (23.8±8.9) points,cognitive dysfunction score was (11.4±4.7) points,social activity score was (17.0±7.5) points,and the emotion score was (6.5±3.1) points.The untreated group had higher emotion scores than the treated group (t=2.024,P=0.045).Compared with the UDCA response group,UDCA non-response group had higher scores in cognitive,social and emotion dimension (t =2.126,2.309,2.062,respectively,P=0.039,0.025,0.045,respectively).Itch score was significantly correlated with total bilirubin (TBil),direct bilirubin (DBil),alkaline phosphatase (ALP) and total bile acid (TBA) (r=0.349,0.345,0.324,0.427,respectively,P＜0.01),while the social scores were correlated with TBil,DBil,aspartate aminotransferase (AST) and TBA (r=0.361,0.383,0.316,0.331,P＜0.01) and emotion scores were associated with ALT,TBil,GGT,ALP,AST and TBA (r=0.332,0.430,0.265,0.326,0.297,0.353,P＜0.05).ConclusionPBC-40 can be used as a health-related quality of life assessment for PBC patients inChinese population.Itch,social and emotion dimensions are correlated with clinical activity indicators.Hyperbilirubin,ALP and TBA can predict low health quality of life in PBC patients.Conclusion PBC-40 can be used as a health-related quality of life assessment for PBC patients in Chinese population.Itch,social and emotion dimensions are correlated with clinical activity indicators.Hyperbilirubin,ALP and TBA can predict low health related quality of life in PBC patients.
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To establish a serological classification tree model for rheumatoid arthritis (RA), protein/peptide profiles of serum were detected by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF-MS) combined with weak cationic exchange (WCX) from Cohort 1, including 65 patients with RA and 41 healthy controls (HC). The samples were randomly divided into a training set and a test set. Twenty-four differentially expressed peaks (P < 0.05) were identified in the training set and 4 of them, namely m/z 3,939, 5,906, 8,146, and 8,569 were chosen to set up our model. This model exhibited a sensitivity of 100.0% and a specificity of 96.0% for differentiating RA patients from HC. The test set reproduced these high levels of sensitivity and specificity, which were 100.0 and 81.2%, respectively. Cohort 2, which include 228 RA patients, was used to further verify the classification efficiency of this model. It came out that 97.4% of them were classified as RA by this model. In conclusion, MALDI-TOF-MS combined with WCX magnetic beads was a powerful method for constructing a classification tree model for RA, and the model we established was useful in recognizing RA.
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Artrite Reumatoide/classificação , Artrite Reumatoide/diagnóstico , Proteínas Sanguíneas/análise , Árvores de Decisões , Proteômica/estatística & dados numéricos , Adolescente , Adulto , Idoso , Artrite Reumatoide/sangue , Artrite Reumatoide/patologia , Proteínas Sanguíneas/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Imãs , Masculino , Pessoa de Meia-Idade , Proteômica/métodos , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Terminologia como AssuntoRESUMO
Autoimmune blistering skin diseases are a group of organ-specific autoimmune disorders that are characterized by autoantibodies against desmosome and hemidesmosome which are structural proteins of the epidermis or the dermal-epidermal junction and clinically by blisters and erosions on skin and/or mucous membranes.According to the skin level at which the blister occurs and the structural proteins that the autoantibodies target,autoimmune blistering diseases can be categorized into intraepithelial blister group and subepidermal blister group.The treatment options and prognosis are different among the various diseases.Since clinical criteria and histopathological characteristics are not sufficient for an accurate diagnosis of autoimmune blistering skin diseases,direct immunofluorescence microscopy,indirect immunofluorescence microscopy,ELISA,immunoblotting and immunoprecipitation are needed for exact diagnosis.The detection of serum autoantibodies have been shown to correlate with disease activity and thus may be helpful in deciding treatment options for the patients.
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According to the consensus criteria of antiphospholipid syndrome (APS),the diagnosis of APS requires the persistent presence of antiphospholipid antibodies (aPLs),indicating the critical role of aPLs in the diagnosis of APS.During the last decade,great efforts have been made to improve the laboratory detection and standardization of aPLs testing.Unfortunately,the heterogeneous nature of aPLs,lacking of standardization in aPLs test,and significant inter-laboratory variation have hampered the clinical application of aPLs test.In this commentary,the clinical application and standardization of aPLs test are focused on,and how to establish the standardization system in aPLs test in order to improve the performance of aPLs test in clinical practice are discussed.
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Objective To investigate the growth and exocrine function of BM-MSC derived from PBC patients.Methods To compare the growth patterns and cytokines secretions between PBC patients and healthy controls by student's t test.Results ① There was no difference in growth profile and speed between PBC patients and healthy controls.② The level of TGF-β1 was much lower in the supernatant of BM-MS from OBC patients than health controls [(2.6±1.9)vs (8.2±6.7)ng/ml,t=-3.641,P=0.001].There were no other differences between two groups' BM-MSC.③ The super natant concentration of interlukin-10 of the third BM-MSC subculture from healthy controls was lower than that of the primary subculture [(18.5±5.0) vs (12.4±3.1) pg/ml,t=2.368,P=0.045],and that of hepatic growth factor from the second subcuhure was higher than the primary subculture [(0.21±0.07) vs (0.35±0.08) ng/ml,t=-2.874,P=0.021].There were seldom discrepancies in other cytokines between different generations of BM-MSC.Conclusion BM-MSC from PBC patients may have almost the similar characters in growth pattern and cytokines secretion as,except the TGF-β1,which was much lower than those from healthy controls.The second subculture of BM-MSC might be more suitable for the treatment to patients with PBC.
