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Laboratory biomarkers of autoimmune diseases have faced promising prospects and challenges in various aspects of clinical application, including disease warning, diagnosis, prognostic evaluation, and therapeutic monitoring. There is an urgent need for standardization of clinical applications of relevant biomarkers, such as antinuclear antibodies, antidrug antibodies, immune disease-associated cytokines, and novel autoantibodies associated with autoimmune diseases complicated with infection, and malignancy. It is imperative to expand the application scenarios and explore the potential applications of novel biomarkers in order to promote the high-quality development of laboratory medicine in the field of autoimmune diseases.
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Autoimmune diseases are a series of diseases that induce the damage and dysfunction of human immune-system due to the destruction of immune homeostasis. The discovery and application of biomarkers provide important value for early clinical diagnosis, disease activity monitoring, improved prognosis and more effect treatment. Proteomics related methods are important strategies to discover biomarkers for autoimmune diseases, and certain progress has been made in the related field. With the development of technology and the deepening of research, proteomics will have a greater value in the future.
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The autoimmune cardiomyopathy is a variety of myocardial diseases with significant individual heterogeneity that is mediated by autoimmunity reaction. However, the pathogenesis of the autoimmune cardiomyopathy has not been clearly known. Multiple autoantibodies have been detected in the sera of patients with autoimmune cardiomyopathy, and the studies of related autoantibody profile contributes to understanding the pathogenesis, improving screening and diagnosis, supervising disease progression, estimating prognosis and therapeutic effects. This review will summarize the progress and clinical application of the autoantibody profile in patients with autoimmune cardiomyopathy, providing a reference for clinical practice.
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Objectives:the purpose of this study was to systematically evaluate the clinical value of cytokines in autoimmune diseases (AID). It was a kind of complex disease, and its pathogenesis involved cytokines, autoantibodies, immune cells and other immune factors. Especially some AID, such as Adult still′s disease (AOSD) and Takayasu arteritis(TA), had no specific biomarkers at present. This study was a retrospective case-control study.Methods:the data of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8(IL-8) and interleukin-10(IL-10) in 834 AID patients from January 2019 to August 2022 were collected, and the serum levels of those cytokines in 30 healthy controls (HC) were detected at the same time. And AOSD, TA, systemic lupus erythematosus (SLE) and Behcet′s syndrome (BS) were divided into active group and inactive group. In addition, we also made a subgroup analysis of two important organs involved in SLE (kidney and nervous system). GraphPad Prism 9 and R 4.2.2 software were used. Nonparametric tests (Kruskal-Wallis H test, Mann-Whitney U test) were used to compare the differences among groups, and Dunn′s method was used to correct the false positive caused by multiple tests. Results:To compare the level of IL-6 in each group, except Behcet syndrome (BS) group and antiphospholipid syndrome (APS) group, the serum IL-6 level of AID group was higher than that of HC group, with antineutrophil cytoplasmic antibodies associated vasculitis(AAV) [3.85(2.00,8.55) pg/ml], idiopathic inflammatory myopathies(IIM) [7.80(2.50,6.50)pg/ml], IgG4-related disease(IgG4RD) [3.65(2.08,12.83) pg/ml], rheumatoid arthritis (RA) [5.50(2.20,16.10) pg/ml], SLE[4.70(2.75,16.55) pg/ml], Sj?gren syndrome(SS) [3.20(2.00,8.90) pg/ml], systemic sclerosis(SSc) [2.70(2.00,8.90) pg/ml], TA[3.40 (2.00,6.50) pg/ml], other AID diseases[4.40(2.00,11.10) pg/ml], especially AOSD [15.20(2.10, 39.20) pg/ml]. After correction, the differences were statistically significant ( P c<0.05). At the same time, the levels of serum TNF-α [7.40(5.60,10.95) pg/ml]and IL-10 [5.00(5.00, 7.58) pg/ml] in AOSD group were significantly higher than those in HC group[7.15(5.93,8.00) pg/ml,5.00(5.00,5.00) pg/ml] after correction ( P c<0.05). At the same time, the levels of serum TNF-α and IL-10 in AOSD group were higher than those in HC group. The serum levels of IL-6 and IL-8 in patients with active AOSD, BS, SLE and TA were significantly higher than those in patients without active disease (all P<0.05). In addition, the level of serum IL-8 in lupus nephritis group was significantly higher than that in non-lupus nephritis group ( P<0.05). At the same time, the serum levels of IL-6, IL-8 and TNF-α in neuropsychiatric lupus erythematosus group were significantly higher than those in non-neuropsychiatric lupus erythematosus group ( P<0.05), but there was no significant difference in IL-10 between neuropsychiatric lupus group and non-neuropsychiatric lupus erythematosus group. Conclusions:there was a close relationship between AID and cytokines. At present, the change of serum IL-6 level was the most classic one in clinical routine.
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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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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 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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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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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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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.
Subject(s)
Arthritis, Rheumatoid/classification , Arthritis, Rheumatoid/diagnosis , Blood Proteins/analysis , Decision Trees , Proteomics/statistics & numerical data , Adolescent , Adult , Aged , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/pathology , Blood Proteins/metabolism , Case-Control Studies , Female , Humans , Magnets , Male , Middle Aged , Proteomics/methods , Sensitivity and Specificity , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Terminology as TopicABSTRACT
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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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.
ABSTRACT
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 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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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 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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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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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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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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Antiphospholipid antibodies (APLs) are important for the diagnosis of antiphospholipid syndrome (APS),especially for predicting the risk of thrombosis and pathological pregnancy.However,the heterogeneity of antiphospholipid antibodies,lacking of standardization and significant interlaboratory variation binder the clinical application of APLs and better understanding of APS diagnosis and treatment.Therefore,it is urgent to establish a standardize system for antiphospholipid antibodies test and to improve the performance of the test and perform well-designed clinical evaluation.