Autoantibodies In Chinese Patients Research Articles

Cell-based vs enzyme-linked immunosorbent assay for detection of anti-Tribbles homolog 2 autoantibodies in Chinese patients with narcolepsy.

Narcolepsy type 1 is attributed to a deficiency in cerebrospinal fluid orexin and is considered linked to autoimmunity. The levels of anti-Tribbles homolog 2 (TRIB2) autoantibodies are elevated in the sera of some patients with narcolepsy with cataplexy. Additionally, injecting mice with serum immunoglobulin from patients with narcolepsy with positive anti-TRIB2 antibodies can induce hypothalamic neuron loss and alterations in sleep patterns. Consequently, we hypothesized the existence of a potential association between anti-TRIB2 antibodies and narcolepsy. To test this possibility, we used cell-based assays (CBAs) and enzyme-linked immunosorbent assays (ELISAs) to detect the presence of anti-TRIB2 antibodies in Chinese patients with narcolepsy. We included 68 patients with narcolepsy type 1, 39 patients with other central disorders of hypersomnolence, and 43 healthy controls. A CBA and a conventional ELISA were used to detect anti-TRIB2 antibody levels in patients' sera. CBA was used to detect serum anti-TRIB2 antibodies in Chinese patients with narcolepsy, and the results were negative. However, when the ELISA was used, only 2 patients with narcolepsy type 1 had TRIB2 antibody titers higher than the mean titer plus 2 standard deviations of the healthy controls. In our study, ELISA identified TRIB2 autoantibodies in sera of patients with narcolepsy where CBA failed to demonstrate them. Contrary to our hypothesis, this intriguing finding deserves further research to elucidate the potential association between TRIB2 and narcolepsy type 1. Exploring the implications of TRIB2 autoantibodies in narcolepsy and disparate outcomes between ELISA and CBA could provide crucial insights. Zhong X, Yuan Y, Zhan Q, etal. Cell-based vs enzyme-linked immunosorbent assay for detection of anti-Tribbles homolog 2 autoantibodies in Chinese patients with narcolepsy. J Clin Sleep Med. 2024;20(6):941-946.

Serological and clinical associations of autoantibodies in Chinese patients with new-onset systemic lupus erythematosus

To study the clinical significance of autoantibodies in Chinese patients with new-onset systemic lupus erythematosus (SLE), we enrolled 526 new-onset patients who met the 1997 Updated American College of Rheumatology SLE Classification Criteria for a retrospective cohort study. Chi-square test and Wilcoxon rank-sum test were used to detect the relationship of autoantibodies with clinical manifestations and serological results respectively. Our results demonstrated that the positive rate of anti-ribosomal P protein (anti-P) antibody in female patients was higher than that in male patients (41.2% vs. 22%, P = 0.008). Patients with anti-SSB (43.95 ± 73.12 vs. 40.92 ± 75.75, P = 0.004; 63.93 ± 103.56 vs. 55.06 ± 120.84, P = 0.008 respectively) antibodies had higher levels of alanine aminotransferase (ALT) and aspartate transaminase (AST), whereas those with anti-P antibody (28.90 ± 25.70 vs. 50.08 ± 93.00, P = 0.014; 38.51 ± 48.19 vs. 69.95 ± 142.67, P = 0.047, respectively) had lower levels of them. Anti-dsDNA antibody (P = 0.021) was associated with pulmonary arterial hypertension (PAH). The patients with anti-Ro60 (P = 0.044), anti-P (P = 0.012) and anti-dsDNA (P = 0.013) antibodies were less likely to develop Interstitial lung disease. Anti-SmRNP antibody was correlated to lower prevalence of neuropsychiatric symptoms (P = 0.037), and patients with anti-centromere antibody (ACA) were more likely to develop serositis (P = 0.016).We identified five clusters of SLE-related autoantibodies, confirmed previously reported associations of autoantibodies, and discovered new associations.

IgE and IgG Anti-Thyroid Autoantibodies in Chinese Patients With Chronic Spontaneous Urticaria and a Literature Review

Immunoglobulin (Ig) E and IgG anti-thyroid autoantibodies (AAbs) play important roles in the immunopathogenesis of chronic spontaneous urticaria (CSU). To date, association of IgE and IgG AAbs with Chinese CSU patients has not been fully investigated. We aimed to explore prevalence rates of IgE and IgG AAbs in Chinese CSU patients and their association with clinical and laboratory parameters. Serum IgE and IgG AAbs against thyroid peroxidase (TPO) and thyroglobulin (TG), total IgE (tIgE) and specific IgEs were measured using enzyme-linked immunosorbent assay, chemiluminescence microparticle immunoassay and immunoblotting. Meta-analyses and literature review were conducted. The meta-analyses indicated that CSU cases were 4.98, 6.90 and 6.68 times more likely to have positive anti-TPO IgE, anti-TPO IgG and anti-TG IgG (all P < 0.001) compared with controls, respectively, and revealed a positive correlation between the prevalence rates of anti-TPO IgE and anti-TPO IgG (r = 0.53, P = 0.025). A total of 1,100 Chinese Han adult CSU patients and 1,100 ethnicity-, age- and sex-matched healthy controls were recruited from 15 centers. Prevalence rates of anti-TPO IgE, anti-TPO IgG, anti-TG IgE or anti-TG IgG in the patients were all significantly higher than those in the controls. Significant correlations were observed between prevalence rates of anti-TPO IgE and anti-TPO IgG (r = 0.297, P < 0.001) as well as between those of anti-TG IgE and anti-TG IgG in the patients (r = 0.137, P < 0.001). Patients with anti-TPO IgE or anti-TPO IgG had significantly lower tIgE levels (P < 0.001). Positive anti-TPO IgE, positive anti-TPO IgG and tIgE < 40 IU/mL were independent predictors of antihistamine-refractory cases. In conclusion, the prevalence rates of IgE and IgG AAbs in Chinese CSU patients are significantly elevated and reciprocally correlated. This study verifies the results of previous case-control studies of CSU patients from other populations and ethnicities.

Characteristic phenotype of Chinese patients with adult-onset diabetes who are autoantibody positive by 3-Screen ICA\u2122 ELISA

AimsTo assess the prevalence of diabetes-associated autoantibodies in Chinese patients recently diagnosed with adult-onset diabetes and to evaluate the potential role of the autoantibody markers for characterization of disease phenotype in the patient population.MethodsThe study included 1273 recent-onset adult patients with phenotypic type 2 diabetes mellitus (T2DM). Serum samples were tested using the 3-Screen ICA™ ELISA (3-Screen) designed for combined measurement of GADAb and/or IA-2Ab and/or ZnT8Ab. 3-Screen positive samples were then tested for individual diabetes-associated and other organ-specific autoantibodies. Clinical characteristics of patients positive and negative in 3-Screen were analysed.ResultsForty-four (3.5%) of the T2DM patients were positive in 3-Screen, and 38 (86%) of these were also positive for at least one of GADAb, IA-2Ab and ZnT8Ab in assays for the individual autoantibodies. 3-Screen positive patients had lower BMI, higher HbA1c, lower fasting insulin levels and lower fasting C-peptide levels compared to 3-Screen negative patients. Analysis using a homeostatic model assessment (HOMA2) indicated that HOMA2-β-cell function was significantly lower for the forty-four 3-Screen positive patients compared to 3-Screen negative patients.Twenty (45%) 3-Screen positive patients were also positive for at least one thyroid autoantibody.ConclusionsThe 3-Screen ELISA has been used successfully for the first time in China to detect diabetes autoantibodies in patients with phenotypic T2DM. 3-Screen positive patients presented with poorer β cell function.

Autoimmune liver disease-associated serologic profiling in Chinese patients with acute hepatitis E virus infection

The association between hepatitis E virus (HEV) and autoimmune liver diseases has been well-researched; however, the focus has been on autoimmune hepatitis (AIH) and not primary biliary cholangitis (PBC). Therefore, we aimed to investigate the prevalence and evolution of AIH- and PBC-related autoantibodies in Chinese patients with HEV infection. In this retrospective study, 164 patients with acute HEV were included, specifically those whose liver autoantibody results were available and who had no pre-existing liver disease at the time of HEV diagnosis. Positive liver autoimmune serology was present in 69 (42.1%) patients and 21 (12.8%) had at least two autoantibodies at diagnosis. Greater age and alkaline phosphatase levels were independent risk factors for autoantibody positivity. Follow-up serologic tests, which were available for 27 of the 69 autoantibody-positive patients, showed that although antinuclear antibodies disappeared in 11/20 (55.0%) and antimitochondrial antibodies disappeared in 4/5 (80%) patients, 16 still remained positive for autoantibodies and two of them even developed new PBC-related antibodies, as described below. One patient developed a rim-like ANA pattern, accompanied by an enhancement of anti-gp210 positivity; and the other was diagnosed as PBC, based on chronic elevation of cholestatic enzymes and presentation with de novo AMA-M2, 18 months after HEV clearance. In conclusion, AIH- and PBC-related autoantibodies are frequently present during acute HEV infection, indicating that HEV should be excluded before diagnosing AIH and/or PBC. Importantly, some cases maintained or developed autoantibodies after viral clearance, and one patient subsequently developed PBC, highlighting that these individuals warrant long-term follow-up.

Analysis of myositis autoantibodies in Chinese patients with cancer-associated myositis.

BackgroundCancer‐associated myositis (CAM) has poor prognosis and causes higher mortality. In general, myositis‐specific autoantibodies (MSAs) and myositis‐associated autoantibodies (MAAs) have been shown to be useful biomarkers for its diagnosis.MethodsIn the present study, focus was given in assessing the presence, prevalence, and diagnostic values of myositis autoantibodies in Chinese patients diagnosed with CAM. The sera collected from 49 CAM patients, 108 dermatomyositis/polymyositis (DM/PM) patients without cancer, 105 disease controls, and 60 healthy controls were detected for the presence of 16 autoantigens (Jo‐1, OJ, EJ, PL‐7, PL‐12, MDA5, TIF1γ, Mi‐2α, Mi‐2β, SAE1, NXP2, SRP, Ku, PM‐Scl75, PM‐Scl100, and Ro‐52) using a commercial Euroline assay.ResultsThe frequency of anti‐TIF1γ was significantly higher in CAM patients than in DM/PM patients without cancer (46.9% vs 14.8%, P < .001). Importantly, the sensitivity and specificity for this MSA were 46.9% and 85.2%, respectively. These helped to differentiate CAM patients from DM/PM patients without cancer. However, there was no difference in other MSAs and MAAs between CAM and DM/PM patients without cancer.ConclusionThe present study indicates that anti‐TIF1γ levels can serve as important biomarkers for CAM diagnosis and help in distinguishing between CAM and DM/PM patients without cancer.

Organ-specific autoantibodies in Chinese patients newly diagnosed with type 1 diabetes mellitus.

This study aims to investigate the prevalence of islet autoantibodies and other organ-specific autoantibodies in type 1 diabetes mellitus (T1DM) patients and characterize their clinical features. Glutamic acid decarboxylase antibody (GADA), insulinoma antigen 2 antibody (IA-2A), zinc transporter 8 antibody (ZnT8A) and tetraspanin7 antibody (TSPAN7A) were assayed by radioligand or luciferase immunoprecipitation system assays in 205 newly diagnosed acute-onset T1DM patients and 170 healthy controls. Other organ-specific autoantibodies, including thyroid peroxidase antibody (TPOA), thyroglobulin antibody (TGA), tissue transglutaminase antibody (tTGA) and 21-hydroxylase antibody (21-OHA), were also measured. The prevalence of GADA, IA-2A, ZnT8A, TSPAN7A, TPOA, TGA and 21-OHA was higher in T1DM patients than in healthy controls. The combinational assay of various islet autoantibodies could increase the frequency of autoantibody positivity in T1DM to 85.4%. GADA+ IA-2A+ T1DM patients preferentially had TPOA and TGA, while IA-2A+ patients often had tTGA. Patients positive for two or more islet autoantibodies often had TPOA and TGA. BMI of multiple islet autoantibody-positive patients was lower than that of patients with single or no islet autoantibodies, and there were no significant differences in C-peptide and glycated hemoglobin between patients positive for islet autoantibodies combined with other organ-specific antibodies and noncombined patients. Younger female patients who were islet autoantibody positive were more likely to have TPOA and TGA. The frequency of Graves' disease was much higher in T1DM patients than in healthy controls. T1DM usually occurs together with other organ-specific autoantibodies. Measuring of other organ-specific autoantibodies will be beneficial for T1DM patients.

The spectrum and clinical significance of myositis-specific autoantibodies in Chinese patients with idiopathic inflammatory myopathies.

The aim of this study is to analyze the prevalence of myositis-specific autoantibodies (MSAs) and to elucidate their associations with clinical features in Chinese patients with polymyositis (PM) and dermatomyositis (DM). Twelve subsets of MSAs including anti-Mi-2, anti-TIF1-γ, anti-MDA5, anti-NXP2, anti-SAE1, anti-SRP, anti-Jo-1, anti-PL-7, anti-PL-12, anti-EJ, anti-OJ, and anti-HMGCR antibodies were tested. Four hundred and ninety-seven PM/DM patients were enrolled. Clinical features and laboratory data were collected. The frequency of MSAs and the correlations with clinical phenotypes were calculated by SPSS 21.0. MSAs were present in 65.4% in PM/DM patients. Anti-TIF1-γ (14.3%), anti-MDA5 (12.5%), and anti-Jo-1 (10.1%) were the three commonest MSAs. Anti-SAE1 (OR 14.877, 95% CI 1.427-155.074), anti-SRP (OR 4.339, 95% CI 1.529-12.312) and anti-TIF1-γ (OR 2.790, 95% CI 1.578-4.935) were associated with dysphagia. In contrast, anti-MDA5 (OR 0.356, 95% CI 0.148-0.856) might decrease the frequency of this manifestation. Interstitial lung disease (ILD) was observed more frequently in patients carrying anti-EJ (OR 14.202, 95% CI 1.696-118.902), anti-Jo-1 (OR 11.111, 95% CI 3.306-37.335), and anti-MDA5 (OR 3.109, 95% CI 1.578-6.128). On the contrary, anti-Mi-2 (OR 0.180, 95% CI 0.055-0.589), anti-TIF1-γ (OR 0.163, 95% CI 0.080-0.333), and anti-HMGCR (OR 0.058, 95% CI 0.007-0.451) were protective factors against developing ILD. Anti-TIF1-γ was an independent risk factor for cancer-associated myositis (OR 4.237, 95% CI 1.712-10.487). PM/DM patients had high frequencies of MSAs. Several MSAs were independent factors in determining unique clinical phenotypes.

Anti‐LRP4 autoantibodies in Chinese patients with myasthenia gravis

We assessed antibodies against low-density lipoprotein receptor-related protein 4 (LRP4-Ab) in a Chinese population with myasthenia gravis (MG). Serum samples from 116 patients and 80 controls were collected. Acetylcholine receptor antibodies(AChR-Ab) and muscle-specific receptor tyrosine kinase antibodies (MuSK-Ab) were tested using an enzyme-linked immune absorption assay, and LRP4-Ab was identified using a cell-based assay. MG patients with neither AChR-Ab nor MuSK-Ab were defined as double-seronegative MG (dSN-MG). Two of 116 (1.7%) of all patients and 2 of 50 (1%) dSN-MG patients were positive for LRP4-Ab. These 2 patients had ocular MG. Following treatment with acetylcholinesterase inhibitor and prednisone, both achieved full remission. This study shows that LRP4-Ab is a pathogenic antibody in MG. LRP4-MG seems to be characterized by mild disease severity and favorable therapeutic effect in contrast with other types of MG. Muscle Nerve 56: 938-942, 2017.

Meta-analysis Followed by Replication Identifies Loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as Associated with Systemic Lupus Erythematosus in Asians

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic involvement and ethnic differences. Susceptibility genes identified so far only explain a small portion of the genetic heritability of SLE, suggesting that many more loci are yet to be uncovered for this disease. In this study, we performed a meta-analysis of genome-wide association studies on SLE in Chinese Han populations and followed up the findings by replication in four additional Asian cohorts with a total of 5,365 cases and 10,054 corresponding controls. We identified genetic variants in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with the disease. These findings point to potential roles of cell-cycle regulation, autophagy, and DNA demethylation in SLE pathogenesis. For the region involving TET3 and that involving CDKN1B, multiple independent SNPs were identified, highlighting a phenomenon that might partially explain the missing heritability of complex diseases.

Prevalence of Autoimmune Liver Disease Related Autoantibodies in Chinese Patients with Primary Biliary Cirrhosis

The prevalence of autoimmune liver disease (AiLD)-related autoantibodies has not been defined in Chinese patients with primary biliary cirrhosis (PBC) and therefore needs to be characterized. The purpose of this study was to explore the prevalence of AiLD-related autoantibodies in Chinese patients with PBC. Indirect immunofluorescence was used to detect anti-mitochondrial antibodies (AMA) in the sera from 198 PBC, 44 autoimmune hepatitis (AIH) and 41 non-autoimmune liver disease controls (LDC). ELISA assays were used to test the presence of anti-M2, anti-gp210, anti-sp100, anti-SLA, anti-LC1 and anti-LKM-1 antibodies. AMA was present in 92.4, 15.9 and 7.3%, respectively, of patients with PBC, AIH and LDC. Anti-M2 was present in 87.4% of the PBC patients, but only in 4.5 and 4.9%, respectively, of AIH and LDC patients. Anti-gp210 and anti-sp100 were detected in 34.3 and 25.8% of PBC, 6.8 and 15.9% of AIH and in 4.9 and 17.1% of LDC patients. Anti-LC1, anti-SLA and anti-LKM-1 were, respectively, present in 1.5, 0.0 and 0.5% of PBC, and 9.1, 11.4 and 2.3% of AIH, and none of LDC. PBC patients that were AMA-positive presented with higher IgM levels but lower CRP levels than negative ones. ALT, TBIL, DBIL, GGT, ALP, and AST were detected at higher levels and ALB at lower levels in PBC positive for anti-gp210 (P<0.05). The prevalence of AiLD-related autoantibodies we provided might help define PBC in China. Anti-sp100 is not a better prognostic marker for Chinese PBC patients compared to anti-gp210. The identification of effective diagnostic biomarkers for AMA-negative PBC patients is still needed.

Clinical and serological correlates of anti-Sm autoantibodies in Chinese patients with systemic lupus erythematosus: 1,584 cases

To investigate the association of anti-Sm antibodies with clinical and serological features in systemic lupus erythematosus. A group of 1,584 patients with SLE was recruited. Clinical and laboratory data were compared between patients with and without anti-Sm antibodies. There were 1,424 females and 160 males, the mean age of the patients was 33.2 +/- 12.3 years, and the mean duration of disease was 32.5 +/- 59.4 months. A total of 469 (29.6%) were anti-Sm antibodies positive. The presence of anti-Sm antibodies was associated with arthritis, renal involvement, malar rash, vasculitis and low serum complement C3. The positive rate of anti-nuclear, anti-dsDNA, anti-La/SSB and anti-U1RNP antibodies were significant higher in anti-Sm positive group when compared with anti-Sm negative group. A trend towards a higher presence of anti-Sm antibodies related to an early disease onset was observed. In conclusion, Anti-Sm antibodies are associated with lupus related clinical and laboratory profiles and correlated significantly with disease activity.

Significantly higher frequencies of presence of serum autoantibodies in Chinese patients with oral lichen planus

Previous studies have shown the presence of serum anti-nuclear (ANA), anti-smooth muscle (SMA), anti-mitochondrial (AMA), anti-gastric parietal cell (GPCA), anti-thyroglobulin (TGA) and anti-thyroid microsomal autoantibodies (TMA) in small groups of patients with oral lichen planus (OLP). In this study, the serum levels of ANA, SMA, AMA, GPCA, TGA and TMA were measured in a group of 320 Chinese OLP patients and 53 healthy control subjects to assess whether Chinese OLP patients had significantly higher frequencies of serum autoantibodies than healthy control subjects and to assess which risk factors had a significant influence on the possession of a specific serum autoantibody in OLP patients. We found that autoantibodies were present in 195 (60.9%) of the 320 OLP patients. The frequencies of presence of serum ANA (28.1%), GPCA (26.3%), TGA (21.3%) and TMA (24.4%) in OLP patients were significantly higher than those (5.7%, 1.9%, 1.9% and 1.9%, respectively) in healthy control subjects (all P-values were < 0.005). Forty-one (12.8%) OLP patients also had anti-hepatitis C virus antibody (HCVA) in their sera. The multivariate logistic regression found that major erosive OLP (EOLP) [odds ratio (OR) = 1.786], TGA/TMA-positivity (OR = 2.517), and HCVA-positivity (OR = 2.214) were significant risk factors to influence ANA-positivity in OLP patients. Moreover, only major EOLP (OR = 1.879) and ANA-positivity (OR = 2.581) were significant risk factors to influence TGA/TMA-positivity in OLP patients. There are significantly higher frequencies of presence of ANA, GPCA, TGA and TMA in Chinese OLP patients than in healthy control subjects.

Clinical significance of serum auto-antibodies in Chinese patients with chronic hepatitis C: negative role of serum viral titre and genotype.

Positive serum anti-nuclear antibody (ANA) and anti-smooth muscle antibody (SMA) have been reported in 10-66% of patients with chronic hepatitis C virus (HCV) infection from Western countries. However, the mechanism involved in this immunological disorder is still unknown. This study was carried out to evaluate the prevalence and clinical significance of positive serum auto-antibodies in Chinese patients with chronic hepatitis C and to assess the role of serum HCV-RNA titre and HCV genotype in the presence of serum auto-antibodies. Serum ANA, SMA and anti-mitochondrial antibody (AMA) were measured in 122 patients with chronic hepatitis C. Clinical, biochemical and virological data (serum HCV-RNA titre and HCV genotype) were compared between patients with and without serum auto-antibodies. Fifty-eight (48%) patients were associated with positive serum auto-antibodies: 42 (34%) positive for ANA, six (5%) positive for SMA, nine (7%) positive for both ANA and SMA and one (1%) positive for AMA. Clinical parameters (age, sex, blood transfusion history), liver biochemical tests, the presence of cryoglobulinaemia or cirrhosis, and the response to interferon treatment were not significantly different between patients with and without positive serum auto-antibodies. Serum HCV-RNA levels and HCV genotypes were also not significantly different between the two groups. Logistic regression analysis showed that none of the previously mentioned parameters were significant predictors to associate with serum auto-antibodies in chronic hepatitis C. We concluded that 48% of Chinese patients with chronic hepatitis C were associated with positive serum auto-antibodies. Hepatitis C virus genotypes and serum HCV-RNA levels were not correlated to the presence of serum auto-antibodies. The clinical significance and actual pathogenesis of this phenomenon remain to be clarified.