Liming Tan

STUDY OF ASSOCIATION BETWEEN HLA-DR4 AND DR53 AND AUTOANTIBODY DETECTION IN RHEUMATOID ARTHRITIS

The present study explored the association between human leukocyte antigen (HLA)-DR4, DR53, and auto antibodies in rheumatoid arthritis (RA) and its clinical significance. A total of 305 patients with RA and 50 healthy subjects who underwent medical examination were evaluated. HLA-DR4 and HLA-DR53 and auto antibodies were detected. The results showed that frequencies of HLA-DR4 and HLA-DR53 alleles in RA patients were 42.95% and 54.75%, respectively, which were significantly different from those in control group (p < 0.01). Frequencies of anti-cyclic citrullinated peptide antibody (CCP), anti-RA33, anti-keratin antibody (AKA), and anti-nuclear antibody (ANA) in RA patients (n = 305) were 72.13%, 36.39%, 44.92%, and 60.98%, respectively. Results of rheumatoid factor (RF) and C-reactive protein (CRP) were 148.29 ± 391.01 IU/mL and 18.14 ± 26.87 mg/L, respectively, which were significantly different from those in control group (p < 0.01, t-test). The results indicated that the HLA- DR4 gene was clearly associated with susceptibility of RA. Combined detection of related auto antibodies might improve diagnosis rate of RA significantly, and the positive rate was higher than that for a single antibody.

The significance of serum IgG4 and CA19-9, autoantibodies in diagnosis and differential diagnosis of IgG4-related sclerosing cholangitis

Abstract Objective: To investigate the value of serum levels of IgG4 and CA19-9, and autoantibodies in the diagnosis of IgG4-related sclerosing cholangitis (IgG4-SC). Methods: We detected the serum IgG4 and CA19-9 of 45 IgG4-SC patients, 173 non-IgG4-SC patients and 48 healthy controls by immunoassay and chemiluminescence, respectively, with antinuclear antibody (ANA), anti-neutrophil antibody (ANCA), anti-smooth muscle antibody (SMA) and anti-mitochondrial antibody (AMA) level detected by indirect immunofluorescence. Then analyze the detection results. Results: (1) The positive rates of ANA, ANCA, SMA and AMA in patients with IgG4-SC were 40%, 6.67%, 0 and 2.22%. Among them, the positive rate of ANA was significantly higher than that of the healthy control group (p < .01), and the positive rate of ANA, ANCA, SMA and AMA were significantly different from that of the non-IgG4-SC group (p < .05). (2) Serum levels of IgG4 and CA19-9 increased significantly in patients with IgG4-SC compared with the healthy controls (p < .01). The areas under the ROC curve (AUC) of IgG4 and CA19-9 were 0.9750 and 0.6498, respectively (p < .05). Conclusion: The high levels of serum IgG4 and CA19-9, and autoantibodies detections are of great important clinical value in diagnosis and differential diagnosis of IgG4-SC.

Detection of Anti-Lactoferrin Antibodies and Anti-Myeloperoxidase Antibodies in Autoimmune Hepatitis: A Retrospective Study

Anti-lactoferrin antibodies (ALA) and anti-myeloperoxidase antibodies (AMPA) are specific serological markers for autoimmune hepatitis (AIH). The project aimed to detect ALA and AMPA and explore their clinical significances in AIH patients. 59 AIH patients, 217 non AIH patients, and 50 healthy controls were enrolled in this study. ALA and AMPA were detected by ELISA. Antineutropil cytoplasmic antibodies (ANCA) and anti-smooth muscle antibodies (ASMA) were examined by indirect immunofluorescence. Antimitochondrial antibody M2 subtype (AMA-M2), anti-liver kidney microsomal antibody Type 1 (LKM1), anti-liver cytosol antibody Type 1 (LC1), and anti-soluble liver antigen/liver-pancreas antibodies (SLA/LP) were tested by immunoblot. The positivity for ALA was 18.6% in AIH group, only one patient in non-AIH group was positive for ALA; the positivity for AMPA was 59.3% in AIH group, with significant differences (P < 0.01) compared with other groups. The specificities for ALA and AMPA were 99.63% and 97.75%; the sensitivities were 18.64% and 59.32%; and the accuracy rates were 84.97% and 90.80%, respectively. A certain correlation was observed between ALA and SLA/LP, AMPA and ANCA, ASMA in AIH group. ALA and AMPA were associated with AIH, and had high clinical diagnostic value. Co-detection with other relative autoantibodies could play an important role in differential diagnosis of AIH.

Neutrophil-to-C3 ratio and neutrophil-to-lymphocyte ratio were associated with disease activity in patients with systemic lupus erythematosus

Systemic lupus erythematosus is prone to recurrent attacks, and its treatment is related to disease activities. It is important to accurately assess the patients disease activity. So, the purpose of this study was to investigate the relation between neutrophil‐to‐C3 ratio (NC3R), neutrophil‐to‐lymphocyte ratio (NLR), and disease activity in patients with Systemic lupus erythematosus (SLE).

Noninvasive indices for monitoring disease course in Chinese patients with autoimmune hepatitis

OBJECTIVE Noninvasive and simple tests to forecast cirrhosis is in great need clinically. This study aimed to assess the clinical significance of several noninvasive indices in predicting cirrhosis in Chinese patients with autoimmune hepatitis (AIH). MATERIALS AND METHODS Liver function test and blood cell analysis were conducted in 76 AIH patients and 75 paired healthy subjects to calculate aspartate aminotransferase to alanine aminotransferase ratio(AAR), aspartate aminotransferase to platelet ratio index (APRI), fibrosis index based on the four factors (FIB-4), gamma-glutamyl transferase to platelet ratio (GPR), red blood cell distribution width (RDW), neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), and platelet to lymphocyte ratio (PLR). Binary logistic regression was performed to analysis the risk factors of liver cirrhosis and receiver operating characteristic (ROC) curve was conducted to evaluate the diagnostic value of each index and compare their diagnostic performance with serum biomarkers commonly used in the clinical setting for liver fibrosis assessing including hyaluronic acid (HA), laminin(LN), procollagen III N terminal peptide (PIIINP) and type IV collagen (ColIV). RESULTS AAR, APRI, FIB-4, GPR, NLR and RDW were elevated remarkably in AIH patients with cirrhosis; AAR, FIB-4 and RDW were identified to be independent risk factors of cirrhosis with OR (95%CI) of 3.517 (1.300-9.514), 1.247(1.032-1.506) and 1.414 (1.086-1.842) respectively; ROC analysis showed that the area under the ROC curve (AUC) of AAR, FIB-4 and RDW were 0.801,0.82 and 0.739, with moderate diagnostic value and better than HA, LN, PIIINP and ColIV in identifying those with cirrhosis from AIH patients. CONCLUSION AAR, FIB-4 and RDW were independent risk factors of AIH cirrhosis and can be served as reference indices to monitor disease course in AIH.

BPI-ANCA in chronic obstructive pulmonary disease with pulmonary Pseudomonas aeruginosa colonisation: a novel indicator of poor prognosis

Bactericidal/permeability-increasing protein (BPI) is one of the target antigens of anti-neutrophil cytoplasmic antibodies (ANCA), which have clinical and laboratory significance in systemic and rheumatoid vasculitides. The detection rate of BPI-ANCA in pulmonary disease has increased in recent years: pulmonary inflammation of BPI-ANCA(+) in patients with cystic fibrosis and chronic pulmonary infection is linked to declining lung function [1]. Pseudomonas aeruginosa is one of the most common pathogens of respiratory infections in patients with chronic obstructive pulmonary disease (COPD), which significantly increases the chances of lower respiratory tract infections and acute exacerbation of COPD, resulting in increased hospitalisation. Although there is literature on BPI-ANCA in lung disease such as cystic fibrosis and pulmonary tuberculosis [1–3], there is none on its presence in COPD or links with clinical manifestations, hospitalisations and prognosis. We hypothesised that BPI-ANCA status is linked to lung function and a physiological test of general health (the six-minute walking time) and predicts poor outcome in patients with COPD. To test our hypothesis, we recruited 126 patients with chronic COPD and P. aeruginosa colonisation from the Second Affiliated Hospital of Nanchang University from June 2014 to August 2016. The diagnostic criteria for inclusion and acute exacerbations met the 2014 GOLD Global Initiative for Chronic Obstructive Pulmonary Disease [4]. Isolation of P. aeruginosa in three or more consecutive sputum cultures, taken at least one month apart during a 6-month period, was considered as chronic colonisation. Exclusion criteria were respiratory, cardiovascular, haematological or immune system diseases and severe metabolism abnormalities. The study was in accordance with the 1964 Helsinki declaration and approved by ethics committee of the Second Affiliated Hospital of Nanchang University with written informed consents obtained from all participants. Lung function tests (predicted% forced expiratory volume in 1 min (FEV1%pred) and forced expiratory volume in 1 s/forced vital capacity ratio (FEV1/FVC)), COPD assessment test (CAT) and the 6min walking test (6MWT) were conducted for each patient during a clinically stable period at entry and at 6, 12 and 18 months. Hospital readmissions for acute exacerbations and days of hospitalisation were noted. CAT consisted of eight items covering the most burdensome symptoms and limitations of COPD; each item had a score of 0–5 points and a total score of 0– 40 points [5]. Pulmonary function tests were performed using a German-born Master Screen Diffusion Pulmonary Function Tester. Lung ventilation function tests were performed in strict accordance with the quality control standards of the American Thoracic Society [6]. Lung volume measurements and flow rate capacity curves were performed to evaluate patients’ pulmonary function. Each item was conducted three times repeatedly, and the best value of FEV1%pred and FEV1/FVC(%) was taken as the result [5]. 6MWD was the best of two walks [7]. Five millilitre fasting blood was collected, and serum were obtained after a centrifugation at 1026 g for 10 min. Serum IgG-BPI-ANCA was detected by ELISA (Catalogue number E180104AH: EuroImmun Medical Diagnostics, Beijing, China). At the termination of antigen–antibody reaction, optical density (OD) was detected by a Multiskan Mk3 Plate Reader (ThermoFisher Scientific, Shanghai, China), with a cut-off value of 0.2× ODcalibration. BPI-ANCA considered positive (BPI-ANCA(+)) when ratio (ODsample to cut-off) >1 and negative (BPI-ANCA(−)) otherwise. SPSS23.0 software was used for statistical analysis. K-S test and Levene’s test were used to analyse the normality and variance homogeneity of measurements. Data are presented as mean with

14-3-3η protein: a promising biomarker for rheumatoid arthritis

Effective management of rheumatoid arthritis (RA) depends on early identification followed by timely invention and proper monitoring of treatment responses which remain challenges facing rheumatologists for lacking biomarkers of high sensitivity and specificity. 14-3-3η has been reported to be a novel RA-related biomarker inducing the expression of multiple factors mediating the pathogenesis of RA, and increasing the diagnostic capture when combined with rheumatoid factor and anticyclic citrullinated peptide antibody. Besides, elevated serum 14-3-3η was relevant to more serious joint erosion and worse therapy outcomes. Here, we summarized the emerging knowledge regarding the roles 14-3-3η plays in RA and its clinical implications as diagnostic, prognostic and therapeutic response surrogate as well as potential drug target for RA.

Analysis of Antineutrophil Cytoplasm Antibody from 118 730 Patients in Tertiary Hospitals in Jiangxi Province, China

Background The discovery of antineutrophil cytoplasm antibody (ANCA) makes the early diagnosis of primary vasculitis possible, and also has important guiding significance for the diagnosis and treatment of secondary vasculitis. This study aimed to investigate the clinical significance of ANCA. Material/Methods ANCA was detected by indirect immunofluorescence assay (IIF), and anti-myeloperoxidase (MPO) antibody, and anti-proteinase 3 (PR3) antibody were detected by ELISA. The results were analyzed retrospectively. Results Among 118 730 patients, a total of 5853 (4.93%) were positive for ANCA. In the positive cases, 3.98% were male and 6.33% were female, with significant differences (χ2=123.38, P<0.01). For ANCA, the department with the highest positive rate (15.06%) was the Department of Rheumatology, followed by 7.78% in the Department of Dermatology, 6.79% in the Department of Nephrology, and 5.72% in the Department of Traditional Chinese Medicine (TCM). Anti-PR3 and cANCA were highly specific in primary vasculitis (P<0.01). Anti-MPO and pANCA had high specificity for other autoimmune diseases (P<0.01). Conclusions ANCA has important guiding significance for vasculitis-related diseases. Therefore, it is important in the diagnosis and treatment of this disease and has value in clinical practice.