Abstract Background Antineutrophil cytoplasmic autoantibodies against neutrophil granule bactericidal/permeability‐increasing protein (BPI‐ANCA) has been found in many inflammatory diseases, such as COPD, which can reduce the killing effect of BPI on Gram‐negative bacteria. This study was aimed to assess the clinical significance of BPI‐ANCA detecting in COPD patients with Pseudomonas aeruginosa ( P aeruginosa ) colonization. Methods A total of 216 COPD patients with lung P aeruginosa colonization, 244 patients with P aeruginosa infection from June 2015 to June 2018, and 100 healthy individuals were included. Serum BPI‐ANCA, tumor necrosis factor (TNF)‐α, and interleukin (IL)‐6 and IL‐1β levels were detected by ELISA, and the lung function of the patients was measured at stable clinical stages. Patients with COPD were grouped according to BPI‐ANCA detection and GOLD criteria, and serum TNF‐α, IL‐6, and IL‐1β levels and indices reflecting lung function were compared and analyzed between groups. Results Positive rate of BPI‐ANCA in COPD patients with P aeruginosa colonization was 48.15%; and compared with BPI‐ANCA(‐) group, FEV 1 %pred and FEV 1 /FVC(%) in BPI‐ANCA(+) patients were significantly decreased, while TNF‐α, IL‐6, and IL‐1β levels were elevated. There were 31.73% and 36.54% BPI‐ANCA(+) patients with severe and very severe airflow limitation, respectively, which was significantly higher than that in the BPI‐ANCA(‐) group. FEV 1 %pred and FEV 1 /FVC(%) were negatively correlated with TNF‐α, IL‐6, IL‐1β, and NEU%. C‐reactive protein (CRP) was negatively correlated with FEV 1 %pred, yet not significantly correlated with FEV 1 /FVC(%). Conclusion BPI‐ANCA positivity is associated with inflammatory status in COPD patients with pulmonary P aeruginosa colonization and can be used as a potential biomarker assessing disease severity.
To investigate the value of serum levels of IgG4 and CA19-9, and autoantibodies in the diagnosis of IgG4-related sclerosing cholangitis (IgG4-SC).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.(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).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.
Abstract Background The clinical significance of serum collagen triple helix repeat protein‐1 (CTHRC1) and mitotic spindle apparatus antibody (MSA) in the diagnosis of small cell lung cancer (SCLC). Methods Of the 229 lung tumor patients selected, 62 patients were divided into SCLC, 94 patients with non‐small cell lung cancer (NSCLC), and 73 patients with benign lung disease (BLD). The health controls (HC) had a span of 66 cases with normal physical condition. The serum extracted from each participator and enzyme‐linked immunosorbent assay was adopted for measuring the serum CTHRC1 and MSA; in the meantime, automatic electrochemiluminescence immunoassay was used for the quantitative determination of serum NSA and CEA. And then, the differences in serum CTHRC1, MSA, NSE, and CEA were compared among involved groups. Results ① Compared with other groups, the concentrations of CTHRC1, MSA, and NSE showed a marked increase in the group of SCLC (all p < 0.01). Especially for SCLC patients with lymph node metastasis, CTHRC1 provided a notably higher level than those without metastasis. ② CTHRC1 and MSA established a diagnostic criterion with the specificity of 90.99% and 86.27% for SCLC, respectively. ③ In series, the specificity of CTHRC1 and NSE was the highest (99.30%), while MSA and NSE had the highest sensitivity (96.72%) in parallel. ④ Both CTHRC1 and MSA were hazardous factors interconnected with SCLC. Conclusion Serum CTHRC1 and MSA had a more exciting prospect of application. When used in conjunction with NSE and CEA, they could optimize the clinical diagnosis value of SCLC.
To detect the value of serum interleukin-17 (IL-17), tumour necrosis factor-α (TNF-α), and Dickkopf-1 (DKK-1) in rheumatoid arthritis (RA) at different disease stages. 141 RA patients were randomly obtained and diagnosed in a large tertiary first-class hospital in Jiangxi Province from November 2021 to January 2022. RA was divided into 38 low activity and remission phase (low remission patients), 72 moderate activity patients, 41 high activity patients, according to the disease activity score 28 (DAS28) of RA and 70 healthy controls. IL-17 and TNF-α in serum detected by flow cytometry; DKK-1by ELISA; rheumatoid factor (RF) and C-reactive protein (CRP) by rate scattering turbidimetry; erythrocyte sedimentation rate (ESR) by Widmanstat method; anti-cyclic citrullinated polypeptide antibody (Anti-CCP) by chemiluminescence. The changes among the groups were statistically analysed and evaluated their diagnostic value. ①Anti-CCP, CRP, and ESR levels in the moderate-to-high activity group were higher than controls, while IL-17, TNF-α, and DKK-1levels higher than low remission group, moderate activity group and controls (p < 0.05). ②IL-17, TNF-α and DKK-1 were positively correlated with RA disease activity, with the correlations of IL-17, TNF-α and DKK-1 all over 0.5 (p < 0.05). ③The ROC curve showed that among all indices the AUC of DKK-1 was the largest, 0. 922, and has the highest sensitivity and negative predictive value for RA, 0.965 and 0.953, respectively. The specificity and positive predictive value of TNF-α is highest, 0.918 and 0.921, respectively, combined them had the highest predictive value in moderate-to-high activity RA, with AUC of 0.968, and had the highest sensitivity of 0.965. The IL-17, TNF-α and DKK-1 levels were elevated in RA and positively correlated with disease activity, involved in the Wnt signalling pathway of inflammatory and joint destructive effects, combining them to monitor the RA disease process and biologically treat the cytokines in the pathogenesis of RA were valuable.
To explore the clinical significance of tumor necrosis factor receptor-associated protein (TRAP1), mitotic arrest deficient 2 (mad2) and anti-nuclear mitotic spindle apparatus antibody (MSA) in the diagnosis of small cell lung cancer (SCLC).Serum concentrations of TRAP1 and MSA were determined by enzyme-linked immunosorbent assay (ELISA), including SCLC group (Num.=86), non-small cell lung cancer (NSCLC) group (Num.=105), pulmonary nodules (PN) group (Num.=94), and 60 healthy subjects as control group (Num.=60). Whereas fluorescence quantitative PCR (qt-PCR) method was used to detect the expression of mad2.The expression of TRAP1 was low in SCLC and NSCLC compared with the other two groups, and was the lowest in SCLC, which was negatively correlated with the occurrence of the disease (P<0.05); the sensitivity and specificity of TRAP1 for SCLC were 75.29%, 93.33%, and the area under SCLC curve was 0.903; compared with the other three groups, the level of MSA was the highest in the SCLC, and the results were significantly different (P<0.05), while the area under the SCLC curve was 0.856, and the sensitivity and specificity were 62.78% and 95.24%, respectively. Mad2 is overexpressed in SCLC, but not in PN. The area under the SCLC curve is 0.835, and the sensitivity and specificity are 56.98% and 92.38%; TRAP1 levels are negatively correlated with SCLC tumor stage, the level of TRAP1 was significantly lower in stage III-IV than in stage I-II (P<0.05); combined analysis of TRAP1 and MAD2 and MSA showed that the sensitivity and specificity for SCLS were 95.35% and 99.05%, respectively.TRAP1 is of great value in the early diagnosis of SCLC as well as differential diagnosis with NSCLC. TRAP1 combined with MAD2 and MSA improved the sensitivity and specificity and provided a new idea for the clinical diagnosis of SCLC.
ABSTRACT Overexpression of NorA, an endogenous efflux transporter of Staphylococcus aureus , confers resistance to certain fluoroquinolone antimicrobials and diverse other substrates. The norA gene was amplified by PCR and cloned in the expression vector pTrcHis2. Histidine-tagged NorA (NorA-His) was overexpressed in Escherichia coli cells to prepare two experimental systems, everted membrane vesicles enriched with NorA-His and proteoliposomes reconstituted with purified NorA-His. In membrane vesicles, NorA-His actively transported Hoechst 33342, a dye that is strongly fluorescent in the membrane but has low fluorescence in an aqueous environment. Transport was activated by the addition of ATP or lactate and reversed by the addition of nigericin, with the addition of K + -valinomycin having little effect. Transport of Hoechst 33342 was inhibited competitively by verapamil, a known inhibitor of NorA, and by other NorA substrates, including tetraphenyl phosphonium and the fluoroquinolones norfloxacin and ciprofloxacin. In contrast, sparfloxacin, a fluoroquinolone whose antimicrobial activity is not affected by NorA expression, exhibited noncompetitive inhibition. NorA induction and overexpression yielded 0.5 to 1 mg of a largely homogeneous 40- to 43-kDa protein per liter of culture. NorA-His incorporated into proteoliposomes retained the ability to transport Hoechst 33342 in response to an artificial proton gradient, and transport was blocked by nigericin and verapamil. These data provide the first experimental evidence of NorA functioning as a self-sufficient multidrug transporter.
To research the diagnostic performance of clinical potential bone turnover indexes in rheumatoid arthritis (RA) complicated with osteoporosis (OP).This study involved 87 RA patients, 48 with OP, and 39 without OP, and 204 non-RA control patients, including those with systemic lupus erythematosus, ankylosing spondylitis, primary Sjogren's syndrome, systemic sclerosis, and healthy patients. The levels of 25-hydroxyvitamin D [25(OH)D], β-crosslaps (β-CROSSL), parathyroid hormone (PTH) were measured by electrochemiluminescence (ECLIA), and the level of bone alkaline phosphatase (BALP) was measured by lectin affinity method.The serum concentration of 25(OH)D in the RA with OP group was significantly lower than the control group (P<0.01), while the levels of β-CROSSL, BALP in the RA with OP group considerably exceeded those found in the control group (P<0.01). The levels of β-CROSSL and PTH were significantly higher in RA patients with OP than without OP (P<0.01), while the level of 25(OH)D was statistically lower than without OP (P<0.01). An unconditional logistical regression analysis proved an association with low 25(OH)D and elevated β-CROSSL in RA with OP, with 25(OH)D demonstrating greatest diagnostic potential according to the ROC curve.The significantly reduced levels of 25(OH)D and excessive β-CROSSL may indicate a high risk of the secondary osteoporosis in RA patients.
The project is aimed to detect anti-mitotic spindle apparatus antibody (MSA) and anti-centromere antibody (ACA) and explore the clinical value for the diagnosis of small cell lung cancer (SCLC), providing clinical evidence for molecular studies of SCLC.93 SCLC patients, 208 patients with other cancers and 50 healthy controls were enrolled in this study. MSA antibodies were detected by enzyme linked immunosorbent assay (ELISA). MSA, ACA and anti nuclear antibodies (ANA) were examined by indirect immuno-fluorescence (IIF). And the results were retrospectively analyzed.① the positivity for MSA and ACA by IIF assay was respectively 36.56% and 30.11% in SCLC group, higher than in other tumor groups (P<0.01), ② in correlative analysis, the RR (Relative Ratio) value between MSA and SCLC was as high as 12.93, 12.74, and the RR value of ACA and ANA with SCLC was respectively 4.31 and 3.48. ③ the area under ROC (Receiver operating characteristic) curve (AUC) of MSA detection for SCLC was 0.778, with medium diagnostic value.MSA and ACA might serve as a new marker for SCLC because of its high detection rate. These two markers may participate in the occurrence and development of SCLC, resulting from the highly strong risk. So, the study have some application value for early detection, clinical diagnosis and potential treatments of SCLC.
Acute rejection is one major reason of the graft loss in renal transplantation. Most of the allograft rejections are due to the existence of the antibodies. The importance of the series tests of HLA and HLA antibodies associated with transplantation has been widely recognized. Although considerable rejection episodes can be explained by the appearance of the donor specific anti-HLA antibodies (DSA), it is reported that even in the case of ‘ideal’ HLA identical donor grafts transplanted into ‘ideal’ recipients, 23% are rejected within 10 years [1]. So effect of HLA antibodies accounts for only some of the immunological failures of allograft and there must be large fraction of undetected antibodies against non-HLA mismatches.
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