Detection of Plasma Antibodies Against CD25-Derived Peptide Antigens in Bladder Cancer.

BACKGROUND: Altered anti-CD25 antibody levels in plasma have been observed in patients with various solid malignancies. The present study aimed to determine whether circulating anti-CD25 antibody levels were altered in bladder cancer (BC). METHODS: An enzyme-linked immunosorbent assay was developed in-house to detect plasma IgG antibodies against three CD25-derived linear peptide antigens in 132 patients with BC and 120 control subjects. RESULTS: The Mann-Whitney U-test indicated that the plasma levels of anti-CD25a (Z = -10.11, p < 0.001), anti-CD25b (Z = -12.79, p < 0.001), and anti-CD25c IgG (Z = -11.95, p < 0.001) were significantly lower in BC patients than in the control group. Further analysis indicated that the plasma levels of anti-CD25a IgG antibody were stage-dependent and associated with different postoperative histological grades (U = 977.5, p = 0.003). The receiver operating characteristic curve analysis showed that the area under the ROC curve (AUC) was 0.869 for anti-CD25a IgG (95%, 0.825 - 0.913), 0.967 for anti-CD25b IgG (95%, 0.945 - 0.988), and 0.936 for anti-CD25c IgG (95%, 0.905 - 0.967), with a sensitivity of 91.3% for the anti-CD25a IgG assay, 98.8% for the anti-CD25b IgG assay, and 96.7% for the anti-CD25c IgG assay, against a specificity of 95%. CONCLUSIONS: The present study suggests that circulating anti-CD25 IgG may have a potential predictive value for clinical staging and histological grading of BC.

Further analysis of natural antibodies against ischemic stroke.

Background: Our previous study revealed that circulating levels of IgG natural antibodies (NAbs) for vascular endothelial growth factor receptor 1 (VEGFR1) were significantly decreased in patients with arteriosclerosis compared with control subjects. To enhance the sensitivity of an enzyme-linked immunosorbent assay (ELISA) developed in-house for antibody testing, the present work was designed to investigate additive signals in the in-house ELISA developed with the combination of two or more linear peptide antigens derived from target proteins of interest, including VEGFR1, oxidized low-density lipoprotein receptor 1 (LOX-1), interleukins 6 (IL6) and 8 (IL8). Methods: A total of 218 patients with ischemic stroke and 198 healthy controls were enrolled and an in-house ELISA was developed with linear peptides derived from VEGFR1, LOX-1, IL6, and IL8 to detect their IgG levels in plasma. Results: Compared with control subjects, plasma levels of IgG NAbs for the IL6-IL8 combination were significantly lower in female patients (Z = -3.149, P = 0.002), whereas male patients showed significantly lower levels of plasma anti-VEGFR IgG (Z = -3.895, P < 0.001) and anti-LOX1a IgG (Z = -4.329, P < 0.001). Because plasma levels of IgG NAbs for both the IL6-IL8-LOX1a-LOX1b combination and the VEGFR1a-VEGFR1b-LOX1a-LOX1b combination were significantly lower in the patient group than the control group, receiver operating characteristic (ROC) analysis was performed and the results showed that the VEGFR1a-VEGFR1b-LOX1a-LOX1b combination had an area under the ROC curve (AUC) of 0.70 for its IgG assay with a sensitivity of 27.1% against the specificity of 95.5% and that the IL6-IL8-LOX1a-LOX1b combination had an AUC of 0.67 for its IgG assay with a sensitivity of 21.1% against the specificity of 95.5%. Spearman correlation analysis showed that plasma IgG NAbs against the IL6-IL8 combination were positively correlated with carotid plaque size only in male patients (r = 0.270, p = 0.002). Conclusions: Circulating IgG NAbs for the target molecules studied may be potential biomarkers for a subgroup of ischemic stroke and also contribute to the gender differences in clinical presentation of the disease.

Detection of circulating natural antibodies against CD25, MUC1, and VEGFR1 for early diagnosis of non-small cell lung cancer.

We previously demonstrated that a deficiency of natural antibodies against CD25, Mucin 1 (MUC1), and vascular endothelial growth factor receptor 1 (VEGFR1) could contribute to high risk of non-small cell lung cancer (NSCLC). This study was designed to investigate whether natural IgG antibodies against POU domain class 5 transcription factor 1 (POU5F1), tumor necrosis factor-α (TNF-α), and the combination of CD25, VEGFR1, and MUC1 could play an anti-tumorigenic role against developing NSCLC. An ELISA was developed in-house to examine plasma IgG against peptide antigens derived from POU5F1, TNF-α, and a combination of peptide antigens derived from CD25, MUC1, and VEGFR1 in 211 patients with NSCLC and 200 healthy controls. Mann-Whitney U test demonstrated that plasma IgG levels for the combination of peptide antigens derived from CD25, MUC1, and VEGFR1 were significantly lower in NSCLC patients than control subjects (Z = -12.978, P < 0.001) although plasma levels of IgG antibodies for POU5F1 and TNFα were not significantly changed. The in-house ELISA made with the CD25-MUC1-VEGFR1 combination had a sensitivity of 49.6% against a specificity of 95% to detect early-stage NSCLC. In conclusion, natural antibodies against the combination of CD25, VEGFR1, and MUC1 may be an effective biomarker for early diagnosis of NSCLC.

Role of Rho kinase signal pathway in inflammatory bowel disease.

Inflammatory Bowel Disease (IBD) is nonspecific inflammation in the intestinal track, including Ulcerative Colitis (UC) and Crohn's disease (CD). The incidence of IBD has increased significantly, with its numerous rising up to five million globally, more than 1,700,000 in China. Pathological character of IBD is the inflammation of intestinal mucosa and intestinal fibrosis. Although the pathogenesis of the disease has not yet been fully clarified, some evidence suggests that excessive intestinal inflammation reaction, intestinal barrier impairment and abnormal immune response can initiate IBD. As research continues, some of them have provided new insights toward understanding of Rho kinase signal pathway function at the occurrence and development of IBD. This review aims to summarize the general principles of Rho kinase signal pathway in the pathological procedure of IBD.