Capability of SART3(109-118) peptide to induce cytotoxic T lymphocytes from prostate cancer patients with HLA class I-A11, -A31 and -A33 alleles.

We previously reported the SART3 gene to be a tumor-rejection antigen gene encoding a peptide at positions 109-118 (SART3(109-118)) with the ability to induce HLA-A24-restricted cytotoxic T lymphocytes. In this study, we investigated both humoral and cellular responses to this peptide in cancer patients with alleles other than HLA-A24 to explore the possibility of using this peptide as a cancer vaccine for these patients. IgG reactive to SART3(109-118) peptide was identified in sera of the vast majority of non-cancer subjects (n=50) and all cancer patients (n=50) tested without apparent HLA-A association. Levels of anti-SART3(109-118) peptide antibody in cancer patients were significantly higher than those of non-cancer subjects, but no difference was found between HLA-A24+A2- and HLA-A24-A2+ cancer patients. This peptide induced cancer cell-reactive cytotoxic T lymphocytes from peripheral blood mononuclear cells of both healthy donors and prostate cancer patients with HLA-A11, HLA-A31 and HLA-A33 alleles, but not with HLA-A2. These results suggest that this peptide can be applicable as a cancer vaccine not only for HLA-A24+, but also for HLA-A11+, HLA-A31+ and HLA-A33+ prostate cancer patients.

Circulating matrix metalloproteinase-2 is an independent correlate of proteinuria in patients with chronic kidney disease.

BACKGROUND/AIM: Matrix metalloproteinase-2 (MMP-2) has been implicated in chronic kidney disease (CKD) and cardiovascular disease. However, there is no knowledge about the correlations between serum levels of MMP-2, proteinuria and atherosclerosis in patients with CKD. We investigated whether serum MMP-2 levels were associated with proteinuria, intima media thickness (IMT), and the presence of carotid atherosclerotic plaque in CKD patients. METHODS: CKD patients without hemodialysis (n = 99) were enrolled. MMP-2 levels were measured by an ELISA system. IMT and carotid atherosclerotic plaque were evaluated by a high-resolution ultrasonography. RESULTS: Multivariate analyses revealed that low-density lipoprotein (p < 0.001), MMP-2 (p = 0.001) and systolic blood pressure (p = 0.011) were independent correlates of proteinuria. Age- and serum creatinine-adjusted MMP-2 levels were significantly increased (p = 0.001) in proportion to the increasing levels of proteinuria. Further, age (p < 0.001), systolic blood pressure (p = 0.015) and MMP-2 levels (p = 0.042) were independent correlates of IMT. MMP-2 levels were significantly (p < 0.01) higher in patients with atherosclerotic plaque than those without it. CONCLUSIONS: The present study demonstrated that serum levels of MMP-2 were one of the independent correlates of proteinuria and IMT in patients with CKD. Our results suggest that serum MMP-2 levels may be one of the risk factors for renal damage and atherosclerosis in CKD patients.

A correlation between symptom severity and unbalanced reactive IgA production in Japanese cedar pollinosis patients.

To better understand the unbalanced immunoglobulin production that occurs in pollinosis, we measured the levels of IgG, IgA, and IgE reactive to either Japanese cedar pollen, Cry j 1 protein, or Cry j 2 protein in the sera of pollinosis patients. As expected, the levels of these immunoglobulins (Igs) reactive to the three antigens were significantly higher in the patients than in the controls, and the RAST scores correlated with the levels of these Igs. Only the levels of IgA reactive to the Cry j 2 protein and IgG reactive to the Japanese cedar pollen antigen did not correlate with the RAST scores. We classified the patients into mild and severe, based on the severity of their allergic symptoms, and compared their levels of Igs. As expected, the levels of IgE reactive to Japanese cedar pollen and Cry j 1 of the severe group were significantly higher than those of the mild group. It is of note that the ratio of anti-Cry j 1 IgE to anti-Japanese cedar pollen IgA was significantly higher in the patients with severe symptoms suggesting that decreased IgA production could be responsible for the severity of pollinosis.

Detection of IgE antibody specific to a hepatitis C virus-derived peptide being recognized by cellular immunity in patients with HCV infection.

The determination of immunogenic peptides of hepatitis C virus (HCV) is pivotal for vaccine development. We previously reported that the majority of patients infected with HCV have significant levels of IgG specific to an HCV-derived peptide at positions 35-44 of core protein (C35-44), a major epitope recognized by cellular immunity. This study addresses whether or not the other subclasses of immunoglobulins to this peptide exist. As a result, IgE, but not IgM or IgA, specific to this peptide is consistently detectable in the majority of patients with HCV infection, regardless of the different HLA types and disease conditions. These results provide additional information on this immunogenic peptide with new insights that contribute to a better understanding of host responses to HCV.