Ruishu Deng

Shantou University, Peping, Beijing, China

Are you Ruishu Deng?

Claim your profile

Publications (4)20.96 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: How does the placenta protect the fetus from immune rejection by the mother? The placenta can produce IgG that is glycosylated at one of its Fab arms (asymmetric IgG; aIgG) which can interact with other antibodies and certain leukocytes to affect local immune reactions at the junction between the two genetically distinct entities. The placenta can protect the semi-allogenic fetus from immune rejection by the immune potent mother. aIgG in serum is increased during pregnancy and returns to the normal range after giving birth. aIgG can react to antigens to form immune complexes which do not cause a subsequent immune effector reaction, including fixing complements, inducing cytotoxicity and phagocytosis, and therefore has been called 'blocking antibody'. Eighty-eight human placentas, four trophoblast cell lines (TEV-1, JAR, JEG and BeWo), primary culture of human placental trophoblasts and a gene knock-out mouse model were investigated in this study. The general approach included the techniques of cell culture, immunohistochemistry, in situ hybridization, immuno-electron microscopy, western blot, quantitative PCR, protein isolation, glycosylation analysis, enzyme digestion, gene sequencing, mass spectrophotometry, laser-guided microdissection, enzyme-linked immunosorbent assay, pulse chase assay, double and multiple staining to analyze protein and DNA and RNA analysis at the cellular and molecular levels. Three major discoveries were made: (i) placental trophoblasts and endothelial cells are capable of producing IgG, a significant portion of which is aberrantly glycosylated at one of its Fab arms to form aIgG; (ii) the asymmetrically glycosylated IgG produced by trophoblasts and endothelial cells can react to immunoglobulin molecules of human, rat, mouse, goat and rabbit at the Fc portion; (iii) asymmetrically glycosylated IgG can react to certain leukocytes in the membrane and cytoplasm, while symmetric IgG from the placenta does not have this property. Most of the experiments were performed in vitro. The proposed mechanism calls for verification in normal and abnormal pregnancy. This study identified a number of new phenomena suggesting that aIgG produced by the placenta would be able to react to detrimental antibodies and leukocytes and interfere with their immune reactions against the placenta and the fetus. This opens a new dimension for further studies on pregnancy physiology and immunology. Should the mechanism proposed here be confirmed, it will have a direct impact on our understanding of the physiology and pathology of human reproduction and offer new possibilities for the treatment of many diseases including spontaneous abortion, infertility and pre-eclampsia. It also sheds light on the mechanism of immune evasion in general including that of cancer. Funded by the Li KaShing Foundation and the National Natural Science Foundation to Jiang Gu, grant no. 30971150 and 81030033. There is no competing interest. Trial registration number: N/A. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    Human Reproduction 12/2014; 30(2). DOI:10.1093/humrep/deu323 · 4.59 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In spite of recent advances in treatment strategies, prostate cancer (PCa) remains the second leading cause of cancer death in men with its genetic and biologic behaviors still poorly understood. Recently, accumulating evidence indicates that cancer cells, as well as some normal cells can secret IgG. This study was designed to evaluate IgG gene expression and its possible significance in PCa tissue samples and cell lines. IgG expression was assessed by immunohistochemistry, in situ hybridization, immunofluorescence, RT-PCR, and Western blot. The possible significance of IgG was evaluated on tissue array and cell lines. To assess cell viability and proliferation, MTS assay was carried out. Apoptosis was evaluated with propidium iodide and annexin-V staining. Expressions of IgG and its related genes were detected in cell lines. Abundant gene expressions of Igγ and Igκ chain were detected in PCa tissue samples, but not in normal prostate tissues. In addition, IgG expression was significantly higher in PCa tissues than in the benign prostate hyperplasia tissues (P < 0.001). Igγ expression was positively correlated to Gleason score and histological grade (P < 0.05). Furthermore, in vitro experiments showed that anti-human monoclonal IgG antibody suppressed cell proliferation and increased apoptosis in cultured PCa cells. IgG gene expression in PCa is related to cell differentiation and clinical status. PCa cell produced IgG is involved in the biological behavior of this cancer and may serve as a useful marker for cancer cell differentiation and prognosis. Locally produced IgG could be a potential target for therapy.
    The Prostate 05/2012; 72(6):690-701. DOI:10.1002/pros.21476 · 3.57 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The pathogenesis of human H5N1 influenza remains poorly understood and controversial. 'Cytokine storm' has been hypothesized to be the main cause of the severity of this disease. However, the significance of this hypothesis has been called into question by a recent report, which demonstrates that inhibition of the cytokine response did not protect against lethal H5N1 influenza infection in mice. Here we showed discrepant findings in two adult H5N1 autopsies and a fetus obtained at autopsy which also raise doubt about this hypothesis. Antigens of 10 cytokines/chemokines which were found to be significantly elevated in previous H5N1-infected patients and in vitro experiments, and mRNA of eight of these, were absent from the lungs of a pregnant woman and her fetus. In contrast, antigens of seven cytokines/chemokines and mRNA of six of these were found to be increased in the lungs of a male autopsy. The cells expressing these cytokines and chemokines were identified as type II pneumocytes, bronchial epithelial cells, macrophages and vascular endothelial cells. Levels of cytokines and chemokines in the serum of the male case were also significantly higher than those of infectious (infection other than by H5N1) and non-infectious controls. In comparison with results from our previous study, it appeared that the male case had increased cytokine/chemokine expression but reduced viral load, while the pregnant female had diminished cytokine/chemokine expression but a significantly increased viral load in the lungs. These disparate findings in these two cases suggest that 'cytokine storm' alone could not be a sufficient explanation for the severe lung injury of this newly emerging disease.
    The Journal of Pathology 08/2008; 216(3):328-36. DOI:10.1002/path.2417 · 7.33 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: It has been proposed that immune injury is the central mechanism of pathogenesis of the infectious disease, severe acute respiratory syndrome (SARS). To gain a better understanding of immune injury in the spleen, we investigated the number and distribution of various immune cell types in the spleens of SARS patients. We performed autopsies on six confirmed SARS cases, with six normal subjects as controls; spleen samples from these autopsies were examined with hematoxylin and eosin (H&E) sections, in situ hybridization for SARS virus genomic sequences, and immunohistochemistry with seven monoclonal antibodies to five cell types. The number and distribution of these cells were measured and analyzed using an image analysis system. SARS genomic sequences were detected in all SARS spleens. The SARS spleens all had severe damage to the white pulp and showed an alteration of the normal distribution of various cell types. Immunocytes in the red pulp were decreased by 68.0-90.7% except for CD68+ macrophages and human leukocyte antigen (HLA)-DR positive antigen-presenting cells (APC), which were decreased to a lesser degree. On average, CD68+ macrophages were increased in size by 2.21-fold. We hypothesize that the collapse of the splenic immune system plays a key role in the clinical outcome of these patients.
    The FASEB Journal 11/2006; 20(13):2321-8. DOI:10.1096/fj.06-6324com · 5.48 Impact Factor