Array technology and proteomics in autoimmune diseases

Department of Pathology, Universitätsklinikum Charité, Schumannstrasse 20121, Berlin 10117, Germany.
Pathology - Research and Practice (Impact Factor: 1.4). 02/2004; 200(2):95-103. DOI: 10.1016/j.prp.2004.02.005
Source: PubMed


Two new technologies (tissue microarrays (TMAs) and proteomics) have generated a great amount of data in life science. High-density TMAs allow for the simultaneous analysis of proteins and RNA by various methods (immunohistochemistry, in situ hybridization, FISH) on a large scale and under highly standardized conditions. Proteomics includes a variety of techniques that are partly high throughput. These techniques aim at the innovation of proteins, the description of the domain structure, the determination of protein sequences and epitope characterization, and ultimately the definition of protein function and protein reactivities in immunologic processes. Proteins that have been characterized accordingly require validation mostly at the morphologic level of defined tissue, linking proteomics to TMAs. In autoimmune diseases, array-based antigenic fingerprinting of autoantibodies will drive the development and the selection of antigen-specific diagnostic tools and therapies. The powerful combination of genomics and proteomics formed in tissue arrays has the potential to change the way the biology of autoimmunity is studied. Novel targets of drug discovery, based on antigen-specific therapies to induce anergy, or regulatory T-cells using the targeted autoantigens of individual patients could be developed in the coming decades.

Download full-text


Available from: Zoltán Konthur
  • Source
    • "Despite overcoming issues of protein quantity, these techniques do not fully address issues of post-translational and disease-relevant modification of the proteins that could affect the specific autoantibody target. In order to attempt to address both issues, tissue microarrays (TMA's) are beginning to be applied to autoimmune disease (Krenn et al. 2004), in which tiny tissue cylinders embedded in paraffin blocks are all sectioned and stained together by immunohistochemistry to co-localize autoantibody binding with known proteins stained with specific antibodies. As for all array data, suspect proteins identified as targets by these techniques require follow-up analysis to determine the specificity of the binding and the association of those autoantigens with disease states in order to determine pathogenic or diagnostic potential. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent advances in genomics-based identification of gene families and gene polymorphisms associated with immune system dysfunction have answered basic questions in immunology and have begun to move forward our understanding of immune-related disease processes. In toxicology, "omic" technologies have the potential to replace or supplement current immunotoxicological screening procedures, to provide insight into potential mode or mechanisms of action, and to provide data suitable for risk assessment. The application of omic technologies to the study of the immune system also has great potential to appreciably impact the diagnosis and treatment of immune-related diseases. This review focuses on the use of omic technologies in immunopharmacology and immunotoxicology, specifically considering the potential for these technologies to impact chemical hazard identification, risk characterization and risk assessment, and the development and application of novel therapeutics. The state of the science of omics technologies and the immune system is addressed in terms of a continuum of understanding of how omics technologies can and cannot yet be applied in the various aspects of immunopharmacology and immunotoxicology. Additionally, information gaps are identified that, once addressed, will move each area further down the continuum of understanding.
    Full-text · Article · Jan 2006 · Toxicology mechanisms and methods
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Protein microarray technology has emerged as a powerful tool for comparing binding interactions, expression level, substrate specificities, and posttranslational modifications (PTMs) of different proteins in a parallel and high-throughput manner. The ability to immobilize proteins to a solid surface and register the specific address of each protein has bridged major limitations for investigating the proteome in biological samples, namely, the wide dynamic range of protein concentrations and the perturbation of the physical and chemical properties of proteins by their modification. Recent advances introduced the use of functional mammalian cell extracts to assay PTMs under different cellular conditions. This assay offers a new approach for performing large-scale complex biochemical analysis of protein modifications. Here, we review studies of PTM profiling using protein microarrays and discuss the limitations and potential applications of the system. We believe that the information generated from such proteomic studies may be of significant value in our elucidation of the molecular mechanisms that govern human physiology. WIREs Syst Biol Med 2011 3 347–356 DOI: 10.1002/wsbm.120 For further resources related to this article, please visit the WIREs website
    Preview · Article · May 2011 · Wiley Interdisciplinary Reviews Systems Biology and Medicine
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The deciphering of the sequence of the human genome has raised the expectation of unravelling the specific role of each gene in physiology and pathology. High-throughput technologies for gene expression profiling provide the first practical basis for applying this information. In rheumatology, with its many diseases of unknown pathogenesis and puzzling inflammatory aspects, these advances appear to promise a significant advance towards the identification of leading mechanisms of pathology. Expression patterns reflect the complexity of the molecular processes and are expected to provide the molecular basis for specific diagnosis, therapeutic stratification, long-term monitoring and prognostic evaluation. Identification of the molecular networks will help in the discovery of appropriate drug targets, and permit focusing on the most effective and least toxic compounds. Current limitations in screening technologies, experimental strategies and bioinformatic interpretation will shortly be overcome by the rapid development in this field. However, gene expression profiling, by its nature, will not provide biochemical information on functional activities of proteins and might only in part reflect underlying genetic dysfunction. Genomic and proteomic technologies will therefore be complementary in their scientific and clinical application.
    Full-text · Article · Feb 2004 · Arthritis research & therapy
Show more