DNA microarrays or DNA chips are rapidly evolved technologies. Hybridization of labeled cDNA or cRNA to DNA probes on the solid phases enables analyses of transcriptome of particular cells. Storage and analysis of microarray data are also important factors. Several studies have been published on the gene expression in the immune cells during immune responses and immune mediated diseases.

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  The increasing prevalence of allergic diseases in developed countries is considered to be caused, at least in part, by rapid improvement of human hygiene. In human beings, the immune system developed as an ingenious device for defending against frequent attacks by microbes. Therefore, our immune system seems to have become deranged in our recent, unprecedentedly hygienic environment. It is now necessary to understand the total functional elements comprising the immune system, not just a single molecule present in an immunocyte working in our immune system. Microarray analysis is now becoming capable of detecting the whole transcripts present in a cell. It is anticipated that we can understand the deranged human immunity using the system biology. It is also expected to predict previously unexpected drug-related adverse events caused by interaction of a drug with responsible molecules present in vital organs.

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  Although recent advances in immunosuppressive therapy have dramatically enhanced the early survival of solid organ transplant recipients, acute rejection still occurs in some recipients. Long-term immunosuppressive drug administration, furthermore, entails a number of potentially significant problems such as infection, spontaneous neoplasm and drug toxicity. Alloantigen specific tolerance induction is the ultimate goal in transplant immunology, and can be induced in a rodent model; however, the precise mechanism by which specific tolerance is affected are not clearly understood, and the current immunosuppression regimens have all failed to achieve this goal in a clinical setting.
  DNA microarray technology has made it possible to analyze the expression of a large number of genes and revolutionized many areas of biology and medicine. This new technology can provide non-biased, global expressions of tens of thousands of genes simultaneously. Recent studies on gene expression profiles in various diseases, including allograft rejection, have successfully provided important information and new insights into the biological mechanisms of these diseases. In this article, we reviewed these insights, especially with the viewpoint of appliance of microarray technology to clinical solid organ transplantation.

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  The interdisciplinary field called osteoimmunology has attracted much attention, due to the observations that bone destruction is caused by an abnormal activation of the immune system in rheumatoid arthritis, and mice lacking immunomodulatory molecules often exhibit an unexpected bone phenotype. Osteoclasts are cells of monocyte/macrophage origin that degrade the bone matrix in health and disease. Receptor activator of NF-κB ligand (RANKL), a tumor necrosis factor (TNF) family cytokine, is an essential osteoclastogenic factor linking the bone and the immune system. In the genomewide screening of RANKL-inducible genes using GeneChip, we identified nuclear factor of activated T cells c1 (NFATc1) as the master transcription factor for osteoclastogenesis. We also applied the GeneChip method to the analysis of osteoimmunological regulation : analysis of costimulatory signal for RANKL and the target genes of antirheumatic drugs. Here we summarize our recent findings in the field of osteoimmunology obtained by GeneChip.

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  DNA arrays are useful for determining the expression levels of a number of genes at once. We utilized this technique to evaluate the Th1/Th2 balance in vivo. Immune responses are controlled by two types of helper T cells, Th1 and Th2. Once the balance of Th1/Th2 immunity is disrupted, various immune diseases can develop. Thus, it is important to evaluate the Th1/Th2 balance in each patient for diagnosis, treatment and/or prophylaxis of immune diseases. We have identified a number of genes specifically expressed in Th1 or Th2 cells, and developed a DNA array filter spotted with these genes. We confirmed that this filter is useful for the evaluation of changes in the immune balance in vivo. Clinical application of this technology may lead to the tailor-made therapy of immune diseases through the evaluation of the immune balance in each patient.

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  A 6-month-old boy was diagnosed as having Crohn's disease (CD) by the endoscopic examination. Primary immunodeficiency syndrome was initially suspected due to a refractory infection that occurred just after birth and a family history that his older brother died at the age of 3 months of septicemia associated with perirectal abscess. Thalidomide was used because conventional medical treatment by steroids and immunosuppressives was ineffective. Thalidomide improved the symptoms of diarrhea, abdominal pain, high fever and fistula, and the PCDAI score decreased markedly from 45 to 15. Although thalidomide was discontinued after three months because of the onset of side effects, including edema, rash and the peripheral neuropathy, the effect on the fistula closure was maintained over a long period of time. Further studies will be necessary to determine the dosage of thalidomide that does not elicit side effects, but thalidomide seems to be effective in patients with refractory CD.
  Infantile CD is very rare and the diagnosis is often delayed. CD is generally resistant to medical treatment. More detailed information of infantile CD will be needed to elucidate the pathogenesis of this disease and progress of treatment. Recently the incidence of inflammatory bowel diseases has increased. CD shoud be suspected in any infant with the perianal lesion (fissures, fistula, skin tag and abscesses) especially when prolonged gastrointestinal symptoms, stomatitis or fever coexist.

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  We reported here on a case of limited cutaneous sysytemic sclerosis (lcSSc) with aplastic anemia treated by anti-thymocyte globulin and cyclosporin A. The use of this therapy resulted not only in marrow recovery but also in resolution of the skin sclerosis. A 68 year-old woman was diagnosed as lcSSc accompanied by Hashimoto's thyroiditis and primary biliary cirrhosis. Treatment by D-penicillamine was started. After 11 months, She complained of nasal bleeding and subcutaneous bleeding. Her laboratory data revealed pancytopenia. White blood cell count, hemoglobin concentration and platelet count were decreased at 2300/μl, 8.2 g/dl, and 3000/μl respectively. Bone marrow was severely hypoplastic, suggesting aplastic anemia. The etiology of hypopastic marrow was considered to be D-penicillamine which had been frequently reported to cause hematopoietic cell suppression. We immediately started methylprednisolone pulse therapy combined with G-CSF and cyclosporin A, which showed little effectiveness. Next we tried the anti-thymocyte globulin therapy combined with G-CSF and cyclosporin A. Her blood cell counts gradually improved. After 4 months, she did not need the blood transfusion anymore. Furthermore, the sclerosis of her skin began to improve gradually, and the titer of anti-centromere antibody also decreased. Thus, anti-thymocyte globulin and cyclosporin A combined therapy can be considered among the therapies of systemic sclerosis.

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  Microscopic polyangiitis (MPA) is a systemic disorder characterized by inflammation of small vessels mainly affecting the kidneys and lungs.
  We describe a 72-year-old woman who developed multiple cartilage involvements as well as major manifestations of MPA. The left ear biopsy demonstrated cartilaginous inflammation and small vessel vasculitis. She also had conjunctivitis, hearing impairment, interstitial lung disease, glomerulonephritis with vasculitis and mononeuritis multiplex. Serological examinations revealed a positive antineutrophil cytoplasmic antibody (PR-3 ANCA). Cyclophosphamide and oral corticosteroid therapy was instituted and remission achieved. Due to lacks of nasal and bronchial involvements, as well as the evidence of auricular vasculitis, we concluded that her findings mimicking relapsing polychondritis developed as systemic manifestations of MPA.

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