Mikulicz's disease represents persistent enlargement of the lacrimal and salivary glands, and autoimmune pancreatitis is shown with diffuse pancreatic swelling. Both diseases are characterized with elevated IgG4 concentrations in the serum and prominent infiltration by plasmacytes expressing IgG4 in the glands. Clinical analyses were performed in 40 patients with systemic IgG4-related plasmacytic syndrome (SIPS) who consulted the doctors in Sapporo Medical University Hospital. Our patients were mainly middle-aged or elderly females. The average age was 58.9 years. The diagnosis was following ; 33 cases with Mikulicz's disease, 3 cases with Küttner's tumor, and 4 cases with IgG4-related dacryoadenitis. Slight dysfunction of lacrimal and salivary gland was observed in about 60% of them. Antinuclear antibodies were detected in only 15% of the cases with SIPS. Almost all, except one case, did not have anti-SS-A or anti-SS-B antibodies. Interestingly, hypocomplementemia was revealed in 30% of them. The complications of SIPS include autoimmune pancreatitis, tubulointerstitial nephritis, retroperitoneal fibrosis, prostatitis, and so on. SIPS is mainly treated by the administration of steroids. We started to prescribe much quantity of prednisolone to the patients with organ failure. The recurrence was admitted in the 3 patients for the followed 16 years. We present here the problems and prospects in SIPS.

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  Common variable immunodeficiency (CVID) is a primary immunodeficiency that is characterized by low level of serum immunoglobulins and an increased susceptibility to infections. The patients show a variety of clinical, cellular, and immunological defects, may develop autoimmune disease, and are susceptible to malignancy. The recent identification of four genetic defects that result in the CVID phenotype demonstrates that the genetic basis of CVID is highly variable. The responsible gene products include, ICOS, TACI, BAFF-R, CD19. Insufficiency of each molecule disrupts B cell maturation, function and differentiation at a different stage. Despite the elucidation of responsible genes, the molecular mechanisms leading to the immune defects are still yet to be understood. In this paper, we overview the molecular basis of CVID, and will provide some data on how the defect leads to autoimmunity.

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  A gene therapy of synovial tissue is potentially a novel therapeutic method in rheumatoid arthritis (RA). The method induces expression of anti-arthritic molecules in target cells, and is also useful for the investigation of novel therapeutic targets in vitro. Previous studies showed that viral vectors, which can infect non-proliferative cells well, i.e. adenovirus-based vector, were effective in gene transfer to synovial tissue. In this review, we discuss the properties and effectiveness of these methods and our investigations in forcing expression in synovial tissue or cells. The methods of gene transfer are classified into two categories : virus vectors and virus-free vectors. The virus vectors seem to be more applicable to clinical approaches since clinical trials of adeno-associated virus mediated gene therapy were performed in 2007. At the same time, many effective novel virus-free vectors have been developed.
  Although these gene transfer technologies still have to be improved more to warrant their safety, the gene therapy is an ideal technique in performing “Bench to Clinic and Clinic to Bench” research studies. We hope that it will be applied to RA therapy in near future.

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  Systemic sclerosis (SSc, scleroderma) is an autoimmune disease characterized by excessive extracellular matrix deposition and vascular injury in the skin and internal organs. Although the pathogenesis remains unclear, Raynaud's phenomenon, a kind of ischemia-reperfusion, usually precedes the development of skin sclerosis. Therefore, it is possible that endothelial cell injury caused by recurring ischemia-reperfusion induces inflammatory cell infiltration and subsequent cytokine production, leading to the development of tissue fibrosis. During this process, chemokines likely have important roles via mediating chemotaxis and activation of leukocytes, result in the interaction between leukocytes and fibroblasts. While chemokine abnormalities of SSc have been reported in amounts of literatures, monocyte chemoattractant protein-1 (MCP-1/CCL2) and its receptor, CCR2, likely have the most critical role for the development of SSc. Here recent data will be reviewed on the potential role of chemokines and their receptors in SSc.

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  Small GTPases (G-proteins) play important roles in various signal transduction pathways by working as molecular switches. Among them, some of these GTPases don't have functional features of typical GTPases, therefore they are called “atypical GTPases”. Recently, these less known atypical Rho GTPases have received increased attention. This review will focus on the novel aspects of biological function of atypical Rho GTPases, especially a newly found function of RhoH on signal transduction in T cell development.

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  Fifty years have passed since anti-mitochondrial antibodies were found in patients with primary biliary cirrhosis (PBC). PBC is an autoimmune hepatic disease in which 85-90% of patient antibodies bind to mitochondrial antigens that include pyruvate dehydrogenase complex (PDC)-E2 and other members of the oxaloacid dehydrogenase family. In addition, indirect immunofluorescence (IIF) assays utilizing HEp-2 cell substrates have been used to identify anti-centromere antibodies in 20-30% of PBC sera. These antibodies are generally easily recognized, however, anti-nuclear envelope and anti-multiple nuclear dot antibodies are occasionally more difficult to recognize with certainty by IIF. The use of enzyme linked immunosorbent assays that utilize recombinant gp210 (an autoantigen of the nuclear envelope) and/or sp100 (a protein target represented by multiple nuclear dots) should be particularly considered in anti-mitochondrial antibody negative PBC sera. Although the clinical significance of these antibodies still remains to be determined, there is evidence that the existence of anti-gp210 antibodies are related to poorer prognosis and more aggressive disease progression.

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  Pneumomediastinum is a rare complication of dermatomyositis (DM) and Polymiositis (PM). We report here three cases of PM/DM who developed pneumomediastinum. First case was 61 years old woman with amyopathic dermatomyositis (aDM). Her aDM was complicated with skin ulceration due to vasculopathy, but complicated interstitial pneumonia was not severe. She developed subcutaneous emphysema and pneumomediastinum. Second case was 57 years old woman with DM, who had intractable skin phenomena and mild interstitial pneumonia. The patient became subcutaneous emphysema and pneumomediastinum following severe vasculopathy of skin. The last case was 63 years old man with PM. His PM was complicated with interstitial pneumonia. He had intractable respiratory symptom. Ten years later, he became subcutaneous emphysema and pneumomediastinum following pneumothorax.
  First and second cases suggest that their pneumomediastinum were due to vasculopathy. On the other hand, pneumomediastinum of the last patient seemed to be associated with interstitial pneumonia and steroid.

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  A 64-year-old woman had been treated with prednisolone (PSL) for interstitial pneumonia (IP) of unknown origin since 1988. The IP progressed gradually, however, and home oxygen therapy was instituted in 1993. In 2002, persistent arthritis of the hands appeared and diagnosis of rheumatoid arthritis (RA) was finally established based on radiological and pathological findings. Salazosulfapyridine was given with only partial effect. On October 2002, she was hospitalized because of back pain followed by dyspnea. Chest X-ray revealed multiple giant bullae on bilateral upper lung fields, accompanied by deterioration of IP. Methyl-prednisolone pulse therapy followed by 30 mg/day of PSL was instituted and the bullae were diminished with gradual improvement of IP and synovitis. On the 55th hospital day, she complained of chest oppression, and chest X-ray revealed a complication of pneumomediastinum. Since IP was still active and serum KL-6 remained high, 3 mg/day of tacrolimus was added to control IP further and to reduce the dosage of PSL which was recognized as one of the aggravation factors of pneumomediastinum. As a result, pneumomediastinum disappeared gradually along with amelioration of IP. PSL was successfully tapered to 15 mg/day by the 87th hospital day and the patient was discharged. Although the efficacy of tacrolimus on IP complicated with polymyositis / dermatomyositis and other autoimmune diseases has been reported, this case first suggests its efficacy on IP associated with RA.

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  A 22-year old female suffering from recurrent oral ulcers, genital ulcers, erythema nodosum, and folliculitis, was diagnosed as having Behcet's disease (BD). She has also hypopigmentation of skin and hair, and optic changes associated with albinism including hypopigmentation of the retina, nystagmus, strabismus, and reduced visual acuity. In this report, we discuss the possibility of precipitating factor in BD that the hypersensitivity, mental stress, and drug resistance which is caused by albinism.

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  A 58-year-old female with systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APS) was referred and admitted to our hospital because of fever and pancytopenia. She had been taking small dose of prednisolone and azathiprine since 2003 with stable SLE and APS. Two weeks before the admission, she developed fever and common cold-like symptoms and was admitted to a hospital. Antibiotics were ineffective and thrombocytopenia manifested. Under a diagnosis of progressive SLE, bolus methylprednisolone was administrated. However, she became pancytopenic and was transferred to our hospital. A bone marrow aspirate showed the hemophagocytosis and chest CT scanning revealed interstitial pneumonia. Cytomegalovirus (CMV) antigenemia test gave a positive result. A diagnosis of CMV-induced hemophagocytic syndrome (HPS) and CMV pneumonia was made. Gancyclovir resolved the pancytopenia, pneumonia, and fever. There have been only 3 reported cases of CMV-related HPS in collagen disease.

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