Humans establish acquired immune systems during the growth, which can sufficiently eliminate pathogen avoiding immune responses to self, such as allergy and autoimmunity. An imbalance of the acquired immune system leads up to immune-mediated disorders. Ultraviolet (UV) exposure helps to establish the normal peripheral tolerance to contact allergen avoiding excessive immune responses. By contrast, UV develops kinds of autoimmune diseases on rare occasions, suggesting that abnormality in the process of UV-induced peripheral tolerance may induce these diseases. To elucidate the mechanism of UV-induced tolerance is possible to provide a new approach for the management of immune diseases. In the current review, focus is on the suggested players of UV-induced tolerance, blocking mechanisms on the elicitation phase of contact hypersensitivity, and the association between UV and autoimmunity. The major impact in basic immunology in this area is the discovery of cell surface marker of regulatory T cells. Therefore, we first discuss about the association of regulatory/suppressor T cells with UV-induced tolerance. Since the elicitation phase depends on cellular influx into the inflammatory sites, which is tightly regulated by adhesion molecules, we also focused on the role of adhesion molecules. Finally, this paper also includes statistical findings concerning the association between UV-radiation and the prevalence of a myositis specific autoantibody. Thus, UV is one of the nice regulators of an immune network and the knowledge of UV-mediated immune regulation will be translated into new therapeutic strategies to human immune-mediated disorders.

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  On a global scale, gastric carcinoma is the second leading course of the cancer-related deaths. Recent studies have provided evidence that cagA-positive Helicobacter pylori plays a causal role for the development of gastric carcinoma. The cagA-encoded CagA protein is delivered into H. pylori-attached gastric epithelial cells via the bacterial type IV secretion system (TFSS). Delivered CagA undergoes tyrosine phosphorylation by Src family kinases at the conserved EPIYA motifs and then specifically binds and deregulates SHP-2 tyrosine phosphatase, a bona fide oncoprotein involved in human malignaicies. As a result, CagA causes aberrant mitogenic signal as well as elevated cell motility in gastric epithelial cells. Also, CagA specifically interacts with and inhibits PAR1b/MARK2 polarity-regulating kinase to disrupt tight junctions and cause loss of epithelial apical-basolateral cell polarity. These CagA activities have been suspected to play an important role in gastric carcinogenesis. Indeed, recently generated cagA-transgenic mice expressing CagA systemically developed gastrointestinal carcinomas as well hematopoietic malignancies such as myeloid leukemia and B-cell lymphoma. The observations collectively indicate that H. pylori CagA is the first identified bacterial oncoprotein in volved in gastric carcinogenesis.

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  Epstein-Barr virus (EBV) belong to herpes virus group. This virus is transmitted by human contact and cause primary infection and may exist even for years in a latent state in healthy individuals. This virus may be reactivated by the dysregulation of the host immune system or possibly by virus mutation. Here we have firstly demonstrated the host defense of EBV infection and association of EBV with rheumatoid synovitis, and then discussed our own ideas of the possible treatment in near future. The key points of this new therapy are SAP (signaling lymphocytic-activation molecule associated protein) or SH2D1A (Src homology 2 domain-containing protein). SAP (or SH2D1A), an adaptor-like molecule expressed in immune cells, is composed almost exclusively of a Src homology 2 (SH2) domain. In humans, SAP is mutated and either absent or non-functional in X-linked lymphoproliferative (XLP) syndrome (Duncan disease), a disease characterized by an inappropriate response to EBV infection. SAP is essential for late B cell help and the development of long-term humoral immunity. New approach to the therapeutic method for EBV might be opened by the regulation of this molecule (SAP)

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  Antiphospholipid antibodies are serological markers of antiphospholipid syndrome (APS). Diversity of so-called antiphospholipid antibodies is well-known. These antibodies are directed against phospholipid binding proteins such as β₂-glycoprotein I and prothrombin as well as against phospholipids such as cardiolipin. Thrombosis and pregnancy morbidity are clinical features of APS. In addition, cardiovascular manifestations, neurological disorders, skin manifestations, renal involvements and thrombocytopenia are reported to be significant in clinical aspects of APS. Anticoagulation therapy and antiplatelet therapy are effective for the secondary prevention of thrombosis in APS.

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  Although not common, thrombotic thrombocytopenic purpura (TTP) is one of the most serious complications in patients with systemic lupus erythematosus (SLE). This study aimed to characterize the association between SLE and TTP by examining clinical features and treatment outcomes. We evaluated eight patients diagnosed over two years in our hospital. The mean disease duration of SLE until TTP onset was 13.2 years. One patient had a simultaneous diagnosis of SLE and TTP. CNS lupus and lupus nephritis were involved in 6 patients, respectively. The mean value of the SLE disease activity index was 40.5. Five out of 7 patients who have been examined the von Willebrand factor cleaving protease showed moderately decreased activity. Seven out of the 8 patients were treated with plasmapheresis, and 7 received immunosuppressive therapy including cyclophosphamide and rituximab. Seven patients recovered, but one died from an exacerbation of the disease. These data indicated that plasmapheresis and immunosuppressive therapy improved prognosis of TTP associated with SLE.

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  Sjögren syndrome (SS) is a common autoimmune disease that exhibits broad organ-specific and systemic manifestations, the most prevalent being decreased lacrimal and salivary gland function, xerostomia, and keratoconjunctivitis sicca. Secondary SS occurs associated with autoimmune diseases, most commonly systemic lupus erythematosus (SLE). Thirty-four childhood-onset SLE patients (2 boys and 32 girls, mean onset age 11.5±2.6 years) were evaluated for the presense of secondary SS using the classification criteria for SS revised by Japanese Ministry of Welfare in 1999. Clinical manifestations, selorogical findings, and renal pathology in SLE patients complicated with SS (SLE+SS, n=14) were compared with those in SLE with no SS autoantibodies (Ro/SS-A or La/SS-B) (SLE-no SS antibodies, n=14). Of all 34 cases, 20 (58.8%) were with positive Ro/SS-A or La/SS-B antibody. Fourteen of the 20 (70.0%) were diagnosed as having secondary SS and all of them were subclinical SS with no sicca symptoms. However, findings of Schirmer test, salivary flow test and minor salivary gland biopsy were positive in 2 of 16 (13.3%), 5 of 16 (31.3%), and 14 of 17 (82.4%) patients, respectively. Compared with the SLE-no SS antibodies group, patients with SLE+SS showed higher level of serum IgG and had higher frequency of anti-U1 RNP antibody and significantly more severe renal involvement. The revised criteria is useful for diagnosis of SS in early stage before the development of exocrine gland damage and appears to be helpful for long term follow-up in childhood-onset SLE associated with SS.

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  We herein report two female siblings with childhood-onset Systemic Lupus Erythematosus (SLE) who developed membranous lupus nephritis. The children were diagnosed as having SLE in reverse birth order at ages 11 and 14 years. Younger sister's initial symptom was edema and laboratory findings indicated proteinurea, hypocomplementemia and positive ANA/anti-dsDNA antibody. She was diagnosed as being SLE with membranous lupus nephritis based on International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification. Elder sister manifested general fatigue and edema twelve months after her sister. Laboratory findings showed proteinurea, hypocomplementemia, and positive ANA/anti-dsDNA antibody. A renal biopsy revealed mixed form of mesangial proliferative glomerulonephritis and membranous nephritis. Moreover, both of them were complicated with secondary Sjögren's syndrome. HLA typing was performed and the siblings were noted to have the same haplotype; A^*0207, A^*2402, B^*4601, B^*5201, B^*5201, Cw^*0102, Cw^*1202, DRB1^*0101, DRB1^*0803.

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  A 67-year-old female patient with rheumatoid arthritis (RA) developed minimal change nephrotic syndrome (MCNS) while under treatment with etanercept (ETN). Histopathological examination of renal biopsy specimens showed minimal-change nephropathy. Almost complete resolution of the MCNS was achieved by discontinuation of ETN and initiation of steroid therapy. There have been no reports from Japan of the occurrence of MCNS caused by ETN administration in RA patients, and only very few cases have been reported from around the world. Therefore, this case was considered to be very uncommon and worthy of reporting, and herein is a report of our patient.

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  The patient was a 74-year-old woman. As the history of the present illness, Raynaud's phenomenon appeared in 1998, antinuclear antibody positivity was detected in 2002, and she visited our department for the first time. Leukopenia and positivity for anti-DNA and anti-RNP antibodies were present, but active lesions were not, and thus, course observation was selected. Pollakiuria and a sensation of residual urine appeared in February 2005, diarrhea and nausea developed in November, and she was admitted to our hospital. Abdominal CT detected bilateral hydronephrosis, marked hydroureter, and hypertrophy of the urinary bladder wall, cystoscopy detected trabeculation, and features of interstitial cystitis were noted on biopsy. Edematous colon mucosa was noted on lower endoscopy, submucosal inflammatory cell infiltration on biopsy, and IgG deposition in the small vascular wall on immunostaining. Systemic lupus erythematosus (SLE) that developed as lupus cystitis was diagnosed. The clinical findings were improved by 50 mg of prednisolone. Although she developed lupus cystitis at an elderly age of 74 years, IgG deposition in the small vascular wall was detected by immunostaining of the intestinal mucosa. It is a valuable case proved that causative disease of a digestive tract symptom was enterocolitis through an immune complex as autoimmune reaction by SLE immunohistologically. There are 46 cases of lupus cystitis in Japan by 2007 since Kato reported lupus cystitis in 1985. We summarize clinical features of 46 cases and discuss difference with this case.

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  A 56-year-old woman was admitted to our hospital in April 2007 due to a history of polyarthralgia. In 1999, She had been diagnosed as having gout by monoarthritis of the first metatarsophalangeal joint. She was treated with only cholchine. Subsequently she repeatedly got acute attack once a year. In 2006, episodic monoarthritis became to be continuous polyarthritis. Laboratory examination at admission showed remarkable hyperuricemia. At 3 day after hospitalization, she experienced acute attack and high fever. Diagnosis of chronic gout was confirmed by the identification of monosodium urate crystals in the synovial fluid. Her symptom improved by a treatment with dexamethasone 4 mg/day i.m. and cholchine, and did not experience acute attack for 5 months. We suggest that prophylactic administration of cholchine is beneficial in refractory chronic gout patient.

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