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Antisynthetase syndrome is characterized by the presence of anti-aminoacyl-tRNA synthetase antibodies and characteristic clinical features. We report an anti-EJ antibody-positive case presenting an ILD with slight hyperkeratotic skin changes on the fingertips that appeared simultaneously with respiratory symptoms. We suspected those skin changes of a disease manifestation of antisynthetase syndrome, and thus investigated anti-synthetase antibodies. This case implies that broader spectrum of the patients should fall in antisynthetase syndrome even though the present diagnostic criteria call for mechanic's hand as a skin manifestation. Careful examination of the finger skin and antibody testing should lead to a proper understanding of the pathological processes.

A 59-year-old man, who suffered from periodic fever with continuous elevation of the C-reactive protein (CRP) level was referred to our hospital. He had frequent respiratory infections and diarrhea since his childhood. The serum immunoglobulin (Ig) G level was low (537 mg/dl) while IgA and IgE were undetectable. The serum IgM level was elevated (737 mg/dl). Based on these clinical features, he was diagnosed with primary immune deficiency, hyper IgM syndrome. He had past histories of aortic aneurysm, which had been repaired surgically in his fifties. His persistent proteinuria made us to perform renal biopsy, which revealed nephrosclerotic changes. During the hospitalization, multiple events of subcortical brain hemorrhage, subarachnoid hemorrhage, and pulmonary alveolar hemorrhage occurred. Bleeding time and coagulation tests were normal. Antinuclear antibody, anti-neutrophil cytoplasmic antibody, or anti-cardiolipin antibody was absent. Herein, we described the first case of the immune deficiency associated with severe arteriosclerosis and hemorrhage.

MicroRNAs (miRNAs) are endogenous non-coding small RNAs of approximately 22 nucleotides in length. miRNAs repress expression of target genes at the posttranscription level. Biological relevance of miRNAs have been investigated in physiological and pathological conditions, revealing their involvement in fine tuning of the biological events, such as cell proliferation, differentiation and cell death. In 2008, miR-146a and miR-155 were reported to be involved in the pathology of rheumatoid arthritis. Subsequently, expression and function of other miRNAs in rheumatoid arthritis have been reported. These reports suggest that miRNAs could be novel candidates for the therapeutic target or biomarker of rheumatoid arthritis. Further investigations are required to identify, characterize and modulate the key miRNA in the pathology of rheumatoid arthritis.

Triggering receptor expressed on myeloid cells (TREM)-1 belongs to an immunoglobulin super family and is expressed on neutrophils, mature monocytes and macrophages. The engagement of TREM-1 synergizes with several Toll Like Receptors (TLR) activation in amplifying the inflammatory response. TREM-1 blockade using a fusion protein containing murine TREM-1 extracellular domain and human immunoglobulin Fc portion was reported to prevent death in mouse models of microbial peritonitis and protect from organ damage during other inflammatory diseases. There are many reports suggesting the involvement of TREM-1 in the pathogenesis of rheumatoid arthritis. Blockade of TREM-1 could be a new therapeutic target in rheumatoid arthritis without impairing the host defense against microbes. In this report, we outline the role of TREM-1 and the trial of developing anti-rheumatic drugs by targeting its ligand.

Triggering receptor expressed on myeloid cells (TREM)-1 is inducible on monocyte/macrophages and neutrophils and accelerates tissue destruction by propagating inflammatory responses in diseases related to bacterial infection. Its blockade suppressed fatal immune responses in mice models of sepsis without impairing the host defense. However, the influence of TREM-1 on non-bacterial diseases was not elucidated. We describe here that TREM-1 expression was up-regulated by prostaglandin (PG) E(2) as well as lipopolysaccharide. Activation of TREM-1 expressed on PGE(2)-pretreated peripheral blood mononuclear cells by an agonistic TREM-1 mAb significantly enhanced the production of TNFalpha. Indeed, monosodium urate monohydrate (MSU) crystals induced TREM-1 expression in vitro and in vivo. MSU crystals and an anti-TREM-1 agonistic antibody synergistically increased the production of interleukin-1beta compared with stimulation with the crystals alone. Furthermore, TREM-1 was expressed on CD14+ cells in rheumatoid synovial tissue and synovial macrophages from mice with collagen-induced arthritis (CIA). Blockade of TREM-1 ameliorated CIA without affecting T cell and B cell immune responses to the inducing antigen. These results provide evidence that TREM-1 may contribute the development of non-microbial inflammatory diseases through the enhancement of inflammatory responses.

The idiopathic inflammatory myopathies, polymyositis (PM) and dermatomyositis (DM), are evaluated as systemic autoimmune diseases without the pathology determined. Past immunohistochemical findings suggested that the effector response is driven predominantly by CD4 T cells and by humoral immunity in DM, and by cytotoxic T cells in PM. However, histological observations of muscle tissue do not necessarily distinguish DM and PM. Thus, the two diseases including amyopathic DM might represent a spectrum of illness in which some patients suffer only from a muscle disease or from a skin disease. In comparison with research studies on other rheumatic diseases, there are much fewer research studies conducted on PM/DM. The relationship between PM and DM is not clear yet. We reviewed past clinical and basic research on the pathology of PM/DM, including research on relevant T cells, B cells and cytokines.

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.

Here we described an autopsy case of intestinal Behcet's disease with sacroiliitis associated with myelodysplastic syndrome (RAEB-t, 8+). Over twenty cases of Behcet's disease associated with myelodysplastic syndrome have been reported in preliterature so far. The majority of them are incomplete type of Behcet's disease having intestinal ulceration. Of those, trisomy 8 is the most common chromosomal abnormality. We reviewed similar cases reported and investigated the association of intestinal Behcet's disease with trisomy 8. The association of sacroiliitis with Behcet's disease is also studied.

We have experienced a case of chronic active Epstein-Barr virus infection (CAEBV) complicated in systemic lupus erythematosus (SLE) and antiphospholipid antibody syndrome (APS). A 35-year-old woman was admitted to our hospital with complaints of fever and dyspnea on exertion. She was diagnosed as having SLE on the basis of arthritis, oropharyngeal ulcer, lymphopenia, and positive autoantibodies against DNA, RNP and SSA. The diagnosis of APS was also made because of positive anti-cardiolipin IgG antibodies and the existence of multiple pulmonary infarction with pulmonary hypertension. The administration of 30 mg/day of prednisolone and anti-coagulation significantly improved clinical symptoms. However, she was again admitted to the hospital four months later because of progressive liver damage and pancytopenia. Increment of prednisolone did not improve the clinical situation and she expired because of pulmonary hemorrhage. At autopsy, there were a significant increase of histiocytes with hemophagocytosis and a dense infiltration of atypical lymphocytes in the liver, spleen, lymph nodes and bone marrow. Infiltrated lymphocytes were positive for CD 3 and EBER 1 in immunohistochemical staining and EBVmRNA was detected by in situ hybridization. Final pathological diagnosis was CAEBV with hemophagocytic syndrome in association with lupus nephritis, pulmonary hemorrhage and pulmonary infarction.

We report a case of a 27-year-old Japanese female with Sjogren's syndrome (SS), who suffered from several episodes of subcutaneous and mesenteric panniculitis with a recurrence within one year. After a history of fever and skin rash, the patient underwent surgery at a local hospital with a diagnosis of acute appendicitis complicated with an ileocecal abscess. She was also diagnosed as having SS. After the operation, the fever and skin rash persisted. She was treated with prednisolone (PSL), and her symptoms resolved. A recurrent bout of abdominal pain with fever, annular erythema on the trunk and a nodular erythematous rash on the lower extremities occurred six months after the operation. A skin biopsy from the lower extremities showed findings that were compatible with panniculitis. Abdominal computer tomography (CT) showed a diffuse swelling with soft tissue density in the intestinal mesenterium and para aortic area. A retrospective examination of the operative specimen obtained from the local hospital revealed centrilobular infiltration of neutrophils in the mesenteric adipose tissue with fat necrosis, which is compatible with mesenteric panniculitis. Twenty mg/day of PSL was successful in treating the systemic panniculitis, and the abnormal diffuse soft tissue density on the abdominal CT disappeared after three weeks of PSL administration. Systemic panniculitis is a rare complication in SS, and the pathogenesis is unclear.

A 36-year-old man was admitted to a hospital with complaints of fever, polyarthralgia and dyspnea. Erythema was observed on his face, extensor surface of the fingers and extremities, and a chest X-ray revealed massive bilateral pleural effusion. He had no sign of myopathy at this point. Pleural fluid was proved to be exudative and contained extremely high levels of hyaluronic acid. He was also complicated with interstitial pneumonitis and was given a pulse therapy with methyl prednisolone followed by daily administration of 55 mg prednisolone (PSL). Twenty days after the commencement of the therapy, pleural effusion decreased but muscle weakness gradually appeared, accompanied by elevation of myogenic enzymes. Myogenic changes on electromyogram, and irregularity of the muscle fibers with slight inflammatory cell infiltrates in a biopsy specimen were demonstrated. He was transferred to our hospital, and a diagnosis of dermatomyositis was made. Later, pleural effusion waxed and waned depending on the dosage of PSL, but no other causative disorder was demonstrated by extensive examinations. This case indicates that the pleuritis could be one of the vasculitic manifestations of dermatomyositis.

A 20-year-old man was admitted to a hospital complaining a slight fever lasting for 3 months associated with a dull headache and weight loss. A tumor was found in the nasopharynx of which biopsy specimen revealed granulomas with Langhans' giant cells. He was given antituberculous agents without symptomatic improvement, and transferred to our hospital. Serum levels of soluble IL-2 receptor and lysozyme were increased, and a significant uptake was observed by Ga scintigraphy at the nasopharynx and bilateral hilar lymphnodes. Furthermore, spinal fluid contained increased number of mononuclear cells, and T2-weighted MRI scans showed an enhanced lesion at the pituitary stalk. The specimen of both TBLB and repeated biopsy of the nasopharyngeal tumor showed granulomas without caseous necrosis. Taken together with these findings, a diagnosis of sarcoidosis with CNS involvement was finally made, and he made a favorable progress by treatment with prednisolone. This is an unique case which emphasizes importance of differential diagnosis of nasopharyngeal tumors with neurological manifestations in the clinicalsetting of rheumatology.

We experienced a case of Takayasu's arteritis (TA) with ulceritive colitis (UC) having the onset of carotodynia, not accompanied by ischemic symptoms. MRI findings of the neck demonstrated a thickening of the bilateral carotid artery walls. The patient was treated by prednisolone with a marked improvement in both clinical symptoms and MRI findings. The patient had a unique HLA haplotype reported to correlate with both TA and UC. Carotodynia is an early but pathognomonic symptom of TA and MRI is helpful for the early diagnosis of TA.

We report here a case of adult-onset Still's disease (AOSD), who finally responded to a combination of cyclophosphamide (CPA) and gold sodium thiomalate (GST) after two years of active disease. A 23-year-old man having continuous high fever with skin rash, polyarthralgia and increased serum ferritin, was diagnosed as AOSD, and oral corticosteroid was initially effective. His symptoms recurred one year later without clinical improvement to increased dosage of steroid. He was admitted to our hospital with pericarditis and pleural effusion but did not respond to either intravenous (i.v.) pulse steroid therapy, methotrexate (MTX) or high dose i.v. gamma-globulin. He was partly responsive to monthly i.v. injection of CPA, but clinical symptoms did not completely subside and hyperferritinemia persisted. GST, initiated in combination with CPA, however, was successful to induce complete remission. MTX has recently been reported to be efficacious to steroid-resistant AOSD, but CPA and gold compounds might be useful to refractory case of AOSD.