Chronic active Epstein-Barr virus (EBV) infection (CAEBV), characterized by proliferation of EBV-infected T or NK cells, is a disease of unknown pathogenesis and requires hematopoietic stem cell transplantation for curative treatment. Here we show that intravenous injection of peripheral blood mononuclear cells (PBMCs) isolated from patients with CAEBV to NOD/Shi-scid/IL-2R γ^null (NOG) mice leads to engraftment of EBV-infected T or NK cells. Analysis of TCR repertoire identified an identical predominant EBV-infected T-cell clone both in a patient and a mouse transplanted with his PBMCs. EBV-infected T or NK cells infiltrated to most major organs including the liver, spleen, lungs, kidneys, adrenal glands, and intestine, showing histological characteristics of CAEBV. Expression of EBNA1, LMP1, and LMP2A, but not EBNA2, in these cells indicated the latency II program of EBV gene characteristic to CAEBV. High levels of TNF-α, IFN-γ, and RANTES were detected in the peripheral blood of these mice. EBV-containing fractions of either CD8⁺, γδT, or NK cell lineages failed to engraft, once they were isolated from PBMCs ; they could engraft only when CD4⁺ cell fraction was transplanted in parallel. Isolated EBV-containing CD4⁺ T cells, in contrast, did engraft on their own. This is the first report of an animal model of CAEBV and suggest that EBV-infected T or NK cells in CAEBV are not truly neoplastic but are dependent on CD4⁺ T cells for their proliferation in vivo.

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  IgG4-related disease is thought to show good prognosis because of positive responsiveness to corticosteroids. Increased long-term observations of IgG4-related disease have provided clinical data regarding the functional prognosis of organs. We analyzed the necessity for early intervention based on those findings and our own experience. It is important for the recovery and maintenance of salivary gland function to start corticosteroid treatment within 2 years after onset, and to maintain clinical remission in cases of IgG4-related dacryoadenitis and sialoadenitis (so-called Mikulicz's disease). Early intervention might be useful in cases of IgG4-related kidney disease because recovery of renal function is insufficient when estimated glomerular filtration before treatment is <60 ml/min. Corticosteroid treatment significantly suppresses relapse in patients with autoimmune pancreatitis showing a relatively high rate of spontaneous remission. Long-term observational studies have demonstrated the transformation of autoimmune pancreatitis into chronic pancreatitis presenting with pancreatic atrophy and stone formation. The treatment protocol and timing of initiation should thus be considered. Although organ dysfunction in IgG4-related disease proceeds more slowly than in conventional chronic inflammatory disorders, sustained IgG4-related lesions still cause accumulation of organ damage with expansion of fibrosis. Intervention as soon as possible would favorably impact IgG4-related disease, considering the side effects of treatments such as corticosteroids.

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  There are no effective treatments for fibrosis, an out-of-control wound-healing process in which excessive deposition of extracellular matrix (ECM) such as collagen, resulting in significant morbidity and mortality. Endostatin is a natural proteolytic fragment of collagen XVIII, which is known to possess potent antiangiogenic activity. Many clinical trials of endostatin have been conducted for anti-cancer therapy. In addition to antiangiogenic effects, recent studies have revealed that endostatin may suppress aberrant tissue remodeling and scarring. Neutralization of endogenous endostatin in rat myocardial infarction (MI) model worsened the outcomes of MI, indicating that endostatin may have protective role against left ventricular remodeling and heart failure after MI. Recently, we also reported inhibitory effects of peptides derived from endostatin on fibrosis. A peptide derived from the C-terminus of endostatin suppressed ECM production in fibroblasts in the presence of transforming growth factor-β (TGF-β), prevented TGF-β-induced dermal fibrosis ex vivo in human skin, and ameliorated skin and pulmonary fibrosis induced by bleomycin in vivo. The antifibrotic capacity was accompanied by reduced cell apoptosis and lower levels of lysyl oxidase and early growth response gene-1. Endostation may have the therapeutic potential for inhibiting fibrosis.

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  Giant cell arteritis (GCA) is a granulomatous arteritis and it occurs older (more than 50 years) individuals. As GCA frequently involves temporal artery, this disease had been called as temporal arteritis. However, except for the temporal artery, GCA affects branches of the carotid arteries, as well as aorta and its major branches preferentially. Thus, this arteritis is collectively called as GCA from the characteristic histological findings. We systematically introduce the clinical pictures of GCA in the first half of this article. Because affected arteries of GCA are different in each patient, some patients do not present with classical clinical features, such as headache and tenderness of temporal artery. Recently, there are several variant forms of GCA have been recognized. Certain subtypes demonstrate organ dysfunction, such as visual loss or peripheral neuropathy with minimal or absent classical and systemic manifestations. This form of GCA is referred to as occult GCA. On the other hand, other form of GCA presents with a systemic inflammatory syndrome in the absence of focal ischemic symptoms. This is referred to as silent or masked GCA. In the latter half of this article, we introduce two patients presenting with such atypical presentations. One could be diagnosed as occult GCA, and the other was diagnosed as silent GCA with large vessel type. GCA is a heterogenous disease with more than a single clinical picture. This article can provide considerations of the wide spectrum of presentation of this characteristic systemic arteritis.

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  We report a 33-year-old female who developed a movement disorder during maintenance therapy for systemic lupus erythematosus (SLE). She was diagnosed with SLE at the age of 25, and experienced an episode of SLE-associated hemophagocytic syndrome at age 27, which was successfully treated with intensive immunosuppressive therapy. In November 2012, during maintenance therapy with prednisolone (PSL) 5 mg/day and tacrolimus 0.5 mg/day, she developed acute-onset involuntary movements that were classified as chorea in combination with athetosis in her right limbs and right homonymous hemianopia, which subsided after about 1 h. Her laboratory tests on admission showed an elevated serum anti-double- stranded DNA antibody, positive serum anti-cardiolipin IgG, and an elevated IgG index in cerebrospinal fluid. Magnetic resonance imaging (MRI) showed no significant abnormality on admission, but an ischemic change in her left pallidum appeared on day 7. She was treated with a combination of high-dose corticosteroid, immunosuppressive agents (rituximab, cyclophosphamide, mycofenolate mofetil), antithrombotic therapy (heparin, cilostazol), and dopamine antagonists. Her symptoms remitted partially. Chorea in SLE is recognized as an anti-phospholipid-antibody-associated disorder. In our case, both immunological and ischemic mechanisms were thought to be involved.

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  Seronegative spondyloarthritis is strongly correlated to HLA-B27, and in the long term, it causes limitations to the movements of vertebral joints. In recent years, the numbers of patients diagnosed with axial spondyloarthritis have increased due to the widespread use of magnetic resonance imaging (MRI) for diagnostic imaging. We report the cases of 2 pediatric patients diagnosed with axial spondyloarthritis, and whose disease activity was successfully controlled using adalimumab. In case 1, the patient was a 15-year-old boy. The onset of the disease was marked by neck pain ; HLA-B27 was positive, and the MRI revealed sacroiliac arthritis. After being diagnosed with axial spondyloarthritis, he began receiving oral steroid therapy. Gradual recurrence was observed, and adalimumab treatment was initiated. In case 2, the patient was a 9-year-old boy. Bilateral pain was present in the shoulder joints, ankles, and knee joints. The patient was diagnosed with polyarticular juvenile idiopathic arthritis, and treatment using oral steroids, immunosuppressants and tocilizumab. The arthralgia disappeared, but at the age of 12 years, pain recurred in the sacroiliac joint and the Achilles tendon, the HLA-B27 was positive, and the MRI revealed sacroiliac arthritis. The condition was diagnosed as axial spondyloarthritis; adalimumab treatment was initiated. Adalimumab was effective in the treatment of axial spondylitis occurring in childhood.

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  A 35-year-old woman was admitted to a hospital because of fever, sore throat, cervical lymph node swelling, and skin rashes. Laboratory data revealed leukocytosis and elevated C-reactive protein (CRP), aspartate aminotransferase, alanine aminotransferase, and ferritin levels. No antinuclear antibody or rheumatoid factor was found. She was diagnosed as having adult-onset Still's disease (AOSD). Although treatment with high-dose glucocorticoid (GC) and cyclosporine (CsA) was started, her condition did not improve because of complication with severe hemophagocytic syndrome (HPS). Therefore, she was transferred to our hospital. Immediately after admission, GC pulse therapy was started again, and treatment with CsA was replaced with tacrolimus (TAC), in addition, plasma exchange therapy was initiated. After treatment, her condition improved. However, 1 week after plasma exchange was discontinued, her condition deteriorated slightly with a slight fever and elevation of CRP level. This indicated that her condition could not be managed with GC and TAC, therefore, tocilizumab (TCZ) was added to her treatment, which improved her symptoms and enabled reduction in GC and TAC doses. Although many reports have indicated that biological agents are effective for refractory AOSD, their safety and efficacy in cases of AOSD complicated with HPS are controversial as these agents may exacerbate HPS. Our present case indicates that TCZ can be used after control of the disease activity by plasma exchange against refractory AOSD complicated with HPS.

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