Pentraxin 3 (PTX3) is suggested to play important roles in the innate resistance against pathogens, regulation of inflammatory reactions, and clearance of apoptotic cells. PTX3 is the first long pentraxin identified. Long pentraxin shares a C-terminal pentraxin domain with the classical short pentraxin (C-reactive protein, serum amyloid P), but holds an unrelated N-terminal domain that is unique to the long pentraxin. While the short pentraxin is produced only in the liver, PTX3 is made by diverse types of cells, prominently endothelial cells and macrophage, in response to inflammatory signals. Unlike the short pentraxin, the expression of PTX3 in multiple types of tissue cells implies a mechanism for local amplification of innate resistance at the site of infection and inflammation. PTX3 plasma levels are very low in normal subjects but are rapidly increased by inflammatory conditions resulting from a wide range of diseased states, from infection to autoimmune and degenerative disorders. Critically ill patients show elevated circulating levels of PTX3 which are determined by the severity of the disease. Clinical evidence has demonstrated that the elevated PTX3 levels might be a useful early and sensitive marker for severely ill patients. Further studies will definitely be needed to deepen our understanding of PTX3.

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  Retinoid is a collective term for compounds which bind to and activate retinoic acid receptors (RARα, β, γ and RXRα, β, γ), members of nuclear hormone receptor superfamily. The most important endogeneous retinoid is all-trans-retinoic acid (ATRA) which is an RARα, β and γ ligand. ATRA and its mimics have been in clinical use for treatment of acute promyelocytic leukemia (APL) and some skin diseases. Many synthetic retinoids have been developed and attempts to improve their medicinal properties have been made. Among them, tamibarotene (Am80) is an RARα- and RARβ- specific (but RARγ- and RXRs-nonbinding) synthetic retinoid that is effective in the treatment of psoriasis patients and relapsed APL. Experimentally, this compound is also active in animal models of rheumatoid arthritis and experimental autoimmune encephalomyelitis. On this background, possible application of retinoids for the treatment of autoimmune diseases was discussed. In particular, Th1 dominant autoimmune diseases may be the targets of the retinoids.

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  The property of nucleosome in systemic lupus erythematosus (SLE) is reviewed. Nucleosome, complex of histone and DNA, is thought to have a pivotal role in pathogenesis of SLE. It is formed during apoptosis that is increased in peripheral lymphocytes of SLE. The concentration of nucleosome is elevated in SLE, probably related with disease activity. Nucleosome is speculated that the clearance from peripheral blood is decreased and that is modified by viral infection to become more immunogenic. Anti-nuleosome antibody is highly positive in majority of SLE, and is very specific for SLE except scleroderma and mixed connective tissue disease. This antibody is thought as a diagnostic marker and probably an activity marker for SLE. Anti-nucleosome antibody forms immune complex with nucleosome. As histone has strong positive charge, it is demonstrated that this nucleosome/anti-nucleosome complex is bound to negatively charged heparan sulfate of glomerular basement membrane in kidney. Then, complements bind to this antibody to generate lupus glomerulonephritis.
  Although main site of apoptosis in SLE is considered as lymphocytes, we experienced a case with SLE who had liver dysfunction with elevated soluble Fas ligand (sFasL) and apoptosis in her hepatocytes in the active stage of SLE. We measured serum sFasL, and found the relation of sFasL and liver involvement in active SLE. As major source of nucleosome should be apoptosis of lymphocytes in SLE, hepatocytes could be another candidate of apoptosis in some SLE.

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  The maintenance of genomic stability is an essential cellular function for a variety of well-coordinated regulation of biological activities of organisms, and a failure in its function results in the accumulation of mutations and/or abnormality in the induction of apoptosis, eventually leading to onsets of various diseases, including malignant tumors. DNA damage responses, in particular cell-cycle checkpoint regulation, play important roles in maintaining genomic integrity. In response to DNA damages induced by γ-irradiation, ultraviolet irradiation, various chemicals, or reactive oxygen species (ROS), intrinsic cell-cycle checkpoint machinery is rapidly activated to arrest cells at particular cell-cycle points, and during cell-cycle checkpoint arrest cells may try to repair damaged DNAs, and then re-start cell-cycle upon the completion of DNA repair. Alternatively, if the extents of DNA damage overwhelm the capacity of the cellular repair machinery, cells may undergo apoptosis to prevent the accumulation of mutations within the organisms. In this article, we will first explain about our current view of DNA damage responses, in particular cell-cycle checkpoint regulation, and summarize our knowledge of the relationships between abnormalities of genes involved in DNA damage responses and malignant tumors, including hematopoietic malignancies. We will also discuss a possible implication of DNA damage responses in autoimmune diseases, such as rheumatoid arthritis.

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  Pure red cell aplasia (PRCA) is a rare cause of anemia associated with SLE. We herein report a case presenting with SLE and PRCA. A 33-year-old woman, who had been suffering from photosensitivity, proteinuria, and pancytopenia, was diagnosed to have SLE. She showed normochromatic normocytic anemia. The serum level of haptoglobin was <10 mg/dl, and Direct Coombs' test was negative. Her reticulocyte count was 0.8%. Her clinical and laboratory features, except for anemia, had recovered in response to 50 mg/day of prednisolone. The serum level of haptoglobin had normalized, but the reticulocyte count remained low. The bone marrow findings revealed erythroid hypoplasia, and she was diagnosed to have PRCA complicated with SLE. No viral DNA of human parvovirus B19 in her bone marrow was detected. The anemia gradually improved following the further use of 50 mg/day prednisolone. In order to disclose the mechanism of PRCA in this patient, we examined the effects of her peripheral T lymphocytes on erythrogenesis, using erythroid colony-forming cells (ECFC) in her peripheral blood. When we co-cultured peripheral T cells and ECFC, her T cells inhibited erythroid colony formation in a dose dependent manner. Several reports have shown the presence of inhibitory factors in SLE patients' serum such as antibodies against erythroid progenitors or erythropoietin, while other reports have shown abnormal T cells that inhibit the growth of erythroid progenitors. Our study suggests that these inhibitory T cells may therefore have played an important role in the pathogenesis of this patient.

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  The patient was a 13-year-old girl. In August 2000, she presented with a fever, together with diarrhea, vomiting, arthralgia, nasal bleeding and malaise, and was examined by another physician. Because her platelet count was low, and there were positive reactions for anti-nuclear antibodies, anti-DNA antibodies and platelet-associated IgG, idiopathic thrombopenic purpura, and systemic lupus erythematosus (SLE) was suspected. From January 2001, when she caught measles, she reported abdominal pain, and urinalysis indicated urinary protein and occult blood, and the left kidney was found hydronephrotic. At the same time left ureter stenosis and dilatation were demonstrated. Symptoms were disappeared by hydration and treatment with NSAIDs, but 2 months later fever and erythematous patches seen on both cheeks led to the proper diagnosis of SLE, and she was admitted to our hospital. Intravenous pyelography revealed hydronephrosis on left kidney, constriction and dilatation of the left ureter, and intracystic endoscopy showed erythema at the orifice of the left ureter. The pathological examination indicated the presence of vasculitis, and finally lupus cystitis was diagnosed. Intravenous cyclophosphamide (IVCY)-pulse therapy was introduced to a total of 8 times over the period of a year, and maintenance therapy with predonisolone and azathioprin was also used. After completion of the IVCY-pulse therapy, the hydronephrosis and constriction of the ureter were disappeared. No side effects of IVCY-pulses were observed, and the patient is now in remission. We reported a case of childhood SLE complicated with lupus cystitis and successfully treated by IVCY-pulse therapy and maintenance predonisolone and azathioprin.

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  The subject was a 22-year-old woman who developed high fever and arthralgias and eruptions in the extremities around June 2005. She sought medical advice at a nearby dermatology clinic, where hepatic dysfunction was noted on blood testing. The patient was thus hospitalized the next day. Although CRP levels were significantly high, no sign of infection was observed and bone marrow cell differentiation was normal. Adult onset Still's disease was diagnosed based on the observation of persistent high fever >39°C, eruptions, increased leukocytes, pharyngeal pain, splenomegaly, hepatic dysfunction, negative autoantibody results from blood testing, and high serum ferritin levels. Administration of prednisolone 30 mg/day was initiated, but proved ineffective. Steroid pulse therapy was conducted, and the subject was transferred to our medical facility for continued treatment. Attempts were made to control the disease using combined steroid and cyclosporine administration ; but exacerbation of high serum ferritin levels and hepatic dysfunctions were observed, so a second course of steroid pulse therapy was conducted. Symptoms improved temporarily, but steroid levels were difficult to reduce. Cyclosporine was therefore replaced by methotrexate, and administration of infliximab was initiated. In the course of treatment, administration of a sulfamethoxazole/trimethoprim combination was initiated, but was discontinued due to suspicion of drug-induced hepatic injury. A second administration of infliximab was conducted in late August, and rapid improvements in clinical symptoms and abnormal test values was observed. However, high fever and headache developed suddenly in early September. Based on the results of spinal fluid testing, blood and spinal fluid cultures and MRI of the head, Listeria meningoencephalitis was diagnosed. Diplopia and impaired consciousness occurred during the disease course, and formation of a brain abscess was observed on imaging. However, symptoms were controlled by long-term combination administration of ampicillin and gentamicin. Administration of infliximab was discontinued for treatment of adult onset Still's disease, and steroid levels were reduced following double-membrane filtration plasma exchange. On follow-up, no relapse of symptoms or abnormalities in blood test values were observed, so the subject was discharged from our medical facility in December 2005. In treatment for rheumatic diseases, a dramatic improvement in treatment results for pathologies displaying tolerance against conventional treatments has been acquired with the development of biological drugs. However, opportunistic infections represent a serious problem, and appropriate preventative measures are required. The present report describes a case in which the subject was affected by Listeria meningoencephalitis during administration of infliximab for steroid-dependent adult Still's disease. Since listeriosis is one of the complications, along with tuberculosis, that warrants precautionary measures, this case is reported and discussed.

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