Antiphospholipid syndrome (APS) is well known as an autoimmune thrombotic syndrome with recurrent thromboses. In APS, thromboses occurs both artery and vein, and from large to micro vessels. In contrast, so called catastrophic antiphospholipid syndrome, CAPS, develops multiple thromboses at microvessels mainly within a few weeks and induces to poor prognosis. CAPS often occurs in patients with SLE or primary APS after a change of antithrombotic therapy, infection, and operation. Treatments for CAPS have not established although plasma exchange is carried out usually as well as intensive anticoagulation and immunosuppressive therapy. We treated with immunoadsorption plasmapheresis (IAPP) for 5 CAPS patients and they improved their clinical symptoms and ameliorated their titers of antiphospholipid antibodies. IAPP could be an useful treatment skill for CAPS and we have started prospective study.

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  Rheumatoid arthritis (RA) is an autoimmune disease that affects 1% of the population worldwide, however the pathogenic role remains elusive. Successful treatment with anti-CD20 therapy highlighted the importance of B cells in RA. Several antibodies (Abs) were identified from sera from RA patients such as rheumatoid factor, anti-CCP Abs, anti-glucose-6-phosphate isomerase Abs, anti-calpastatin Abs, anti-soluble gp130 Abs, anti-collagen type II Abs, etc. In this review, we will focus on the pathogenicity and production system of auto-Abs in RA, and also explain about recent advance from human study.

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  Iron is an essential trace element for human beings, but at the same time, it is toxic for us to generate free radicals because of its high reactivity to molecular oxygen. Therefore, iron metabolism is tightly regulated. Recently, hepcidin, a peptide hormone secreted by hepatocytes in response to iron overload and inflammation, has been identified to be a predominant negative regulator of iron absorption in the duodenum and iron release from tissue macrophages. The discovery of hepcidin unexpectedly revealed the link between iron metabolism and host defense. Here we describe recent advance in our understanding on the regulation of iron metabolism, including our findings and discuss its relationship to various diseases.

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  We investigated the role of galectin-9 (Gal-9) in maturation of dendritic cells (DC). Culture of immature DCs with exogenous Gal-9 markedly increased the surface expression of CD40, CD54, CD80, CD83, CD86, and HLA-DR in a concentration-dependent manner, although Gal-9 had no effect on differentiation of human monocytes into immature DCs. Gal-9-treated DCs secreted IL-12 but not IL-10, and they elicited the production of Th1 cytokines (IFN-γ and IL-2), but not that of the Th2 cytokines (IL-4 and IL-5) by allogeneic CD4⁺ T cells. These effects of Gal-9 on immature DCs were not essentially dependent on its lectin properties, given that they were only slightly inhibited by lactose. We further found that a Gal-9 mutant that lacks β-galactoside binding activity reproduced the above activities, and that an anti-Gal-9 mAb suppressed them. Gal-9 induced phosphorylation of the p38 MAPK and ERK1/2 in DCs, and an inhibitor of p38 signaling, but not inhibitors of signaling by either ERK1/2 or phosphatidylinositol 3-kinase, blocked Gal-9-induced up-regulation of costimulatory molecule expression and IL-12 production. These findings suggest that Gal-9 plays a role not only in innate immunity but also in acquired immunity by inducing DC maturation and promoting Th1 immune responses.

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  The efficacy and safety of MTX in active RA were evaluated based on patient medical records. The study population consisted of 460 patients with active RA who had received no prior MTX therapy and started it at our hospital between August 1998 and December 2003 (80 men and 380 women with a mean age of 59.3 years).
  After 24 weeks of MTX therapy, 61.3% of patients showed a 20% improvement, and 30.4% achieved a 50% improvement according to the ACR criteria. The cumulative rate of patients who continued MTX therapy for 48 weeks was 0.567.
  During the observation period, 260 patients (56.5%) experienced 304 adverse reactions. 52 patients (11.3%) discontinued treatment because of adverse reactions, and 10 patients (2.2%) died. The adverse reactions that occurred in at least 1% of patients were: abnormal hepatic function (31.7%), infection (6.1%), gastrointestinal symptoms (5.0%), stomatitis (3.9%), hematological abnormalities (3.5%), fracture (3.5%), malignant tumor (2.6%), interstitial pneumonia (2.0%), cerebrovascular or cardiovascular disorder (2.0%), headache (1.7%), eruption (1.3%), and alopecia (1.1%). Adverse reactions were more common in the elderly and patients with advanced stage disease.
  This study reaffirms the therapeutic benefit of MTX, but suggests that careful monitoring is of great importance.

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  Sjögren's syndrome is not one of the forty-five diseases included in the incurable disease treatment research project funded by the government. However, it is approved as a designated incurable disease for government funded treatment in Tokyo. The criteria of approval are based on diagnostic criteria revised in 1999. Complications and other factors are taken into consideration in the recognition standard established independently in Tokyo. In this study we examined the recognition standard of approval and their significance by analyzing the clinical questionnaires of patients with Sjögren's syndrome in Tokyo through 2003. The major objective of the recognition standard (2003) appears to have been the approval of subjects with severe Sjögren's syndrome with such conditions as advanced glandular involvement xerosis affecting their daily lives and visceral complications. However, examinations using biopsy, salivary gland scintigraphy, and contrast sialography can only be performed at an institution with appropriate facilities. For an approval process that is impartial and accomplished with ease, we believe that combinations of simple multiple tests should be considered as auxiliary items which could be substituted for the aforementioned examinations. In addition, future investigation is necessary to examine the high cost incurred in requiring findings within six months for an approval application, performing of annual invasive tests, and the validity of the process for determining the approved or unapproved status using the present clinical questionnaire profiles.

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  Indoleamine 2,3-dioxygenase (IDO), one of the enzymes of tryptophan catabolism, has been shown to play an essential role for successful pregnancy through the inhibition of allogenic fetus-induced T-cell proliferation, and interferon-γ (IFN-γ) induces the expression of IDO in CD14-positive (CD14⁺) cells. On the other hand, prolactin (PRL) is the hormone whose serum levels drastically elevate during pregnant period and is shown to play an important role in the early stages of pregnancy including implantation. However little is known about the physiological significance of the elevation of PRL from second trimester except for its fundamental role in lactation. Since receptors of PRL and IFN-γ share their structure and the signal transduction pathway, we hypothesized the potential crosstalk between two substances. To test this idea, we examined the effect of PRL on IFN-γ-induced IDO expression in CD14⁺ cells. CD14⁺ cells were prepared from peripheral blood of 12 healthy controls who had informed consent, and IDO expression and transcriptions were analyzed by flow cytometry and RT-PCR. The results showed that although PRL by itself had little effect on IDO expression, PRL significantly enhanced the IFN-γ-induced IDO expression at comparable to those seen in a pregnant period. In contrast, no such effect was observed with PRL at lower concentrations comparable to those seen in a non-pregnant period. These findings suggest that PRL may contribute to the maintenance of pregnancy by augmenting IFN-γ induction of IDO expression.

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  The patient was a 37-year-old female, who was diagnosed as having systemic lupus erythematosus (SLE) with nephrotic syndrome in 1991. SLE has been well controlled with a combination therapy of prednisolone, cyclophosphamide and mizoribine. She was admitted to our hospital for chest pain on exertion in June 2002. A grade of 2 systolic murmur was heard along left sternal border and edema in the both lower legs was present. Laboratory findings showed proteinuria and anemia. Serological tests did not show decrease in complements and was negative for autoantibodies including anti-ds-DNA antibody. The serum level of brain natriuretic peptide was 651 pg/ml. On chest X-ray films, there were no remarkable findings. An electrocardiogram showed a pattern of left ventricular hypertrophy with inverted T wave. The heart ultrasonic test recognized asymmetric hypertrophy of the septum, being more prominent in the apex, but there was no obstruction of the left ventricular outflow tract. Examination of an endomyocardial biopsy specimen showed disarray and mild hypertrophy of myocardial cells, which were compatible with hypertrophic cardiomyopathy (HCM), but there were no pathological findings specific for SLE. Additional treatment with β-blocker under a diagnosis of HCM resulted in a favorable response. Although 7 SLE patients with HCM have been reported, endomyocardial biopsy was not performed. There appears to have been a chance association between SLE and HCM, considering the clinical courses in reported cases and the pathological findings in our case.

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