Anti-tumor necrosis factor (anti-TNF) biologics are effective in the treatment of rheumatoid arthritis (RA); however, it is still not clear whether this treatment promotes the development of malignancies such as lymphoma. Human T-lymphotropic virus type 1 (HTLV-1), which is a causative agent of adult T-cell lymphoma (ATL), is prevalent in Japan. Many HTLV-1-positive patients with RA are assumed to exist; however, there have thus far been no reports on the effect of anti-TNF biologics on HTLV-1-positive patients. We analyzed the response to treatment with anti-TNF biologics and change of HTLV-1 markers in two cases of RA. The two cases showed no response based on the European League Against of Rheumatism response criteria 60-96 weeks after administration of anti-TNF biologics (infliximab and etanercept). No signs of ATL were observed and HTLV-1 markers, such as proviral load and clonality of HTLV-1-infected cells, showed no significant change in either of two cases. Therefore, treatment with anti-TNF biologics did not induce activation of HTLV-1, although the effect on RA was not as effective as in HTLV-1-negative patients in this limited study. Further long-term study with a greater number of patients is necessary to clarify the safety and efficacy of anti-TNF biologics in HTLV-1-positive patients with RA.

A 63-year-old woman presented to our hospital with fever, purpura and pain in both legs and died 4 days after admission. Her blood smear and skin biopsy showed cylinder-like bodies (20×120 μm). She was diagnosed to have monoclonal gammopathy (IgG, lambda type). An autopsy revealed cylinder-like bodies in the vasculature of various organs. We noted a proliferation of atypical plasma cells in her bone marrow, suggesting pre-existing myeloma. Crystalglobulinemia is a rare manifestation of hypergammaglobulinemia that can cause multiple embolisms of the small vessels, and this resulted in the patient's fulminant course. The identification of cylinder-like bodies in the peripheral blood may help in reaching a diagnosis in such cases.

Microparticles (MPs) are believed to play an important role in inflammatory diseases such as rheumatoid arthritis (RA). Leukocytapheresis (LCAP) is one of the options available for the treatment of RA. We analyzed the levels of MPs in RA, by flow cytometry, especially in relation to the effect of LCAP. Twenty female patients with RA were recruited into this study. Six of the 20 patients with RA further received LCAP. Plasma levels of platelet-derived MPs were high in patients with RA and are correlated with disease activity. LCAP significantly improved RA in all six patients. The numbers of platelet-derived MPs significantly decreased after the first session of LCAP, which was probably due to direct removal by LCAP. Mean numbers of platelet-derived MPs after four sessions of LCAP markedly decreased. The numbers of granulocyte-derived MPs, which are suggested to have an anti-inflammatory effect, were markedly increased after the first session of LCAP. These data suggest that removal of platelet-derived MPs and increase of granulocyte-derived MPs are novel mechanisms of LCAP as effective treatment in RA.

Objective. To investigate the response to and safety of anti-tumor necrosis factor (anti-TNF) therapy in human T lymphotropic virus type I (HTLV-I)-positive patients with rheumatoid arthritis (RA).Methods. Therapeutic response was evaluated in 10 HTLV-I-positive and 20 HTLV-I-negative patients with RA (sex and age matched) at 3 months after the beginning of anti-TNF therapy using the European League Against Rheumatism improvement criteria. As secondary end points, the discontinuation rate of anti-TNF therapy and its safety, especially the development of adult T cell leukemia (ATL), were evaluated over a 2-year period. Results. Significantly higher baseline levels of C-reactive protein (CRP) were observed in HTLV-I-positive patients than in HTLV-I-negative patients (P ‫؍‬ 0.0003). The response rate to anti-TNF therapy was lower in HTLV-I-positive patients than in HTLV-I-negative patients. The median CRP level, erythrocyte sedimentation rate, and Disease Activity Score in 28 joints at 3 months after anti-TNF treatment in HTLV-I-positive patients were significantly higher than in HTLV-Inegative patients (P ‫؍‬ 0.003, P ‫؍‬ 0.03, and P ‫؍‬ 0.003, respectively). The discontinuation rate due to insufficient response was significantly higher in HTLV-I-positive patients than in HTLV-I-negative patients (P ‫؍‬ 0.013). During the 2-year observation period, no patients developed ATL. Conclusion. These data suggest that HTLV-I-positive patients with RA had higher inflammation and greater resistance to anti-TNF treatment than HTLV-I-negative patients. Further study is necessary to determine whether HTLV-I infection should be measured when anti-TNF agents are administered to patients with RA, especially in areas were HTLV-I is endemic.

Few studies have specifically examined defective provirus in asymptomatic human T-lymphotropic virus Type 1 (HTLV-1) carriers and its relation to proviral DNA loads (PVLs). To assess the significance of defective provirus in asymptomatic carriers, we examined PVLs in peripheral blood mononuclear cells of 208 asymptomatic HTLV-1 carriers. The mean PVLs determined using primers for the pol region were less than that for the pX region in these carriers. Analysis of seven carriers with high PVLs for the pX region but lower PVLs for the pol region showed that four had single nucleotide polymorphisms of proviral genomes for the pol region and three had HTLV-1-infected cells with defective provirus. Three carriers with defective provirus showed high PVLs at their initial screens, and PVLs increased after a 10-to 12-year interval in two carriers. Southern blot assay showed clonal expansion of HTLV-1-infected cells, and the predominant clones changed during the observation period. These data suggest that although HTLV-1-infected cells with defective provirus may have a growth advantage, the predominant clones of HTLV-1-infected cells do not always survive for many years in asymptomatic carriers.

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Background: This study was undertaken to analyze the

Microparticles (MPs) are believed to play an important role in inflammatory diseases such as rheumatoid arthritis (RA). Leukocytapheresis (LCAP) is one of the options available for the treatment of RA. We analyzed the levels of MPs in RA, by flow cytometry, especially in relation to the effect of LCAP. Twenty female patients with RA were recruited into this study. Six of the 20 patients with RA further received LCAP. Plasma levels of platelet-derived MPs were high in patients with RA and are correlated with disease activity. LCAP significantly improved RA in all six patients. The numbers of platelet-derived MPs significantly decreased after the first session of LCAP, which was probably due to direct removal by LCAP. Mean numbers of platelet-derived MPs after four sessions of LCAP markedly decreased. The numbers of granulocyte-derived MPs, which are suggested to have an anti-inflammatory effect, were markedly increased after the first session of LCAP. These data suggest that removal of platelet-derived MPs and increase of granulocyte-derived MPs are novel mechanisms of LCAP as effective treatment in RA.