Y Tokano

Juntendo University, Tokyo, Tokyo-to, Japan

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Publications (85)195.6 Total impact

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    ABSTRACT: The relation between long term-prognosis and renal biopsy data or therapy were evaluated, and their contribution to remission was also considered. In total, 112 patients with new lupus nephritis who underwent renal biopsy and without other severe organ involvements were selected. These patients were divided into subgroups according to their renal biopsy data, and their clinical data were accumulated. Patients with World Health Organization (WHO) classification types III and IV had poor outcomes. Patients with mild lesions (WHO types I and II) had good outcomes when treated with low-dose steroid, while patients with severe lesions (WHO types III and IV) had better outcomes following medication with immunosuppressive agents. In particular, patients who received intravenous cyclophosphamide (IVCY) showed the best outcomes. Patients with WHO type III or IV classification without remission had poor outcomes, while those with complete remission had better outcomes. We conclude that renal biopsy data and course of therapy showed some relation in longterm prognosis, and the grade of remission was also related.
    Modern Rheumatology 01/2014; 9(2):135-145. DOI:10.1007/BF03041270 · 2.21 Impact Factor
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    ABSTRACT: B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are known to be crucial for B cell maturation and survival, and increased expression of these factors in various autoimmune diseases has been reported. Human B cells produce two IgA subclasses: IgA1 and IgA2, the latter being abundant in the distal intestine, saliva, colostrum and bronchial fluid. We investigated these parameters in patients with mixed connective tissue disease (MCTD) complicated by interstitial lung disease (ILD+), and compared them with those in MCTD patients without ILD (ILD-). Sixty-three MCTD patients were divided into two groups: 21 ILD+ patients and 42 ILD- patients. In each patient group we analyzed soluble BAFF/APRIL using ELISA, and IgA1 and IgA2 using double immunodiffusion. Furthermore, we analyzed BAFF-APRIL receptors, BCMA, BAFF-R and TACI, using flow cytometry. The ILD+ patients had significantly higher levels of BAFF/APRIL than the ILD- patients. There were significant correlations between BAFF/APRIL, BAFF/KL-6 and APRIL/KL-6. Although there was no significant inter-group difference in the serum IgA1 level, ILD+ patients had a significantly elevated IgA2 level in comparison with ILD- patients. Moreover, although there were no significant inter-group differences in the expression of BCMA, BAFF-R and TACI on B cells, the expression of BAFF-R was significantly decreased in the ILD+ patients. In recent years, relationships between BAFF/APRIL and IgA subclass have been reported. Our results suggest that an elevated level of BAFF/APRIL drives the maturation of B cells, subsequently leading to IgA2 class switching, and possibly to the development of ILD in patients with MCTD.
    Modern Rheumatology 11/2013; DOI:10.3109/14397595.2013.843748 · 2.21 Impact Factor
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    ABSTRACT: Systemic lupus erythematosus (SLE) is characterized by loss of B cell tolerance and by the presence of polyclonal B cell activation. Syndecan-1 (CD138) is expressed on plasma cells derived from B cells, and is suspected to play a role in SLE. We evaluated the level of soluble CD138 (sCD138) and cell surface expression of CD138 in patients with active SLE, and also examined correlations among the serum levels of BAFF, a proliferation-inducing ligand (APRIL), and CD138 in these patients. Peripheral blood samples were obtained from 22 SLE patients in an active disease state and 14 normal controls. The levels of serum sCD138, sBAFF, and sAPRIL were measured using ELISA, and cell surface CD138 was analyzed by flow cytometry. The levels of CD138 mRNA were analyzed by RT-PCR. Blood samples were obtained longitudinally when the patients were in an inactive disease state. The levels of circulating CD138, CD138 mRNA in PBMC, and the numbers of CD20(- )CD38(+)CD138(+) plasma cells were increased in patients with active SLE in comparison with normal controls. Furthermore, the serum sCD138 level in SLE patients was found to correlate with the proportion of CD20(- )CD38(+)CD138(+) plasma cells. On the other hand, patients with active SLE showed a reduced level of sCD138, and this was inversely correlated with the serum level of sAPRIL. These results suggest that sCD138 may be applicable as a surrogate marker of disease activity, and that syndecan-1/APRIL signaling may be a potential therapeutic target for patients with active SLE.
    Autoimmunity 02/2011; 44(5):357-62. DOI:10.3109/08916934.2010.545846 · 2.75 Impact Factor
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    ABSTRACT: FTY720 is a novel investigational agent targeting the sphingosine 1-phosphate (S1P) receptors with an ability to cause immunosuppression by inducing lymphocyte sequestration in lymphoid organs. Systemic lupus erythematosus (SLE) is refractory autoimmune disease characterized by the production of a wide variety of autoantibodies and immune complex (IC)-mediated lupus nephritis. Among several SLE-prone strains of mice, BXSB is unique in terms of the disease-associated monocytosis in periphery and the reduced frequency of marginal zone B (MZ B) cells in spleen. In the present study, we examined the effect of FTY720 on lupus nephritis of BXSB mice. FTY720 treatment resulted in a marked decrease in lymphocytes, but not monocytes, in peripheral blood, and caused relocalization of marginal zone B (MZ B) cells into the follicle in the spleen. These changes did not affect the production of autoantibodies, thus IgG and C3 were deposited in glomeruli in FTY720-treated mice. Despite these IC depositions, FTY720-treated mice showed survival advantage with the improved proteinuria. Histological analysis revealed that FTY720 suppressed mesangial cell proliferation and inflammatory cell infiltration. These results suggest that FTY720 ameliorates lupus nephritis by inhibiting the end-stage inflammatory process following IC deposition in glomeruli.
    Biochemical and Biophysical Research Communications 03/2010; 394(3):804-10. DOI:10.1016/j.bbrc.2010.03.078 · 2.28 Impact Factor
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    ABSTRACT: Patients with lupus nephritis receiving intravenous cyclophosphamide (IVCY) therapy were divided into groups according to their clinical course, and the long-term prognosis was evaluated. A total of 67 patients with lupus nephritis were enrolled and divided as follow into the following groups: Group A: patients with fresh nephritis, Group B: patients with relapse nephritis, Group C: patients with nephritis as a transition of the main clinical manifestation. IVCY (500 mg or 750 mg) was administered every month, and continued for two to more than six months. The rate of remission was 78%; group A revealed a significantly higher rate of remission as compared with the other groups. Although long-term remission was revealed in most patients, some patients in Group B demonstrated a decreased rate of remission. Concerning the total dose administered, there was no relation to prognosis; a high dose was not required, especially for patients in Group A. On the other hand, the combination of steroid pulse therapy with IVCY revealed a moderate relation to the increased rate of remission in Group A. However, this combination therapy was not related to the maintenance of remission. There was no adverse effect at late onset. The long-term prognosis of IVCY differed according to the patient's clinical course, and the result differed from those reported in other countries. Therefore, we should consider the clinical course and race specificity for the Japanese subject.
    Internal Medicine 01/2010; 49(9):823-8. DOI:10.2169/internalmedicine.49.2291 · 0.97 Impact Factor
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    ABSTRACT: Twenty patients with collagen diseases complicated with Pneumocystis pneumonia (PCP) were retrospectively examined in reference to the criteria for its protective therapy provided by the Ministry of Health Labor and Welfare. The breakdown of 20 patients was rheumatoid arthritis (RA) in 5 cases, systemic lupus erythematosus (SLE) in 5, dermatomyositis (DM) in 2, systemic scleroderma (SSc) in 1, mixed connective tissue disease (MCTD) in 1, Sjögren syndrome (SjS) in 1, polyarteritis nodosa (PN) in 3, rapidly progressive glomerulonephritis (RPGN) in 1, Schönlein-Henoch purpura in 1. Patients having interstitial pneumonia (IP) or renal dysfunction before acquiring PCP showed poor prognosis. High level of beta-D glucan was observed in all patients, and elevated levels of LDH and KL-6 were also characteristic of PCP. For the treatment of their own collagen diseases, high dose steroids had been given in 11 patients (55%), and immunosuppressive agents in 12 (60%), resulting in severe suppression of immune function in these patients. They were treated with Sulfamethoxazole/trimethoprim (ST) after Pneumocystis infection, however, 10 patients died and 8 of them died of respiratory failure in spite of high dose steroids. Nine patients fulfilled the criteria for PCP protective therapy provided by Ministry of Health Labor and Welfare, and 7 of them died of respiratory failure. The frequency of PCP remarkably decreased in our hospital after we had started the protective therapy with ST using the criteria, suggesting that it is effective for the protection of PCP. However, some patients who do not fulfill the criteria may acquire severe PCP.
    Japanese Journal of Clinical Immunology 09/2009; 32(4):256-62. DOI:10.2177/jsci.32.256
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    ABSTRACT: Psychiatric manifestations are relatively common in systemic lupus erythematosus (SLE) patients. Since there are factors causing psychiatric manifestations other than SLE, the diagnosis of lupus psychosis (LP) is often difficult. Previous studies disclosed that cerebrospinal fluid (CSF) IL-6 was elevated in SLE patients with neuropsychiatric manifestation. The current studies were therefore designed to examine the efficacy of CSF IL-6 in diagnosis of LP. Multicenter retrospective study was performed with 45 SLE patients who showed psychiatric manifestations between 1993 and 2000. The diagnosis of LP and psychosis due to causes other than SLE (non-LP) was confirmed by retrospective review of the clinical records. Thirty-two of the 45 patients were reconfirmed as LP in the retrospective study. Receiver operating characteristic curve analysis revealed that the sensitivity and specificity of CSF IL-6 for diagnosis of LP were 87.5% and 92.3%, respectively, at the cut-off value of 4.3 pg/ml. These results indicate that CSF IL-6 might be an effective measure in diagnosing LP, although exclusion of infectious meningoencephalitis and cerebrovascular accident is necessary.
    Clinical Rheumatology 08/2009; 28(11):1319-23. DOI:10.1007/s10067-009-1226-8 · 1.77 Impact Factor
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    ABSTRACT: Tyrosine kinase 2 (TYK2) is a type I interferon (IFN) signaling pathway gene and was previously reported to be a risk factor for systemic lupus erythematosus (SLE) in Caucasian populations. In order to test for its genetic association with SLE in a Japanese population, TYK2 single nucleotide polymorphisms (SNPs), rs2304256, rs12720270 and rs280519, were genotyped. A case-control association study was performed in a total of 411 Japanese SLE patients and 467 healthy controls. Linkage disequilibrium (LD) among TYK2 SNPs was examined. According to the data from 94 healthy controls, non-synonymous rs2304256 resulting in Val --> Phe substitution was revealed to be in a LD with rs12720270 and rs280519. Therefore, we further genotyped rs2304256 as a tag SNP in the full sample sets. As a result, no differences in genotype distribution and allelic frequencies of rs2304256 were found between SLE patients and healthy controls. In conclusion, TYK2 is not a genetic risk factor for SLE in a Japanese population. Our result suggests that there is an ethnic difference in the susceptibility genes for SLE.
    Modern Rheumatology 06/2009; 19(4):401-6. DOI:10.1007/s10165-009-0173-1 · 2.21 Impact Factor
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    ABSTRACT: Foxp3(+) CD4(+) regulatory T (T(reg)) cells play a pivotal role in the maintenance of dominant self tolerance. Understanding how the failures of immune control by T(reg) cells are involved in autoimmune diseases is important for the development of effective immunotherapies. In the present study, we analyzed the characteristics of endogenous T(reg) cells in (NZB x NZW) F1 (BWF1) mice, a murine model of systemic lupus erythematosus. Unexpectedly, T(reg) number and frequency in aged BWF1 mice with developing lupus nephritis were increased, not decreased, and in vitro suppressive activity in lymphoid organs was intact. In addition, T(reg) cells trafficked to target organs because cells were present in the kidney and lung. T(reg) cells of aged BWF1 mice exhibited altered localization within lymph organs, however, and an altered phenotype, with higher expression levels of chemokine receptors and activation markers, suggesting a highly activated cellular state. Notably, the expression levels of co-stimulatory molecules were also markedly enhanced in the T(reg) cells of aged BWF1 mice. Furthermore, T(reg) cells of BWF1 mice did not show any suppressive effects on antibody production in vitro. Taken together, we conclude that T(reg) cells in BWF1 mice are not predisposed to functional incompetence but rather are present in a highly activated state.
    American Journal Of Pathology 01/2009; 173(6):1682-92. DOI:10.2353/ajpath.2008.080314 · 4.60 Impact Factor
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    ABSTRACT: Proliferative lupus nephritis (PLN) is the common, severe, and important form of lupus nephritis. Recent report showed that T cells producing Interferon (IFN)gamma (Th1 cells) increased in patients with World Health Organization class IV. However, the relation between the increase of Th1 cells and the pathogenesis has been made unclear. The aim of this study was to examine the chemoattractant mechanism of Th1-producing cells and whether in vitro IFNgamma secretion from Th1-producing cells in PLN. The Th1:Th2 ratio in peripheral blood was measured by flow cytometry. The serum levels of IL-2, IFNgamma, IL-13, monocyte chemoattractant protein-1 (MCP-1) and IP-10 were determined by using enzyme-linked immunosorbent assay. In in vitro IFNgamma production assay, CD4(+)T cells co-cultured with IL-12 and/or IL-18. Th1:Th2 ratio in PLN was high and not correlated with the serum Th1 cytokine level. This Th1-producing cell tended to go toward the inflammatory lesion by low CD62L expression and chemokines. The level of MCP-1 and IP-10 in patients with PLN significantly increased. Lastly, in vitro IFNgamma production assay, patients with PLN CD4(+)T cells produced IFNgamma by the addition of IL-12 and IL-18, while CD4(+)T cells in normal controls did not produce. These findings suggest that combination of Th1 inducers and chemokine inhibition might be powerful threrapeutic approach in PLN.
    Autoimmunity 12/2008; 42(2):143-9. DOI:10.1080/08916930802438790 · 2.75 Impact Factor
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    ABSTRACT: The expression of CD25 or CD28 on T cells was examined in patients with rheumatic diseases associated with interstitial pneumonitis (IP), in order to investigate the conditions of CD4+CD25+ regulatory T cells and CD8+CD28- suppressor T cells. Fifty-five patients with various rheumatic diseases and 23 normal controls were enrolled. CD4+CD25+ T cells of patients with IP were significantly decreased in comparison with non-IP patients, and the ratio of CD8+CD28- T cells in patients with IP was significantly higher than that in non-IP patients or normal controls. These results for CD8+CD28- T cells were in accord with the decrease in CD8+CD28+ T cells, and may be related to activation-induced CD8+CD28+ T-cell death. Thus, the abnormality of CD4+CD25+ regulatory T cells may be related to the pathogenesis of IP, and the survival and activation of CD8+ T cells.
    Modern Rheumatology 07/2008; 18(6):562-9. DOI:10.1007/s10165-008-0090-8 · 2.21 Impact Factor
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    ABSTRACT: Toll-like receptor 9 (TLR9) is a pattern-associated receptor functioning in innate immunity that may be involved in the recognition of self-antigens and the production of pathogenic auto-antibodies. Therefore, we examined the expression of TLR9 in systemic lupus erythematosus (SLE) to determine whether TLR9 is involved in the production of pathogenic auto-antibodies. B cells were collected from patients with active SLE, and subjected to analysis of the TLR9 molecule using flow cytometry fluorescence activated cell sorting (FACS) and TLR9 mRNA by reverse-transcriptase polymerase chain reaction. SLE B cells were stimulated with CpG-ODN, and subsequent cytokine and anti-dsDNA antibody production was measured by enzyme-linked immunosorbent assay. The expression and mRNA level of TLR9 on B cells was up-regulated in SLE patients, and SLE disease activity index (SLEDAI) and CH50 were correlated with TLR9 expression on CD20+ B cells. Moreover, TLR9-CpG interaction enhanced the production of anti-dsDNA antibody and IL-10. The present study demonstrated that higher expression of TLR9 on peripheral blood B cells from patients with active SLE was significantly correlated with CH50 and SLEDAI to TLR9, and induced the production of anti-dsDNA antibody and IL-10 by TLR9-CpG ligation. These results suggest that an abnormality of innate immunity plays a crucial role in the pathology of SLE, and that blockade of CpG-TLR9 interaction may be a new therapeutic approach for SLE.
    Rheumatology (Oxford, England) 03/2008; 47(2):145-9. DOI:10.1093/rheumatology/kem327 · 4.44 Impact Factor
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    ABSTRACT: Recent studies have revealed new populations of T/B cells, including central/effector memory, follicular T cells and CXCR3+ or CXCR4+ B cells. In the present study, changes in these populations of CD4+ T cells were examined on the basis of the expression of CD62L, CCR7 and CXCR5 in patients with systemic lupus erythematosus (SLE) in relation to CCL21 and CXCL10. Changes in CXCR3+, CXCR4+ and CXCR5+ B cells were also examined. CD62L and various chemokine receptors were examined by flow cytometry analysis using monoclonal antibodies, and CCL21 and CXCL10 were examined by sandwich enzyme-linked immunosorbent assay. In patients with SLE, a decrease of naive T cells and an increase in the ratio of activated effector memory T cells were associated with an increase of CCL21 and CXCL10 in serum, although the correlation was not significant. An increase in the ratio of CXCR3+ B cells was also recognized. These results suggest that naive T cells are transferred to lymphoid tissue by CCL21, and that effector memory T cells are activated by CXCL10. It is also suggested that B cells responsive to follicular helper T cells tend to migrate to inflammatory tissue.
    Lupus 02/2008; 17(1):26-33. DOI:10.1177/0961203307085246 · 2.48 Impact Factor
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    ABSTRACT: We describe a female Japanese patient with concomitant hypocomplementemic urticarial vasculitis, Jaccoud's arthropathy and valvular heart disease. In 1996, she developed arthritis with swelling of both proximal interphalangeal joints and urticarial vasculitis on both arms that was resolved by administration of glucocorticoid (prednisolone 30 mg/day). Tests for antineutrophil cytoplasmic antibodies, antinuclear antibody and rheumatoid factor gave negative results. The findings of a skin biopsy examination were consistent with 'leukocytoclastic vasculitis'. During 10 years of observation, the patient manifested polyarthritis leading to progressive deformity of the joints of the hands and feet (without loss of cartilage or erosion of bone), persistent urticaria exacerbated by cold and accompanied by hypocomplementemia and progressive cardiac valvular disease with mitral valve regurgitation. There are only three reports described previously documenting five patients with this rare combination of manifestations.
    Lupus 02/2008; 17(9):837-41. DOI:10.1177/0961203308090113 · 2.48 Impact Factor
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    ABSTRACT: B cells in patients with rheumatoid arthritis (RA) are hyperactivated. Although B cell receptor signal transduction may be affected by various response regulators, CD22 plays an important role as a response regulator of B cells. Therefore, we investigated and examined CD22 expression on peripheral blood B cells of patients with RA. Thirty-two RA patients and 16 controls were enrolled in this study, and CD22 expressions on B cells were analyzed by flow cytometry. In patients with RA, CD22(+) B cells significantly decreased in comparison to the controls (ratio: P < 0.05). However, there was no correlation between this decrease and the clinical data. Interestingly, CD5(+) CD22(-) B cells significantly increased in RA patients. The decrease in CD22(+) B cells and increased in CD5(+)CD22(-) B cells play critical roles in the pathogenesis of RA mediated by the activation of B cells.
    Clinical Rheumatology 10/2007; 26(10):1721-3. DOI:10.1007/s10067-007-0665-3 · 1.77 Impact Factor
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    ABSTRACT: To determine whether B cell activating factor of the tumour necrosis factor family (BAFF) is involved in T cell-dependent B cell pathogenic autoantibody production in systemic lupus erythematosus (SLE). Peripheral blood mononuclear cells (PBMCs) from 23 SLE patients were analysed by flow cytometry to examine the intracellular expression of BAFF in CD4+ and CD8+ T cells and the surface expression of BAFF-receptor (R) and TACI on CD20+ B cells. Moreover, peripheral blood was used to determine the level of BAFF messenger RNA (mRNA) in CD4+ and CD8+ T cells and the level of BAFF-R mRNA in CD20+ B cells. Blocking of BAFF function with TACI-Ig measured anti-double-stranded DNA (dsDNA) antibodies by enzyme-linked immunosorbent assay (ELISA). CD4+ and CD8+ T cells from patients with active SLE expressed intracellular BAFF whereas those from normal subjects did not. BAFF-R and TACI were expressed on B cells from both normal controls and patients with active SLE and there was no significant difference. CD4+ and CD8+ T cells from SLE patients expressed BAFF mRNA whereas those from normal controls did not. Expression of BAFF-R mRNA in CD20+ B cells showed no significant difference between SLE patients and normal controls. TACI-Ig suppressed spontaneous in vitro T cell-dependent B cell anti-dsDNA antibodies production on active SLE with kidney involvement. BAFF may play a pathogenic role in SLE by stimulating T cell-dependent B cell autoantibodies production. Blockade of BAFF is a promising therapeutic approach for SLE especially in patients with kidney involvement.
    Rheumatology 08/2007; 46(7):1083-6. DOI:10.1093/rheumatology/kem097 · 4.44 Impact Factor
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    ABSTRACT: The significance of both the acceleratory and inhibitory functions of the CD72 molecule was investigated among patients with systemic lupus erythematosus (SLE) during modification of B cell differentiation. Expression of the CD72 molecule and mRNA on B cells was decreased in SLE with lupus nephritis, while CD100 expression on both CD4+ T cells and CD8+ T cells was not significant in comparison with the controls. When the relationship between CD72 expression and other B cell markers was examined, decreased expression of CD72 was associated with differences in the stage of differentiation. In patients with decreased expression of CD72, switching to IgG was evident, and the disease stage was started to severe. In patients with lupus nephritis, the decreased expression of CD72 was related to class switching on B cells, suggesting that CD72 is a useful marker for determining class switching of B cells in lupus nephritis.
    Autoimmunity 03/2007; 40(1):9-15. DOI:10.1080/08916930601118890 · 2.75 Impact Factor
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    ABSTRACT: Although it has been reported that the numbers of both CD4(-)CD8(-) and CD4(+) natural killer T (NKT) cells are selectively decreased in the peripheral blood of patients with rheumatic diseases, there have been no reports concerning a novel subpopulation of CD8(+) NKT cells. To examine whether CD161(+)CD8(+) T cells, which are closely related to CD8(+) NKT cells, are also decreased in patients with rheumatic diseases, we have investigated the expression of CD161, together with that of CD28, CD25 and CD62L, on T cells in the peripheral blood of these patients. The rheumatic diseases evaluated in this study were systemic lupus erythematosus (SLE) (n= 54), mixed connective-tissue disease (MCTD) (n= 15), systemic sclerosis (SSc) (n= 14), polymyositis/dermatomyositis (PM/DM) (n= 13) and rheumatoid arthritis (RA) (n= 24). Healthy donors were examined as controls (n= 18). The expression of CD161, CD28, CD25 and CD62L on T cells was analysed by flow cytometry. Both the frequency of CD161 expression on CD8(+) cells and the absolute number of CD161(+)CD8(+) cells were significantly decreased in patients with SLE, MCTD, SSc and PM/DM. Only the absolute number of CD161(+)CD8(+) T cells was significantly decreased in RA. CD161 expression on CD28(-)CD8(+) T cells was significantly decreased in SLE, MCTD and SSc. The absolute number of CD161(+)CD8(+)CD62L(-) T cells was significantly decreased in SLE, MCTD and SSc. Both the frequency and the absolute number of CD161(+)CD8(+) T cells were decreased in the peripheral blood of patients suffering from SLE, MCTD, SSc and PM/DM. This result suggests that there is also an abnormality of NKT cells in the CD8(+) population.
    Rheumatology 01/2007; 45(12):1477-84. DOI:10.1093/rheumatology/kel119 · 4.44 Impact Factor
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    ABSTRACT: B cells in patients with systemic lupus erythematosus (SLE) are hyperactivated and B-cell receptor signal transduction may be affected by various response regulators. CD19 and CD22 play a major role as regulators of B-cell response. Therefore, we examined CD19 and CD22 expressions on B cells of patients with SLE, and how they were related to disease activity. Thirty-one patients with active SLE were selected and enrolled in this study. Evaluation of CD19 and CD22 expressions on B cells was performed prior to and after treatments with flow cytometry analysis. Disease activity was determined according to the SLE disease activity index score. CD19 and CD22 expressions on B cells in SLE patients revealed no significant differences when compared with the controls. However, improvement of SLE was recognized among patients with an increased ratio of CD22-positive cells. Our results suggest that this balance is a useful marker for determining improvement of SLE disease activity, although the CD19/22 balance does not contribute to the pathogenesis of SLE.
    Modern Rheumatology 02/2006; 16(4):235-8. DOI:10.1007/s10165-006-0497-z · 2.21 Impact Factor
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    ABSTRACT: The relationship between clinical manifestations and prognosis was examined and evaluated among systemic lupus erythematosus (SLE) patients. A total of 542 patients with SLE were selected and divided into nine groups according to their main clinical manifestation at the time of initial diagnosis. The relationship between these clinical manifestations and long-term prognosis was evaluated in respect to the survival, remission, relapse rates, the development of a new clinical manifestation, and/or damage index. Patients with neuropsychiatric SLE (NPSLE), accompanied with acute confusional state/seizure disorder, cerebral vascular disease, or pneumonitis had poor survival rates with cause of death related to their major organ involvement. Patients with nephropathy or leukopenia had lower remission rates, and an increase in relapse rates was frequently recognized in patients with pneumonitis. Body damage (damage index) was higher in patients with lupus psychosis, pneumonitis, and/or arthritis. The translation of the main manifestations after diagnosis was confirmed in 64 patients (11.8%), and often observed in patients with autoimmune hemolytic anemia and arthritis. The majority of these manifestations were nephropathy, NPSLE, thrombocytopenia, and pneumonitis, and the prognosis of patients with nephropathy and thrombocytopenia as a new main manifestation had a poor outcome. The results of long-term prognosis in SLE greatly differed with respect to the initial clinical manifestation at the time of diagnosis.
    Modern Rheumatology 02/2005; 15(4):275-82. DOI:10.1007/s10165-005-0411-0 · 2.21 Impact Factor

Publication Stats

1k Citations
195.60 Total Impact Points


  • 1988–2014
    • Juntendo University
      • • Department of Medicine
      • • Department of Pathology and Oncology
      • • Division of Rheumatology
      • • Department of Internal Medicine
      Tokyo, Tokyo-to, Japan
  • 1995
    • University of California, Davis
      • Department of Plant Pathology
      Davis, CA, United States