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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. · 2.47 Impact Factor
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ABSTRACT: The transmembrane endoplasmic reticulum (ER) protein UNC93B plays an essential role in the normal response to signalling through intracellular Toll-like receptor (TLR)3, TLR7, TLR8 and TLR9. In the current study, we examined the level of UNC93B expression on peripheral B cells from patients with active SLE, and investigated any correlation with SLE pathogenesis.
Peripheral blood mononuclear cells (PBMCs) and B cells from 43 active SLE patients were analysed by quantitative RT-PCR to determine the precise levels of UNC93B mRNA. We also analysed UNC93B protein expression on B cells from SLE patients using immunoblotting.
The expression of UNC93B mRNA on PBMCs from active SLE patients was significantly higher than that of controls (P < 0.05). The intracellular expression level of UNC93B protein on CD20(+) B cells from active SLE patients was also higher than in the controls. Moreover, the expression of UNC93B on B cells from lupus patients correlated significantly with high titres of anti-dsDNA antibody (P < 0.05).
Up-regulation of the ER membrane protein UNC93B on human lupus B cells suggests that TLR9 and UNC93B play a partial role in the pathogenesis of SLE by inducing defective peripheral B-cell tolerance.
Rheumatology (Oxford, England) 02/2010; 49(5):876-81. · 4.24 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. · 2.47 Impact Factor
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Akira Katagiri,
Shinji Morimoto,
Yutaka Nakiri, Souichiro Nakano,
Akiko Mitsuo,
Jun Suzuki,
Hirofumi Amano,
Kazuhisa Nozawa,
Masanao Asano,
Yoshiaki Tokano,
Hiroshi Hashimoto,
Yoshinari Takasaki
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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. · 1.58 Impact Factor
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Souichiro Nakano,
Shinji Morimoto,
Jun Suzuki,
Akiko Mitsuo,
Yutaka Nakiri,
Akira Katagiri,
Kazuhisa Nozawa,
Hirofumi Amano,
Yoshiaki Tokano,
Hiroshi Hashimoto,
Yoshinari Takasaki
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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. · 2.47 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. · 1.58 Impact Factor
