Su-Jin Moon

Catholic University of Korea, Sŏul, Seoul, South Korea

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Publications (22)39.98 Total impact

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    ABSTRACT: Acute graft-versus-host disease (aGVHD) is a major cause of mortality in allogeneic bone marrow transplantation. Here, the diminishing effect of activator protein-1 (AP-1) blocking with a synthetic retinoid (SR11302) on the severity of aGVHD in a murine model was investigated. MHC-mismatched strain combinations were used in vivo: C57BL/6 (H-2k(b)) donors into lethally irradiated BALB/c (H-2k(d)) recipients. SR11302 inhibited alloreactive T cell response in a dose-dependent manner and negatively regulated STAT3 activation. AP-1 blocking in T cells inhibited the differentiation of Th1 and Th17. Conversely, Foxp3(+) regulatory T cells (Treg) population dramatically expanded. Transfer of SR11302-treated donor splenocytes into lethally irradiated recipients diminished the lethality and clinical severity of aGVHD. In line with these results, AP-1 blocking in donor splenocytes exhibited reduced Th17/Th1 population and enhanced in vivo Treg population. Beneficial Treg expanding property of SR11302 was associated with the induction of Foxp3 and STAT5 transcription factor where the inhibiting property of Th17 was achieved by suppressing the phosphorylated form of STAT3 and enhancing SOCS3. Conclusively, the preventive potential of AP-1 inhibitor in aGVHD may be accomplished by altering CD4(+) T cell differentiation through modulating transcription factors.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 05/2014; · 3.15 Impact Factor
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    ABSTRACT: Graft-versus-host disease (GVHD) caused by transplanted donor T cells remains the major obstacle of allogeneic bone marrow transplantation (BMT). Previous reports have suggested that IL-17-producing helper T (Th17) cells mediate the development of acute GVHD (aGVHD). Protein inhibitor of activated STAT3 (PIAS) inhibits the activity of the transcription factor STAT3, which is a pivotal transcription factor for Th17 differentiation. To elucidate whether PIAS3 could inhibit the development of aGVHD, pcDNA-PIAS3 or mock vector was administered in a murine model of aGVHD by intramuscular injection and subsequent electroporation. The results demonstrated that PIAS3 overexpression by pcDNA-vector administration significantly attenuated the clinical severity and histopathological severities of aGHVD involving the skin, liver, intestine, and lung. Additionally, the STAT3 activities in aGVHD target organs were suppressed by PIAS3 overexpression. Furthermore, phosphorylated (p) STAT3 activity in the spleen was profoundly attenuated in PIAS3-overexpressing GVHD mice. Interestingly, flow cytometric analysis demonstrated that the populations of CD21(high)CD23(low) marginal zone B cells were dramatically expanded in PIAS3-overexpressing mice. PIAS3-induced inhibition of aGVHD was largely related to the downregulation of Th1 and Th17 and the upregulation of Th2 and Treg populations. Both populations of pSTAT3(Tyr705)-expressing Th17 cells and B cells were significantly reduced in the spleens of PIAS3-overexpressing mice, whereas pSTAT5 activity was increased. In addition to CD4(+)CD25(+)Foxp3(+) Treg cells, the populations of CD8(+)CD25(+)Foxp3(+) Treg cells were also expanded by treatment with PIAS3. These data suggest the therapeutic potential of PIAS3 in the development of aGVHD through reciprocal regulation of Th17/Treg lineages.
    Immunology letters 04/2014; · 2.91 Impact Factor
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    ABSTRACT: Rebamipide, a gastroprotective agent, has the ability to scavenge reactive oxygen radicals. Increased oxidative stress is implicated in the pathogenesis of rheumatoid arthritis (RA). We undertook this study to investigate the impact of rebamipide on the development of arthritis and the pathophysiologic mechanisms by which rebamipide attenuates arthritis severity in a murine model of RA. Collagen-induced arthritis (CIA) was induced in DBA/1J mice. Anti-type II collagen antibody titers and interleukin-17 (IL-17) levels were determined using enzyme-linked immunosorbent assay. The expression of transcription factors was analyzed by immunostaining and Western blotting. Frequencies of IL-17-producing CD4+ T cells (Th17 cells) and CD4+CD25+FoxP3+ Treg cells were analyzed by flow cytometry. Rebamipide reduced the clinical arthritis score and severity of histologic inflammation and cartilage destruction in a dose-dependent manner. The joints isolated from rebamipide-treated mice with CIA showed decreased expression of nitrotyrosine, an oxidative stress marker. Rebamipide-treated mice showed lower circulating levels of type II collagen-specific IgG, IgG1, and IgG2a. Whereas the number of Th17 cells in spleens was decreased in rebamipide-treated mice with CIA, a significant increase in the number of Treg cells in spleens was observed. In vitro, rebamipide inhibited Th17 cell differentiation through STAT-3/retinoic acid receptor-related orphan nuclear receptor γt and reciprocally induced Treg cell differentiation through FoxP3. Rebamipide increased Nrf2 nuclear activities in murine CD4+ T cells and LBRM-33 murine T lymphoma cells. Heme oxygenase 1 (HO-1) expression in the spleens was markedly increased in rebamipide-treated mice. The inhibitory effects of rebamipide on joint inflammation are associated with recovery from an imbalance between Th17 cells and Treg cells and with activation of an Nrf2/HO-1 antioxidant pathway.
    Arthritis & rheumatology (Hoboken, N.J.). 04/2014; 66(4):874-85.
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    ABSTRACT: Osteoarthritis (OA) is a degenerative joint disease characterized by a progressive loss of cartilage. And, increased oxidative stress plays a relevant role in the pathogenesis of OA. Ursodeoxycholic acid (UDCA) is a used drug for liver diseases known for its free radical-scavenging property. The objectives of this study were to investigate the in vivo effects of UDCA on pain severity and cartilage degeneration using an experimental OA model and to explore its mode of actions. OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA) to the knee. Oral administration UDCA was initiated on the day of MIA injection. Limb nociception was assessed by measuring the paw withdrawal latency and threshold. Samples were analyzed macroscopically and histologically. Immunohistochemistry was used to investigate the expression of interleukin-1β (IL-1β), IL-6, nitrotyrosine and inducible nitric oxide synthase (iNOS) in knee joints. UDCA showed an antinociceptive property and attenuated cartilage degeneration. OA rats given oral UDCA significantly exhibited a decreased number of osteoclasts in subchondral bone legion compared with the vehicle-treated OA group. UDCA reduced the expression of IL-1β, IL-6, nitrotyrosine and iNOS in articular cartilage. UDCA treatment significantly attenuated the mRNA expression of matrix metalloproteinase-3 (MMP-3), -13, and ADAMTS5 in IL-1β-stimulated human OA chondrocytes. These results show the inhibitory effects of UDCA on pain production and cartilage degeneration in experimentally induced OA. The chondroprotective properties of UDCA were achieved by suppressing oxidative damage and inhibiting catabolic factors that are implicated in the pathogenesis of cartilage damage in OA.
    Immune Network 02/2014; 14(1):45-53.
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    ABSTRACT: Graft-versus-host disease (GVHD) caused by transplanted donor T cells remains the major obstacle of allogeneic bone marrow transplantation (BMT). Previous reports have suggested that IL-17-producing helper T (Th17) cells mediate the development of acute GVHD (aGVHD). Protein inhibitor of activated STAT3 (PIAS) inhibits the activity of the transcription factor STAT3, which is a pivotal transcription factor for Th17 differentiation. To elucidate whether PIAS3 could inhibit the development of aGVHD, pcDNA-PIAS3 or mock vector was administered in a murine model of aGVHD by intramuscular injection and subsequent electroporation. The results demonstrated that PIAS3 overexpression by pcDNA-vector administration significantly attenuated the clinical severity and histopathological severities of aGHVD involving the skin, liver, intestine, and lung. Additionally, the STAT3 activities in aGVHD target organs were suppressed by PIAS3 overexpression. Furthermore, phosphorylated (p) STAT3 activity in the spleen was profoundly attenuated in PIAS3-overexpressing GVHD mice. Interestingly, flow cytometric analysis demonstrated that the populations of CD21highCD23low marginal zone B cells were dramatically expanded in PIAS3-overexpressing mice. PIAS3-induced inhibition of aGVHD was largely related to the downregulation of Th1 and Th17 and the upregulation of Th2 and Treg populations. Both populations of pSTAT3Tyr705-expressing Th17 cells and B cells were significantly reduced in the spleens of PIAS3-overexpressing mice, whereas pSTAT5 activity was increased. In addition to CD4+CD25+Foxp3+ Treg cells, the populations of CD8+CD25+Foxp3+ Treg cells were also expanded by treatment with PIAS3. These data suggest the therapeutic potential of PIAS3 in the development of aGVHD through reciprocal regulation of Th17/Treg lineages.
    Immunology Letters. 01/2014;
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    ABSTRACT: Acute graft-versus-host disease (aGVHD) is a major cause of mortality in allogeneic bone marrow transplantation. Here, the diminishing effect of activator protein-1 (AP-1) blocking with a synthetic retinoid (SR11302) on the severity of aGVHD in a murine model was investigated. MHC-mismatched strain combinations were used in vivo: C57BL/6 (H-2kb) donors into lethally irradiated BALB/c (H-2kd) recipients. SR11302 inhibited alloreactive T cell response in a dose-dependent manner and negatively regulated STAT3 activation. AP-1 blocking in T cells inhibited the differentiation of Th1 and Th17. Conversely, Foxp3+ regulatory T cells (Treg) population dramatically expanded. Transfer of SR11302-treated donor splenocytes into lethally irradiated recipients diminished the lethality and clinical severity of aGVHD. In line with these results, AP-1 blocking in donor splenocytes exhibited reduced Th17/Th1 population and enhanced in vivo Treg population. Beneficial Treg expanding property of SR11302 was associated with the induction of Foxp3 and STAT5 transcription factor where the inhibiting property of Th17 was achieved by suppressing the phosphorylated form of STAT3 and enhancing SOCS3. Conclusively, the preventive potential of AP-1 inhibitor in aGVHD may be accomplished by altering CD4+ T cell differentiation through modulating transcription factors.
    01/2014;
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    ABSTRACT: Interleukin 34 (IL-34) is a recently discovered cytokine that binds macrophage colony-stimulating factor (M-CSF) receptor. Rheumatoid arthritis (RA) is characterized by increased osteoclastogenesis. To identify the significance of IL-34 in RA, the IL-34 concentration was measured in serum and synovial fluid (SF). IL-34 concentrations were measured in serum from patients with RA (n = 113), patients with osteoarthritis (OA; n = 56), and controls (n = 36), and in SF isolated from patients with RA (n = 36) or OA (n = 24). Correlations between serum IL-34 levels and clinical features in RA were assessed. The levels of IL-1β, IL-6, IL-17α, interferon-γ-induced protein 10, receptor activator of nuclear factor κB ligand (RANKL), and Dickkopf-1 were also measured. Patients with RA had a higher mean serum level of IL-34 than did patients with OA and controls (188.0 ± 550.3, 36.6 ± 38.0, and 49.1 ± 78.5 pg/ml, respectively). Similarly, SF IL-34 concentration was higher in patients with RA than in those with OA. IL-34 levels were positively associated with IL-6 levels in serum from patients with RA and OA. SF IL-34 concentration correlated significantly with IL-6 and RANKL levels only in RA. The serum level of IL-34 was not correlated with systemic osteoporosis and radiographic joint damage in RA. IL-34 levels in the serum from patients with RA were positively correlated with rheumatoid factor and anticyclic citrullinated peptide antibody titers (r = 0.282 and 0.491, respectively). Circulating IL-34 levels in RA correlated with autoantibody production. Further investigations of localized and systemic effects of IL-34 are warranted to elucidate RA pathogenesis.
    The Journal of Rheumatology 09/2013; · 3.26 Impact Factor
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    ABSTRACT: Bone destruction and inflammation are closely linked. Cytokines play an important role in inflammatory bone destruction by upregulating the receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL). The direct role of cytokines that act in a non-RANKL-dependent manner has yet to be elucidated. The aim of this study was to investigate the direct osteoclastogenic properties of inflammatory cytokines at different time-points of osteoclastogenesis. Mouse bone marrow macrophages were stimulated with the macrophage colony-stimulating factor (M-CSF) and various concentrations of RANKL. Inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-17 and IL-23, were added to the culture system of osteoclastogenesis. Two time-points of cytokine treatment were set. The 'early' effect of each cytokine was investigated at the time of first RANKL treatment, whereas the 'late' effect was investigated 48 h after the first RANKL challenge. Osteoclast differentiation and function were assessed using an osteoclast marker [tartrate-resistant acid phosphatase (TRAP)] and by visualization of pit formation. A permissive level of RANKL was required for cytokine-associated osteoclastogenesis in all experiments. In the M-CSF/RANKL monocellular culture system, IL-1β enhanced and IL-6 decreased osteoclast formation in a dose-dependent manner, regardless of temporal differences. Other cytokines showed various responses according to the phase of osteoclast maturation and the concentration of each cytokine and RANKL. Furthermore, luciferase assays showed that both IL-1β and RANKL activated the NF-κB signaling pathway. Collectively, our data revealed that targeting IL-1β may be a promising strategy to inhibit inflammation-associated bone destruction and osteoporosis.
    International Journal of Molecular Medicine 04/2013; 31(4):769-77. · 1.96 Impact Factor
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    ABSTRACT: Abstract Purpose: To determine whether the frequencies of specific killer cell immunoglobulin-like receptors (KIR) genotypes are associated with the incidence of uveitis in ankylosing spondylitis (AS) and Behçet disease (BD). Methods: The authors analyzed the frequency of 16 KIR genes in Koreans with either AS (110 patients, all HLA-B27-positive) or BD (86 patients), using polymerase chain reaction sequence-specific oligonucleotide probing. Results: The frequency of the inhibitory receptor KIR3DL1 was lower in AS patients affected by uveitis than that in the general population (p < 0.05). The frequency of the KIR3DL1(-)/2DS3(-) was significantly higher in AS patients with uveitis (odds ratio = 9.306, p = 0.007). Conclusions: The study suggests that KIR3DL1 might associate with the resistance to AS-associated uveitis by influencing natural killer cell activity.
    Ocular immunology and inflammation 04/2013; 21(2):135-143. · 0.72 Impact Factor
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    ABSTRACT: We aimed to quantify periarticular osteoporosis and investigate its significance in 45 patients with rheumatoid arthritis (RA) and 106 controls. Dual-energy X-ray absorptiometry (DXA) was used to determine the ratio of shaft to periarticular bone mineral density (BMD) as an index of periarticular demineralization. Periarticular osteoporosis was measured by conventional radiography. The BMDs of shaft and periarticular regions in eight designated areas on proximal phalanges were quantified. Clinical variables were examined to identify risk factors for periarticular osteoporosis. The assessment of periarticular osteoporosis on X-ray images reached a moderate degree of interobserver agreement among four physicians (ĸ = 0.47). For BMD quantification, we designed three types of mathematical formulae: the ratio of shaft to periarticular BMD, the mean of the ratios, and the ratio of the sums. These ratios were significantly higher in the patients with early RA (disease duration ≤ 3 yr) than in controls (P < 0.01). The findings were not as distinctive in patients with established RA. Body mass index, cumulative dose of corticosteroid, and C-terminal telopeptide were correlated with BMD ratios. Conclusively, DXA-assisted localized quantification and BMD ratio calculations are feasible for assessing periarticular demineralization. Periarticular osteoporosis is a relatively distinctive feature of early RA.
    Journal of Korean medical science 02/2013; 28(2):287-94. · 0.84 Impact Factor
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    ABSTRACT: Osteoarthritis (OA) is a degenerative joint disease characterized by the progressive loss of articular cartilage and chronic pain. Although cyclooxygenase-2 (COX-2) inhibitors such as celecoxib are recommended to patients at high risk of gastrointestinal (GI) adverse events, COX-2 inhibitors do not completely prevent GI adverse events. Rebamipide, a gastroprotective agent, has anti-inflammatory properties and acts as an oxygen radical scavenger. The aim of this study was to investigate the in vivo effects of coadministration of rebamipide and celecoxib in an OA rat model. OA was induced by intra-articular injection of monosodium iodoacetate. Oral administration of rebamipide was initiated on the day of OA induction. In this study, rebamipide showed antinociceptive properties and attenuated cartilage degeneration. Rebamipide reduced the expression of matrix metalloproteinase 13, interleukin-1β, inducible nitric oxide synthase, and nitrotyrosine in OA cartilage. OA rats treated with celecoxib in combination with rebamipide demonstrated a higher pain threshold than those treated with monotherapy. Histological examination also showed that the joints from OA animals treated with combination therapy demonstrated less cartilage damage than those of animals treated with monotherapy. We showed that the potential benefit of combination therapy with celecoxib and rebamipide on pain and cartilage degeneration in OA.
    Archives of Pharmacal Research 01/2013; · 1.54 Impact Factor
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    ABSTRACT: Grape seed proanthocyanidin extract (GSPE) is a natural flavonoid that exerts anti-inflammatory properties. Obesity is an inflammatory condition and inflammatory cells and their secretion of pro-inflammatory molecules contribute to the pathogenesis of obesity. Rheumatoid arthritis (RA) is a chronic autoimmune disease that is characterized by inflammation of joints lined by synovium. Previously, we demonstrated that obesity augmented arthritis severity in collagen induced arthritis (CIA), a murine model of human RA. Here, we investigated whether oral administration of GSPE showed antiobesity and anti-arthritic effects in high-fat diet-induced obese (DIO) mice and in obese CIA mice, respectively. The pathophysiologic mechanisms by which GSPE attenuates weight gain and arthritis severity in vivo were also investigated. In DIO mice, GSPE administration significantly inhibited weight gain, reduced fat infiltration in liver and improved serum lipid profiles. The antiobesity effect of GSPE was associated with increased populations of regulatory T (Treg) cells and those of decreased Th17 cells. Decrease of Th17 cells was associated with significant inhibition of their key transcriptional factors, pSTAT3(Tyr705) and pSTAT3(Ser727). On the contrary, GSPE-induced Treg induction was associated with enhanced pSTAT5 expression. To identify the anti-arthritis effects of GSPE, GSPE was given orally for 7 weeks after type II collagen immunization. GSPE treatment significantly attenuated the development of autoimmune arthritis in obese CIA model. In line with DIO mice, GSPE administration decreased Th17 cells and reciprocally increased Treg cells by regulating STAT proteins in autoimmune arthritis model. The expressions of pro-inflammatory cytokines and nitrotyrosine in synovium were significantly inhibited by GSPE treatment. Taken together, GSPE functions as a reciprocal regulator of T cell differentiation - suppression of Th17 cells and induction of Tregs in both DIO and obese CIA mice. GSPE may act as a therapeutic agent to treat immunologic diseases related with enhanced STAT3 activity such as metabolic disorders and autoimmune diseases.
    PLoS ONE 01/2013; 8(11):e78843. · 3.73 Impact Factor
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    ABSTRACT: In this study we examined the in vivo and in vitro effects and mechanisms of action of curcumin on the development of acute graft-versus-host disease (GVHD) using a murine model. Mixed lymphocyte reactions were used to determine the in vitro effects of curcumin. Treatment with curcumin attenuated alloreactive T cell proliferation and inhibited the production of interferon (IFN)-γ and interleukin (IL)-17. In a murine acute GVHD model, transplantation of curcumin-treated allogeneic splenocytes into irradiated recipient mice significantly reduced the clinical severity scores of acute GVHD manifested in the liver, skin, colon and lung as compared with animals receiving vehicle-treated splenocytes. c-Fos and c-Jun expression levels in the skin and intestine, which are major target organs, were analyzed using immunohistochemical staining. Expression of both proteins was reduced in epithelial tissues of skin and intestine from curcumin-treated GVHD animals. The IFN-γ-expressing CD4(+) splenocytes and IFN-γ-expressing lymph node cells were dramatically decreased in curcumin-treated mice. In contrast, CD4(+)Foxp3(+) splenocytes were increased in the curcumin-treated acute GVHD animals. Flow cytometric analysis revealed that animals transplanted with curcumin-treated allogeneic splenocytes showed increased populations of CD4(+) regulatory T cells (Tregs) as well as CD8(+) Treg cells, compared to animals administered vehicle-treated splenocytes. Curcumin-treated acute GVHD animals could have a change in B cell subpopulations. In the present study, we investigated the efficacy and mechanism of action of curcumin treatment against acute GVHD. The acute GVHD mice administered with curcumin-treated splenocytes showed significantly reduced severity of acute GVHD. Curcumin exerted in vivo preventive effects on acute GVHD by reciprocal regulation of T helper 1 (Th1) and Treg (both CD4(+) and CD8(+) Treg) cell lineages as well as B cell homeostasis.
    PLoS ONE 01/2013; 8(6):e67171. · 3.73 Impact Factor
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    ABSTRACT: Interleukin (IL)-27 is a novel cytokine of the IL-6/IL-12 family that has been reported to be involved in the pathogenesis of autoimmune diseases and has a pivotal role as both a pro- and anti-inflammatory cytokine. We investigated the in vivo effects of IL-27 on arthritis severity in a murine collagen-induced arthritis (CIA) model and its mechanism of action regarding control of regulatory T (Tregs) and IL-17-producing T helper 17 (Th17) cells. IL-27-Fc-treated CIA mice showed a lower severity of arthritis. IL-17 expression in the spleens was significantly decreased in IL-27-Fc-treated CIA mice compared with that in the CIA model. The Th17 population was decreased in the spleens of IL-27-Fc-treated CIA mice, whereas the CD4(+)CD25(+)Foxp3(+) Treg population increased. In vitro studies revealed that IL-27 inhibited IL-17 production in murine CD4(+) T cells, and the effect was associated with retinoic acid-related orphan receptor γT and signal transducer and activator of transcription 3 inhibition. In contrast, fluorescein isothiocyanate-labeled forkhead box P3 (Foxp3) and IL-10 were profoundly augmented by IL-27 treatment. Regarding the suppressive capacity of Treg cells, the proportions of CTLA-4(+) (cytotoxic T-lymphocyte antigen 4), PD-1(+) (programmed cell death protein 1) and GITR(+) (glucocorticoid-induced tumor necrosis factor receptor) Tregs increased in the spleens of IL-27-Fc-treated CIA mice. Furthermore, in vitro differentiated Treg cells with IL-27 exerted a more suppressive capacity on T-cell proliferation. We found that IL-27 acts as a reciprocal regulator of the Th17 and Treg populations in CD4(+) cells isolated from healthy human peripheral blood mononuclear cells (PBMCs), as well as from humans with rheumatoid arthritis (RA) PBMCs. Our study suggests that IL-27 has the potential to ameliorate overwhelming inflammation in patients with RA through a reciprocal regulation of Th17 and Treg cells.
    Experimental & molecular medicine. 01/2013; 45:e46.
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    ABSTRACT: OBJECTIVES: The present paper aims at identifying the predictors of end-stage renal disease (ESRD) and at determining the long-term outcome of ESRD patients according to renal replacement modality in Korean patients with lupus nephritis (LN). METHODS: Between 1985 and 2010, 321 Korean patients with LN were enrolled in this study. We analysed the clinical and laboratory indices, the treatment responses and the biopsy findings. The events of interest were estimated by the Kaplan-Meier method and the risk factors were assessed by univariate and multivariate Cox proportional hazards regression analyses. RESULTS: The median follow-up time after the diagnosis of LN was 84 months. During follow-up, twenty-nine patients evolved to ESRD. Renal survival rate at 5 and 10 years after LN onset was 95.9% and 91.1%, respectively. Deteriorated renal function (estimated glomerular filtration rate <60 ml/min/1.73m2) at LN onset (hazard ratio: 9.223) was found to be an independent risk factor for the development of ESRD. Recurrence of lupus nephritis in renal allograft and flare-ups of lupus activity were not observed among the patients undergoing kidney transplantation (KT) (n=11). In contrast, those with maintenance dialysis (n=18) developed 13 episodes of lupus flare in 10 patients and 5 died of either infection (n=2) or lupus flare (n=3). CONCLUSIONS: The impaired renal function at baseline is an independent predictor of ESRD in Korean patients with LN. The benefits of KT on the control of lupus activity and survival should be emphasised.
    Clinical and experimental rheumatology 08/2012; · 2.66 Impact Factor
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    ABSTRACT: Disease progression of ankylosing spondylitis has been considered irreversible. However, we report a case of spontaneous regression of syndesmophyte development following allogeneic peripheral blood stem cell transplantation in a patient with acute myeloid leukemia, who was also diagnosed as having ankylosing spondylitis. To the best of our knowledge, this is the first case report presenting the partial radiologic regression of syndesmophytes. A 39-year-old man with active ankylosing spondylitis achieved clinical remission and partial radiological regression of cervical spine syndesmophytes following a peripheral blood stem cell transplantation for acute myeloid leukemia. Our patient received an allogeneic peripheral blood stem cell transplantation following a pre-transplantation conditioning regimen of total body irradiation and cyclophosphamide. The donor was a human leukocyte antigen-matched 29-year-old man. Our patient has remained asymptomatic and has received no medication for ankylosing spondylitis for nearly three years. Several explanations are proposed for the regression of syndesmophytes and clinical improvement in active ankylosing spondylitis observed in our patient, including changes in bone remodeling and immune reconstitution following stem cell transplantation, the effect of immunosuppressive agents, or fluctuation in the natural course of ankylosing spondylitis although further studies are required. The regression of syndesmophytes in ankylosing spondylitis in this case raises the possibility that stem cell transplantation might contribute to the development of a novel therapeutic strategy for treatment of the disease.
    Journal of Medical Case Reports 08/2012; 6(1):250.
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    ABSTRACT: OBJECTIVE.: To investigate the impact of STAT3-mediated regulation on Th17 differentiation in patients with rheumatoid arthritis (RA). METHODS.: CD4(+) T cells isolated from peripheral blood (PB) and synovial fluid (SF) were stimulated to differentiate into Th17 or regulatory T cells (Tregs). The activity of STAT3 was knocked down by transfecting small interfering RNA (siRNA) into CD4(+) T cells. After 3 days in culture, the proportions of Th17 cells and Tregs were measured by flow cytometry, and the production of IL-17 was measured by RT-PCR and ELISA. RESULTS.: The levels of interleukin-17 (IL-17), IL-6, IL-23, and IL-1, and tumor necrosis factor-α were significantly higher in RA SF and synovial tissue (ST) than in SF and ST from osteoarthritis patients. In RAST, the expression of STAT3 increased in proportion to the severity of synovitis, as shown by stromal cellularity, intimal hyperplasia, and inflammatory infiltration. The degree of Th17 differentiation decreased in the order RASF > RAPB > normal. In CD4(+) T cells, transfection with STAT3 siRNA prevented Th17 differentiation of mononuclear cells from RA PB and SF but increased the proportion of Tregs. By contrast, inhibition of STAT5, the transcription factor for Tregs, increased the proportion of Th17 cells and reduced that of Tregs. CONCLUSION.: Modulation of STAT3 in CD4(+) T cells affected the differentiation of Th17 cells and Tregs in patients with RA. This role of STAT3 in RA synovial T cells may provide a new therapeutic target for the management of RA.
    Arthritis & Rheumatology 06/2012; · 7.48 Impact Factor
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    ABSTRACT: Since chronic kidney disease (CKD) is closely associated with cardiovascular disease and mortality as well as endstage renal disease, prediction of progressive CKD is a clinically important issue. We investigated the independent risk factors for the development of CKD in patients with lupus nephritis (LN). The cohort included 322 Korean patients diagnosed with LN between 1985 and 2010. We retrospectively analyzed the clinical and laboratory indices, treatment response, the final renal function, and the biopsy findings. The timing and cumulative risk of developing CKD were identified by Kaplan-Meier methods. The independent risk factors for developing CKD were examined by univariate and multivariate Cox proportional hazards regression analyses. The median followup time after the diagnosis of LN was 84 months. CKD occurs in 22% of the patients within 10 years after the diagnosis of LN. The probability of developing CKD was significantly associated with the onset time of LN (delayed-onset LN vs initial-onset LN; HR 2.904, p = 0.003), deteriorated renal function [an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m(2) body surface area] at the onset of LN (HR 7.458, p < 0.001), relapse of LN after achieving remission (HR 2.806, p = 0.029), and resistance to induction therapy (HR 8.120, p < 0.001). Our results demonstrate that delayed-onset LN, a decreased eGFR at the time of LN onset, and the failure to achieve a sustained remission are predictors for the development of CKD in Korean patients with LN.
    The Journal of Rheumatology 10/2011; 38(12):2588-97. · 3.26 Impact Factor
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    ABSTRACT: The interleukin-33 (IL-33)/ST2 pathway has emerged as an intercellular signaling system that participates in antigen-allergen response, autoimmunity and fibrosis. It has been suggested that IL-33/ST2 signaling has been involved in the pathogenesis of rheumatoid arthritis (RA), because IL-33 and its receptor have been specifically mapped to RA synovium. The aim of this study was to determine the levels of IL-33 and sST2 in sera and synovial fluids in patients with RA. The serum level of IL-33 was significantly higher in patients with RA (294.9 ± 464.0 pg/mL) than in healthy controls (96.0 ± 236.9 pg/mL, P = 0.002). The synovial fluid level of IL-33 was significantly higher in RA patients than in osteoarthritis patients. The level of serum sST2 was higher in RA patients than in healthy controls (P = 0.042). A significant relationship was found between the levels of IL-33 and IL-1β (r = 0.311, P = 0.005), and IL-33 and IL-6 (r = 0.264, P = 0.017) in 81 RA patients. The levels of IL-33, sST2 and C-reactive protein decreased after conventional disease-modifying antirheumatic drugs treatment in 10 patients with treatment-naïve RA. Conclusively, IL-33 is involved in the pathogenesis of RA and may reflect the degree of inflammation in patients with RA.
    Journal of Korean medical science 09/2011; 26(9):1132-9. · 0.84 Impact Factor
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    ABSTRACT: We report an 18-year old female patient with systemic lupus erythematosus (SLE), who developed fever, pancytopenia, abdominal pain, and watery diarrhea. Computed tomography (CT) and bone marrow aspirate revealed lupus mesenteric vasculitis (LMV) and hemophagocytic syndrome (HPS). Serologic tests for Epstein-Barr virus (EBV) indicated its reactivation. This case demonstrates that HPS and concomitant LMV associated with viral reactivation can occur as clinical manifestations of SLE flare.
    Modern Rheumatology 01/2011; 21(3):330-3. · 1.72 Impact Factor