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1.
Int J Mol Sci ; 23(4)2022 Feb 20.
Article in English | MEDLINE | ID: mdl-35216458

ABSTRACT

This study aimed to examine the role of CD70, which is highly expressed on fibroblast-like synoviocytes (FLS), in rheumatoid arthritis (RA) patients. FLS isolated from RA (n = 14) and osteoarthritis (OA, n = 4) patients were stimulated with recombinant interleukin-17 (IL-17; 5 ng/mL) and tumor necrosis factor alpha (TNF-α; 5 ng/mL) for 24 h. Expression of CD70, CD27/soluble CD27 (sCD27), and hypoxia-inducible factor-2 alpha (HIF-2α) was analyzed by RT-qPCR, flow cytometry, and ELISA assays, respectively. Reactive oxygen species (ROS) expression and cell migration were also examined. The HIF-2α inhibitor PT-2385 and CD70 inhibitor BU69 were used to specifically suppress these pathways. Stimulation with IL-17 and TNF-α significantly induced CD70 expression in RA FLS. Although the synovial fluids from patients with RA contained high levels of sCD27, surface expression of CD27, a ligand of CD70, was rarely detected in RA FLS. Cytokine-induced CD70 expression was significantly decreased following antioxidant treatment. Following HIF-2α inhibition, RA FLS had decreased expression of CD70 and ROS levels. Migration of RA FLS was also inhibited by inhibition of CD70 or HIF-2α. The surface expression of CD70 is regulated by HIF-2α and ROS levels and is a key contributor to cytokine-enhanced migration in RA FLS.


Subject(s)
Arthritis, Rheumatoid , Basic Helix-Loop-Helix Transcription Factors , CD27 Ligand , Osteoarthritis , Oxidative Stress , Synoviocytes , Arthritis, Rheumatoid/metabolism , Basic Helix-Loop-Helix Transcription Factors/metabolism , CD27 Ligand/metabolism , Cells, Cultured , Fibroblasts/metabolism , Humans , Hypoxia/metabolism , Interleukin-17/metabolism , Interleukin-17/pharmacology , Osteoarthritis/metabolism , Reactive Oxygen Species/metabolism , Synovial Membrane/pathology , Synoviocytes/metabolism , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/pharmacology
2.
Emerg Infect Dis ; 28(2): 411-414, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34852213

ABSTRACT

Ten days after receiving the first dose of coronavirus disease vaccine, a 22-year-old woman in South Korea experienced myocarditis, myopathy, pericarditis, and gastroenteritis; rash subsequently developed. There was no evidence of prior infection with severe acute respiratory syndrome coronavirus 2. The diagnosis was multisystem inflammatory syndrome resulting from coronavirus disease vaccination.


Subject(s)
COVID-19 , Adult , COVID-19 Vaccines , Female , Humans , Republic of Korea , SARS-CoV-2 , Vaccination , Young Adult
3.
Arch Rheumatol ; 37(3): 335-343, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36589618

ABSTRACT

Objectives: This study aims to investigate the role of cluster of differentiation 14 (CD14) expressed monocytes and soluble CD14-mediated pathway in the synovial inflammation of knee osteoarthritis (OA). Patients and methods: Between May 2012 and July 2013, a total of 35 patients with knee OA (9 males, 26 females; mean age: 66.3±8.8 years; range, 52 to 79 years) were included in this cross-sectional study. Synovial fluid was obtained from knee joints of 35 OA patients. The CD14+ monocytes from synovial fluid mononuclear cells (SFMCs) were isolated using the MACS. The fibroblast-like synoviocytes (FLSs) isolated from knee joint tissue were incubated with recombinant CD14 and lipopolysaccharide (LPS) for 24 h. Cytokine profiling was performed with the Luminex® Performance Assay or magnetic bead panel kit. The expression of CD14 and CD16 was analyzed by immunohistochemistry and flow cytometry. Results: The concentration of sCD14 in synovial fluid was correlated with the interleukin-6 (IL-6) level (n=35) (ρ=0.654, p<0.001). The culture supernatants of CD14+ monocytes isolated from SFMC (n=15) showed a correlation between sCD14 and IL-6 (ρ=0.784, p=0.001), along with complement component 3 (ρ=0.756, p=0.010), IL-1b (ρ=0.652, p=0.012), and tumor necrosis factor-alpha (ρ=0.806, p=0.001). Following recombinant CD14 and LPS treatment, OA FLS synergistically enhanced the secretion of IL-6, IL-8, and matrix metalloproteinase 3 (n=3, p<0.05). In five paired-samples from identical patients, the proportions of CD14+ monocytes were significantly elevated in recurred synovial fluid compared to those in initial synovial fluid (p=0.043). When monocyte subsets were analyzed in SFMC (n=26), CD14+CD16+monocytes were abundant (p=0.019) and had higher toll-like receptor 4 expression than CD14+CD16- (p<0.001). Conclusion: Our study results suggest that CD14+ monocytes and the sCD14-mediated pathway play an important role in OA aggravation through inflammatory cytokine secretion.

4.
J Clin Med ; 10(22)2021 Nov 16.
Article in English | MEDLINE | ID: mdl-34830606

ABSTRACT

There is growing evidence that apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) regulates inflammatory responses. Rheumatoid arthritis (RA) is an autoimmune disease, which is characterized with synovitis and joint destruction. Therefore, this study was planned to investigate the relationship between APE1/Ref-1 and RA. Serum and synovial fluid (SF) were collected from 46 patients with RA, 45 patients with osteoarthritis (OA), and 30 healthy control (HC) patients. The concentration of APE1/Ref-1 in serum or SF was measured using the sandwich enzyme-linked immunosorbent assay (ELISA). The disease activity in RA patients was measured using the 28-joint disease activity score (DAS28). The serum APE1/Ref-1 levels in RA patients were significantly increased compared to HC and OA patients (0.44 ± 0.39 ng/mL for RA group vs. 0.19 ± 0.14 ng/mL for HC group, p < 0.05 and vs. 0.19 ± 0.11 ng/mL for OA group, p < 0.05). Likewise, the APE1/Ref-1 levels of SF in RA patients were also significantly increased compared to OA patients (0.68 ± 0.30 ng/mL for RA group vs. 0.31 ± 0.12 ng/mL for OA group, p < 0.001). The APE1/Ref-1 concentration in SF of RA patients was positively correlated with DAS28. Thus, APE1/Ref-1 may reflect the joint inflammation and be associated with disease activity in RA.

5.
Yonsei Med J ; 62(5): 424-430, 2021 May.
Article in English | MEDLINE | ID: mdl-33908213

ABSTRACT

PURPOSE: To investigate correlations between myositis-specific autoantibodies (MSA) or myositis-associated antibodies (MAA) and clinical features, thereby demonstrating the utility of clinicoserologic classification in idiopathic inflammatory myopathies (IIM) patients. MATERIALS AND METHODS: We conducted a multicenter study of 108 adult patients (age ≥18 years) who were diagnosed with IIM by Peter and Bohan criteria or 2004 European Neuromuscular Centre (ENMC) criteria. Clinical data were obtained by medical record review. Immunoblot assay with Euroline strip (EUROIMMUN, Germany) was performed using the sera of dermatomyositis (DM, n=56), polymyositis (PM, n=45), amyopathic DM (n=5), DM sine dermatitis (n=1), and immune mediated necrotizing myopathy (n=1) patients. Patients were classified based on two classifications: 2017 EULAR/ACR and novel clinicoserologic classification. RESULTS: According to 2017 EULAR/ACR criteria, DM and PM were the most and the second most frequent entities. Overlap myositis was the major entity of IIM, and the frequency of PM was significantly lower when applying clinicoserologic classification criteria. Sixty-nine (63.9%) patients had one or more MSA, and 61 (56.5%) patients had one or more MAA. Interstitial lung disease was closely associated with anti-MDA5 and anti-ARS, and DM-specific skin lesions were frequently observed in patients with anti-TIF1γ, anti-SRP, and anti-MDA5. CONCLUSION: The clinicoserologic criteria based on MSA/MAA positivity could reflect more precise clinical features of IIM. Establishment of a laboratory system routinely available to screen for MSA/MAA status will be beneficial to provide precise diagnosis and proper management of IIM patients.


Subject(s)
Autoimmune Diseases , Myositis , Adolescent , Adult , Autoantibodies , Humans , Myositis/diagnosis , Republic of Korea , Retrospective Studies
6.
Arthritis Res Ther ; 22(1): 116, 2020 05 15.
Article in English | MEDLINE | ID: mdl-32414400

ABSTRACT

BACKGROUND: Reactive oxygen species (ROS) regulate the migration and invasion of fibroblast-like synoviocytes (FLS), which are key effector cells in rheumatoid arthritis (RA) pathogenesis. Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) induces ROS generation and, consequently, enhances cell migration. Despite the important interrelationship between RA, FLS, and ROS, the effect of NOX4 on RA pathogenesis remains unclear. METHODS: FLS isolated from RA (n = 5) and osteoarthritis (OA, n = 5) patients were stimulated with recombinant interleukin 17 (IL-17; 10 ng/ml) and tumor necrosis factor alpha (TNF-α; 10 ng/ml) for 1 h. Cell migration, invasion, adhesion molecule expression, vascular endothelial growth factor (VEGF) secretion, and ROS expression were examined. The mRNA and protein levels of NOX4 were analyzed by RT-qPCR and western blotting, respectively. The NOX4 inhibitor GLX351322 and NOX4 siRNA were used to inhibit NOX4 to probe the effect of NOX4 on these cellular processes. RESULTS: Migration of RA FLS was increased 2.48-fold after stimulation with IL-17 and TNF-α, while no difference was observed for OA FLS. ROS expression increased in parallel with invasiveness of FLS following cytokine stimulation. When the expression of NOX was examined, NOX4 was significantly increased by 9.73-fold in RA FLS compared to unstimulated FLS. Following NOX4 inhibition, cytokine-induced vascular cell adhesion molecule 1 (VCAM1), VEGF, and migration and invasion capacity of RA FLS were markedly decreased to unstimulated levels. CONCLUSION: NOX4 is a key contributor to cytokine-enhanced migration and invasion via modulation of ROS, VCAM1, and VEGF in RA FLS.


Subject(s)
Arthritis, Rheumatoid/pathology , NADPH Oxidase 4/metabolism , Synoviocytes/cytology , Arthritis, Rheumatoid/metabolism , Cell Movement , Cell Proliferation , Cells, Cultured , Fibroblasts , Humans , Oxidoreductases , Reactive Oxygen Species/metabolism , Synovial Membrane , Vascular Endothelial Growth Factor A
7.
Arch Rheumatol ; 34(2): 211-219, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31497768

ABSTRACT

OBJECTIVES: This study aims to examine the possible associations of mitochondrial single nucleotide polymorphisms (SNPs) and Behçet's disease (BD) in a larger patient group. PATIENTS AND METHODS: Whole blood or buffy coat was collected from 98 BD patients (31 males, 67 females; mean age 48±2.8 years; range 20 to 60 years) from four university hospitals located in the Chung-Cheong district of the Republic of Korea, and 196 age- and sex-matched healthy controls (HCs) (62 males, 134 females; mean age 46.91±12.90 years; range 20 to 68 years) from Konyang University Hospital. Twenty targeted mitochondrial deoxyribonucleic acids (DNAs) were genotyped and compared using the revised Cambridge Reference Sequence. Chi square and Fisher's exact tests were used to analyze association of mitochondrial DNA SNPs with BD susceptibility and its clinical characteristics. RESULTS: There were no differences for m.248A>G, m.304C>A, m.709G>A, m.3010G>A, m.3970C>T, m.4883C>T, m.5178C>A, m.6392T>C, m.6962G>A, m.10310G>A, m.10609T>C, m.12406G>A, m.12882C>T, m.13928G>C, m.14668C>T, m.16129G>A, and m16304T> between patient and HC groups. However, m.16182A>C and m.16183A>C were more frequently observed in the patient group than the HC group (22 [22.4%] vs. 24 [12.2%], p=0.061 and 32 [32.7%] vs. 42 [21.4%], p=0.092) but without statistical significance. m.4883C>T and m.5178C>A were associated with posterior location of oral ulcers (p=0.025 for each) and m.16183A>C was associated with deep oral ulcers (p=0.001), while m.16189T>C was associated with deep oral ulcers and thrombosis (p=0.042, 0.048, respectively). CONCLUSION: m.16182A>C and m.16183A>C may be associated with BD in the Korean population.

8.
Rheumatology (Oxford) ; 58(1): 154-164, 2019 01 01.
Article in English | MEDLINE | ID: mdl-30204915

ABSTRACT

Objectives: This study investigated the expression of proviral-integration site for Moloney murine leukaemia virus (PIM) -1 kinase in RA synovium and RA fibroblast-like synoviocytes (FLSs) along with its impact on RA-FLS aggressiveness. Methods: The expression of PIM kinases was assessed in synovial tissues by immunohistochemistry and double IF. After PIM-1 inhibition using either small-interfering RNA or the chemical inhibitor AZD1208, we performed proliferation and migration assays and measured the levels of MMPs and IL-6 released from RA-FLSs under stimulation with proinflammatory cytokines (TNF-α, S100A4 and IL-6/soluble IL-6 receptor). Additionally, PIM-1-associated downstream signalling pathways were analysed by immunoblotting. Results: Three isoforms of PIM kinases were immunodetected in the synovial tissues from patients with RA or OA. Specifically, PIM-1 and PIM-3 were upregulated in RA synovium and PIM-1 was expressed in T cells, macrophages and FLSs. Additionally, upon stimulation of RA-FLSs with TNF-α, S100A4 and IL-6/sIL-6R, PIM-1 and PIM-3, but not PIM-2, were significantly inducible. Moreover, PIM-1 knockdown or AZD1208 treatment significantly suppressed basal or cytokine-induced proliferation and migration of RA-FLS and the secretion of MMPs from stimulated RA-FLSs. PIM-1 knockdown significantly affected the phosphorylation levels of extracellular signal-regulated kinase and cAMP responsive element binding protein in RA-FLSs. Conclusion: PIM-1 was upregulated in RA synovial tissues and RA-FLSs and its inhibition significantly reduced the proliferation, migration and MMP production of RA-FLSs in vitro. These findings suggest PIM-1 as a novel regulator of the aggressive and invasive behaviour of RA-FLSs and indicate its potential as a target for RA treatment.


Subject(s)
Arthritis, Rheumatoid/metabolism , Biphenyl Compounds/pharmacology , Cytokines/metabolism , Osteoarthritis/metabolism , Synoviocytes/enzymology , Thiazolidines/pharmacology , Animals , Cell Movement/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Humans , Matrix Metalloproteinases/metabolism , Mice , Proto-Oncogene Proteins c-pim-1 , RNA, Small Interfering/pharmacology , Signal Transduction , Synovial Membrane/enzymology , Up-Regulation/drug effects
9.
Int J Rheum Dis ; 22(2): 314-320, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30398003

ABSTRACT

OBJECTIVE: Anti-transcriptional intermediary factor 1 (TIF1) antibody is associated with idiopathic inflammatory myopathies (IIMs). The aim of this study was to investigate the expression of TIF1s in IIMs. METHOD: TIF1α, ß or γ expression in the skin and muscle of patients and controls was studied by immunohistochemistry. Serum myositis-specific autoantibodies were detected by immunoblot. RESULTS: TIF1α was expressed in the skin of most dermatomyositis (DM) patients but not in the controls (80% vs 0%, P < 0.001). TIF1ß was expressed in all tissues of patients and controls. TIF1γ was expressed in the muscle of DM patients compared to controls (42.1% vs 0%, P = 0.039) and associated with tubuloreticular bodies (P = 0.003). Anti-TIF1γ was related with TIF1γ expression in the muscle (P = 0.042). CONCLUSION: TIF1α expression in the skin and TIF1γ in the muscle of DM was increased compared to controls. TIF1γ expression in the muscle of IIMs was related to anti-TIF1γ antibody.


Subject(s)
Autoantibodies/immunology , Muscle, Skeletal/immunology , Myositis/immunology , Skin/immunology , Transcription Factors/immunology , Adult , Aged , Autoantibodies/blood , Case-Control Studies , Female , Humans , Male , Middle Aged , Myositis/blood , Myositis/diagnosis , Nuclear Proteins/analysis , Transcription Factors/analysis , Tripartite Motif-Containing Protein 28/analysis
10.
Echocardiography ; 35(6): 809-816, 2018 06.
Article in English | MEDLINE | ID: mdl-29451950

ABSTRACT

PURPOSE: Although cardiac manifestation of Behçet disease (BD) has been described in sporadic reports, its timely diagnosis remains difficult. The objective of this study was to describe early cardiac manifestations of BD. We also performed a comprehensive classification of systemic BD activity and compared their cardiac manifestations. METHODS: A prospective screening using speckle tracking echocardiography was performed in 85 patients with BD who had no history of heart disease. After excluding subjects with left ventricular (LV) ejection fraction (LVEF) <50% (n = 1), atrial fibrillation (n = 2), or inadequate echocardiographic images (n = 1), we analyzed their clinical and echocardiographic parameters including LV global longitudinal strains (GLS) and compared them with those of an age- and gender-matched control group (n = 145). Systemic BD activity was classified as minimal (Group A), controlled (Group B), and active (Group C). RESULTS: In 81 study patients (59 females, age of 51 ± 11 years), echocardiography revealed a mean LVEF of 64 ± 5% without any significant valvular dysfunction or aortic aneurysm. Although there was no difference in LVEF between the control group and the patient group, the patient group showed significant reduction in GLS (-17.1 ± 2.9% vs -20.8 ± 2.2%, P < .001). Groups A (n = 21, 26%), B (n = 47, 58%), and C (n = 13, 58%) consistently showed reduction in GLS compared with the control group. However, there was no significant difference in cardiac manifestations among these groups according to systemic disease activity. CONCLUSION: Patients with BD present intrinsic LV dysfunction despite no apparent abnormality on routine echocardiography. However, their cardiac manifestations are not proportional to systemic BD activity.


Subject(s)
Behcet Syndrome/complications , Echocardiography, Three-Dimensional/methods , Heart Ventricles/diagnostic imaging , Stroke Volume/physiology , Ventricular Dysfunction, Left/diagnosis , Ventricular Function, Left/physiology , Behcet Syndrome/diagnosis , Behcet Syndrome/physiopathology , Disease Progression , Female , Heart Ventricles/physiopathology , Humans , Male , Middle Aged , Prospective Studies , Ventricular Dysfunction, Left/etiology , Ventricular Dysfunction, Left/physiopathology
11.
Int J Rheum Dis ; 21(1): 148-154, 2018 Jan.
Article in English | MEDLINE | ID: mdl-27315340

ABSTRACT

AIM: There is growing evidence that cold-inducible RNA-binding protein (CIRP) promotes inflammatory responses. This study investigated the relationship between CIRP and rheumatoid arthritis (RA). METHODS: Peripheral blood and synovial fluid were collected from 15 patients with RA and from 16 patients with osteoarthritis (OA). The concentration of CIRP was measured with the sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: The concentration of serum CIRP was significantly elevated in the RA patient group (RA patients = 26.39 ± 10.48 pg/mL, OA patients = 17.14 ± 7.24 pg/mL, P = 0.009). Furthermore, the RA patient group had a significantly higher CIRP concentration than that of the OA patient group in synovial fluid (153.56 ± 108.93 pg/mL vs. 23.63 ± 16.18 pg/mL, P < 0.001). The mean synovial fluid concentration of CIRP was significantly higher than that of the serum concentration in the RA patient group (serum concentration = 26.39 ± 10.48 pg/mL, synovial fluid = 153.56 ± 108.93 pg/mL, P < 0.001). Disease Activity Score of 28 joints (DAS28)-ESR (erythrocyte sedimentation rate) and DAS28-CRP (C-reactive protein) were positively correlated with the synovial fluid concentration of CIRP (DAS28-ESR: r = 0.582, P = 0.023; DAS28-CRP: r = 0.541, P = 0.037). CONCLUSION: The serum and synovial concentrations of CIRP in the RA patients were increased compared to the OA patients. Additionally, the synovial concentration of CIRP in RA patients correlated well with disease activity, that is, the DAS28-ESR/CRP. Based on these results, CIRP mediates inflammation and is a potential marker for synovial inflammation.


Subject(s)
Arthritis, Rheumatoid/blood , Inflammation Mediators/blood , RNA-Binding Proteins/blood , Synovial Fluid/chemistry , Adult , Aged , Arthritis, Rheumatoid/diagnosis , Biomarkers/blood , Blood Sedimentation , C-Reactive Protein/analysis , Disability Evaluation , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged , Osteoarthritis/blood , Osteoarthritis/diagnosis , Severity of Illness Index , Up-Regulation
12.
Lung ; 194(5): 745-53, 2016 10.
Article in English | MEDLINE | ID: mdl-27372294

ABSTRACT

OBJECTIVE: Lung diseases (LD) are common extra-articular manifestations in rheumatoid arthritis (RA). However, little is known about factors associated with susceptibility to rheumatoid arthritis-related lung diseases (RA-LD). The aim of the present study was to investigate whether the single nucleotide polymorphisms (SNPs) of PADI4 and HLA-DRB1 alleles were associated with RA-LD. METHODS: Blood samples and clinical data were collected from 116 consecutive RA patients who satisfied the 1987 American College of Rheumatology classification criteria. RA-LD was diagnosed using high-resolution computed tomography of the chest. All patients were genotyped for SNPs of PADI4 and HLA-DRB1 alleles and analyzed for full amino acid sequence of the HLA protein corresponding to a 4-digit HLA typing. Data were analyzed by independent t test (or Mann-Whitney test) for continuous variables, Chi-square test (or Fisher's exact test) and trend test for categorical variables, and logistic regression analysis. RESULTS: Ninety-four (81.0 %) RA patients had LD, of which eight (6.9 %) had interstitial lung disease (ILD) and 92 (79.3 %) had airway abnormalities in which 64 (55.2 %) showed bronchiectasis and 47 (40.5 %) revealed bronchial wall thickening. The recessive genotype of padi4_92 was susceptible to airway abnormalities (OR = 2.22, 95 % CI = 1.05-4.49, p = 0.034). Tryptophan at position 9 of HLA-DRB1 sequence was associated with the susceptibility to RA-ILD (OR = 22.89, 95 % CI = 1.20-432.56, p = 0.037). CONCLUSION: PADI4 polymorphisms and HLA-DRB1 alleles could attribute differently to the development of airway abnormalities and ILD, respectively, in RA.


Subject(s)
Arthritis, Rheumatoid/complications , Genetic Predisposition to Disease , HLA-DRB1 Chains/genetics , Lung Diseases, Interstitial/genetics , Protein-Arginine Deiminases/genetics , Respiratory System Abnormalities/genetics , Adult , Aged , Bronchi/pathology , Bronchiectasis/etiology , Female , Genotype , Humans , Lung Diseases, Interstitial/etiology , Male , Middle Aged , Polymorphism, Single Nucleotide , Protein-Arginine Deiminase Type 4
13.
J Cardiovasc Ultrasound ; 24(4): 312-316, 2016 Dec.
Article in English | MEDLINE | ID: mdl-28090259

ABSTRACT

BACKGROUND: Pulmonary arterial hypertension (PAH) is a major cause of morbidity and mortality among patients with systemic sclerosis (SSc). Early detection and prompt treatment of PAH associated with SSc (SSc-PAH) result in better prognosis. We conducted echocardiographic study to presume the prevalence of PAH in Korean adult SSc patients and to diagnose SSc-PAH in their early stages with right heart catheterization (RHC). METHODS: We performed free of charge echocardiographic study including 37 adult SSc patients at the Chungnam National University Hospital. The possibility of PAH is determined by the estimation of pulmonary arterial pressure by peak tricuspid regurgitation velocity of > 3.0 m/s. Patients with possible PAH were recommended to undergo RHC to confirm the diagnosis. RESULTS: In 37 patients, 8 patients were suspected with PAH. Among them, 6 patients agreed to be examined with RHC, and 4 were confirmed with PAH. The prevalence of possible PAH was 21.6% (8 of 37 patients), and that of confirmed PAH was 10.8% (4 of 37 patients). Four patients who were confirmed with SSc-PAH through RHC have been treated with specific pulmonary vasodilators and maintained stable. CONCLUSION: Eight patients (21.6%) were possible PAH and 4 (10.8%) were diagnosed as SSc-PAH by RHC after the echocardiographic screening study of 37 adult SSc patients.

14.
J Biol Chem ; 291(8): 4048-57, 2016 Feb 19.
Article in English | MEDLINE | ID: mdl-26702052

ABSTRACT

B7-H3, a newly identified B7 family member, has functional duality as a co-stimulator and co-inhibitor that fine-tunes T cell-mediated immune responses. Given that B7-H3 expression on human monocytes and dendritic cells is enhanced by inflammatory cytokines, its potential inmmunoregulatory role at sites of inflammation has been suggested. Further, monocytes play crucial roles in the pathophysiology of various inflammatory disorders including autoimmune diseases; however, the immunological role of B7-H3 in rheumatoid arthritis (RA) has not been defined. Thus, we aimed to investigate the possible roles of monocyte B7-H3 in the pathogenesis of RA. Synovial monocytes, but not peripheral monocytes, in RA patients predominantly express surface B7-H3. The 4Ig isoform of B7-H3 is exclusively induced on the cell surface, whereas the 2Ig B7-H3 isoform is constitutively expressed in the intracytoplasmic region of both peripheral and synovial monocytes. B7-H3 knockdown experiments reveal that surface B7-H3 has an inhibitory effect on IFN-γ production in CD4 memory cells. Moreover, surface B7-H3 expression on synovial monocytes inversely correlates with RA clinical parameters. Our findings demonstrate that activation-induced B7-H3 expression on synovial monocytes has the potential to inhibit Th1-mediated immune responses and immunomodulatory roles affecting RA pathogenesis.


Subject(s)
Arthritis, Rheumatoid/immunology , B7 Antigens/immunology , Gene Expression Regulation/immunology , Monocytes/immunology , Synovial Membrane/immunology , Adult , Aged , Arthritis, Rheumatoid/pathology , Female , Humans , Immunologic Memory , Interferon-gamma/immunology , Male , Middle Aged , Monocytes/pathology , Synovial Membrane/pathology , Th1 Cells/immunology , Th1 Cells/pathology
15.
PLoS One ; 9(10): e109775, 2014.
Article in English | MEDLINE | ID: mdl-25329467

ABSTRACT

Monocytes function as crucial innate effectors in the pathogenesis of chronic inflammatory diseases, including autoimmunity, as well as in the inflammatory response against infectious pathogens. Human monocytes are heterogeneous and can be classified into three distinct subsets based on CD14 and CD16 expression. Although accumulating evidence suggests distinct functions of monocyte subsets in inflammatory conditions, their pathogenic roles in autoimmune diseases remain unclear. Thus, we investigated the phenotypic and functional characteristics of monocytes derived from synovial fluid and peripheral blood in RA patients in order to explore the pathogenic roles of these cells. In RA patients, CD14+CD16+, but not CD14dimCD16+, monocytes are predominantly expanded in synovial fluid and, to a lesser degree, in peripheral blood. Expression of co-signaling molecules of the B7 family, specifically CD80 and CD276, was markedly elevated on synovial monocytes, while peripheral monocytes of RA and healthy controls did not express these molecules without stimulation. To explore how synovial monocytes might gain these unique properties in the inflammatory milieu of the synovial fluid, peripheral monocytes were exposed to various stimuli. CD16 expression on CD14+ monocytes was clearly induced by TGF-ß, although co-treatment with IL-1ß, TNF-α, or IL-6 did not result in any additive effects. In contrast, TLR stimulation with LPS or zymosan significantly downregulated CD16 expression such that the CD14+CD16+ monocyte subset could not be identified. Furthermore, treatment of monocytes with IFN-γ resulted in the induction of CD80 and HLA-DR expression even in the presence of TGF-ß. An in vitro assay clearly showed that synovial monocytes possess the unique capability to promote Th1 as well as Th17 responses of autologous peripheral CD4 memory T cells. Our findings suggest that the cytokine milieu of the synovial fluid shapes the unique features of synovial monocytes as well as their cardinal role in shaping inflammatory T-cell responses in RA.


Subject(s)
Arthritis, Rheumatoid/metabolism , Monocytes/metabolism , Synovial Fluid/cytology , T-Lymphocyte Subsets/metabolism , Arthritis, Rheumatoid/immunology , B7-1 Antigen/genetics , B7-1 Antigen/metabolism , Case-Control Studies , Cells, Cultured , Humans , Interferon-gamma/pharmacology , Interleukin-1beta/pharmacology , Interleukin-6/pharmacology , Lipopolysaccharide Receptors/genetics , Lipopolysaccharide Receptors/metabolism , Lymphotoxin-alpha/pharmacology , Monocytes/drug effects , Monocytes/immunology , Phenotype , Receptors, IgG/genetics , Receptors, IgG/metabolism , T-Lymphocyte Subsets/drug effects , T-Lymphocyte Subsets/immunology , Tumor Necrosis Factor-alpha/pharmacology
16.
Yonsei Med J ; 55(5): 1354-8, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25048496

ABSTRACT

PURPOSE: The function of regulatory B lymphocytes is known to be abnormal in inflammatory diseases. However, a recent study indicates that IL-10+ B cells seem to be expanded in rheumatoid arthritis (RA). Therefore, the state of IL-10+ B cells in the peripheral blood from RA patients and healthy controls were investigated. MATERIALS AND METHODS: CD19+ cells in peripheral blood mononuclear cells were purified from blood samples of RA patients and age and gender-matched healthy controls, and stimulated with CD40 ligand and CpG for 48 hours. Then, intracellular IL-10 in CD19+ cells was analyzed using flow cytometry. RESULTS: There was no significant difference in the proportion of IL-10+ B cells between 10 RA patients and 10 healthy controls (RA, 0.300±0.07 vs. healthy control 0.459±0.07, p=0.114). The proportion of induced IL-10+ B cells to total B cells in RA patients was significantly higher than those in controls (RA, 4.44±3.44% vs. healthy control 2.44±1.64%, p=0.033). However, the proportion of IL-10+ B cells to total B cells correlated negatively with disease activity in RA patients (r=-0.398, p=0.040). Erythrocyte sedimentation rate or C-reactive protein or medication was not associated with the proportion of IL-10+ B cells. CONCLUSION: The proportion of induced IL-10+ B cell increased in RA patients compared to healthy control, however, negatively correlated with disease activity in RA.


Subject(s)
Arthritis, Rheumatoid/immunology , B-Lymphocytes, Regulatory/physiology , Adult , Aged , Antigens, CD19/metabolism , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/pathology , B-Lymphocytes, Regulatory/metabolism , Biomarkers/blood , Female , Humans , Interleukin-10/metabolism , Male , Middle Aged , Severity of Illness Index
18.
Int J Rheum Dis ; 15(6): 531-7, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23253236

ABSTRACT

AIM: There is growing evidence that two recently recognized, unique subsets of CD4(+) T-cells, T-helper 17 cells (Th17) and CD4(+) CD25(+) regulatory T-cells (Treg), may play important roles in the pathogenesis of psoriasis. This study sought to investigate the relationship between Th17 cells and psoriasis or psoriatic arthritis (PsA). METHODS: Peripheral blood CD4(+) T-cells were isolated from 47 patients with psoriasis and 47 controls, and were cultured under various stimulatory conditions. The Th17 cells and regulatory Treg cells were detected by flow cytometry. Plasma interleukin (IL)-17 was measured by enzyme-linked immunosorbent assay. RESULTS: The proportion of Th17 and Treg cells from peripheral blood mononuclear cells showed no difference between patients with psoriasis and controls. However, psoriasis and PsA patients demonstrated a higher proportion of induced Th17 cells, which was correlated with psoriasis area severity index score. The level of plasma IL-17A in psoriasis was higher than that in controls. CONCLUSION: Th17 cells may play important roles in the pathogenesis of psoriasis and psoriatic arthritis.


Subject(s)
Arthritis, Psoriatic/immunology , Psoriasis/immunology , Th17 Cells/immunology , Adolescent , Adult , Aged , Arthritis, Psoriatic/blood , Arthritis, Psoriatic/diagnosis , Biomarkers/blood , Case-Control Studies , Cells, Cultured , Enzyme-Linked Immunosorbent Assay , Female , Flow Cytometry , Humans , Interleukin-17/blood , Male , Middle Aged , Psoriasis/blood , Psoriasis/diagnosis , Severity of Illness Index , T-Lymphocytes, Regulatory/immunology , Young Adult
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