Serum Levels of Interleukin 33 and Soluble ST2 Are Associated with the Extent of Disease Activity and Cutaneous Manifestations in Patients with Active Adult-onset Still’s Disease

Han, Jae Ho,Suh, Chang-Hee,Jung, Ju-Yang,Ahn, Mi-Hyun,Kwon, Ji Eun,Yim, Hyunee,Kim, Hyoun-Ah Journal of Rheumatology Pub. Co 2017 The Journal of rheumatology Vol.44 No.6

<P>Conclusion. We found significantly higher serum IL-33 and soluble ST2 levels in patients with active AOSD. Results indicate that the IL-33/ST2 signaling pathway may play a role in the pathogenesis of the acute inflammation and skin manifestations associated with AOSD.</P>

The Interleukin 33/ST2 Axis in Patients with Primary Sjögren Syndrome: Expression in Serum and Salivary Glands, and the Clinical Association

Jung, Seung Min,Lee, Jaeseon,Baek, Seung Ye,Lee, Jae Ho,Lee, Jennifer,Park, Kyung-Su,Park, Sung-Hwan,Kim, Ho-Youn,Kwok, Seung-Ki Journal of Rheumatology Pub. Co 2015 The Journal of rheumatology Vol.42 No.2

<P>Objective. To evaluate the expression of interleukin 33 (IL-33) and its receptor in sera and salivary tissues of patients with primary Sjogren syndrome (pSS), and to investigate the association with clinical profiles. Methods. Serum IL-33 and soluble ST2 (sST2) of 55 patients with pSS and 48 controls were determined by ELISA and assessed for clinical correlation. The expression of IL-33/ST2 in salivary tissues was investigated by immunohistochemical staining and was further characterized by confocal microscopy. We also measured IL-33 production in salivary glandular epithelial cells by proinflammatory stimuli. Results. Serum levels of IL-33 and sST2 were higher in patients with pSS compared to those in controls (p = 0.018 and p < 0.0001, respectively). Among patients with pSS, sST2 concentration was associated with thrombocytopenia (p = 0.029) and correlated with disease duration (p = 0.013) and the European League Against Rheumatism Sjogren Syndrome Disease Activity Index (p = 0.042). The expression of IL-33 and ST2 was elevated in salivary glands of patients with pSS with grade 2 inflammation, and diminished in advanced inflammation. In patients with pSS, IL-33 was mainly observed in epithelial and endothelial cells of glandular tissue. The production of IL-33 mRNA by salivary gland epithelial cell line increased under stimulation with interferon-gamma. Conclusion. The expression of IL-33 and its receptor was elevated in sera and salivary tissues of patients with pSS. These results suggest that the IL-33/ST2 axis might have a role in the pathogenesis of pSS.</P>

Downregulation of Tryptophan-related Metabolomic Profile in Rheumatoid Arthritis Synovial Fluid

Kang, Kwi Young,Lee, Soo Hyun,Jung, Seung Min,Park, Sung-Hwan,Jung, Byung-Hwa,Ju, Ji Hyeon Journal of Rheumatology Pub. Co 2015 The Journal of rheumatology Vol.42 No.11

<B>Objective.</B><P>Synovial fluid (SF) is one of the most important materials that reflect the pathophysiological process of arthritis. A metabolomic and lipidomic study of SF was performed with the aim of identifying tentative diagnostic markers or therapeutic candidates for rheumatoid arthritis (RA).</P><B>Methods.</B><P>SF was aspirated from 10 patients with RA and 10 patients with osteoarthritis (OA). RA SF and OA SF were collected and analyzed by ultraperformance liquid chromatography quadruple time-of-flight mass spectrometry. Associations among clinical variables, laboratory results, and metabolic profiles were investigated.</P><B>Results.</B><P>The metabolic pathways for carnitine, tryptophan, phenylalanine, arachidonic acid, and glycophospholipid were significantly upregulated in OA SF. The metabolic pathways for taurine, cholesterol ester, and the β-oxidation of pristine acid, linolenic acid, and sphingolipid were activated more in RA SF than in OA SF. In particular, the tryptophan pathway, which comprises kynurenine, indoleacetic acid, indole acetaldehyde, and N′-formylkynurenine, was downregulated. Interestingly, the levels of tryptophan metabolites kynurenine and N′-formylkynurenine, which are involved in immune tolerance, were significantly lower in RA SF compared with OA SF (p < 0.05), but the opposite pattern was observed for erythrocyte sedimentation rate (p < 0.01) and the levels of C-reactive protein (CRP; p < 0.01), rheumatoid factor (p < 0.01), and anticyclic citrullinated peptide antibody (p < 0.05). Kynurenine concentration correlated inversely with CRP concentration in RA SF but not in OA SF (r −0.65, p < 0.05).</P><B>Conclusion.</B><P>Advances in metabolomic techniques enabled us to delineate distinctive metabolic and lipidomic profiles in RA SF and OA SF. RA SF and OA SF showed distinct metabolic profiles.</P>

Association of Guanosine Triphosphate Cyclohydrolase 1 Gene Polymorphisms with Fibromyalgia Syndrome in a Korean Population

KIM, SEONG-KYU,KIM, SEONG-HO,NAH, SEONG-SU,LEE, JI HYUN,HONG, SEUNG-JAE,KIM, HYUN-SOOK,LEE, HYE-SOON,KIM, HYOUN AH,JOUNG, CHUNG-IL,BAE, JISUK,CHOE, JUNG-YOON,LEE, SHIN-SEOK Journal of Rheumatology 2013 The Journal of rheumatology Vol.40 No.3

<P><B>Objective.</B></P><P>Guanosine triphosphate cyclohydrolase 1 (GCH1) is the rate-limiting enzyme in the synthesis of tetrahydrobiopterin, which is an essential cofactor in nitric oxide (NO) production. Polymorphisms in the <I>GCH1</I> gene have been implicated in protection against pain sensitivity. The aim of our study was to determine whether single-nucleotide polymorphisms (SNP) in the <I>GCH1</I> gene affect susceptibility and/or pain sensitivity in fibromyalgia syndrome (FM).</P><P><B>Methods.</B></P><P>A total of 409 patients with FM and 422 controls were enrolled. The alleles and genotypes at 4 positions [rs3783641(T>A), rs841(C>T), rs752688(C>T), and rs4411417(T>C)] in the <I>GCH1</I> gene were analyzed. The associations of the <I>GCH1</I> SNP with susceptibility and clinical measures in patients with FM were assessed.</P><P><B>Results.</B></P><P>The frequencies of alleles and genotypes of the 4 SNP did not differ between patients with FM and healthy controls. Among 13 constructed haplotypes, we further examined 4 (CCTT, TTCT, TTCA, and CCTA) with > 1% frequency in both FM and controls. No associations of <I>GCH1</I> polymorphisms with FM-related activity or severity indexes were found, although the number and total score of tender points in patients with FM differed among the 4 haplotypes (p = 0.03 and p = 0.01, respectively). The CCTA haplotype of <I>GCH1</I> was associated with significantly lower pain sensitivity and occurred less frequently than the CCTT haplotype in patients with FM (p = 0.04, OR 0.45, 95% CI 0.21–0.96).</P><P><B>Conclusion.</B></P><P>Our study provides evidence that certain <I>GCH1</I> haplotypes may be protective against susceptibility and pain sensitivity in FM. Our data suggest that NO is responsible for pain sensitivity in the pathogenesis of FM.</P>

Relation of Autoimmune Cytopenia to Glandular and Systemic Manifestations in Primary Sjögren Syndrome: Analysis of 113 Korean Patients

Koh, Jung Hee,Lee, Jennifer,Chung, So-Hyang,Kwok, Seung-Ki,Park, Sung-Hwan Journal of Rheumatology 2015 The Journal of rheumatology Vol.42 No.10

<P>Objective. To investigate the characteristics of patients with primary Sjogren syndrome (pSS) who have autoimmune cytopenia. Methods. We analyzed 113 participants from the Korean Initiative of Primary Sjogren Syndrome, a prospective pSS cohort. Autoimmune cytopenia was defined as autoimmune origin neutropenia, anemia, and/or thrombocytopenia without vitamin or iron deficiency, or drug-induced cytopenia. To identify the association between autoimmune cytopenia and the clinical characteristics of pSS, extraglandular manifestations were analyzed according to the European League Against Rheumatism Sjogren's syndrome disease activity index (ESSDAI) definition. Xerophthalmia was assessed with the Ocular Surface Disease Index, Schirmer I test, ocular stain score (OSS), and tear film breakup time. Results. The median total ESSDAI score was 2 (interquartile range 1-6). About a quarter of patients had no systemic activity. Autoimmune cytopenia was observed in 23.9% of patients (n = 27). Moderate biological features were more frequently observed in patients with autoimmune cytopenia than in patients without [10 (37%) and 11 (12.8%), respectively, p = 0.016]. Articular involvement was exhibited in 1 patient with autoimmune cytopenia, but in 23 patients (27.4%) without autoimmune cytopenia (p = 0.013). Higher OSS (p = 0.002) and lower mean Schirmer I test (p = 0.029) were observed in patients with autoimmune cytopenia than in those without. Neutrophils and lymphocytes negatively correlated with OSS (rho = -0.204, p = 0.041 and r = -0.230, p = 0.020, respectively). Conclusion. Autoimmune cytopenia is closely associated with severe ocular surface damage in pSS. Therefore, assessment of xerophthalmia by ophthalmologists may be mandatory, particularly in patients with pSS with cytopenia, even if patients do not complain of eye dryness.</P>

Association of Polymorphisms Modulating Low-density Lipoprotein Cholesterol with Susceptibility, Severity, and Progression of Rheumatoid Arthritis

Park, Yune-Jung,Yoo, Seung-Ah,Choi, Susanna,Yoo, Hee-Soo,Yoon, Ho-Sung,Cho, Chul-Soo,Yoo, Ki-Dong,Kim, Wan-Uk Journal of Rheumatology 2013 The Journal of rheumatology Vol.40 No.6

<P><B>Objective.</B></P><P>Dyslipidemia, a risk factor for cardiovascular diseases, is more prevalent in patients with rheumatoid arthritis (RA) than in the general population. We investigated whether single-nucleotide polymorphisms (SNP) modulating low-density lipoprotein (LDL) cholesterol affect susceptibility, severity, and progression of RA.</P><P><B>Methods.</B></P><P>We enrolled 302 patients with RA and 1636 healthy controls, and investigated the SNP modulating LDL cholesterol. Clinical characteristics of RA, serum adipocytokine concentrations, and radiographic severity were analyzed according to genotype score based on the number of unfavorable alleles. The influence of genotype score on radiographic progression was also investigated using multivariable logistic models.</P><P><B>Results.</B></P><P>We identified 3 SNP (rs688, rs693, and rs4420638) modulating LDL cholesterol in Koreans, which correlated well with LDL cholesterol levels in both patients with RA and controls. Among them, 2 SNP, rs688 and rs4420638, were more prevalent in patients with RA than in controls. In patients with RA carrying more unfavorable alleles (genotype score ≥ 3), disease activity measures, serum adipocytokine levels, and radiographic severity were all increased. The genotype score was an independent risk factor for radiographic progression of RA over 2 years, and its effect was greater than the influence of conventional risk factors.</P><P><B>Conclusion.</B></P><P>SNP modulating LDL cholesterol influence the risk, activity, and severity of RA. These results provide the first evidence that genetic mechanisms linked to dyslipidemia may directly contribute to the susceptibility and prognosis of RA, a representative of chronic inflammatory diseases, explaining the high incidence of dyslipidemia in RA.</P>

Role of Fractalkine in the Pathogenesis of Primary Sjögren Syndrome: Increased Serum Levels of Fractalkine, Its Expression in Labial Salivary Glands, and the Association with Clinical Manifestations

Lee, Jae Ho,Kwok, Seung-Ki,Jung, Seung Min,Lee, Jennifer,Lee, Jae-Seon,Baek, Seung Ye,Kim, Eun-Kyung,Ju, Ji Hyeon,Park, Sung-Hwan,Kim, Ho-Youn Journal of Rheumatology 2014 The Journal of rheumatology Vol.41 No.12

<P><B>Objective.</B></P><P>To investigate the expression of fractalkine and identify the clinical effects of fractalkine and its receptor (CX3CR1) in patients with primary Sjögren syndrome (pSS).</P><P><B>Methods.</B></P><P>Serum fractalkine levels were determined by ELISA. Immunohistochemical staining was done to compare the expression of fractalkine and CX3CR1 between salivary glands (SG) of patients with SS and controls. The cells to be merged with fractalkine were evaluated by confocal microscopy. Type of CX3CR1-expressing cells among infiltrating lymphocytes in SG was analyzed by confocal microscopy. Further, associations among fractalkine, proinflammatory cytokines, and clinical profiles were investigated.</P><P><B>Results.</B></P><P>Serum fractalkine levels in patients with pSS were higher than those in the control group (p = 0.026). SG expression of fractalkine and its receptor was upregulated in patients with pSS compared to that in the controls by immunohistochemistry. Higher histological grade was associated with more fractalkine-positive cells per total epithelial cells. Epithelial cells were the main fractalkine-expressing cell type in the SG. Serum fractalkine levels were significantly correlated with proinflammatory cytokines levels (interleukin 17: r = 0.685, p = 0.029; tumor necrosis factor-α: r = 0.444, p = 0.003), antinuclear antibody (r = 0.349, p = 0.022), and immunoglobulin G levels (r = 0.325, p = 0.044). Serum fractalkine levels in patients with extraglandular manifestations of pSS were significantly higher than in those without extraglandular manifestations (p = 0.026).</P><P><B>Conclusion.</B></P><P>Fractalkine and CX3CR1 may play a role in the pathogenesis of pSS, including extraglandular manifestations.</P>

Severity of Sacroiliitis and Erythrocyte Sedimentation Rate are Associated with a Low Trabecular Bone Score in Young Male Patients with Ankylosing Spondylitis

Kang, Kwi Young,Chung, Min Kyung,Kim, Ha Neul,Hong, Yeon Sik,Ju, Ji Hyeon,Park, Sung-Hwan Journal of Rheumatology Pub. Co 2018 The Journal of rheumatology Vol.45 No.3

<P>Conclusion. The TBS in young male patients with AS is associated with the ESR and severity of sacroiliitis. The TBS may be useful as a tool for assessing osteoporosis in AS.</P>

Anti-cyclic citrullinated peptide antibodies distinguish hepatitis B virus (HBV)-associated arthropathy from concomitant rheumatoid arthritis in patients with chronic HBV infection.

Lim, Mi-Kyoung,Sheen, Dong-Hyuk,Lee, Yun Jung,Mun, You Ri,Park, Mira,Shim, Seung-Cheol Journal of Rheumatology Pub. Co 2009 The Journal of rheumatology Vol.36 No.4

<P>OBJECTIVE: To determine whether anti-cyclic citrullinated peptide (anti-CCP) antibodies, which are a highly specific test for rheumatoid arthritis (RA), could differentiate between hepatitis B virus (HBV)-associated arthropathy and concomitant RA in Korean patients with chronic HBV infection. METHODS: We investigated 240 patients with HBV infection. Anti-CCP antibodies were measured by ELISA and rheumatoid factor (RF) by the latex fixation test. Patient records were reviewed, and a standard form was used to record all demographic, clinical, and laboratory characteristics. Patients were divided into 4 groups according to joint symptoms: asymptomatic, arthralgia, oligoarthritis, and RA. We categorized liver disease into 3 groups: carrier, chronic hepatitis, and cirrhosis. RESULTS: Anti-CCP antibodies and RF were detected in 11 and 28 of 240 patients, respectively. Anti-CCP antibodies were detected in 9 of 10 RA (90%) and 2 of 230 non-RA patients (0.86%). The positive rate for RF was 90% in RA and 8.3% in non-RA. Eight of 10 RA patients were positive for both RF and anti-CCP antibodies. RF was detected in 11 patients without joint symptoms, 4 with arthralgia, and 4 with oligoarthritis, whereas anti-CCP antibodies were found in 1 patient without joint symptoms and 1 with oligoarthritis. Specificity of anti-CCP antibody for RA was 99.1%, whereas RF showed 91.7% specificity (p<0.0002). We compared the titers and positive detection rates of anti-CCP antibodies and RF among liver disease subgroups. There was no significant between-subgroup difference. CONCLUSION: Measurement of anti-CCP antibodies is better than RF detection to discriminate HBV-associated arthropathy from concomitant RA in patients with chronic HBV infection.</P>

Elevated Serum Levels of Syndecan-1 Are Associated with Renal Involvement in Patients with Systemic Lupus Erythematosus

Kim, Ki-Jo,Kim, Ji-Young,Baek, In-Woon,Kim, Wan-Uk,Cho, Chul-Soo Journal of Rheumatology Pub. Co 2015 The Journal of rheumatology Vol.42 No.2

<P><B>Objective.</B></P><P>Syndecan-1 (SDC-1) is a major constituent of the endothelial glycocalyx, which plays a role in maintaining vascular homeostasis and functions as a glomerular filtration barrier. SDC-1 is readily shed into the blood under various conditions, but the clinical implication of circulating SDC-1 in patients with systemic lupus erythematosus (SLE) remains unclear. We aimed to investigate the association of serum SDC-1 level with certain clinical manifestations of SLE.</P><P><B>Methods.</B></P><P>We measured serum SDC-1 levels by ELISA in 111 patients with SLE, 18 with rheumatoid arthritis (RA), and 20 healthy subjects, and investigated its association with clinical manifestations and laboratory variables.</P><P><B>Results.</B></P><P>Serum SDC-1 levels were higher in patients with SLE than in those with RA and healthy controls (both p < 0.001) and were positively correlated with SLE Disease Activity Index (SLEDAI; r = 0.367, p < 0.001) and anti-dsDNA antibody level (r = 0.259, p = 0.007), but inversely correlated with serum C3 and CH50 levels (r = −0.305, p = 0.001 and r = −0.244, p = 0.012). Patients with active nephritis had higher serum SDC-1 levels than patients with inactive nephritis and those without nephritis (both p < 0.001). In addition, serum SDC-1 levels were correlated with renal SLEDAI score (r = 0.540, p < 0.001) and excretion of proteinuria as measured by spot urine protein/creatinine ratio (r = 0.538, p < 0.001). In 14 patients with lupus nephritis (LN) whose serum samples were obtained at the time of renal biopsy, there was a positive correlation between serum SDC-1 levels and activity index (r = 0.632, p = 0.015).</P><P><B>Conclusion.</B></P><P>Serum SDC-1 levels are increased in SLE patients with nephritis, indicating that SDC-1 might be a useful serum biomarker for active LN.</P>