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>

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>

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>

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>

Response to Intravenous Cyclophosphamide Treatment for Lupus Nephritis Associated with Polymorphisms in the <i>FCGR2B-FCRLA</i> Locus

Kim, Kwangwoo,Bang, So-Young,Joo, Young Bin,Kim, Taehyeung,Lee, Hye-Soon,Kang, Changwon,Bae, Sang-Cheol Journal of Rheumatology Pub. Co 2016 The Journal of rheumatology Vol.43 No.6

<P>Objective. Cyclophosphamide (CYC) is an immunosuppressant drug widely used to treat various diseases including lupus nephritis, but its efficacy highly varies from individual to individual. This pharmacogenomics association study searched for genetic variations associated with CYC efficacy. Methods. Genome-wide association scan was performed for 109 Korean patients with systemic lupus erythematosus with lupus nephritis (classes III-V) who received intravenous CYC induction therapy. Genetic differences between responders and nonresponders were examined using Cochran-Armitage trend tests, and genotype imputation was used for defining the association locus. Results. Genetic polymorphisms in the Fc gamma receptor gene (FCGR) cluster at human chromosome 1q23, previously associated with lupus nephritis susceptibility, were associated with the response to CYC treatment for lupus nephritis. Significant response association was found for 3 perfectly correlated (r(2) = 1) single-nucleotide polymorphisms (SNP): rs6697139, rs10917686, and rs10917688, located between the FCGR2B and FCRLA genes (p = 3.4 x 10(-8)). Carriage of the minor alleles in these SNP was found only in nonresponders (31%) and none in responders (0%). Conclusion. This first genome-wide association approach for CYC response yielded a robust profile of genetic associations including large-effect SNP in the FCGR2B-FCRLA locus, which may provide better insights to CYC metabolism and efficacy.</P>

Application of the 2016 EULAR/ACR/PRINTO Classification Criteria for Macrophage Activation Syndrome in Patients with Adult-onset Still Disease

Ahn, Sung Soo,Yoo, Byung-Woo,Jung, Seung Min,Lee, Sang-Won,Park, Yong-Beom,Song, Jason Jungsik Journal of Rheumatology Pub. Co 2017 The Journal of rheumatology Vol.44 No.7

<P>Conclusion. The 2016 EULAR/ACR/PRINTO classification criteria for MAS are potentially useful for the identification of patients with AOSD at high risk for a poor outcome. Febrile patients with AOSD should be monitored with the 2016 classification criteria for MAS in the early diagnosis and proper treatment of MAS.</P>

Safety, and Humoral and Cell-mediated Immune Responses to Herpes Zoster Vaccine in Patients with Rheumatoid Arthritis

Koh, Jung Hee,Lee, Jaeseon,Kim, Seo Hwa,Kwok, Seung-Ki,Ju, Ji Hyeon,Park, Sung-Hwan Journal of Rheumatology Pub. Co 2018 The Journal of rheumatology Vol.45 No.4

<B>Objective.</B><P>To examine humoral and cellular immune responses induced by a live attenuated herpes zoster (HZ) vaccine in patients with rheumatoid arthritis (RA) compared with osteoarthritis (OA) patients.</P><B>Methods.</B><P>This was an observational study of a live attenuated HZ vaccine in 41 patients with RA receiving conventional disease-modifying antirheumatic drugs (cDMARD) and/or low-dose glucocorticoids (GC) and in 28 patients with OA. Blood samples were obtained before and at 12 weeks after HZ vaccination. Immunogenicity was assessed using varicella zoster virus (VZV)-specific interferon gamma ELISA and an in-house ELISA. Clinical outcomes, including adverse events, HZ occurrence, and RA flares, were analyzed.</P><B>Results.</B><P>No patients developed vaccination-induced HZ during the followup period (median = 1.6 yrs). The HZ vaccine induced a significant increase in the VZV-specific enzyme-linked immunospot spot-forming units and anti-VZV immunoglobulin G antibodies in patients with RA and OA. The number of spot-forming units was lower in patients with RA than in patients with OA both at baseline and at 12 weeks after vaccination. The disease activity index for patients with RA was similar at baseline and at 12 weeks after vaccination. However, 6 patients with RA (14.6%) experienced a flare during the 12 weeks. Overall, 17 (24.6%) participants reported a mild adverse event such as an injection site reaction (11.6%).</P><B>Conclusion.</B><P>The HZ vaccine induced VZV-specific cellular and humoral responses in patients with RA. Although patients with RA showed a weaker vaccine-induced VZV-specific cellular immune response than patients with OA, the vaccine may be considered in patients with RA receiving cDMARD and/or low dose GC.</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>