H.-A. Kim

Carotid subclinical atherosclerosis is associated with disease activity but not vitamin D in Korean systemic lupus erythematosus

Atherosclerosis develops early in systemic lupus erythematosus (SLE) patients and is an important cause of mortality. Vitamin D deficiency is found to be associated with cardiovascular disease and autoimmunity. We evaluated the extent of carotid subclinical atherosclerosis and analyzed its correlation with vitamin D in SLE. One hundred and two female patients with SLE and 52 normal controls (NCs) were recruited. The mean carotid intima-media thickness (IMT) of SLE patients was 0.41 ± 0.08 mm, which was higher than that of NCs (0.32 ± 0.08 mm, p = 0.012). In addition, carotid plaques were more frequent and the plaque index was higher in SLE patients than in NCs (0.68 ± 1.39 vs. 0.26 ± 0.87, p = 0.026). Carotid IMT was correlated with age, body mass index, SLE disease activity index, and aspirin use in SLE patients. The plaque index was correlated with renal involvement. Vitamin 25(OH)D3 level was not correlated with carotid IMT, plaque index or disease activity markers. In SLE, the risk of cardiovascular disease is higher than that in NCs, which may be derived from systemic inflammation. It may be not suitable to assess vitamin D as a marker of disease activity or subclinical atherosclerosis in SLE patients.

Circulating hsa-miR-30e-5p, hsa-miR-92a-3p, and hsa-miR-223-3p may be novel biomarkers in systemic lupus erythematosus.

MicroRNAs (miRNAs) are short, non‐coding RNAs that regulate gene expression at the post‐transcriptional level, which can be measured in cells, tissues, and body fluids including plasma. Differences in miRNA expression levels suggest an epigenetic mechanism and changed expression levels are emerging as a novel biomarker for various diseases. We attempted to identify circulating miRNAs associated with susceptibility to systemic lupus erythematosus (SLE) in the Korean population and elucidate their significance for clinical phenotype. An expression profiling analysis using miRNA polymerase chain reaction (PCR) array was conducted with pooled miRNA from 10 patients with SLE and 10 healthy controls (HCs). Nine miRNAs were differentially expressed between the SLE and HC. To verify this, we performed quantitative PCR for various miRNA from SLE patients (n = 70) and HCs (n = 40). The hsa‐miR‐30e‐5p, hsa‐miR‐92a‐3p, and hsa‐miR‐223‐3p were significantly up‐regulated in plasma of SLE patients (P = 0.048, P = 0.039, and P = 0.046, respectively). Especially, the hsa‐miR‐223‐3p was significantly associated with oral ulcer (P < 0.001) and lupus anticoagulant (P = 0.031). Thus, plasma hsa‐miR‐30e‐5p, hsa‐miR‐92a‐3p, and hsa‐miR‐223‐3p may be promising novel biomarkers in the diagnosis and clinical manifestation of SLE.

Identifying fibromyalgia subgroups using cluster analysis: Relationships with clinical variables

Patients with fibromyalgia (FM) exhibit significant clinical heterogeneity, in terms of physical, social and psychological functions, as well as therapeutic responses. Here, we examined FM patients in terms of pain, physical, social and psychological variables to identify clinical subgroups that may be predictive of treatment patterns.

Concordance between the tuberculin skin test and interferon gamma release assay (IGRA) for diagnosing latent tuberculosis infection in patients with systemic lupus erythematosus and patient characteristics associated with an indeterminate IGRA

Objective We investigated the agreement between the tuberculin skin test (TST) and the QuantiFERON-TB gold (QFT-G) assay in the diagnosis of latent tuberculosis infection (LTBI) in patients with systemic lupus erythematosus (SLE). Furthermore, we evaluated the factors associated with indeterminate results in the QFT-G assay in patients with SLE. Methods We enrolled 136 patients with SLE prospectively, and compared them to 66 patients with rheumatoid arthritis (RA). In addition to the TST, QFT-G assay, patients’ medications, and Bacillus Calmette-Guérin (BCG) vaccination status were also investigated. A positive TST or QFT-G assay result without an active tuberculosis lesion on chest x-ray was considered to indicate a diagnosis of LTBI. Results The prevalence of LTBI was 26.5% in patients with SLE and 30.3% in patients with RA. The agreement between the TST and QFT-G assay was fair in SLE patients, but poor in RA patients. BCG vaccination was one factor associated with discordance between TST and QFT-G. Older age and higher SLE Disease Activity Index (SLEDAI) score were associated with a negative TST/positive QFT-G result in patients with SLE. Higher SLEDAI score and increased glucocorticoid dose were associated with an indeterminate result in the QFT-G assay for patients with SLE. Conclusions Agreement between the QFT-G assay and TST in patients with SLE was found to be fair. However, BCG vaccination status, age, and SLEDAI score are all factors that could result in discordance between the two tests. Indeterminate results from the QFT-G assay may be caused by a higher SLEDAI score or increased glucocorticoid dose.

Association between variable number tandem repeats within the 3′ flanking region of the interleukin-6 gene and systemic lupus erythematosus in Korean patients

Variable number tandem repeat (VNTR) polymorphism located in the 3′ flanking region of the interleukin-6 (IL-6) gene was examined in Koreans with systemic lupus erythematosus (SLE). We identified 15 VNTR alleles (K1 to K15) in the 3′ flanking region by Genescan analysis. The VNTR K8 allele, a 648-base pair (bp) allele, was most commonly found in Koreans, being present in 74.8% of the SLE patients and 70.3% of the normal controls. The VNTR K9 (642 bp) allele was associated with susceptibility to SLE. In addition, the VNTR K9 was significantly associated with leukopenia (p = 0.048), thrombocytopenia (p = 0.020), and elevated C-reactive protein (p = 0.019). These data suggest that the VNTR K9 in the 3′ flanking region of the IL-6 gene may be associated with disease susceptibility and the clinical phenotypes of SLE.

Association between catechol‐O‐methyl transferase gene polymorphisms and fibromyalgia in a Korean population: A case–control study

Although polymorphisms of the catechol‐O‐methyl transferase (COMT) gene have been implicated in altered pain sensitivity, results concerning the association between COMT gene polymorphisms and fibromyalgia (FM) are equivocal. We assessed the associations between COMT single‐nucleotide polymorphisms (SNP) and FM risk and symptom severity.

Polyamine patterns in plasma of patients with systemic lupus erythematosus and fever

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with various clinical manifestations and serologic markers. In this study, we analyzed nine polyamine (PA) profiles of plasma from patients with SLE and healthy controls (HCs), and the relationship between the PA profiles and disease activity. PA alterations in plasma of 44 patients with SLE and fever were investigated using gas chromatography mass spectrometry (GC-MS) in selected ion monitoring mode using N-ethoxycarbonyl/N-pentafluoropropionyl derivatives, and compared with those of 43 HCs. Patients with SLE and HCs showed differences in five of nine PA profiles. Among five changed PA levels, four PAs, namely N1-acetylcadaverine, spermidine, N1-acetylspermidine, and spermine, were dramatically decreased. However, the level of cadaverine was increased in patients with SLE. In the partial correlation with PA profiles and disease activity markers of SLE, several disease activity markers and nutritional markers were correlated with cadaverine, spermidine, and N 8 -acetylspermidine. Thus, our results provide a comprehensive understanding of the relationship between PA metabolomics and disease activity markers in patients with SLE.

Mesenteric vasculitis after G-CSF administration in a severe neutropenic patient with systemic lupus erythematosus.

Granulocyte colony-stimulating factor (G-CSF) is commonly used with neutropenic patients to accelerate recovery. G-CSF is a hematopoietic cytokine that regulates the proliferation and differentiation of neutrophil precursors, and is known as a safe and effective treatment for chemotherapy-induced neutropenia. However, we encountered a case in which a patient with systemic lupus erythematosus (SLE) developed mesenteric vasculitis after G-CSF administration. The patient was a 36-year-old female admitted with fever, arthralgia, and generalized erythematous rash. Despite symptomatic improvement with a high-dose steroid, severe neutropenia persisted for three weeks, precipitating a decision to use G-CSF to enhance recovery. Mesenteric vasculitis developed 15 hours after administration of G-CSF injection. Because the response of immune cells such as neutrophils and T cells is uncontrolled and dysfunctional in patients with lupus, G-CSF therapy should be used with caution.

AB0029 Characteristic patterns of hla presentation and t cell differentiation in adult-onset still’s disease

Background The role of T cells in AOSD pathogenesis remains controversial. In autoimmune and auto-inflammatory diseases, such as rheumatoid arthritis (RA) and Behçet’s disease, a human leukocyte antigen (HLA)-restricted T cell response to antigen has been shown to affect disease progression, with several HLA alleles strongly associated with disease severity. Objectives In this study, we investigated the frequencies of cells presenting HLA-DP, DQ, and DR, as well as differentiated T cell populations including naïve and effector memory T cells in peripheral blood leukocytes (PBLs) of patients with AOSD. Frequencies of the markers were then compared based on clinical outcomes and disease activity, to better understand the role of these cell populations in the pathogenesis of AOSD. Methods This study enrolled 14 active AOSD patients, 20 rheumatoid arthritis (RA) patients, and 20 healthy controls (HC). The percentage of surface-stained cells presenting HLA–DP, DQ, and DR alleles, and the proportions of differentiated T cell populations in peripheral blood leukocytes (PBLs) were measured by flow cytometry. Results Patients with AOSD exhibited significantly higher percentages of lymphocytes presenting HLA-DP and HLA-DR, and lower percentages of cells presenting HLA-DQ, than patients with RA or HC. The proportions of CD4+, CD4 +CCR7+, CD4 +CD62L-, and CD8 +CD62L- cells in PBLs were decreased in patients with AOSD relative to patients with RA or HCs. In contrast, AOSD patients exhibited increased proportions of CD8 +naïve T cells in whole blood relative to patients with RA or HC. The proportions of CD4 +effector memory T cells, CD8 +naïve T cells, and CD8 +effector memory T cells in whole blood cells and CD4 +effector memory T cell in lymphocytes were significantly associated with systemic score. Conclusions While the frequencies of CD4+, CD8+, CCR7+, CD4 +CCR7+, CD4 +CD62L-, and CD8 +CD62L- cells were significantly decreased in patients with AOSD, the frequency of CD8 +naïve T cells was elevated in patients with AOSD, and correlated with systemic score. Additional studies in a larger cohort of patients will be necessary to evaluate the role of these markers in the pathogenesis of AOSD. Disclosure of Interest None declared

AB0855 The disparities between fracture risk assessment (FRAX) with bmd and without BMD in korean patients with ankylosing spondylitis- multicenter trial

Objectives The aims of this study are to determine the proportion of patients with ankylosing spondylitis (AS) at high risk for major osteoporotic and hip fractures of Fracture risk assessment (FRAX) in Korean and to determine if a care gap exists for high risk. Methods This study is a multicenter study including 163 AS patients in 5. All of the AS patients fulfilled the modified New York criteria. The classification of osteoporosis according to WHO criteria was based on T-score ≤ -2.5. The FRAX criteria for high risk of osteoporotic fracture, which is 10-year probability of ≥20% for major osteoporotic fracture or ≥3% for hip fracture, were calculated by the FRAX tool including the bone mineral density (BMD) values. We assessed various demographic factors, clinical and laboratory findings of AS, and medication use for AS and osteoporosis, and then evaluated the risk factors for osteoporotic fracture. Results The mean age of AS patients was 44.3 years, and 42 patients were female (25.2%) with 23 postmenopausal women 56.1%. Osteoporotic fracture was detected in 16 (9.8%) patients with AS. Among the 16 patients ≥65 years of age, 2 (12.5%) and 8 (50%) were at high risk for a major osteoporotic fracture (10-year probability >20%) and hip fracture (>3%), respectively. Among patients with BMD measurements (n=106), the 10-year risk of a major osteoporotic fracture and hip fracture calculated with BMD was significantly higher than in those without BMD measurements (P=0.001, P=0.002) respectively. The 10-year risk of a major osteoporotic and hip fracture fracture calculated with BMD was significantly higher than in those without BMD measurements (P<0.001, P=0.003) respectively among male patients with BMD measurements (n=74). There is no statistic difference of the 10-year risk of a major osteoporotic fracture and hip fracture between those calculated with BMD and those without BMD measurements (P>0.05) respectively among female patients (n=32). Conclusions A substantial gap exists between FRAX with BMD and without BMD in Korean patients with AS. Disclosure of Interest None declared