Ju-Yang Jung

Korean versions of the Perceived Stress Scale (PSS‐14, 10 and 4): psychometric evaluation in patients with chronic disease

BACKGROUND The Perceived Stress Scale (PSS) is a representative instrument used to measure stress. The original PSS comprises 14 items (PSS-14) in two subscales, but 10- and 4-item versions are also available (PSS-10 and 4, respectively). The target populations of psychometric studies using the PSS have far mainly comprised college students, and the underlying constructs of the PSS versions are controversial: one factor vs. two factors and first order vs. second order. OBJECTIVE The aim of this study was to evaluate the psychometric properties of the Korean versions of the PSS-14, 10 and 4 (designated KPSS-14, 10 and -4, respectively) in patients with chronic disease. METHODS The PSS-14, 10 and 4 were translated into Korean using forward and backward translation. Factorial construct validity was tested using both exploratory and confirmatory factor analyses. Item convergent validity and item discriminant validity were tested. Concurrent validity was examined using the Center for Epidemiologic Studies-Depression scale. Known-groups validity was analysed using t-test and effect size. Reliability was tested using Cronbachs alpha and the intraclass correlation coefficient. RESULTS Exploratory factor analysis supported a two-factor model for all Korean versions of the PSS, and confirmatory factor analysis indicated that the model fit the KPSS-10 well and the KPSS-4 only marginally. The testing of item convergent and discriminant validity revealed a 100% scaling success. As expected, all scores in the KPSS-14, 10 and 4 were moderately correlated with depression scores and differed significantly according to gender. The Cronbachs alpha for the KPSS-14 and 10 exceeded the criterion of 0.70. The intraclass correlation coefficient values of all three Korean versions were satisfied. CONCLUSIONS The KPSS-10 exhibited a first-order, two-factor construct, and excellent reliability and validity were established for Korean patients with chronic disease. The psychometric properties of the shortest version, KPSS-4, were only marginally acceptable.

Reactive hemophagocytic syndrome in adult-onset Still disease: clinical features, predictive factors, and prognosis in 21 patients.

AbstractHemophagocytic syndrome (HPS) is a potentially life-threatening complication of systemic inflammatory disorders. Adult-onset Still disease (AOSD) is one of the systemic autoimmune diseases associated with reactive hemophagocytic syndrome (RHS). This study aimed to evaluate the characteristic findings, predictive factors, and prognosis of RHS in patients with AOSD.We retrospectively evaluated 109 patients diagnosed with AOSD and reviewed their clinical data and laboratory findings, including the biopsy results of 21 AOSD patients with RHS. Moreover, data from 17 hemophagocytic lymphohistiocytosis (HLH) patients evaluated during the same period were compared with those from the RHS patients.Twenty-one patients (19.3%) developed RHS during the course of AOSD, and only 7 patients (6.4%) were confirmed by bone marrow, liver, or lymph node biopsy. AOSD patients with RHS showed significantly higher frequencies of splenomegaly, hepatomegaly, and lymphadenopathy than did those without RHS. Moreover, patients with RHS showed significantly higher relapse rates than those without RHS (61.9% vs 18.2%, P < 0.001). Possible triggering factors inducing hemophagocytosis were detected in 16 of 21 RHS patients (76.2%): disease flare in 12 patients (75%), infection in 3 patients (18.8%), and drug use in 1 patient (6.3%). AOSD patients with RHS showed higher frequencies of leukopenia, anemia, thrombocytopenia, hypoalbuminemia, hypofibrinogenemia, hypertriglyceridemia, hyperferritinemia, and elevated lactate dehydrogenase levels than did those without RHS. Multivariate logistic regression with forward selection procedure showed that low platelet count (<121,000/mm3), anemia, and hepatomegaly were independent predictors of RHS. Patients with definite RHS and those with probable RHS showed comparable results. Although RHS is a life-threatening complication of AOSD, long-term prognosis was observed to be similar in patients with and those without RHS. Compared to RHS patients, HLH patients had poor prognosis, such as higher death rates (52.9% vs 9.5%, P = 0.005).RHS can be considered when an AOSD patient shows at least 2 of the following 3 findings: low platelet count, anemia, and hepatomegaly. Diagnostic confirmation by biopsy may not be essential if typical clinical findings of RHS are present. Moreover, prognosis of RHS was better than that of HLH diagnosed by the presence of trilineage cytopenia at admission.

Serum S100A12 May Be a Useful Biomarker of Disease Activity in Adult-onset Still’s Disease

Objective. S100A12 and soluble receptor for advanced glycation endproducts (sRAGE) have been suggested as biomarkers of disease activity in patients with systemic juvenile idiopathic arthritis. We investigated the clinical significance of these markers in adult-onset Still’s disease (AOSD). Methods. Blood samples were collected from 37 patients with active AOSD and 38 healthy controls (HC). Of the patients with AOSD, followup samples were collected from 19 patients after resolution of disease activity. Results. Serum S100A12 (547.9 ± 148.4 ng/ml) in patients with AOSD was higher than those of HC (272.3 ± 133 ng/ml, p < 0.001). The sRAGE levels of AOSD (514.1 ± 273.6 pg/ml) were lower than those of HC (850.3 ± 405.8 pg/ml, p < 0.001). Serum S100A12 correlated with serum sRAGE (r = −0.228, p = 0.049). Serum S100A12 correlated with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), ferritin, and systemic score, whereas sRAGE did not correlate with any disease activity markers. In addition, the level of S100A12 was decreased after disease activity was resolved in followed-up patients with AOSD (505.7 ± 161.3 ng/ml vs 361.3 ± 162.5 ng/ml, p = 0.01). Further, the change of S100A12 was well correlated with that of ESR, CRP, and systemic score. Conclusion. S100A12 levels showed strong correlations with known disease activity markers such as ESR, CRP, ferritin, and systemic score. In the followup patients with AOSD, most patients showed decreased S100A12 levels after resolution of disease activity. These results suggest that serum S100A12 can be a reliable clinical marker for monitoring disease activity and treatment response.

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.

The pathologic findings of skin, lymph node, liver, and bone marrow in patients with adult-onset still disease: a comprehensive analysis of 40 cases.

AbstractAdult-onset Still disease (AOSD) is characterized by fever, skin rash, and lymphadenopathy with leukocytosis and anemia as common laboratory findings. We investigated the characteristic pathologic findings of skin, lymph node, liver, and bone marrow to assist in proper diagnosis of AOSD.Forty AOSD patients were included in the study. The skin (26 patients), lymph node (8 patients), liver (8 patients), or bone marrow biopsies (22 patients) between 1998 and 2013 were retrospectively analyzed. AOSD patients were diagnosed according to the Yamaguchi criteria after excluding common infections, hematological and autoimmune diseases. Immunohistochemistry, immunofluorescence, and Epstein–Barr virus–encoded RNA (EBER) in situ hybridization were performed.Most skin biopsies revealed mild lymphocytic or histiocytic infiltration in the upper dermis. Nuclear debris was frequently found in the dermis in 14 cases (53.8%). More than half of the cases (n = 14, 53.8%) showed interstitial mucin deposition. Some cases showed interface dermatitis with keratinocyte necrosis or basal vacuolization (n = 10; 38.5%). The lymph node biopsies showed a paracortical or diffuse hyperplasia pattern with immunoblastic and vascular proliferation. The liver biopsies showed sparse portal and sinusoidal inflammatory cell infiltration. All cases showed various degrees of Kupffer cell hyperplasia. The cellularity of bone marrow varied from 20% to 80%. Myeloid cell hyperplasia was found in 14 out of the 22 cases (63.6%). On immunohistochemistry, the number of CD8-positive lymphocytes was greater than that of CD4-positive lymphocytes in the skin, liver, and bone marrow, but the number of CD4-positive lymphocytes was greater than that of CD8-positive lymphocytes in the lymph nodes.The relatively specific findings with respect to the cutaneous manifestation of AOSD were mild inflammatory cell infiltration in the upper dermis, basal vacuolization, keratinocyte necrosis, presence of karyorrhexis, and mucin in the dermis. In all cases, pathologic findings in the lymph nodes included paracortical hyperplasia with vascular and immunoblastic proliferation. Skin and lymph node pathology in addition to clinical findings can aid in the diagnosis of AOSD.

Incomplete clearance of apoptotic cells in systemic lupus erythematosus: pathogenic role and potential biomarker

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with repeated inflammation against multiple organs. Although its pathophysiology is not yet unveiled, uncleared apoptotic cells and their accumulation in tissue contribute to the autoimmune disturbance in SLE. Apoptosis is a programmed cell death process, which maintains tissue homeostasis and inhibits the development of any further immune response against apoptotic remnants. Earlier studies revealed that various ‘eat‐me’ signals on apoptotic cells, bridging molecules and their receptors on phagocytes play a role in such a complicated process. Tyro3‐Axl‐Mer receptors, their bridging molecules, milk fat globulin epidermal growth factor‐8, T‐cell immunoglobulin mucin domain protein family, scavenger receptors, C1q, and pentraxins were found to be abnormal in SLE. In this review, apoptosis and clearance of its remnants are summarized, and the molecules involved in the incomplete clearance of apoptotic cells in SLE are discussed.

The Relevance of miRNA-21 in HSV-Induced Inflammation in a Mouse Model

The purpose of this study was to clarify the correlation between microRNA-21 (miR-21) expression and inflammation in a herpes simplex virus (HSV)-induced Behçet’s Disease (BD) mouse model. miR-21 was compared between BD patients and healthy controls in peripheral blood mononuclear cells (PBMC). For miR-21 inhibition, miR-21 antagomir was applied to BD mice. The change of symptoms was monitored. The levels of cytokines and related molecules were determined by ELISA and real time qPCR. Treatment with colchicine or pentoxifylline down-regulated the level of miR-21 with improved symptoms in mice. miR-21 inhibition was accompanied by down-regulated serum levels of IL-17 and IL-6. The expression levels of PDCD4, RhoB, PD-1, IL-12p35, and toll-like receptor-4 were also regulated by miR-21 inhibition. miR-21 was correlated with HSV-induced BD-like inflammation in mice and BD patients. The expression of miR-21 was regulated by antagomir in mice.

Thrombocytopenia in Systemic Lupus Erythematosus: Clinical Manifestations, Treatment, and Prognosis in 230 Patients

AbstractThe aim of the study was to examine the clinical characteristics and prognosis according to severity of thrombocytopenia and response to treatment for thrombocytopenia in patients with systemic lupus erythematosus (SLE).We retrospectively evaluated 230 SLE patients with thrombocytopenia, and reviewed their clinical data and laboratory findings. Thrombocytopenia was defined as platelet counts under 100,000/mm3, and patients were divided into 3 thrombocytopenia groups according to severity: mild (platelet counts >50,000/mm3), moderate (>20,000/mm3, ⩽50,000/mm3), and severe (⩽20,000/mm3). Clinical characteristics, treatments, and prognoses were compared among the groups. Furthermore, complete remission of thrombocytopenia was defined as platelet counts >100,000/mm3 after treatment.There was no significant difference in clinical or laboratory findings among the groups according to severity of thrombocytopenia. However, hemorrhagic complications were more frequent in severe thrombocytopenia (P < 0.001) and mortality was also higher (P = 0.001). Complete remission was achieved in 85.2% of patients. The clinical characteristics and modality of treatment did not differ between the patients with and without complete remission. Mortality in patients with complete remission (1.5%) was significantly lower than in those without complete remission (29.4%, P < 0.001). Survival was significantly higher in patients with complete remission from thrombocytopenia (odds ratio = 0.049, 95% confidence interval: 0.013–0.191, P < 0.001).The severity of thrombocytopenia in SLE patients can be a useful independent prognostic factor to predict survival. Moreover, complete remission of thrombocytopenia after treatment is an important prognostic factor. The severity of thrombocytopenia and response to treatment should be closely monitored to predict prognosis in SLE patients.

TLR4 Endogenous Ligand S100A8/A9 Levels in Adult-Onset Still’s Disease and Their Association with Disease Activity and Clinical Manifestations

S100A8/A9 has been suggested as a marker of disease activity in patients with adult-onset Still’s disease (AOSD). We evaluated the clinical significance of S100A8/A9 as a biomarker and its pathogenic role in AOSD. Blood samples were collected prospectively from 20 AOSD patients and 20 healthy controls (HCs). Furthermore, skin and lymph node biopsy specimens of AOSD patients were investigated for S100A8/A9 expression levels via immunohistochemistry. Peripheral blood mononuclear cells (PBMCs) of active AOSD patients and HCs were investigated for S100A8/A9 cell signals. S100A8/A9, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) levels in active AOSD patients were higher than those of HCs. S100A8/A9 levels correlated positively with IL-1β, TNF-α and C-reactive protein. The inflammatory cells expressing S100A8/A9 were graded from one to three in skin and lymph node biopsies of AOSD patients. The grading for S100A8/A9 was more intense in the skin lesions with karyorrhexis, mucin deposition, and neutrophil infiltration. Like lipopolysaccharide (LPS), S100A8/A9 induced phosphorylation of p38 and c-Jun amino-terminal kinase (JNK) in PBMCs, suggesting that S100A8/A9 activates Toll-like receptor 4 signaling pathways. These findings suggest that S100A8/A9 may be involved in the inflammatory response with induction of proinflammatory cytokines and may serve as a clinicopathological marker for disease activity in AOSD.