Serum growth arrest-specific protein 6 levels are a reliable biomarker of disease activity in systemic lupus erythematosus.

PURPOSE: Growth arrest-specific protein 6 (Gas6) has been suggested to be a biomarker of disease activity in patients with systemic lupus erthematosus (SLE). We investigated the clinical significance of this protein in Korean SLE. METHODS: Blood samples were collected from 150 SLE patients and 50 normal controls (NC). In addition, follow-up samples were collected from 50 SLE patients. RESULTS: Serum Gas6 levels of SLE patients (43.01 ± 28.02 ng/mL) were higher than those of NC (20.15 ± 9.23 ng/mL, p<0.001). When evaluated sensitivity and specificity of the Gas6 for diagnosing SLE using ROC curves, the sensitivity and specificity were 72.7 % and 84 % with a cut-off value of 25.3 ng/mL. In the ROC analysis of Gas6, anti-dsDNA antibody, ESR, complement 3 and complement 4 to identify patients with active lupus, area under the curve (AUC) of Gas6 was highest with 0.763. Serum Gas6 levels were significantly higher in the patients with serositis (70.04 ± 30.85 ng/mL) and renal disorder (65.66 ± 32.28 ng/mL) compared to those without (41.88 ± 27.44 ng/mL, p=0.033, 40.3 ± 26.33 ng/mL, p=0.001, respectively). Gas6 levels were correlated positively with anti-dsDNA antibody (r=0.199, p=0.015), ESR (r=0.204, p=0.013) and SLEDAI (r=0.512, p<0.001). In addition, serum Gas6 levels were correlated negatively with hemoglobin (r= -0.165, p=0.043), lymphocyte count (r= -0.165, p=0.043), complement 3 (r= -0.343, p<0.001) and complement 4 (r= -0.316, p<0.001). Furthermore, change in serum Gas6 levels was correlated with change in SLEDAI levels in the SLE patients that were followed up (r=0.524, p<0.001). CONCLUSION: These results suggest that serum Gas6 can be a reliable clinical marker for monitoring disease activity and treatment response in SLE.

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

Hemophagocytic 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 growth arrest-specific protein 6 levels are elevated in adult-onset Still's disease.

We investigated the growth arrest-specific protein 6 in adult-onset Still's disease. Serums were collected from 52 adult-onset Still's disease patients with follow-up samples of 21 patients. The growth arrest-specific protein 6 levels in adult-onset Still's disease were higher compared to those in the normal controls (25.37±7.71 vs. 19.86±5.01 ng/mL, p<0.001). However, growth arrest-specific protein 6 did not correlate with disease activity. Also, growth arrest-specific protein 6 was not decreased after activity was resolved in the follow-up. The growth arrest-specific protein 6 in adult-onset Still's disease patients were higher than the normal controls. However, growth arrest-specific protein 6 was not correlated with disease activity.

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.

Promising biomarkers for systemic lupus erythematosus.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with heterogeneous manifestations. Of particular importance for clinicians are the precise assessment of disease activity and the ability to make appropriate therapeutic decisions. Therefore, interest has increased in biomarkers that can be measured as indicators of pathogenic processes, disease activity and response to management. AREAS COVERED: This article introduces well-studied, as well as newly discovered, biomarkers related to SLE, divided into categories for diagnosis, disease activity and organ involvement. EXPERT OPINION: The lack of reliable biomarkers for lupus hampers the assessment of disease activity and impedes the evaluation of treatment response. Although many reports of lupus biomarkers have been published, few longitudinal and interventional studies have validated the utility of any biomarker for monitoring disease activity. Consortiums of investigators will certainly help in recruiting sufficient number of patients and facilitating the development of standardized assays. Moreover, owing to the multifactorial nature of lupus, a multiplexed approach will clearly be essential. Another promising approach is the use of high-throughput technology, including DNA and antibody microarrays, flow cytometry and proteomic techniques.

Caspase-cleaved fragments of cytokeratin-18 as a marker of inflammatory activity in chronic hepatitis B virus infection.

BACKGROUND: The differential diagnosis between inactive carrier and active hepatitis is important in patients with chronic hepatitis B (CHB) virus infection. Serum cytokeratin (CK)-18 fragments (M30-antigen) are proposed as biomarkers of apoptosis. OBJECTIVES: We investigated whether serum M30-antigen levels might help to characterize the various phases of CHB and predict the state of significant inflammation in patients with CHB. STUDY DESIGN: A total of 339 CHB patients who underwent liver biopsy, were included. Serum M30-antigen levels were compared between inactive carriers (n=21), patients with HBeAg-negative hepatitis (n=95), HBeAg-positive hepatitis (n=141) and liver cirrhosis (n=82). RESULTS: Serum M30-antigen levels were correlated significantly not only with AST (r=0.544, p<0.001) and ALT (r=0.315, p<0.001) and but also inflammatory grading score on liver biopsy (r=0.240, p<0.001). Serum M30-antigen level in HBeAg-negative CHB was significantly higher than that of inactive HBV carrier (399.78 U/L vs 148.90 U/L, p<0.001). Multivariate analysis showed that AST (p<0.001), albumin (p=0.009) and M30-antigen (p=0.020) were the independent predictors of significant inflammation. Combined serum M30-antigen level (>344 U/L) and AST (>78 IU/L) measurement provided the most accurate identification of significant inflammation, showing 38.2% sensitivity, 96.1% specificity, 91.0% positive predictive value and 56.1% negative predictive value. CONCLUSIONS: Serum M30-antigen can be a predictive marker for distinguishing between inactive carrier and HBeAg-negative CHB. Serum M30 levels are associated with the presence of significant inflammation, especially in patients with normal or minimally elevated ALT in CHB patients.

Acquired hemophilia successfully treated with activated prothrombin complex concentrate and immunosuppressant combination: a case report.

Acquired hemophilia A is a very rare but life-threatening disorder caused by autoantibody against coagulation factor VIII. The incidence was much rarer in young people. In this case report, a young woman presented with spontaneous muscle hematoma. Because of pain and limited range of motion, she underwent surgery for resolution at first. However, her symptoms and hemorrhage worsened. She was diagnosed with acquired hemophilia A. We started combination treatment with bypassing agent, activated prothrombin complex and immunosuppressants immediately and the results were successful. The acute bleeding was controlled and autoantibody was completely resolved.

Serum markers for predicting significant necroinflammatory activity in patients with chronic hepatitis B.

OBJECTIVES: The aim of this study was to determine the serum markers that predict significant inflammation in patients with chronic hepatitis B (CHB). DESIGN AND METHODS: Between October 2005 and June 2009, 384 subjects with CHB were enrolled. RESULTS: Multiple logistic regression analysis identified the ALT, hyaluronic acid (HA) and procollagen III N-terminal peptide (PIIINP) as independent predictors of significant inflammation (grade≥3). We constructed a formula for predicting significant inflammation. A significant inflammation (SI) score=1.773×ALT score+1.599×PIIINP score+0.677×HA score-1.962. The area under receiver operating characteristic curve of the SI score was 0.831. The sensitivity, specificity, positive predictive value and negative predictive value of the SI score were 79.5%, 70.8%, 76.8% and 74.3%, respectively. CONCLUSIONS: A simple scoring system including ALT, PIIINP and HA is an accurate non-invasive predictor of significant inflammatory activities in patients with CHB.

Association between apolipoprotein E genotype, chronic liver disease, and hepatitis B virus.

BACKGROUND/AIMS: Apolipoprotein E (ApoE) plays an important role in regulating lipid and lipoprotein metabolism, and ApoE genotypes are known to affect plasma lipoprotein concentrations. We investigated whether ApoE genotype determines the disease outcome in hepatitis B virus (HBV)-infected individuals, and verified the association between ApoE genotype and the occurrence of hepatocellular carcinoma (HCC) in patients with chronic liver diseases of various etiologies. METHODS: This hospital-based, case-controlled study enrolled 156 subjects (47 healthy controls, 50 HBV-related liver cirrhosis patients, and 59 HCC patients). ApoE genotypes were determined using PCR-based ApoE genotyping kits. The biological significance of ApoE genotype was verified by measuring serum ApoE levels using an ELISA kits. RESULTS: The ε3 allele was the most common allele, with allele frequencies among the entire cohort of 5.8%, 84.3%, and 9.9% for the ε2, ε3, and ε4 alleles, respectively. Significantly more of those patients carrying the ε3/3 genotype had developed liver cirrhosis compared to the control subjects. Being an ApoE4 carrier was associated with a lower probability of developing liver cirrhosis. The allele frequencies and genotype distribution of ApoE did not differ significantly between the liver cirrhosis and HCC patients. The serum level of ApoE was significantly higher in patients with liver cirrhosis than in the healthy controls, but did not differ significantly with the ApoE genotype. CONCLUSIONS: The ApoE ε3/3 genotype frequency was higher in patients with HBV-associated liver cirrhosis than in the controls.