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We investigated whether serum aminoacyl-tRNA synthetase-interacting multifunctional protein-1 (AIMP1) could predict severe cases of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) based on the Birmingham vasculitis activity score (BVAS). Sixty-one patients with AAV were selected for inclusion from our prospective AAV cohort. AAV-specific indices and clinical manifestations were assessed, and laboratory tests were performed on the day of blood sampling. Patients with severe AAV were defined as those with a BVAS higher than the lower limit of the highest tertile of BVAS (BVAS ≥ 12). We measured serum AIMP1 levels of the stored serum samples. A total of 20 (32.8%) and 41 (67.2%) patients were classified as having severe and nonsevere AAV according to the cut-off of BVAS ≥ 12. Patients with severe AAV showed higher frequencies of general and renal manifestations, along with ANCA positivity, and exhibited a higher mean neutrophil count, erythrocyte sedimentation rate, and C-reactive protein levels, but lower mean haemoglobin and serum albumin levels than those with nonsevere AAV. The mean serum AIMP1 level in patients with severe AAV was significantly higher than that of patients with nonsevere AIMP1 (351.1 vs. 98.4 pg/mL, p = 0.006). Multivariate logistic regression analysis including variables showing significance in univariate analyses revealed that only serum AIMP1 exhibited a significant association with severe AAV (odds ratio 1.004, p = 0.031). When we set the optimal cut-off of serum AIMP1 for severe AAV to 50.28 pg/mL, patients with severe AAV more frequently had AIMP1 levels above the cut-off than those with nonsevere AAV (80.0% vs. 31.7%, relative risk 8.615, p < 0.001). The results from our study suggest that serum AIMP1 can be used to estimate the cross-sectional severe AAV population based on the BVAS.

The aim of this study was to evaluate how the cytokine profiles differed between autoantibody based subgroups of systemic lupus erythematosus (SLE). SLE is a systemic autoimmune disease, characterized by periods of flares (active disease) and remission (inactive disease). The disease can affect many organ systems, e.g., skin, joints, kidneys, heart, and the central nervous system (CNS). SLE patients often have an overproduction of cytokines, e.g., interferons, chemokines, and interleukins. The high cytokine levels are part of the systemic inflammation, which can lead to tissue injury. In the present study, SLE patients were divided into five groups based on their autoantibody profiles. We thus defined these five groups: ANA negative, antiphospholipid (aPL) positive, anti-Sm/anti-RNP positive, Sjögren's syndrome (SS) antigen A and B positive, and patients positive for more than one type of autoantibodies (other SLE). Cytokines were measured using Mesoscale Discovery (MSD) multiplex analysis. On the basis of the cytokine data, ANA negative patients were the most deviating subgroup, with lower levels of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-12/IL-23p40, and interferon gamma-induced protein (IP)-10. Despite low cytokine levels in the ANA negative group, autoantibody profiles did not discriminate between different cytokine patterns.

Objectives: Secreted aminoacyl-tRNA synthetase-interacting multifunctional protein-1 (AIMP1) has been reported to have pro-inflammatory properties. The aim of this study was to evaluate the clinical significance of serum AIMP1 in patients with systemic lupus erythematosus (SLE)., Methods: Serum levels of AIMP1 were measured in 160 patients with SLE using a human AIMP1 ELISA kit. Eighty patients were classified as active SLE (SLEDAI-2K ≥ 5), and 80 patients were classified as stable SLE. Correlation between serum AIMP1, SLE disease activity index-2000 (SLEDAI-2K), and laboratory variables related to disease activity or inflammatory burdens were assessed using Pearson's correlation analysis. The optimal cut-off value for serum AIMP1 to predict active SLE was estimated by using a receiver operator characteristic curve, and logistic regression analysis was used to compare the odds ratios (ORs) of laboratory variables in predicting active SLE., Results: The median serum AIMP1 was higher in patients with active SLE than those with stable SLE (8.0 vs. 6.5 ng/ml, p<0.001). Serum AIMP1 demonstrated correlation with SLEDAI-2K and laboratory variables related to disease activity or inflammatory burdens. The optimal cut-off AIMP1 to predict active SLE was 10.09. Multivariate logistic regression analysis including conventional laboratory variables demonstrated that serum AIMP1 ≥10.09 ng/ml (OR 3.919, 95% confidence interval 1.223-12.564, p=0.022) was useful in predicting active SLE., Conclusions: Serum levels of AIMP1 were associated with disease activity of SLE and could predict active SLE based on SLEDAI-2K.

Objectives: Endothelial monocyte-activating polypeptide II (EMAP II) is a multifunctional polypeptide with proinflammatory and antiangiogenic activity. Hyperglycemia and dyslipidemia appears to be significant factors contributing to increased EMAP-II levels. We determined serum EMAP II in children and adolescents with type 1 diabetes as a potential marker for micro-vascular complications and assessed its relation to inflammation and glycemic control., Methods: Eighty children and adolescents with type 1 diabetes were divided into 2 groups according to the presence of micro-vascular complications and compared with 40 healthy controls. High-sensitivity C-reactive protein (hs-CRP), hemoglobin A1c (HbA1c) and EMAP II levels were assessed., Results: Serum EMAP II levels were significantly increased in patients with micro-vascular complications (1539 ± 321.5 pg/mL) and those without complications (843.6 ± 212.6 pg/mL) compared with healthy controls (153.3 ± 28.3 pg/mL; p<0.001). EMAP II was increased in patients with microalbuminuria than normoalbuminuric group (p<0.001). Significant positive correlations were found between EMAP II levels and body mass index, fasting blood glucose, HbA1c, serum creatinine, triglycerides, total cholesterol, urinary albumin creatinine ratio (UACR) and hs-CRP (p<0.05). A cutoff value of EMAP II at 1075 pg/mL could differentiate diabetic patients with and without micro-vascular complications with a sensitivity of 93% and specificity of 82%., Conclusions: We suggest that EMAP II is elevated in type 1 diabetic patients, particularly those with micro-vascular complications. EMAP II levels are related to inflammation, glycemic control, albuminuria level of patients and the risk of micro-vascular complications., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The atherosclerotic process begins in adolescence, and its progression is determined by the same risk factors as in adults. Endothelial monocyte activating polypeptide-II (EMAP-II) is a multifunctional cytokine with proinflammatory and antiangiogenetic activity that may play a pathogenic role in the development of endothelial dysfunction and atherosclerosis. The aim of our study was to determine the serum level of EMAP-II in childhood-onset type 1 diabetic patients and obese adolescents. We found increased of serum level of EMAP-II in childhood-onset type 1 diabetic patients and in patients with obesity that do not suffer from diabetes. Also, the level of EMAP-II correlated with the serum level of glycosylated hemoglobin and blood glucose, and key markers of lipid metabolism, body mass index. Increased serum level of EMAP-II may be one of the pathway of endothelial dysfunction in type 1 diabetes.

Kisspeptin is an antimetastatic agent in some cancers that has also been associated with lymphoid cell apoptosis, a phenomenon favoring metastases. Our aim was to determine the association of kisspeptin with lymphocyte apoptosis and the presence of metastases in colorectal cancer patients. Blood was drawn from 69 colon cancer patients and 20 healthy volunteers. Tissue specimens from healthy and pathological tissue were immunohistochemically analyzed for kisspeptin and endothelial monocyte activating polypeptide II (EMAP-II) expression. Blood EMAP-II and soluble Fas ligand (sFasL) levels were examined by an enzyme-linked immunosorbent assay method. The kisspeptin and EMAP-II expression and secretion levels in the DLD-1 and HT-29 colon cancer cell lines were examined by quantitative real-time polymerase chain reaction, Western analysis and enzyme-linked immunosorbent assay, whereas lymphocyte viability was assessed by flow cytometry. The effect of kisspeptin on the viability of colon cancer cells was examined by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]. Exogenous, synthetic and naturally produced, kisspeptin induces through the G-protein-coupled receptor 54 (GPR54; also known as the kisspeptin receptor) the EMAP-II expression and secretion in colon cancer cell lines, inducing in vitro lymphocyte apoptosis, as verified by the use of an anti-EMAP-II antibody. These results were reversed with the use of kisspeptin inhibitors and by kisspeptin-silencing experiments. Tumor kisspeptin expression was associated with the tumor EMAP-II expression (p < 0.001). Elevated kisspeptin and EMAP-II expression in colon cancer tissues was associated with lack of metastases (p < 0.001) in colon cancer patients. These data indicate the antimetastatic effect of tumor-elevated kisspeptin in colon cancer patients that may be mediated by the effect of kisspeptin on EMAP-II expression in colon cancer tumors in patients with normal serum EMAP-II levels. These findings provide new insight into the role of kisspeptin in the context of metastases in colon cancer patients.

Endothelial dysfunction is implicated in the pathogenesis of macrovascular complications of diabetes and atherosclerosis. Endothelial monocyte-activating polypeptide-II (EMAP-II) is a multifunctional polypeptide with proinflammatory and antiangiogenic activity. The aim of this study was to investigate the serum level of EMAP-II in obese and nonobese patients with type 2 diabetes. We found an increase of serum level of EMAP-II in obese diabetic patients compared to obese subjects without diabetes. Similar alterations were observed also in non-obese diabetic patients compared to control subjects. Moreover, it was significant elevation of serum EMAP-II in obese patients without diabetes compared to control subjects. In obese and non-obese patients with diabetes it was a significant correlation between HbAc1, blood glucose, body mass index and levels of EMAP-II, total cholesterol, LDL, HDL, triglycerides and EMAP-II. In obese non-diabetic patients it was significant correlation between BMI, triglycerides, total cholesterol and EMAP-II. The revealed change of EMAP-II serum level reflects an endothelial dysfunction in patients with type 2 diabetes. Hyperglycemia, dyslipidemia and obesity appear to be significant factors contributing to elevation of EMAP-II level.

Objective: Apoptosis is a key feature of advanced atherosclerotic plaques. Attraction signals such as p43 released from apoptotic cells play a crucial role in the timely removal of the apoptotic remnants by recruiting fresh phagocytes. Here, we sought to determine whether p43 may link apoptosis to inflammation and plaque progression., Methods and Results: RT-PCR and immunohistochemistry showed that p43 was abundantly expressed in human plaques compared with nonatherosclerotic mammary arteries and colocalized with splicing factor SC-35. Cell culture experiments indicated that p43 expression was associated with enhanced protein translation. On initiation of apoptosis or necrosis, p43 was cleaved by calpains and released as truncated protein p43(apoptosis-released factor [ARF]). Processing of p43 into endothelial monocyte activating polypeptide II was not observed. Full-length p43, but not p43(ARF) or endothelial monocyte activating polypeptide II, activated THP1 monocytes (upregulation of tumor necrosis factor alpha, interleukin 1 beta, interleukin 8, macrophage inflammatory protein (MIP)-1 alpha, MIP1 beta, MIP2 alpha) and endothelial cells (enhanced synthesis of E-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, tissue factor). The chemotactic activity of p43 or fragments thereof was poor compared with ATP. Treatment of smooth muscle cells with p43 did not induce cell death., Conclusions: p43 is cleaved during apoptosis by calpains and released as a truncated protein that is harmless for the structure of the plaque.

The blood concentration of histamine, serotonin, endothelial-monocytic activating polypeptide II (EMAP II). activity of elastase, as well as general clinical markers of inflammation, the leucocytes quantity in peripheral blood and the average mass peptides level in particular, were studied in 72 patients with an acute peritonitis. It was established, that highest level of histamine, serotonin, the elastase activity in serum are characteristic for spread peritonitis and somewhat lower--for the diffuse one. The EMAP II level is most lowered in diffuse and somewhat lesser in case of spread peritonitis. Value of these markers of inflammation had differed concerning the peritonitis cause existed. Between elastase activity raising and EMAP II concentration the back proportional dependence was established. The peritonitis spread stage diagnosis and planning of its treatment become possible when complex considering of the inflammation mediators and EMAP II content is done together with endogenic intoxication indices and clinical symptoms severity.

Background: Endothelial monocyte-activating polypeptide-II (EMAP-II) is a proinflammatory cytokine with antiangiogenic properties. Serum EMAP-II levels have not been investigated previously in non-small-cell lung cancer (NSCLC). The aim of this study was to examine the relationship between serum EMAP-II levels and clinicopathologic features, including prognosis, in patients with NSCLC., Patients and Methods: We measured serum EMAP-II levels in 30 healthy control subjects and 48 patients with untreated NSCLC by enzyme linkedimmunosorbent assay., Results: Patients with NSCLC had significantly higher serum EMAP-II levels than did the control group (492 pg/mL +/- 1126 pg/mL vs. 266 pg/mL +/- 1013 pg/mL; P = .015). No significant association was found between serum EMAP-II levels and various clinicopathologic features (age, smoking history, performance status, histopathology, tumor stage, lymph node stage, or distant metastasis). Median survival time was 10.13 months (range, 2-53.8 months). The high-EMAP-II (>or= 100 pg/mL) group had a shorter survival compared with the low-EMAP-II (< 100 pg/mL) group (P = .023), and the serum EMAP-II level was still an important predictor of survival in a multivariate analysis, along with disease stage., Conclusion: Our results showed that serum EMAP-II levels are significantly higher in patients with NSCLC than in healthy subjects and suggest it is of potential prognostic value.

Neovascularization is essential for growth and spread of primary and metastatic tumors. We have identified a novel cytokine, endothelial-monocyte activating polypeptide (EMAP) II, that potently inhibits tumor growth, and appears to have antiangiogenic activity. Mice implanted with Matrigel showed an intense local angiogenic response, which EMAP II blocked by 76% (P < 0.001). Neovascularization of the mouse cornea was similarly prevented by EMAP II (P < 0.003). Intraperitoneally administered EMAP II suppressed the growth of primary Lewis lung carcinomas, with a reduction in tumor volume of 65% versus controls (P < 0.003). Tumors from human breast carcinoma-derived MDA-MB 468 cells were suppressed by >80% in EMAP II-treated animals (P < 0.005). In a lung metastasis model, EMAP II blocked outgrowth of Lewis lung carcinoma macrometastases; total surface metastases were diminished by 65%, and of the 35% metastases present, approximately 80% were inhibited with maximum diameter <2 mm (P < 0.002 vs. controls). In growing capillary endothelial cultures, EMAP II induced apoptosis in a time- and dose-dependent manner, whereas other cell types were unaffected. These data suggest that EMAP II is a tumor-suppressive mediator with antiangiogenic properties allowing it to target growing endothelium and limit establishment of neovasculature.

Objectives: Endothelial monocyte-activating polypeptide-2 (EMAP-2) is a novel protein that demonstrates potent proinflammatory activity in vivo and in vitro. The purpose of this study was to investigate the expression of EMAP-2 in normal pregnancy and in pregnancies complicated with preeclampsia and to test the hypothesis that EMAP-2 is a causative agent of the endothelial activation of preeclampsia., Methods: Expression of EMAP-2 in the placenta was investigated using reverse transcriptase-polymerase chain reaction to detect mRNA, and immunohistochemistry with an EMAP-2-specific polyclonal antiserum was carried out to detect protein. Levels of circulating EMAP-2 protein were measured in the blood of nonpregnant, normal pregnant, and preeclamptic individuals using a specific enzyme-linked immunoabsorbent assay and the molecular forms present assessed by Western blotting., Results: EMAP-2 is transcribed and translated by the placenta troughout pregnancy and in preeclampsia and can be detected in the plasma of nonpregnant and pregnant individuals. Levels of circulating EMAP-2 antigen are raised in pregnancy compared with nonpregnant controls; however, levels in patients with preeclampsia are identical to those in normal pregnant individuals., Conclusion: While circulating levels of EMAP-2 are increased in pregnancy, there is no evidence that EMAP-2 is involved directly in the pathogenesis of preeclampsia.