Potential Marker Of Disease Activity Research Articles

S100B Is a Potential Disease Activity Marker in Nonsegmental Vitiligo

Vitiligo is a chronic skin condition characterized by progressive depigmentation of the skin. S100B is a damage-associated molecular pattern protein expressed in melanocytes that has been proposed as a marker of melanocyte cytotoxicity. Although the use of S100B as a biomarker in melanoma is well established, to our knowledge its association with vitiligo activity has not yet been investigated. Here, we show that S100B serum levels were significantly increased in patients with active nonsegmental vitiligo and strongly correlated with the affected body surface area. Prospective follow-up showed a predictive value of serum S100B levels on disease progression. Invitro experiments using repeated freeze-thaw procedures showed an intracellular up-regulation of S100B in normal and vitiligo melanocytes before an extensive release in the environment. This phenomenon may explain the increased S100B serum values in the active phase of vitiligo. In a monobenzone-induced vitiligo mouse model we could show the potential of S100B inhibition as a therapeutic strategy in vitiligo. In conclusion, this report shows the possible use of S100B as a biomarker for disease activity in vitiligo. Our data suggest that this damage-associated molecular pattern protein could play a substantial role in the pathogenesis of vitiligo and may be a potential new target for treatment.

Serum Levels of Soluble FLT3 Ligand in Patients with Active Multiple Myeloma Constitute Marker of Bone Marrow Plasma Cell Proliferative Activity.

The FLT3-ligand is a molecule implicated in hematopoiesis. The aim of the present study was to detect any possible connections between serum levels of FLT3-L and multiple myeloma (MM) proliferation markers, such as serum levels of interleukin-6 (IL-6), B-cell activating factor (BAFF), beta-2 microglobulin (B2M), CRP and LDH, as well the percentage of bone marrow infiltration and the plasma cells' proliferation marker Ki-67 PI. We measured the above parameters in 58 patients with active MM. All circulating markers were significantly higher in MM patients compared to controls (p < 0.001 for all cases), and all values were increasing in parallel with disease stage (p < 0.001 for all cases). Positive correlations between FLT3-L were noted with serum levels of BAFF (p < 0.003), IL-6 (p < 0.002), CRP (p < 0.0001), LDH (p < 0.001), and BM Ki-67 PI (p = 0.012), whereas only trends of correlation were noted with the B2M value and the percentage of infiltration. It seems that the increased serum levels of circulating FLT3-L, in parallel with MM activity, reflect their increased presence in the bone marrow microenvironment, probably as an effect of increased angiogenesis and myelosuppression. Consequently, they are potential markers of disease activity.

Blood and urine inducible protein 10 as potential markers of disease activity.

Blood interferon-γ inducible protein 10 (IP-10) has been proposed as a biomarker of disease activity for both tuberculosis (TB) and human immunodeficiency virus (HIV) infection. Urine IP-10 has been detected in adults with active TB, and its level decreases after successful anti-tuberculosis treatment. To evaluate blood and urine IP-10 as biomarker of disease activity. Patients with HIV-TB and active TB were enrolled. Individuals with HIV infection only and healthy donors were included as controls. Blood and urine IP-10 levels were measured using an enzyme-linked immunosorbent assay. Of 39 active TB patients enrolled, 24 were HIV-infected and 15 were HIV-uninfected. Of 87 control subjects without active TB, 54 were HIV-infected and 33 were HIV-uninfected. IP-10 analysis was performed in patients with concomitant blood and urine sample collection. Blood IP-10 was associated with active TB, regardless of HIV infection status; urine IP-10 levels were increased in active TB patients, although the difference was significant in HIV-infected individuals only. Finally, in HIV-infected patients, both blood and urine IP-10 levels were inversely correlated with CD4 T-cell counts. These findings suggest that IP-10 could be used as a biomarker for disease activity (inflammation).

Assessment of Interleukin 16 Serum Levels and Skin Expression in Psoriasis Patients in Correlation with Clinical Severity of the Disease.

Interleukin 16 (IL-16) has been described as a significant cytokine involved in the recruitment of CD4+ cells during inflammation; however, its potential role in psoriasis has not been defined. Our aim was to investigate the IL-16 serum levels and IL-16 mRNA skin expression in psoriasis patients in correlation with disease severity and mRNA skin expression for CD4. Moreover, the IL-16 skin localization was assessed and the -295 T/C IL-16 polymorphism was analyzed. For this exploratory, observational, and cross-sectional study, 97 unrelated patients with chronic plaque type psoriasis and 104 healthy controls were enrolled. IL-16 serum levels were significantly increased in patients compared with controls (P = 0.000022) and positively correlated with Psoriasis Area and Severity Index (r = 0.34, P = 0.0007), Body Surface Area (r = 0.34, P = 0.01) and were significantly higher in individuals with moderate to severe psoriasis (P = 0.0029). There was no significant correlation between IL-16 serum levels and Dermatology Quality of Life Index and no differences in genotype and allele frequencies for -295 T/C IL-16 polymorphism. The expression of IL-16 (mRNA and protein) was elevated in the margin of psoriatic skin while statistically significant increase in IL-16 immunoreactivity, but not in mRNA level, was observed within plaques. Furthermore, the IL-16 mRNA levels within psoriatic lesions positively correlated with the levels of CD4 mRNA, but not with Psoriasis Area and Severity Index. In conclusion, our data revealed an association between circulating IL-16 and severity of psoriasis which indicates that this cytokine could serve as a potential marker of disease activity. However, further investigations are required.

Chemotaxis-driven disease-site targeting of therapeutic adult stem cells in dystrophic epidermolysis bullosa.

BackgroundDystrophic epidermolysis bullosa (DEB), a rare genodermatosis, is characterized by the formation of intra-epidermal blistering and the development of chronic nonhealing skin wounds. Recently, attempts have been made to develop cell-based therapies for this currently intractable disorder. The molecular mechanisms that govern directional migration of the adult stem cells, allowing their efficient and controlled homing to the skin affected with DEB, are poorly understood. The key mechanism that regulates recruitment of leukocytes and progenitor stem cells to distal anatomical tissues affected with disease is chemotaxis, which depends on the signaling molecules, chemokines, and acts primarily as part of the host defense and repair mechanism.MethodsComprehensive proteomic screening of chemokines in the blister fluids of DEB-affected mice was conducted to define the inflammatory and immune activities, thus providing potential to examine local biological mechanisms and define the protein signature within lesional skin as a potential marker of disease activity. Also, the therapeutic relevance of identified chemotactic pathways was investigated in vivo, providing a basis for future clinical investigations.ResultsAssessment of blister fluid-derived chemokines showed a persistent presence of several chemotactic molecules, including CXCL1 + 2 and CXCL5. The majority of blister-originated chemotactic signals were associated with preferential recruitment of CD45+CXCR2+ and CD11b+CXCR2+ leukocytes. Systemic transplantation of an enriched CXCR2 population of mouse adipose-derived stem cells (mADSC) into DEB-affected mice demonstrated effective recruitment of cells to the blistering skin under the influence of blister-derived ligands and deposition of therapeutic type VII collagen.ConclusionsCollectively, these studies demonstrate that recruitment of mADSC into DEB skin is tightly controlled by disease-site chemotactic activities and suggest a potential mechanism for effective application of therapeutic stem cells for DEB.

Serum and Urinary Interleukin-6 in Assessment of Renal Activity in Egyptian Patients with Systemic Lupus Erythematosus.

AIM OF THE WORKThis study investigates whether serum and urinary interleukin-6 (IL-6) represent an early marker of kidney involvement and assesses the difference between them and renal biopsy in lupus nephritis (LN).PATIENTS AND METHODSA total of 60 systemic lupus erythematosus (SLE) patients were compared to 20 healthy controls. Urinary and serum IL-6 were measured in both patients and controls. In addition, renal biopsy was done prior or shortly after urine and blood sampling; the results were classified according to the International Society of Nephrology/Renal Pathology Society classification of LN by recording the activity score and chronicity score for each sample.RESULTSThere was a significant higher level of urinary IL-6 in the SLE patients with biopsy-proven LN than in those without LN and those of the control group. However, no significant difference was reported between the three groups as regards serum IL-6. A strong positive correlation was found between urinary IL-6 and renal disease activity based on the renal SLE disease activity index (SLEDAI) score with no significant correlation regarding the extra renal SLEDAI. Urinary IL-6 was positively correlated with renal biopsy results and with its activity scores but weakly correlated with the chronicity scores.CONCLUSIONUrinary IL-6 may provide a simple noninvasive potential marker of disease activity of renal involvement in adult patients with SLE.

312. Perturbed Response to Experimental Renal Injury in a Mouse Model of Systemic Sclerosis

patient samples. Results: Luminex array profiling of the dermal blister fluid showed increased inflammatory cytokines (mean IL-6 in SSc-77.2 pg/ml, HC17.8 pg/ml, P1⁄40.009, mean IL-17 in SSc-0.61 pg/ml, HC0 pg/ml, P1⁄40.03),and vascular growth factors (VEGF21.7 pg/ml in SSc, HC13.5 pg/ml (P1⁄40.26), PDGF-aa 16.4 pg/ml in SSc, HC-0.97 pg/ml, P1⁄40.049). Additionally MCP-3(CCL7), IL-15 and IFN-g were all significantly increased in SSc compared with HC (P<0.05). Within the serum, Luminex array profiling highlighted a significant increase in mean IL-12p40 (SSc-31.7 pg/ml, HC-2.05 pg/ml, P1⁄40.012) and mean IL-1a (SSc-21.15 pg/ml, HC-2.25 pg/ml, P1⁄4 0.029) in SSc compared with controls. There was no significant difference for other cytokines. Comparing the luminex array profiling of the dermal blister fluid from those with SSc, with the paired serum samples, the only significant correlation was in MCP-3 (r1⁄40.31, P1⁄40.013). Other proinflammatory cytokines [IL-6 (r1⁄40.083, P1⁄40.23), IL-17 (r1⁄40.02, P1⁄40.56)] and growth factors [VEGF (r1⁄40.03, P1⁄40.47), PDGF (r1⁄40.08, P1⁄4 0.22)] showed no correlation between serum samples and dermal blister fluid. Interestingly, the healthy controls showed greater correlation between the Luminex array results from the dermal blister fluid and serum samples, with many reaching significance (IL-10, MCP-3, IL1ra, FGF-2). Conclusion: Our results confirm the potential utility of dermal blister fluid to define local biological processes in SSc, and identifies profibrotic, angiogenic and T-cell derived factors expressed locally within the skin lesions. In contrast, analysis plasma samples revealed elevation of monocyte derived inflammatory proteins. Absence of correlation between the interstitial fluid samples and paired serum samples suggests that the dermal blister sampling method reflects local dermal protein expression rather than exudates from the plasma into the skin. This dermal suction method offers an opportunity to profile the local inflammatory process occurring within the skin and has potential to complement clinical and gene expression based classification to facilitate targeted therapy, as well as providing potential markers of disease activity or treatment effect. Disclosure statement: The authors have declared no conflicts of interest.

Serum amyloid-A in Behçet’s disease

Serum amyloid-A (SAA) is an acute phase protein, synthesized by the liver and previously investigated as a marker of disease activity in many rheumatologic disorders. Its significance in Behçet’s disease (BD), a chronic inflammatory disorder at the crossroad between autoimmune and autoinflammatory syndromes, is still unraveled. Our aim was to assess the role of SAA levels as a potential marker of disease activity in patients with BD. According to our findings, the occurrence of oral aphthosis, neurological impairment, and ocular disease is significantly associated with SAA serum levels higher than 30, 50, and 150 mg/L, respectively. We also suggest that increased SAA levels might identify a thrombotic risk in BD with previous or concurrent vascular involvement.

Simultaneous changes in serum HMGB1 and IFN-α levels and in LAIR-1 expression on plasmatoid dendritic cells of patients with juvenile SLE.. New therapeutic options?

We investigated the simultaneous changes in serum levels of HMGB1 and IFN-α as well as in LAIR-1 expression on plasmatoid dendritic cells (pDCs) of juvenile systemic lupus erythematosus (jSLE) patients in order to explore their involvement in the disease pathogenesis and their correlation with disease activity and other characteristics. In total, 62 blood samples were studied from 26 jSLE patients (18 girls), aged 8-16 years. Twenty healthy subjects (16 girls) of comparable age were included as healthy controls (HCs). Concentrations of serum HMGB1 and IFN-α were assessed by ELISA and LAIR-1 expression on pDCs by five-color flow cytometry. The disease activity index was assessed by SLEDAI and ECLAM scores. It was found that mean serum levels both of HMGB1 and IFN-α were significantly increased in jSLE patients compared to HCs and in jSLE patients with active disease with or without active nephritis compared to those with inactive disease. Mean serum levels of HMGB1 were positively correlated with levels of IFN-α and both were positively correlated with the SLEDAI and ECLAM scores. The expression of LAIR -1 on pDCs of jSLE patients was significantly lower than that of HCs. In conclusion, our findings indicate that serum HMGB1 not only represents a potential marker of disease activity but together with the lack of LAIR-1 inhibitory function may contribute to the sustained inflammatory action of IFN-α in jSLE. In this regard, blocking the action of HMGB1 and its receptors or enhancing the expression/inhibitory function of LAIR-1 on pDCs should be included in future immune interventions for controlling jSLE.

S-calprotectin (S100A8/S100A9): a potential marker of inflammation in patients with psoriatic arthritis.

Objective. To analyse levels of S100A8/S100A9 (calprotectin) and selected cytokines, in blood, in patients with psoriatic arthritis (PsA). Methods. Sixty-five patients with PsA were examined for clinical manifestations and laboratory measurements of S-calprotectin, ESR, hs-CRP, and selected cytokines. Thirty-two patients had mono-/oligoarthritis and 33 had polyarthritis. S-calprotectin, hs-CRP, and cytokines were measured using ELISA, immunoturbidimetry, and multiplex technology (Bio-Plex). Patients with PsA were compared with 31 healthy controls. Results. S-calprotectin and hs-CRP levels were significantly higher in patients with PsA compared with controls (P < 0.001 and P < 0.001, resp.). Patients suffering a polyarthritic disease pattern presented with significantly higher levels of S-calprotectin compared with controls and patients with mono-/oligoarthritis (P < 0.001 and P = 0.017, resp.). The levels of S-calprotectin correlated with hs-CRP (P < 0.001; r s = 0.441), swollen joint count (P = 0.002, r s = 0.397), and CXCL10 (P = 0.046, r s = 0.678) but not with any of the other cytokines evaluated. In multiple logistic regression analysis, S-calprotectin was the only variable significantly associated with psoriatic arthritis (P = 0.002, OR = 1.006, 95% CI = 1.002–1.010). Conclusion. S-calprotectin and hs-CRP levels were significantly higher in patients with PsA. A polyarthritic disease pattern showed higher levels of S-calprotectin than mono-/oligoarthritis. S-calprotectin is considered a potential marker of disease activity in patients with PsA.

Utility of contrast-enhanced ultrasound for the assessment of the carotid artery wall in patients with Takayasu or giant cell arteritis

Carotid contrast-enhanced ultrasound (CEUS) was recently proposed for the evaluation of large-vessel vasculitides (LVV), particularly to assess vascularization within the vessel wall. The aim of this pilot study was to evaluate the potential of carotid colour Doppler ultrasound (CDUS) and CEUS in patients with LVV. This prospective study included seven patients (mean age 48 ± 14 years, all females) with established LVV (Takayasu arteritis or giant cell arteritis). All patients underwent CDUS and CEUS (14 carotid arteries). Intima-media thickness, lumen diameter, Doppler velocities, vessel wall thickening, and lesion thickness were assessed. CEUS was used to improve visualization of the lumen-to-vessel wall border, and to visualize carotid wall vascularization. Four (57%) patients [7 (50%) carotid arteries] exhibited lesions, and the average lesion thickness was 2.0 ± 0.5 mm. According to the Doppler peak systolic velocity, 5 (35%) carotid arteries had a <50% stenosis, 1 (7%) had a 50-70% stenosis, and 1 (7%) had a ≥70% stenosis. The contrast agent improved the image quality and the definition of the lumen-to-vascular wall border. Carotid wall vascularization was observed in 5 (71%) patients [9 (64%) carotid arteries]. Five (36%) carotid arteries had mild-to-moderate vascularization, and 4 (29%) had severe wall vascularization. Carotid CDUS allows the assessment of anatomical features of LVV, including vessel wall thickening and degree of stenosis. Carotid CEUS improves the visualization of the lumen border, and allows dynamic assessment of carotid wall vascularization, which is a potential marker of disease activity in patients with LVV.

Abstract A181: Oxidized macrophage migration inhibitory factor (oxMIF) is a previously unrecognized, disease-related isoform of MIF and a potential new drug target in cancer.

Abstract Background: Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine with pleiotropic biologic effects and which is pathologically associated with several types of cancer. MIF is markedly different from other cytokines in that it is constitutively expressed, is stored in the cytoplasm and is present in the circulation of healthy subjects. Thus, the concept of targeting MIF for therapeutic intervention suffers from the drawback of targeting a ubiquitous protein. Here we report the discovery of a previously unrecognized conformational isoform of MIF that can be mimicked in vitro by mild oxidation of recombinant MIF and has therefore been designated as oxidized MIF (oxMIF). Ex vivo studies show that oxMIF is produced in patients with cancer. Highly selective, fully human monoclonal antibodies that specifically target oxMIF, but do not bind the ubiquitous reduced MIF isoform (redMIF), were shown to inhibit downstream signaling pathways associated with tumor proliferation and progression in vitro and in vivo. Methods: New ELISA methods have been established that allow the detection of oxMIF and redMIF in plasma samples acquired from commercial providers. The effect of highly selective oxMIF-specific antibodies on human cancer cells was explored in vitro and in mouse xenograft models using the cell lines PC-3 (prostate cancer), IGROV-1 (ovarian cancer) and COLO-357 (pancreatic cancer). Results: The baseline level of MIF detected in the plasma of healthy subjects (median 5123 pg/ml, n=69) was as expected according to the literature. However, our analysis revealed that this represents the ubiquitous reduced isoform of MIF, redMIF. OxMIF was, in general, not detected in the plasma from healthy controls (median 0 pg/mL, n=69). By contrast, significantly increased concentrations of oxMIF were detected in plasma from patients with breast cancer (644 pg/mL, p&amp;lt;0.05, n=15), ovarian cancer (3483 pg/mL, p&amp;lt;0.0007, n=42) and prostate cancer (2445 pg/mL, p&amp;lt;0.0005, n=14). Animal studies and in vitro studies revealed that novel human antibodies that selectively target oxMIF (i) inhibit proliferation by reducing phosphorylation of ERK1/2 and AKT, and promote apoptosis by activating caspase 3, (ii) inhibit angiogenesis and metastasis by reduction of VEGF expression and blood vessel density within the tumor, and (iii) reduce cancer-associated inflammation of the tumor by downregulating the production of proinflammatory cytokines. Conclusion: Our studies demonstrate that the oxMIF isoform is associated with cancer. OxMIF is a potential marker for disease activity or disease progression and is a promising new drug target for the treatment of cancer. A phase 1 clinical study of a novel human antibody that selectively targets oxMIF is currently ongoing in patients with solid malignancies (ClinicalTrials.gov identifier: NCT01765790). Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A181. Citation Format: Michael Thiele, Patrice Douillard, Dirk Voelkel, Thorsten Hagemann, Michael Freissmuth, Hartmut Ehrlich, Friedrich Scheiflinger, Randolf J. Kerschbaumer. Oxidized macrophage migration inhibitory factor (oxMIF) is a previously unrecognized, disease-related isoform of MIF and a potential new drug target in cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A181.

THU0181 Serum level of SYNDECAN-1 is associated with disease activity in patients with systemic lupus erythematosus

BackgroundSyndecan-1 (SDC1), a transmembrane heparan-sulfate glycoprotein, is predominantly expressed by plasma cells and is a receptor for a proliferation-inducing ligand (APRIL). SDC1 is readily shed and released into plasma under...

Elevated Serum IL-16 and RANTES Levels in Patients with Autoimmune Thyroid Diseases and Modulation by Methimazole Therapy

Interleukine-16 (IL-16) and RANTES (regulated upon activation, normal T cell expressed and secreted) are 2 cytokines with the function of T helper cell recruitment, which might play a key role in pathogenesis of autoimmune thyroid diseases (AITD). This study was aimed to evaluate the IL-16 and RANTES in patients with AITD. Serum IL-16 and RANTES levels were measured in patients with Graves' disease (GD; n=45), Hashimoto's thyroiditis (HT; n=68), nontoxic multinodular goiter (NTMNG; n=20), and healthy individuals (n=61). The results showed that serum IL-16 and RANTES levels were elevated both in HT and higher in untreated GD patients when compared to NTMNG patients and the healthy individuals, which were decreased after MMI therapy in untreated GD patients. However, in HT patients, serum IL-16 and RANTES levels were comparable among the conditions of hyperthyroid and euthyroid received by l-thyroxine therapy and untreated hypothyroid. Furthermore, serum IL-16 levels were correlated with FT3, FT4, TRAb in GD, but not in HT patients. The data did not show any correlation between RANTES levels and clinical factors. In conclusion, IL-16 and RANTES might be involved in the pathogenesis of GD and HT, and serum IL-16 levels in GD maybe a potential marker of disease activity and severity.

Serum leucine-rich alpha-2 glycoprotein is a disease activity biomarker in ulcerative colitis

Reliable biomarkers for monitoring disease activity have not been clinically established in ulcerative colitis (UC). This study aimed to investigate whether levels of serum leucine-rich alpha-2 glycoprotein (LRG), identified recently as a potential disease activity marker in Crohn's disease and rheumatoid arthritis, correlate with disease activity in UC. Serum LRG concentrations were determined by enzyme-linked immunosorbent assay (ELISA) in patients with UC and healthy controls (HC) and were evaluated for correlation with disease activity. Expression of LRG in inflamed colonic tissues from patients with UC was analyzed by western blotting and immunohistochemistry. Interleukin (IL)-6-independent induction of LRG was investigated using IL-6-deficient mice by lipopolysaccharide (LPS)-mediated acute inflammation and dextran sodium sulfate (DSS)-induced colitis. Serum LRG concentrations were significantly elevated in active UC patients compared with patients in remission (P < 0.0001) and HC (P < 0.0001) and were correlated with disease activity in UC better than C-reactive protein (CRP). Expression of LRG was increased in inflamed colonic tissues in UC. Tumor necrosis factor alpha (TNF-α), IL-6, and IL-22, serum levels of which were elevated in patients with active UC, could induce LRG expression in COLO205 cells. Serum LRG levels were increased in IL-6-deficient mice with LPS-mediated acute inflammation and DSS-induced colitis. Serum LRG concentrations correlate well with disease activity in UC. LRG induction is robust in inflamed colons and is likely to involve an IL-6-independent pathway. Serum LRG is thus a novel serum biomarker for monitoring disease activity in UC and is a promising surrogate for CRP.

High-mobility group box 1 represents a potential marker of disease activity and novel therapeutic target in systemic lupus erythematosus

High-mobility group box 1 (HMGB1) protein is a nuclear DNA-binding protein, which functions as an alarmin when released from cells. Recent studies implicate extracellular HMGB1 in the pathogenesis of systemic lupus erythematosus (SLE), a prototypical autoimmune disease characterized by the formation of multiple autoantibodies, especially those directed against nucleosomes and double-stranded (ds)DNA. Elevated concentrations of HMGB1 are observed in sera as well as in skin lesions of patients with lupus. Of importance, serum HMGB1 and anti-HMGB1 autoantibody levels correlate with disease activity. In the blood of patients with SLE, HMGB1 is complexed with nucleosomes, at least partially. Moreover, HMGB1-nucleosome complexes from apoptotic cells activate antigen-presenting cells. Injection of HMGB1-nucleosome complexes into nonautoimmune mice results in the formation of autoantibodies against dsDNA and histones in a Toll-like receptor (TLR) 2-dependent manner. Additionally, HMGB1, as a part of DNA-anti-DNA immune complexes, can interact with receptor for advanced glycation end products (RAGE) on the surface of plasmacytoid dendritic cells and B cells leading to TLR9-dependent interferon (IFN)α release and activation of autoreactive B cells, respectively. HMGB1 attached to neutrophil extracellular traps may contribute to IFNα production by facilitating the recognition of self-nucleic acids. Furthermore, HMGB1, complexed with DNA and pathogenic anti-DNA autoantibodies, activates its receptors, TLR2, TLR4 and RAGE, and may thereby be involved in anti-DNA autoantibody-induced kidney damage in lupus nephritis. Collectively, these findings suggest that HMGB1 is a potential marker of disease activity and, because of its probable involvement in the pathogenesis, a novel therapeutic target in SLE.

Serum Pro-hepcidin Could Reflect Disease Activity in Patients with Rheumatoid Arthritis

The aim of this study was to analyze the relationship between serum pro-hepcidin concentration and the anemia profiles of rheumatoid arthritis (RA) and to estimate the pro-hepcidin could reflect the disease activity of RA. RA disease activities were measured using Disease Activity Score 28 (DAS28), tender/swollen joint counts, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Anemia profiles such as hemoglobin, iron, total iron binding capacity (TIBC), ferritin, and transferrin levels were measured. Serum concentration of pro-hepcidin, the prohormone of hepcidin, was measured using enzyme-linked immunosorbent assay (ELISA). Mean concentration of serum pro-hepcidin was 237.6±67.9 ng/mL in 40 RA patients. The pro-hepcidin concentration was correlated with rheumatoid factor, CRP, ESR, and DAS28. There was a significant correlation between pro-hepcidin with tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. The pro-hepcidin concentration was significantly higher in the patients with active RA (DAS28>5.1) than those with inactive to moderate RA (DAS28≤5.1). However, the pro-hepcidin concentration did not correlate with the anemia profiles except hemoglobin level. There was no difference of pro-hepcidin concentration between the patients with anemia of chronic disease and those without. In conclusion, serum concentration of pro-hepcidin reflects the disease activity, regardless of the anemia states in RA patients, thus it may be another potential marker for disease activity of RA.

Serum Chromogranin A Concentration in Hyperthyroidism before and after Medical Treatment

The aim was to evaluate changes in chromogranin A (CgA) concentration in hyperthyroidism and to assess its metabolic correlations. We studied CgA levels in hyperthyroidism. First, 38 hyperthyroid patients matched with 86 normal controls were studied after an overnight fast. Second, 30 if the 38 patients were followed up for 6 months with medical antithyroid drug therapy (carbimazole). In the first study, after 10-12 h overnight fasting, blood was collected for measurement of CgA, glucose, insulin, intact proinsulin, and thyroid function. These variables were remeasured in the second study for the patients after attainment of euthyroidism with the antithyroid drug carbimazole for 6 months. Pretreatment CgA level was significantly higher in patients compared with controls. CgA levels dropped significantly to levels similar to those of controls after antithyroid therapy. Although baseline and follow-up fasting glucose, insulin, and intact proinsulin demonstrated similar pattern of CgA changes before and after medical treatment, CgA did not correlate with any of them. However, CgA levels demonstrated a significant positive correlation with free T(3) and free T(4) only. These studies demonstrate that untreated hyperthyroidism is associated with elevated CgA level that changes in parallel to thyroid status. It is therefore possible to use CgA concentration as a potential marker of disease activity in hyperthyroidism.

Plasma resistin and leptin levels in overweight and lean patients with rheumatoid arthritis

Aim: Adipocytokines are now considered important players in the etiopathogenesis of numerous metabolic and inflammatory disorders. However, plasma leptin and resistin levels in rheumatoid arthritis (RA) are still unclear. We aimed to investigate the plasma levels of leptin and resistin in patients with rheumatoid arthritis and to compare them with controls. Materials and Methods: Consecutive 52 patients with RA were compared with 52 control subjects in terms of mean leptin and resistin levels. Results: Patients with RA showed considerably higher plasma levels of leptin (34.3 ± 27.9 vs. 11.1 ± 4.1) and resistin (4.8 ± 0.7 vs. 4.0 ± 1.3) than healthy controls (P < 0.0001). There was no significant difference regarding age, duration of disease, sex, CRP, and leptin and resistin levels between overweight and lean RA subjects. Plasma leptin level was significantly correlated with ESR (Erythrocyte Sedimentation Rate) (r = 0.287, P = 0.039) and swollen and tender joint count (r = 0.563, P < 0.0001) but not with resistin in subjects with RA. Measuring the plasma leptin level may be a potential marker of disease activity in RA. Conclusions: Studies including more RA patients might be needed to define the role of leptin and resistin in RA subjects.

Correlation of Serum-Soluble Triggering Receptor Expressed on Myeloid Cells-1 with Clinical Disease Activity in Inflammatory Bowel Disease

Although triggering receptor expressed on myeloid cells-1 (TREM-1) has recently been shown to be upregulated in the intestines of patients with inflammatory bowel disease (IBD), it remains unclear whether serum-soluble TREM-1 (sTREM-1) level reflects disease activity in patients with IBD. This study aimed to evaluate the correlation of sTREM-1 level with disease activity in IBD. We prospectively enrolled consecutive patients with IBD and assessed their clinical disease activity using the guidelines of the American College of Gastroenterology. At the time that disease activity was assessed, sTREM-1 level (using an enzyme-linked immunosorbent assay method) and other laboratory findings including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were also measured. A total of 31 patients with ulcerative colitis (UC) and 22 with Crohn's disease (CD) were enrolled. The mean sTREM-1 level in patients with either UC (60.4 +/- 41.8 pg/ml) or CD (66.5 +/- 42.4 pg/ml) was significantly higher than in healthy controls (0.6 +/- 1.4 pg/ml) (P = 0.003 and P = 0.002, respectively). In patients with UC, sTREM-1 level was more highly correlated with disease activity (r = 0.849) than was ESR (r = 0.619) or CRP level (r = 0.546). Moreover, sTREM-1 level correlated well with disease activity irrespective of disease extent. In patients with CD, sTREM-1 level was lower in those with remission compared with those without (46.8 +/- 35.3 pg/ml versus 77.8 +/- 43.1 pg/ml), but this trend did not reach statistical significance (P = 0.100). The results of our study suggest that sTREM-1 could be a potential marker for disease activity in IBD patients, especially those with UC.