Usefulness of Serum Pepsinogens in Helicobacter pylori Chronic Gastritis: Relationship With Inflammation, Activity, and Density of the Bacterium

We sought to study the relationship between serum pepsinogens and different histopathologic features of Helicobacter pylori-related chronic gastritis. One hundred forty-nine consecutive dyspeptic patients underwent endoscopy with biopsies; serum pepsinogens I and II were measured by immunoassay. Serum levels of pepsinogens (sPG) were significantly correlated with H. pylori density both of the corpus (sPGI: r = 0.32, P < .001; sPGII: r = 0.56, P < .001) and antrum (sPGI: r = 0.41, P < .001; sPGII: r = 0.43, P < .001) as well as with chronic inflammation (sPGI: r = 0.26, P < .001; sPGII: r = 0.49, P < .001) and activity (sPGI: r = 0.38, P < .001; sPGII: r = 0.50, P < .001) in the antrum. Only sPGII was correlated with chronic inflammation (r = 0.44, P < .001) and activity (r = 0.40, P < .001) in the corpus. SPGI was inversely correlated with atrophy (r = –0.33, P < .001) and intestinal metaplasia (r = –0.37, P < .001) in the corpus. sPGII levels could be considered as markers of gastric inflammation all over in the stomach. sPGI levels are inversely related to atrophic body gastritis.     

Analysis of correlations between selected endothelial cell activation markers, disease activity, and nailfold capillaroscopy microvascular changes in systemic lupus erythematosus patients

The aim of the study was to evaluate the correlation between selected serum endothelial cell activation markers such as vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), soluble thrombomodulin (sTM), soluble E-selectin (sE-selectin), disease activity, and microvascular changes determined by nailfold capillaroscopy in patients with systemic lupus erythematosus (SLE). Serum levels of VEGF, ET-1, sTM, and sE-selectin were determined by an enzyme-linked immunosorbent assay in 80 SLE patients. The disease activity was measured with Systemic Lupus Erythematosus Disease Activity Index score. Nailfold capillaroscopy was performed in all patients. Positive correlation was found between VEGF and both ET-1 (r = 0.294, p < 0.01) and sE-selectin (r = 0.274, p < 0.05) serum levels as well as between sTM and ET-1 (r = 0.273, p < 0.05) serum concentrations. We noticed also positive correlation between VEGF (r = 0.224, p < 0.05) and ET-1 (r = 0.471, p < 0.001) serum levels and disease activity, and also between VEGF serum concentration and grade of morphological changes observed by nailfold capillaroscopy (r = 0.458, p < 0.001). There was also positive correlation between capillaroscopic score and disease activity (r = 0.339, p < 0.01). Our data suggest that correlation between VEGF and both ET-1 and E-selectin serum levels as well as between sTM and ET-1 serum concentrations may reflect their participation in the pathogenesis of SLE. VEGF seems to reflect changes in microcirculation in the course of SLE, visualised by nailfold capillaroscopy. The relationship between changes in nailfold capillaroscopy, endothelial cell activation markers, and the clinical activity of SLE points to an important role of microvascular abnormalities in the clinical manifestation of the disease.     

B-type natriuretic peptide (BNP) levels in female systemic lupus erythematosus patients: what is the clinical significance?

Cardiovascular disease is a major cause of death in patients with systemic lupus erythematosus (SLE) especially during the late phase of the disease. This study was conducted to evaluate B-type natriuretic peptide (BNP) levels in female SLE patients without cardiac symptoms and to investigate whether BNP levels correlated with echocardiographic findings. We studied 59 women with SLE and 33 healthy women. SLE patients with history of cardiac disease, diabetes mellitus, hypertension, and other inflammatory diseases were excluded from the study. All subjects had a complete history and physical examination. Overall disease activity assessment in SLE patients at the time of the study were derived by calculation of SLE disease activity index (SLEDAI). BNP levels were determined, and transthoracic echocardiography were performed in all subjects. There was no difference between SLE patients and controls in terms of age, blood pressure, smoking status, plasma glucose, creatinine levels, and lipid profiles. Nine patients had SLEDAI score greater than 5. All subjects had an EF greater than 55%. Diastolic dysfunction was more frequent in lupus patients than in controls (15 [25.4%] vs. 2 [6%]; p = 0.022). BNP levels of SLE patients were significantly higher than controls (median 17.9 range [5–211] pg/ml vs. median 14.7 range [5–39.7] pg/ml; p = 0.033). Twenty-seven of the SLE patients (46%) and seven of the controls (21%) had BNP levels greater than or equal to 20 pg/ml (p = 0.019). There were no differences in BNP levels of SLE patients with and without diastolic dysfunction (median 17.8 range [5–117] pg/ml vs. median 18.5 range [5–211] pg/mL; p = NS). BNP levels were positively correlated with left atrium diameter (r ² = 0.39, p = 0.001). BNP levels did not correlate with erythrocyte sedimentation rate/C-reactive protein levels, SLEDAI scores, total steroid dosage used, or other echocardigraphic parameters. BNP levels were increased in female SLE patients without cardiac symptoms as compared to healthy controls. Although none of the SLE patients in our study had clinical signs of ischemic heart disease, increased levels of BNP in SLE patients might be a reflection of a ischemic myocardial tissue.     

A cross-sectional study of the relationship between body mass index and clinical characteristics, tenderness measures, quality of life, and physical functioning in fibromyalgia patients

We examined the relationship between body mass index (BMI) and measures of tenderness, quality of life, and physical functioning in female fibromyalgia (FMS) patients. A random sample of 100 female FMS patients from a database of 550 FMS individuals was interviewed and assessed according to a structured questionnaire that included FMS-related symptoms, measures of tenderness (point count and dolorimetry), quality of life (SF-36), physical functioning, and BMI. Weight was defined as normal, overweight, and obesity according to BMI. Twenty-seven percent of the FMS patients had normal BMI, 28% were overweight, and 45% were obese. BMI was negatively correlated with quality of life (r = −0.205, P = 0.044) and tenderness threshold (r = −0.238, P = 0.021) and positively correlated with physical dysfunctioning (r = 0.202, P = 0.047) and point count (r = 0.261, P = 0.011). Obese FMS patients display higher pain sensitivity and lower levels of quality of life. In designing studies that explore factors affecting tenderness, BMI should be included in addition to sex, age, etc.     

Abnormal surface markers expression on bone marrow CD34<Superscript>+</Superscript> cells and correlation with disease activity in patients with systemic lupus erythematosus

Defects of hematopoietic stem cells (HSCs) have been suggested to contribute to the development of systemic lupus erythematosus (SLE). The aim of this study was to investigate the phenotypic characteristics of bone marrow (BM) CD34⁺ cells in patients with SLE and its relationship with SLE disease activity. Ten SLE patients and 10 healthy subjects were recruited and their BM CD34⁺ cells were analyzed by flow cytometric analysis with CD45/SSC gating for the expression of CD90, CD95, CD117, CD123, CD164, CD166, FAS-L, and HLA-DR. The percentage of BM CD34⁺ cells was significantly decreased in active SLE patients (1.48 ± 0.41%, n = 7) compared to the healthy controls (2.31 ± 0.75%, n = 10, p < 0.01), but no significant difference was found between the inactive patients (2.04 ± 0.44%, n = 3) and the controls. The expression of CD95, CD123, and CD166 on BM CD34⁺ cells were significantly increased in SLE patients (48.31 ± 10.59%, 44.9 ± 21.5%, 30.9 ± 19.54%, respectively, n = 10) when compared with the control subjects (24.33 ± 11.1%, 19.5 ± 4.4%, 10.7 ± 5.5%, respectively, n = 10, p < 0.05). The increased CD123 expression was negatively correlated with the number of peripheral white blood cells (r = −0.700, p < 0.05, n = 10). The percentage of CD166 expression was found significantly correlated with the index of SLE disease activity (r = 0.472, p < 0.05, n = 10) and 24 h proteinuria (r = 0.558, p < 0.05, n = 10), but negatively correlated with serum C3 level (r = −0.712, p < 0.01, n = 10). Our study found that the surface marker expression of CD95, CD123, and CD166 on BM CD34⁺ cells were significantly increased in patients. This supports the hypothesis that there are abnormalities of the HSC in SLE. Since CD166 and CD123 correlated with the overall lupus activity, their role as a biomarker of inflammatory disease activity also requires further study.     

High prevalence of low plasma thiamine concentration in diabetes linked to a marker of vascular disease

Aims/hypothesis To assess thiamine status by analysis of plasma, erythrocytes and urine in type 1 and type 2 diabetic patients and links to markers of vascular dysfunction. Methods Diabetic patients (26 type 1 and 48 type 2) with and without microalbuminuria and 20 normal healthy control volunteers were recruited. Erythrocyte activity of transketolase, the concentrations of thiamine and related phosphorylated metabolites in plasma, erythrocytes and urine, and markers of metabolic control and vascular dysfunction were determined. Results Plasma thiamine concentration was decreased 76% in type 1 diabetic patients and 75% in type 2 diabetic patients: normal volunteers 64.1 (95% CI 58.5–69.7) nmol/l, type 1 diabetes 15.3 (95% CI 11.5–19.1) nmol/l, p < 0.001, and type 2 diabetes 16.3 (95% CI 13.0–9.6) nmol/l, p < 0.001. Renal clearance of thiamine was increased 24-fold in type 1 diabetic patients and 16-fold in type 2 diabetic patients. Plasma thiamine concentration correlated negatively with renal clearance of thiamine (r = −0.531, p < 0.001) and fractional excretion of thiamine (r = −0.616, p < 0.001). Erythrocyte transketolase activity correlated negatively with urinary albumin excretion (r = −0.232, p < 0.05). Thiamine transporter protein contents of erythrocyte membranes of type 1 and type 2 diabetic patients were increased. Plasma thiamine concentration and urinary excretion of thiamine correlated negatively with soluble vascular adhesion molecule-1 (r = −0.246, p < 0.05, and −0.311, p < 0.01, respectively). Conclusions/interpretation Low plasma thiamine concentration is prevalent in patients with type 1 and type 2 diabetes, associated with increased thiamine clearance. The conventional assessment of thiamine status was masked by increased thiamine transporter content of erythrocytes.     

Fecal Calprotectin as a Predictor of Abnormal Colonic Histology

Purpose Gastroenterologists have been seeking reliable noninvasive indices of inflammatory and malignant bowel disease. This prospective study was to assess the value of fecal calprotectin in predicting abnormal histologic findings in patients undergoing colonoscopy. Methods Stool specimens supplied before colonoscopy by 72 consecutive patients were measured for calprotectin levels, and the findings correlated with the colonoscopy results and other fecal and blood parameters. Receiver operating characteristics curve analysis was used to determine the predictive value of fecal calprotectin for abnormal colonic histology. Results Patients with abnormal histologic findings had significantly higher calprotectin levels (218 ± 125 mg percent) than patients with normal colonoscopy (77 ± 100 mg percent). There was a highly significant correlation between calprotectin levels and erythrocyte sedimentation rate (r = 0.45, P = 0.008), positive fecal occult blood test (r = 0.57, P = 0.0001), and abnormal colonic histology (r = 0.54, P = 0.0001). Patients with active inflammatory bowel disease had higher calprotectin levels than the rest of the study patients (r = 0.3; P = 0.01). On multivariate analysis, calprotectin was a significant predictor of abnormal colonic histology (P = 0.005; odds ratio, 1.007; 95 percent confidence interval, 1.002–1.012). The area under the receiver operating characteristics curve was 0.79. A fecal calprotectin concentration of 150 μg/ml had a sensitivity of 75 percent, specificity of 84 percent, positive predictive value of 80 percent, and negative predictive value of 75 percent in predicting abnormal colonic histology. Conclusions Fecal calprotectin may serve as a simple, noninvasive surrogate marker of abnormal histologic findings in patients scheduled for colonoscopy. Presented at Digestive Disease Week, Los Angeles, California, May 21 to 24, 2006.     

Urinary mRNA expression of <Emphasis Type="Italic">ACE</Emphasis> and <Emphasis Type="Italic">ACE2</Emphasis> in human type 2 diabetic nephropathy

Aims/hypothesis The interplay of ACE and type 2 ACE (ACE2) has been recognised as playing an important role in the tissue renin–angiotensin system within the kidney. In the present study, we measured urinary mRNA expression of ACE and ACE2 in patients with type 2 diabetic nephropathy. Methods We studied 50 patients with diabetic nephropathy: 26 were being treated by ACE inhibitor (ACEI) alone (ACEI group), the other 24 by ACEI and angiotensin-receptor blocker (ARB) (ACEI+ARB group). mRNA expression of ACE and ACE2 was measured by real-time quantitative RT-PCR at 0 and 12 weeks. All patients were then followed for 56 weeks. Results Proteinuria correlated significantly with urinary ACE (r = 0.454, p = 0.001) and ACE2 expression (r = 0.651, p < 0.001). Urinary ACE2 expression correlated with estimated GFR (r = −0.289, p = 0.042). In the ACEI group, there was a significant inverse correlation between the rate of GFR decline and urinary ACE2 expression at baseline (r = −0.423, p = 0.031) as well as at 12 weeks (r = −0.395, p = 0.046). In contrast, there was no significant correlation between the rate of GFR decline and urinary ACE2 expression at baseline or at 12 weeks in the ACEI+ARB group. The rate of GFR decline did not correlate with the baseline urinary ACE expression of either group. Conclusion/interpretation There was a relationship between urinary mRNA expression of ACE2 and the degree of proteinuria. The physiological implication and possibility of clinical application of quantifying urinary ACE2 expression require further study.     

Circulating soluble adhesion molecules in patients with systemic sclerosis: correlation between circulating soluble vascular cell adhesion molecule-1 (sVCAM-1) and impaired left ventricular diastolic function

The objective of this paper is to investigate the relation between circulating soluble adhesion molecules and cardiac involvement, as assessed by echocardiography in patients with systemic sclerosis (SSc). Nineteen patients with SSc were submitted for assessment of serum levels of circulating soluble intercellular adhesion molecules (sICAM-1), and soluble vascular cell adhesion molecules-1 (sVCAM-1), and echocardiography. Abnormal left ventricular filling patterns (↓E/A ratio) were detected in ten patients (52.6%) with significant negative correlation with sVCAM-1 (r=−0.484, P < 0.05). It was also significantly correlated with age (r=−0.791, P < 0.01), age of onset (r=−0.468, P < 0.05), degree of dyspnea (r=−0.687, P < 0.01), and erythrocyte sedimentation rate (ESR) (r=−0.489, P < 0.05). Our findings suggest an important role for sVCAM-1 as a marker of disease severity and impaired left ventricular filling pattern in SSc. Received: 30 December 1999 / Accepted: 13 July 2000     

The relation of serum vascular endothelial growth factor level with disease duration and activity in patients with rheumatoid arthritis

Vascular endothelial growth factor (VEGF) is known to be involved in the pathogenesis of rheumatoid arthritis (RA). In order to elucidate the association between VEGF levels and RA disease activity, VEGF concentrations were measured in RA patients at different phases and severity levels. Thirty-eight healthy subjects and 40 patients with RA were prospectively included in the study. Subjects were further categorized into four subgroups (high, moderate, low, or remission) using the disease activity score-28 (DAS28) scoring system. VEGF levels were significantly higher in patients than controls (p < 0.001). VEGF levels differed significantly in controls, early and late-phase RA patients (p = 0.002). A significant difference was found between controls and patients with high RA disease activity scores (p < 0.0001). VEGF levels were not correlated with age (r = −0.016; p = 0.921) or sex (r = 0.209; p = 0.921). VEGF values were correlated with erythrocyte sedimentation rate (r = 0.445; p = 0.004), but was not correlated with serum rheumatoid factor levels (r = −0.130; p = 0.424) in the patient group. In conclusion, higher VEGF levels are associated with late phase and high disease activity in RA, independent of age and sex.     

Circulating microRNAs levels in Chinese heart failure patients caused by dilated cardiomyopathy

BackgroundPrevious studies demonstrated dysregulated expression of microRNAs (miRNAs) in the myocardium of patients with dilated cardiomyopathy (DCM). This study investigated levels of miRNAs in the circulation of DCM patients, and the value of miRNAs as biomarkers for DCM.Methods and materialsIn 45 DCM patients and 39 age- and sex-matched controls, circulating miR-423-5p, miR-126, miR-361-5p, miR-155, and miR-146a concentrations were measured and correlated to cardiac functional parameters, including left ventricular ejection fraction (LVEF) and N-terminal pro-brain natriuretic peptide (NT-proBNP).ResultsPlasma levels of miR-126 and miR-361-5P did not differ between the DCM and control groups (p = 0.331 and p = 0.784, respectively). Plasma levels of the immunity-associated miRNAs, miR-146a and miR-155, did not differ between the DCM and control groups (p = 0.437 and p = 0.702, respectively). Levels of circulating miR-423-5p were significantly greater in the DCM group (p = 0.003). Further, there was a positive correlation between plasma levels of miR-423-5p and NT-proBNP (r = 0.430, p = 0.003). MiR-423-5p distinguished DCM cases from controls with an area under the curve (AUC) receiver operating characteristic (ROC) curve of 0.674 (95% CI, 0.555–0.793).ConclusionsPatients with DCM have elevated plasma miR-423-5p levels. The plasma concentration of miR-423-5p was positively correlated with the level of NT-proBNP. Circulating levels of miR-423-5p could be served as a diagnostic biomarker for heart failure caused by DCM. Plasma levels of immunity-associated miR-146a, -155, and -126 were not significantly different between DCM and control groups.     

Tumour-proliferative fraction and growth factor expression as markers of tumour response to radiotherapy in cancer of the uterine cervix

This study seeks to define the role of pre-treatment of evaluation of tumour growth fraction in cervical cancer and its relationship to the clinical course of the disease. In addition, it also seeks to explain whether cell kinetics and growth factor expression have an association with tumour response to radiotherapy and hence could be of value in the management of patients. All pre-treatment biopsies were analysed for the tumour-proliferative compartment by evaluation of Ki67 antigen expression and argyrophilic nucleolar organiser region (AgNOR) counts. Growth factor analysis was done by analysing for expression of epidermal growth factor (EGF), epidermal growth factor receptor (EGF-R) and transforming growth factors α and β (TGFα, TGFβ). A total of 152 patients were evaluated and a correlation obtained between pre-treatment status of the tumour-growth-fraction-associated markers and clinical outcome following radiotherapy. Such patients were either disease-free (group 1, n = 106) or with residual/recurrent disease (group 2, n = 46) at a 16-month follow-up. Pre-treatment analysis of AgNOR significantly correlated to disease status after treatment (r = −0.517, P = 0.0000). This may be due to an effect of cell proliferation. Lower AgNOR counts were significantly associated with recurrent/residual tumours, suggesting that increased proliferative activity may be a positive prognostic indicator. Similar results were also obtained for the other proliferation-associated marker Ki67 (r = −0.443, P = 0.0000). Expression of EGF and EGF-R also showed significant pre-treatment correlations with the final disease outcome (r = 0.248, P = 0.031 and r = 0.503, P = 0.0000 respectively). Both these markers were expressed more by patients belonging to group 2. The opposite was the case for TGFα, where patients belonging to group 1 showed higher values (r = 0.417, P = 0.0001). The other growth factor investigated, TGFβ, also showed a conspicuous differential expression in the two groups of patients (r = −0.604, P = 0.0000). Group 1 patients showed mostly mild to moderate expression while most group 2 patients were negative for the growth factor. It therefore appears that tumours with high AgNOR counts and Ki67 index, along with expression of the two types of transforming growth factor (α and β), responded better to radiotherapy. Received: 9 February 1998 / Accepted: 14 April 1998     

Association of interferon-gamma gene polymorphism (+874A) with arthritis manifestation in SLE

Systemic lupus erythematosus (SLE) is a complex autoimmune disease in which genetic factors strongly influence susceptibility. Cytokines such as the interferon-gamma (IFNG) gene play a key role in controlling the immunity and inflammation, and therefore their polymorphisms may affect these genes’ expression levels among individuals. We investigated the frequency of IFNG gene intron (+874) polymorphism, previously reported to be associated with IFNG production, in SLE patients compared to a control group. This population-based case–control study includes 154 SLE patients and 154 healthy control subjects with similar ethnic backgrounds. The genotyping was determined by polymerase chain reaction sequence-specific primer method and using the Chi-squared test for analyzing the association between this single-nucleotide polymorphism and SLE. The allele frequencies of the IFNG (+874) gene polymorphism were not significantly different between SLE patients and control subjects (72.7 vs 77%). However, there was a significant association between A dominance model of inheritance with arthritis (odds ratio = 7.64, 95% confidence interval = 1.56–41.64, P = 0.006, P _c = 0.03). The result suggested that the +874 intron polymorphism of IFNG can be used as the marker for SLE susceptibility with arthritis in the Thai population.     

Tryptophan degradation and neopterin levels in treated rheumatoid arthritis patients

Increased kynurenine/tryptophan—reflects trytophan degradation—and neopterin levels have been regarded as a biochemical marker of cell-mediated immune response and inflammation. This study was designed to evaluate the usefulness of tryptophan degradation and neopterin levels in active rheumatoid arthritis patients under therapy. In this case–control study, kynurenine and tryptophan levels were determined by HPLC; neopterin and tumor necrosis factor-α levels were measured with ELISA in 32 active rheumatoid arthritis patients and 20 healthy controls. Although mean values of tryptophan, kynurenine, ratio of kynurenine to tryptophan, neopterin, and tumor necrosis factor-α levels did not show statistically significant differences between patient and control groups, neopterin levels correlated positively with kynurenine (r = 0.582, p < 0.02), kynurenine/tryptophan (r = 0.486, p < 0.05), erythrocyte sedimentation rate (r = 0.472, p < 0.05) and RF (r = 0.478, p < 0.05) in the rheumatoid arthritis group. CRP levels of the patient group correlated with kynurenine levels (r = 0.524, p < 0.03). Determination of tryptophan degradation and neopterin levels in chronic inflammatory disease may provide a better understanding of progression of the disease.     

Developmental changes of oxalate excretion in enterally fed preterm infants

Summary  To further substantiate gestational age-related changes in oxalate excretion, we studied urinary oxalate excretion in 66 preterm infants born at 23.4–34.7 weeks of gestation. Spot urine of 66 preterm infants was analysed by ion chromatography as soon as they were completely orally fed with enriched breast milk and/or special preterm milk formula (days 7 to 57 of postnatal life). Infants with evidence of renal, gastrointestinal, muscular or metabolic disease were not included. Newborns on parenteral nutrition were excluded. Oxalate/creatinine ratios (Ox/Cr) decreased with gestational age (three age groups: group 1, 23 0/7–28 0/7; group 2, 28 1/7–32 0/7; and group 3, 32 1/7–35 0/7 weeks of gestation). The mean Ox/Cr was highest in group 1 (398.2 mmol/mol ± 116.8; n = 21). Differences between groups 1 + 3 were statistically significant; p = 0.001; those between groups 1 + 2 and between groups 2 + 3 were not. Ox/Cr correlated inversely with gestational and maturational age (r = −0.41, p = 0.001; r = −0.33, p = 0.007) and positively with postnatal age (r = 0.32, p = 0.008). It correlated inversely with birth weight as well as actual weight at sample collection (r = −0.46 and −0.44, p < 0.001). Ox/Cr was significantly linked to energy and carbohydrate intake (r = 0.3 and 0.4, p = 0.03 and 0.001). These results were independent of sex. In the present study we show that urinary oxalate excretion in preterm infants depends on gestational age. Competing interests: None declared The authors B. Bohnhorst and A. M. Das contributed equally.     

The protein–creatinine ratio in spot morning urine samples and 24-h urinary protein excretion in patients with systemic lupus erythematosus

A 24-h urinary protein is a standard way to diagnose lupus nephritis. Assessment of protein–creatinine (Pr–Cr) ratio in morning spot urine is a valuable method in diabetic patients but not use in systemic lupus erythematous (SLE) patients routinely. In this study Pr–Cr ratio in spot urine was compare with 24-h urine protein; if they have valuable correlation we can use this test instead of 24-h urinary protein. The aim of this study was to evaluate the correlation of spot urine Pr–Cr ratio for prediction of significant proteinuria (≥300 mg/24 h) in patients with SLE. A cross-section study was conducted in 74 hospitalized women with SLE. The correlation between Pr–Cr in first morning urine specimens and urinary protein excretion in 24-h collections were analyzed. Correlation between Pr–Cr ratio in spot morning urine specimens and urinary protein excretion in 24-h collections was significant (P < 0.0001, r = 0.83). A high correlation and precision of agreement were demonstrated between the two methods of assessment proteinuria in lupus patients. The difference between the two methods was less than the biological variability in the protein excretion and its measurement, enabling the methods to be used interchangeably creatinine ratio in spot morning urine samples is a precise indicator of proteinuria in patients with lupus nephritis and represents a simple and inexpensive procedure in establishing severity of proteinuria in patients with SLE.     

Soluble receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin in ankylosing spondylitis: OPG is associated with poor physical mobility and reflects systemic inflammation

The objective of the study was to investigate the role of receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) in ankylosing spondylitis (AS). Serum levels of soluble RANKL (sRANKL) and OPG were measured in 42 AS patients and 26 healthy controls. We evaluated the AS patient's disease activity, functional ability, global assessment, and physical mobility and tested markers of systemic inflammation, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels. Serum levels of sRANKL [mean (SD), 4.75 (1.88) vs. 3.70 (1.14) pmol/l, p = 0.015] and OPG [mean (SD), 5.18 (1.19) vs. 4.52 (0.85) pmol/l, p = 0.026] were significantly higher in the 42 AS patients than the 26 healthy controls. Interestingly, serum OPG levels correlated significantly with ESR (r = 0.417, p = 0.007), CRP (r = 0.524, p < 0.001), tragus-to-wall distance (r = 0.556, p < 0.001), fingertip-to-floor distance (r = 0.423, p = 0.007), and occiput-to-wall distance (r = 0.465, p = 0.002) and correlated inversely with modified Schober index (r = −0.525, p = 0.001), cervical rotation (r = −0.403, p = 0.022), lateral lumbar flexion (r = −0.587, p < 0.001), and chest expansion (r = −0.553, p < 0.001). Moreover, in the AS patients with higher (≥4.925 pmol/l, n = 21) serum OPG levels, there were significant increases in the tragus-to-wall distance (p = 0.007), fingertip-to-floor distance (p = 0.023), and CRP levels (p = 0.014) and decreased in the modified Schober index (p = 0.012), lateral lumbar flexion (p = 0.019), and chest expansion (p = 0.005). Serum levels of sRANKL and OPG are increased in the AS patients and may participate in the disease process of AS. Production of OPG has association with poor physical mobility and may reflect systemic inflammation in AS.     

Anti-C1q antibodies are associated with systemic lupus erythematosus disease activity and lupus nephritis in northeast of China

This study aimed to investigate the associations of anti-C1q antibodies with systemic lupus erythematosus (SLE) disease activity and lupus nephritis (LN) in northeast of China. Ninety patients with SLE, 37 patients with other autoimmune diseases, and 40 healthy donors in northeast of China were enrolled. Serum anti-C1q antibodies were measured by ELISA with 20 RU/ml as the threshold of positive results. The prevalence and levels of anti-C1q antibodies in SLE group (50%, 20.54 ± 34.67 RU/ml) were significantly higher than those in autoimmune disease and healthy control groups (P < 0.05), yet no significant difference between LN patients and non-LN lupus patients (57.14% vs 41.46%, P > 0.05; 25.92 ± 39.94 vs 13.07 ± 27.39 RU/ml, P > 0.05). Anti-C1q antibody levels were positively correlated with levels of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, anti-dsDNA, and anti-cardiolipin and negatively correlated with serum C3 and C4 (P < 0.05). The prevalence of anti-Sm and anti-nucleosome increased in anti-C1q-positive lupus patients (P < 0.05). Compared with anti-C1q-negative lupus patients, patients with 20–40 RU/ml anti-C1q antibodies had comparable disease activity (P > 0.05); patients with 40–80 RU/ml anti-C1q antibodies had significantly lower levels of serum complement (P < 0.05); patients with above 80 RU/ml anti-C1q antibodies had much more severe hypocomplementemia, increased SLEDAI scores, and higher incidence of hematuria and proteinuria (P < 0.05). Furthermore, the specificity and positive predictive value of 80 RU/ml anti-C1q antibodies for LN was 97.56% and 87.50%, respectively. In conclusion, anti-C1q antibodies are associated with SLE and LN disease activity, and the contribution hinges on the titers. Moreover, high-level anti-C1q antibodies are valuable for diagnosing LN.     

Association of IL-18 gene polymorphism (?137C) with arthritis manifestations in SLE: combined effect with IFN gamma gene polymorphism (+874A)

We analyzed the association between single nucleotide polymorphisms in IL-12 and IL-18 genes in disease susceptibility and severity of SLE in Thais. A weak association was observed between A allele of the IL-12 gene at the 3′ untranslated region in SLE patients with proteinuria (OR = 1.89, 95% CI = 1.05–3.40, P = 0.02, Pc = 0.06). In addition, we found a significant association between C allele of IL-18 (−137) with arthritis (OR = 6.88, 95% CI = 1.54–42.93, P = 0.003, Pc = 0.009). The presence of one C allele (C/C+C/G) was associated with significant OR of 8.72 (95% CI = 1.83–56.71, P = 0.001, Pc = 0.003). Interestingly, we found the combined effect between the G/C genotype of IL-18 (−137) and the A/A genotype of IFNG (+874) gene causing susceptibility of arthritis in SLE patients (OR = 13.22, 95% CI = 1.56–291.66, P = 0.004).     

Assay of T- and NK-cell subsets and the expression of NKG2A and NKG2D in patients with new-onset systemic lupus erythematosus

This study aims to explore the percentage of T-cell and NK-cell subsets, the expression of NKG2A and NKG2D on CD3+ T cells and CD3−CD56+ NK cells on the total lymphocytes in new-onset systemic lupus erythematosus (SLE) patients, and explore clinical significance of these cell subsets. Thirty-two SLE patients and 32 normal controls were enrolled. Flow cytometry was used to count T- and NK-cell subsets and to detect the expression of NKG2A and NKG2D on CD3+ T cells and CD3−CD56+ NK cells in patients with new-onset SLE. Results show that CD4+ T (t = 2.04, P < 0.05), CD4+/CD8+ T cell (t = 2.66, P < 0.05), CD4+ CD25+ T (t = 2.48, P < 0.05), CD3+CD56+ natural killer T (NKT) (t = 40.05, P < 0.01), CD3−CD56+CD16+ NK-cell subsets (t = 3.50, P < 0.01) were significantly decreased, CD8+ T-cell subsets was significantly increased in patients with new-onset SLE (t = 3.80, P < 0.01), as compared with healthy controls. CD8+ T-cell subset was significantly increased in patients with vasculitis (t = 2.47, P < 0.05), and CD3−CD56+CD16+ NK was increased in patients with arthritis (t = 3.21, P < 0.01). However, no statistically significant correlation was found among different PBMC subsets and SLEDAI activity scores. Patients with SLE had a lower expression of NKG2A (U = 2.42, P < 0.05) as well as NKG2A/NKG2D ratio (t = 2.61, P < 0.05) and a higher expression of NKG2D (t = 2.21, P < 0.05) on CD3+ T cells, compared with normal controls. However, they had a higher expression of NKG2A (t = 2.59, P < 0.05) as well as NKG2A/NKG2D ratio (t = 49.45, P < 0.01) and a lower expression of NKG2D (t = 3.05, P < 0.01) on CD3−CD56+ NK cells. Taken together, the findings indicate the decreased CD4+ T-cell, CD4+/CD8+ T-cell, CD4+CD25+ T-cell, CD3+CD56+ NKT-, and CD3−CD56+CD16+ NK-cell subsets, increased CD8+ T-cell subsets as well as the abnormal expression of NKG2A and NKG2D on CD3+ T and CD3−CD56 + NK cells may play a role in the etiology of SLE.