Circulating Levels of Osteoprotegerin,Osteocalcin and Osteopontin in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-Analysis

Objective: Currently published data regarding the potential role of osteoprotegerin (OPG), osteocalcin (OCN) and osteopontin (OPN) for the discrimination between rheumatoid arthritis (RA) and osteoarthritis (OA) are contradictory. To derive a more precise evaluation, a meta-analysis was performed. Methods: Published literatures comparing plasma/serum OPG, OCN and OPN levels between RA group and OA controls were searched in PubMed, Embase and the Cochrane Library. The Newcastle-Ottawa Scale was used to assess the study quality. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by random-effect model analysis. Heterogeneity test was performed by the Q statistic and quantified using I². Results: Nine studies including 438 RA patients and 255 OA patients were finally incorporated in the meta-analysis after examining title, type, abstracts and full text. The results showed that RA patients had higher plasma/serum OPN (pooled SMD = ?2.57, 95% CI = ?4.72 to ?0.41) levels when compared to OA patients. No significant difference in plasma/serum OPG (pooled SMD = ?0.29, 95% CI = ?1.07?0.49) and OCN (pooled SMD = ?0.09, 95% CI = ?0.48?0.31) levels were found between RA patients and OA patients. Subgroup analysis indicated that plasma/serum OPG levels had no significant differences between RA patients and OA patients in Europe and Asian. Conclusions: Overall, there is no significant difference in circulating OPG and OCN levels between RA patients and OA patients. However, plasma/serum OPN level is significantly higher in RA patients compared with OA patients.     

Association between CD226 polymorphism and soluble levels in rheumatoid arthritis: Relationship with clinical activity

Objective: To study the relation between CD226 rs763361 gene polymorphism and CD226 serum level and to evaluate their role in susceptibility and disease activity of RA in a cohort of Egyptian individuals.

Methods: The serum level of CD226 was measured using a suitable ELISA kit and the CD226 rs763361 gene polymorphism was typed by PCR-RFLP for 112 RA patients and 100 healthy controls.

Results: Significant association with RA was found with CD226 T allele (OR (95%CI) = 1.6 (1.04–2.4), P = 0.032), and higher CD226 serum level (P = 0.001). Higher CD226 levels were associated with higher ESR values (P = 0.035), positive CRP (0.048), increased number of tender joints (P = 0.045), and higher DAS score (P = 0.035). Serum CD226 is an independent risk factor for the prediction of RA (P = 0.001). No correlations were found between the serum level of CD226 and different CD226 genotypes and also between them and RA activity grades.

Conclusion: The CD226 T allele may be susceptibility risk factors for the development of RA and the higher serum level of CD226 may be involved in the pathogenesis of RA in Egyptian patients. The serum level of CD226 and not CD226 genotypes could be considered as an independent risk factor for the prediction of RA within healthy individuals and also for RA disease activity.     

Histamine influence on apoptosis in trophoblast cell cultures

Introduction

It has been demonstrated that histamine plays an important role in the pathogenesis of preeclampsia. Histamine regulates the process of differentiation of trophoblast cells; it also acts as a growth factor in malignant melanoma cells, and prevents monocytic apoptosis. Trophoblast research has shown that in preeclampsia placentas, trophoblast apoptosis is significantly increased.

Aim of the study

The aim of our study was to demonstrate the influence of histamine on the process of apoptosis in human trophoblast cell cultures.

Materials and methods

Placentas were obtained after vaginal delivery. Tissue samples were excised from placentas and, with the use of modified Kliman’s method, trophoblast cell cultures were established. The cultures were incubated with dexamethasone as an apoptosis inducer 48 hours prior to apoptosis detection assays. Along with dexamethasone, selected cell cultures were incubated with histamine (1 μmol/l) or histamine (1 μmol/l) and terfenadine (from 1 to 5 μmol/l), a H₁ receptor antagonist. For apoptotic activity detection, and quantitative analysis, we used an ELISA assay. M30‐Apoptosense ELISA Kit is based on the M30 monoclonal antibody that binds only the caspase‐cleaved cytokeratin 18 formed during apoptosis in trophoblast cells.

Results

Our investigation showed significantly (p < 0.05) increased apoptotic activity in cultures incubated with dexamethasone, histamine and terfenadine (% of reference value, ±SEM): up to 113.1 ± 4.33%. Cell cultures incubated with dexamethasone and histamine only showed significantly lower apoptotic activity 90.2 ± 5.17%. We suggest that histamine may inhibit apoptotic activity in trophoblast cell cultures via H₁ receptor. Thus histamine may regulate the process of trophoblast differentiation (via integrin aV‐b3 expression, as we previously suggested), and influence cell turnover in the placenta.

     

Analysis of Helios gene expression and Foxp3 TSDR methylation in the newly diagnosed Rheumatoid Arthritis patients

Background: The control of auto-reactive cells is defective in rheumatoid arthritis (RA). Regulatory T (Treg) cells which play a key role in the modulation of immune responses have an impaired function in RA. Foxp3 is a master regulator of Treg cells which its expression is under the tight control of epigenetic mechanisms. In the current study, we analyzed the epigenetic modulation of the Foxp3 Treg-specific demethylated region (TSDR) and Helios gene expression to determine Treg cells alteration in RA patients.

Methods: We have recruited 20 newly diagnosed patients with RA and 41 healthy controls in our study. The measurement of Foxp3 and Helios gene expression was performed by the real-time PCR technique and the methylation level of TSDR was analyzed by bisulfite treatment and quantitative methylation-specific PCR (Q-MSP).

Results: We found that RA patients had significantly lower level of Foxp3 gene expression and TSDR demethylation compared to healthy subjects (P < 0.001 and P = 0.006, respectively). Inversely, the Helios gene expression was elevated significantly in RA patients group (P = 0.048). We also observed a significant correlation between Foxp3 and Helios gene expression (P = 0.016) as well as a significant correlation between FoxP3 expression and demethylation rate of TSDR (P = 0.010).

Conclusion: Our results suggested that both epigenetic modifications and Helios gene expression may have important roles in the pathogenesis of RA through their effects on Foxp3 gene expression.     

Receptive music therapy and salivary histamine secretion

Introduction

Receptive music therapy (rMT) not only provides a good feeling but also a more effective healing process and mastery of stress.

Methods and Results

In a preliminary study it could be shown that American Doudouk-music (feel-good music) suppressed salivary histamine secretion in two groups (n = 4) of allergic and non-allergic young volunteers. Stress was induced by eating adverse food/allergenic food during music exposure. There was no response in the vein blood samples and no significant difference between the allergic and non-allergic groups.

Conclusion

It can be concluded that saliva is an appropriate medium for histamine measurements during music exposure.

     

Circulating levels of calprotectin,a signature of neutrophil activation in prediction of severe respiratory failure in COVID-19 patients: a multicenter,prospective study (CalCov study)

Objective

Severe COVID-19 is characterized by a dysregulated immune response in which neutrophils play a critical role. Calprotectin reflects neutrophil activation and is involved in the self-amplifying thrombo-inflammatory storm in severe COVID-19. We aimed to evaluate the role of calprotectin in early prediction of severity in COVID-19 patients.

Methods

This was a multicenter prospective observational study enrolling consecutive adult COVID-19 patients. On arrival to emergency department, blood samples were collected for laboratory tests, including serum calprotectin. The primary outcome was severe respiratory failure requiring invasive mechanical ventilation and the secondary outcome was need for Intensive Care Unit (ICU) admission.

Results

Study population included 395 patients, 57 (14.4%) required invasive mechanical ventilation and 100 (25.3%) were admitted to ICU. Median serum calprotectin levels were significantly higher in intubated (3.73 mg/L vs. 2.63 mg/L; p?<?0.001) and ICU patients (3.48 mg/L vs. 2.60 mg/L; p?=?0.001). Calprotectin showed a significant accuracy to predict the need for invasive mechanical ventilation (ROC AUC 0.723) and ICU admission (ROC AUC 0.650). In multivariate analysis, serum calprotectin was an independent predictor of invasive mechanical ventilation (OR 1.161) and ICU admission (OR 1.068).

Conclusion

Serum calprotectin can be used as an early predictor of severity in COVID-19 patients.

     

Involvement of histamine and histamine H2 receptors in nicotinamide-induced differentiation of human amniotic epithelial cells into insulin-producing cells

Objective and design

Human amniotic epithelial cells (HAEC) resemble stem cells in their ability to differentiate into all three germ layers: endoderm, mesoderm, and ectoderm. Histamine receptors are expressed on HAEC. We examined the influence of histamine, and H₁ and H₂ antagonists on the generation of pancreatic islet beta-like cells from HAEC.

Materials and methods

HAEC were isolated after term pregnancies (N = 12) and cultured for 14 days with nicotinamide (10 mM) in normoxia. Altogether, 72 cultures were established. Histamine (100 μM) effects were investigated with mepyramine (10 μM) or cimetidine (10 μM). After 7 and 14 days, the mean concentration of C-peptide (MCCP) in the culture medium was measured immunoenzymatically as a marker of pancreatic differentiation.

Results

MCCP was approximately threefold higher on day 14, compared to day 7. Histamine significantly increased MCCP, and more evident differences were observed after 7 days of culture than after 14 days. The mean percent increase ±SEM in MCCP amounted to 142.19 ± 21.7 and 79.03 ± 12.35 compared to the controls on day 7 and 14, respectively. H₂ blockade significantly reduced histamine-related increase in MCCP, both on day 7 and 14 by 88.7 ± 14.3 and 39.2 ± 12.4%, respectively. H₁ receptor antagonist did not affect MCPP.

Conclusion

Nicotinamide-induced pancreatic differentiation of HAEC into beta-like cells may be augmented, probably at its earlier stage, by histamine acting via H₂ receptors.

     

Reduced apoptosis correlates with enhanced autophagy in synovial tissues of rheumatoid arthritis

Objective

Defective apoptosis contributes to the massive synovial hyperplasia in rheumatoid arthritis (RA), but the mechanism is largely unknown. To investigate the reasons for the reduced apoptosis in RA synovium, we analyzed autophagy and its relationship to apoptosis in synovial tissues from RA and osteoarthritis (OA) patients.

Methods

Synovial tissues were obtained from seven RA and 12 OA patients undergoing knee replacement surgery. Apoptosis was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and staining for p85 fragment of PolyADP-ribose polymerase (PARP). Autophagy was determined by immunoblotting for the autophagic markers Beclin-1 and LC3. MicroRNA-30a (miR-30a), which targets Beclin-1, was measured by real-time RT-PCR. The interplay between autophagy and apoptosis was determined via Spearman’s correlation analysis.

Results

In comparison with OA, the synovial tissues from RA displayed decreased TUNEL-positive nuclei (P < 0.01). In contrast, Beclin-1 and LC3 were overexpressed in the synovial lining layers of RA, which was correlated with decreased levels of miR-30a. Moreover, there was a significant reverse relationship between apoptosis and autophagy in RA synovial tissues (P < 0.01 and r = ?0.8937).

Conclusion

The impaired apoptosis in RA synovium might result from increased autophagy, which in turn could be due to the deregulation of miRNA-30a.     

Decrease in expression of histamine H2 receptors by human amniotic epithelial cells during differentiation into pancreatic beta-like cells

Objective and design

Considering the role of histaminergic pathway in the differentiation of stem cells, we compared expression patterns of H₁ and H₂ receptors in the human amniotic epithelial cells (HAEC) culture at different stages of nicotinamide-induced differentiation into PBLC with the control HAEC.

Material and methods

HAEC isolated after term pregnancies (N = 12) were cultured in vitro. Altogether, 72 cultures were established. The culture medium in the studied group was supplemented on Day 5 with nicotinamide (10 mM). C-peptide concentration in the medium collected every 3 days for 15 days was determined immunoenzymatically as a marker of differentiation. At the same intervals the cultures were formalin-fixed and paraffinembedded for H₁ and H₂ receptors immunostaining. Quantitative immunohistochemistry was applied for evaluation of H₁ and H₂ expression.

Results

C-peptide was detected on Day 6 and the levels were kept gradually increased until Day 12, then stayed at almost the same level, 3.7-fold higher than initially. Expression of H₂ was unchanged until Day 9 after nicotinamide addition, then was significantly (p < 0.05) decreased and amounted (mean % value for the measurements performed on Day 12 and Day 15, ±SEM) 49.73 ± 11.03 of the reference value obtained in control HAEC.

Conclusion

Variable expression of H₂ during nicotinamide-induced differentiation of HAEC into PBLC may define a time-point, indicating involvement of histamine at the earlier stages.

     

Increased homocysteine plasma level is associated with shortened prothrombin time in HIV-infected patients

Objective: To find factors associated with increased homocysteine plasma level in HIV-infected patients.

Methods: Cross-sectional study, carried out as a supplementary task to the standard care of HIV-infected patients. The possible association of increased homocysteine plasma level with blood analyses results was assessed with a multiple linear regression analysis, using the automatic linear modeling available in SPSS version 22.

Results: A total of 145 patients were included. Creatinine was higher than normal in 7 patients (5%), prothrombin time was shortened in 36 patients (25%), and a monoclonal gammopathy was detected in 2 patients (1%). In the regression analysis, an association was found between high homocysteine plasma level and the following variables: low prothrombin time (β coefficient ?0.286, confidence interval ?1.1854 to ?0.754, p < 0.001), high creatinine (coefficient 9.926, confidence interval 6.351–15.246, p < 0.001), low folic acid (coefficient ?0.331, confidence interval ?0–483 to ?0.187, p < 0.001), and low vitamin B₁₂ (coefficient ?0.007, confidence interval ?0.01 to ?0.001, p = 0.005).

Conclusion: An association was found between increased homocysteine plasma level and shortened prothrombin time.     

Development of a microcomputed tomography scoring system to characterize disease progression in the Hartley guinea pig model of spontaneous osteoarthritis

Aim: There is potential discrepancy between human and laboratory animal studies of osteoarthritis (OA), as radiographic assessment is the hallmark of the former and histopathology the standard for the latter. This suggests a need to evaluate OA in animal models in a manner similar to that utilized in people. Our study aimed to develop a whole joint grading scheme for microcomputed tomography (microCT) images in Hartley guinea pigs, a strain that recapitulates joint changes highlighted in human spontaneous OA. Materials and Methods: Knees from animals aged 2, 3, 5, 9, and 15 months were evaluated via whole joint microCT and standard histologic scoring. Quantitative microCT parameters, such as bone volume/total volume were also collected. Results: Both whole joint microCT and histologic scores increased with advancing age and showed strong correlation (r = 0.89. p < 0.0001). Histologic scores, which focus on cartilage changes, increased progressively with age. Whole joint microCT scores, which characterize bony changes, followed a stepwise pattern: scores increased between 3 and 5 months of age, stayed consistent between 5 and 9 months, and worsened again between 9 and 15 months. Conclusions: This work provides data that advocates the use of a whole joint microCT scoring system in guinea pig studies of OA, as it provides important information regarding bony changes that occur at a different rate than articular cartilage changes. This grading scheme, in conjunction with histology and quantitative microCT measurements, may enhance the translational value of this animal model as it pertains to human work.     

Effect of antioxidants on airway smooth muscle contraction: action of lipoic acid and some of its novel derivatives on guinea pig tracheal smooth muscle

Objectives and design

The aim of this study was to investigate the ability of (a) antioxidants, some related to α-lipoic acid (LA), (b) histone deacetylase (HDAC) inhibitors, and (c) hybrid compounds possessing both α-lipoic acid-derived antioxidant properties and HDAC inhibitory activity to inhibit guinea pig smooth muscle contraction.

Materials and methods

Guinea pig isolated tracheal rings (GPTR) were prepared and their isometric tension measured using a transducer. Histamine, carbachol and 5-hydroxytryptamine (5-HT) served as agonists. Tests with antigen (ovalbumin) used GPTR from sensitised guinea pigs or rings from non-sensitised animals that had been incubated for at least 2 h with diluted serum from sensitised animals.

Results

All antioxidants tested showed a relaxant effect on resting tension and on tension induced by histamine or carbachol, with EC₅₀(s) of 0.2–5.0 mM and a rank order of potency: LA derivatives > glutathione (GSH) > ascorbic acid (AA). However, low concentrations (<50 μM) of GSH, AA and LA potentiated histamine-induced contractions. The benzamide HDAC inhibitor MGCD0103 inhibited mast cell activation and GPTR contraction produced by antigen and certain agonists, although a 2–6 h pre-incubation was required for those effects to be apparent. Two LA–benzamide HDAC hybrid compounds, UCL M084 and UCL M109 inhibited GPTR contraction after 30 min pre-incubation; however, even after long pre-incubation (up to 6 h) those hybrid compounds showed less potent inhibition of agonist-induced contraction than did MGCD0103.

Conclusions

The results showed that GSH more potently inhibited contraction induced by histamine than that induced by 5-HT or carbachol, whereas LA, and especially UCL M084 and UCL M109, more potently blocked contraction induced by carbachol and 5-HT than that induced by histamine. For GSH, and possibly also for LA-type compounds, the inhibition of agonist-induced tracheal smooth muscle contractions may be due to NO formation. This study did not detect a synergistic relaxant effect in two compounds incorporating the structural union of a benzamide HDAC inhibitor terminus with a LA-derived antioxidant moiety.

     

Serum Calprotectin in Rheumatoid Arthritis: A Promising Diagnostic Marker,How Far Is It Related to Activity and Sonographic Findings?

Background

In the past 2 decades, there has been increasing interest in calprotectin. It is released and detected in serum and body fluids as a potentially useful clinical inflammatory marker. The protein has been described in synovial tissue in rheumatoid arthritis (RA) patients, specifically in the lining layer adjacent to the cartilage–pannus junction, which is the primary site of cartilage destruction and bone erosion. Assessment of inflammatory activity in RA is of pivotal importance for the optimal treatment. Our aim in this study is to measure the serum calprotectin levels in RA patients and to assess its association—if there is any—with disease activity score and radiological findings using the musculoskeletal ultrasound.

Association of IL17 and IL23R gene polymorphisms with rheumatic heart disease in South Indian population

ABSTRACT

Background: IL-23/Th17 signaling pathway plays a crucial role in the cell-mediated immune response against bacterial infections and also in the pathogenesis of inflammatory and autoimmune diseases. Recent studies indicate that Th17 cell-associated cytokines are involved in the progression and maintenance of valvular lesions in rheumatic heart disease (RHD). Variants in the genes of cytokines that are potentially involved in Th17 response may influence interindividual differences in their expression levels, thereby contributing to the pathogenesis of immune-mediated diseases such as RHD.

Objective: The aim of the study is to investigate the association of IL17A, IL17F, and IL23R gene variants with the risk perception of RHD.

Methods: A total of 225 individuals (99 RHD patients and 126 healthy siblings) were recruited for the study. The IL17A (rs2275913), IL17F (rs763780), and IL23R (rs10889677) polymorphisms were determined by polymerase chain reaction restriction fragment length polymorphisms and amplification-refractory mutation system-polymerase chain reaction methods, respectively.

Results: The frequency of IL17A (rs2275913) A/A genotype was significantly high in pooled RHD patients (odds ratio [OR] = 2.76; p_c = 0.021), rheumatic fever (RF) patients (OR = 14.5; p_c = 0.0001), and mitral valvular lesions patients (OR = 2.74; p_c = 0.039) when compared to healthy siblings. However, the IL17F (rs763780) and IL23R (rs10889677) polymorphisms did not show any association with RHD.

Conclusions: The results suggest that IL17A (rs2275913) polymorphism is associated with the development of RF/RHD in South Indian population. Further studies are required to substantiate the association of these genes with the disease risk.     

Astragaloside inhibits IL-1β-induced inflammatory response in human osteoarthritis chondrocytes and ameliorates the progression of osteoarthritis in mice

Abstract

Background: Osteoarthritis (OA) is a chronic joint-degeneration disease and accounts for the most frequent arthritis in aging people. OA is characterized by the degeneration of articular cartilage, subchondral bone sclerosis and synovitis. Inflammation as an important role in OA progression, in that anti-inflammatory agents could effectively inhibit the development of OA with minimal side effects, therefore developing a nature anti-inflammatory compound will be a promising therapy for treating OA.

Methods: We treated patient-derived chondrocytes and mouse models of OA with astragaloside, an effective component of astragalus membranaceus, and measured its effect on pro-inflammatory cytokines and OA progression in mice.

Results: In vitro, astragaloside induced a dose-dependent inhibition of IL-1β-induced the production of inflammatory factors, including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), nitric oxide (NO), prostaglandin E2 (PGE2), expression of MMP 13 and ADAMTS-5, and the activation of NF-κB signaling. In vivo, astragaloside ameliorate the degeneration of cartilage in mouse model of OA.

Conclusion: Astragaloside potentially serve as a promising and effective therapeutic agent for treating OA patients.     

Serum Levels of Calreticulin in Correlation with Disease Activity in Patients with Rheumatoid Arthritis

Objective

The aim of our study was to investigate the contribution of serum calreticulin (CRT) in the assessment of disease activity in rheumatoid arthritis (RA).

Methods

Serum CRT levels were measured by ELISA in 70 patients with established RA, 30 systemic lupus erythematosus (SLE), 25 other autoimmune diseases, 20 osteoarthritis (OA), and 35 of healthy controls (HC). Correlations of CRT serum levels with disease activity [Disease Activity Score for 28 joints (DAS28)], erythrocyte sedimentation rate(ESR) and C-reactive protein (CRP) were assessed. Serum CRT levels were also detected in RA patients whose RF, anti-CCP and anti- MCV antibodies were positive and negative.

Results

Serum CRT levels in RA patients (4.817?±?2.425 ng/ml) was significantly higher (P <0.05) compared with those in the serum of OA (3.574?±?0.942 ng/ml), SLE (4.013?±?1.536 ng/ml), other autoimmune diseases (3.882?±?0.837 ng/ml) and HC (3.726?±?0.627 ng/ml). Significant positive correlation of CRT with DAS28, ESR and CRP was found in RA patients. Furthermore, RA patients whose anti-CCP and anti-MCV antibodies were positive had higher levels of CRT (P?<?0.01).

Conclusion

Serum CRT levels were increased in patients with RA compared with those controls. Moreover, a significant correlation was observed between serum CRT levels and disease activity in RA. It might be used as a potential biomarker for clinical diagnosis and provide additional information regarding disease activity along with the traditional indices such as ESR and CRP.     

Donor-matched comparison of chondrogenic progenitors resident in human infrapatellar fat pad,synovium, and periosteum - implications for cartilage repair

ABSTRACT

Purpose: There is a clinical need to better characterize tissue sources being used for stem cell therapies. This study focuses on comparison of cells and connective tissue progenitors (CTPs) derived from native human infrapatellar fatpad (IPFP), synovium (SYN), and periosteum (PERI).

Materials and Methods: IPFP, SYN, PERI were harvested from twenty-eight patients undergoing arthroplasty. CTPs were quantitatively characterized using automated colony-forming-unit assay to compare total nucleated cell concentration—[Cell], cells/mg; prevalence-(P_CTP), CTPs/million nucleated cells; CTP concentration—[CTP], CTPs/mg; proliferation and differentiation potential; and correlate outcomes with patient’s age and gender.

Results: [Cell] did not differ between IPFP, SYN, and PERI. P_CTP was influenced by age and gender: patients >60 years, IPFP and SYN had higher P_CTP than PERI (p < 0.001) and females had higher P_CTP in IPFP (p < 0.001) and SYN (p = 0.001) than PERI. [CTP] was influenced by age: patients <50 years, SYN (p = 0.0165) and PERI (p < 0.001) had higher [CTP] than IPFP; patients between 60 and 69 years, SYN (p < 0.001) had higher [CTP] than PERI; patients >70 years, IPFP (p = 0.006) had higher [CTP] than PERI. In patients >60 years, proliferation potential of CTPs differed significantly (SYN>IPFP>PERI); however, differentiation potentials were comparable between all three tissue sources.

Conclusion: SYN and IPFP may serve as a preferred tissue source for patients >60 years, and PERI along with SYN and IPFP may serve as a preferred tissue source for patients <60 years for cartilage repair. However, the heterogeneity among the CTPs in any given tissue source suggests performance-based selection might be useful to optimize cell-sourcing strategies to improve efficacy of cellular therapies for cartilage repair.     

Association of Crohn’s Disease with Aryl Hydrocarbon Receptor Gene Polymorphisms in Patients from Southeast China

ABSTRACT

Aims The aryl hydrocarbon receptor (AhR) plays a pivotal role in regulating the innate and the acquired immune systems. The present study aimed to investigate the association of Crohn’s disease (CD) with AhR polymorphisms in a cohort of patients from Southeast China.

Methods An improved multiple ligase detection reaction technique was applied to examine the polymorphisms of rs2158041, rs2066853, and rs10249788 in 310 patients with CD and 573 controls.

Results Compared to the controls, the variant allele (T) and genotype (CT+TT) of rs2158041 were less frequent in patients with CD (both p < 0.05). Similar conclusions were drawn from patients with ileal CD and with stricture CD as compared to the controls (all p < 0.0083). However, no significant differences were observed in allele and genotype frequencies of rs2066853 and rs10249788 between patients with CD and the controls (all p > 0.05). Although rs2158041 and rs10249788 were in complete linkage disequilibrium with rs2066853, respectively, only the frequency of haplotype (TG) formed by rs2158041 and rs2066853 was significantly lower in patients with CD than that in the controls (p < 0.05).

Conclusions AhR (rs2158041) might be a susceptible locus for CD, especially for the two subtypes: ileal CD and stricture CD.     

Soluble TWEAK may predict carotid atherosclerosis in treated HIV infection

Background: Soluble Tumor Necrosis Factor Weak Inducer of Apoptosis (sTWEAK) has been proposed as a novel biomarker of cardiovascular disease risk. This study compares levels of sTWEAK, sCD163 and the sCD163/sTWEAK ratio in HIV-infected and uninfected patients and their associations with cardiovascular and inflammatory factors.

Methods: The data for our analysis come from 274 HIV-infected adults and 59 controls. HIV participants were on stable antiretroviral therapy (ART). Wilcoxon-Mann-Whitney tests were used for comparing markers between HIV-infected participants with HIV viral load <50 copies/mL (aviremic group), HIV-infected participants with detectable viremia (HIV-1 RNA ≥50 copies/mL; viremic group) and HIV negative participants. Multivariable quantile regression analyses were used to assess associations of sTWEAK and sCD163 with other markers of inflammation and carotid intima-media thickness (cIMT).

Results: Overall, 74% of participants were male; 59% were African-Americans; median age was 40 years and CD4 595 cells/mm3. Overall, HIV-infected participants had reduced sTWEAK and increased sCD163 levels compared to HIV-uninfected participants (p = 0.0001 for both markers). In addition, these biomarkers were significantly different between HIV-infected viremic and aviremic patients (p ≤ 0.01 for both markers). In multivariable models, sTWEAK and sCD163 in aviremic patients were significantly correlated with common carotid artery IMT (p ≤ 0.05). In HIV-infected aviremic participants, sTWEAK and sCD163 were both associated with IL-6, CD14 + CD16 + monocytes (p ≤ 0.02); additionally, sCD163 was associated with D-dimer- (β = ?69.5, 0.05), VCAM (β = 72.4, p = 0.05), TNF RI (β = 91.1, p < 0.01), and TNF RII (β = 87.8, p < 0.01).

Conclusions: HIV-infected participants showed increased systemic inflammatory and monocyte activation markers. Soluble CD163 and sTWEAK levels were associated with carotid intima-media thickness.