Concentration Of sCD14 Research Articles

Abstract 44: Soluble CD14 and Risk of Incident Cognitive Impairment: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Introduction: Black adults in the U.S. experience a greater burden of systemic inflammation and cognitive impairment and dementia compared with White adults. Increasing evidence suggests peripheral inflammation is a risk factor for cognitive decline, however few longitudinal studies have investigated these relationships. CD14 is a pattern recognition receptor expressed by monocytes and macrophages that promotes inflammation. Concentrations of the soluble form of CD14 (sCD14) vary by race, and higher sCD14 was associated with incident coronary heart disease (CHD) and stroke in Black but not White participants in the REGARDS cohort study. We hypothesized higher sCD14 would also be more strongly associated with incident cognitive impairment (ICI) in Black compared to White adults. Methods: We performed a nested case-control study of ICI in the REGARDS study, a biracial cohort of 30,239 American adults ≥45 years old. Cases were 495 participants without cognitive impairment or stroke at baseline who developed ICI during a median 3.5 years of follow-up based on abnormal scores on ≥2 of 3 cognitive tests. 587 controls were selected from a cohort random sample and free of cognitive impairment or stroke at baseline. Logistic regression models estimated odds ratios (OR) of ICI by concentration of sCD14 measured from stored baseline serum samples. We tested for a sCD14-by-race interaction a priori. Results: The sCD14-by-race interaction term was statistically significant in each model (p-interaction <0.05). In analyses stratified by race, adjusting for demographic factors (age, sex, and region), a 1-SD increment sCD14 was associated with a 40% higher odds of ICI among Black adults (OR: 1.40; 95% CI: 1.07, 1.95) with no association among White adults (OR: 1.08; 95% CI: 0.90, 1.28). In models adjusted for cognitive and vascular risk factors (income, education, systolic blood pressure, hypertension medication use, dyslipidemia, BMI, history of heart disease, atrial fibrillation, diabetes, smoking, and alcohol use), the relationship was attenuated in Black participants (OR: 1.33; 95% CI: 0.96, 1.84) and remained null among White participants (OR: 0.99; 95% CI: 0.81, 1.22). Comparing those with sCD14 concentration >90th percentile to below, adjusted for risk factors, Black participants had a 2.47 (95% CI: 1.08, 5.67) higher odds of ICI with no association in White participants (OR: 0.91; 95% CI: 0.46, 1.80). Discussion: Higher sCD14 was associated with ICI risk in Black but not White adults, similar to prior observations for stroke. Results suggest that sCD14-associated inflammatory responses may be a risk factor for ICI among Black adults.

Cytokine/chemokine profiles in people with recent infection by Mycobacterium tuberculosis.

The risk of progression to tuberculosis disease is highest within the first year after M. tuberculosis infection (TBI). We hypothesize that people with newly acquired TBI have a unique cytokine/chemokine profile that could be used as a potential biomarker. We evaluated socio-demographic variables and 18 cytokines/chemokines in plasma samples from a cohort of people deprived of liberty (PDL) in two Colombian prisons: 47 people diagnosed with pulmonary TB, 24 with new TBI, and 47 non-infected individuals. We performed a multinomial regression to identify the immune parameters that differentiate the groups. The concentration of immune parameters changed over time and was affected by the time of incarceration. The concentration of sCD14, IL-18 and IP-10 differed between individuals with new TBI and short and long times of incarceration. Among people with short incarceration, high concentrations of MIP-3α were associated with a higher risk of a new TBI, and higher concentrations of Eotaxin were associated with a lower risk of a new TBI. Higher concentrations of sCD14 and TNF-α were associated with a higher risk of TB disease, and higher concentrations of IL-18 and MCP-1 were associated with a lower risk of TB disease. There were cytokines/chemokines associated with new TBI and TB disease. However, the concentration of immune mediators varies by the time of incarceration among people with new TBI. Further studies should evaluate the changes of these and other cytokines/chemokines over time to understand the immune mechanisms across the spectrum of TB.

BIOMARKERS OF CYTOKINE STORM AND INFLAMMATION IN SEPSIS, POST-COVID-19 PATIENTS AND COVID-19 VACCINATED INDIVIDUALS

<h3>Introduction</h3> COVID-19 is associated with changes in biomarkers of inflammation and cytokine storm compared with sepsis. <h3>Methods</h3> 39 patients with sepsis (21 men and 18 women, age 57.2±20.2 years; blood was taken on 3-4 days from the diagnosis sepsis), 20 patients who had undergone the COVID-19 infection (10 men and 10 women, age 37.6±17.0 years, 124.9±27.5 days after the first symptoms) and 22 patients who were vaccinated with Sputnik-V (8 men and 14 women, age 53.3±12.8 years, 38.5±2.6 days after the first vaccination) were assessed. Procalcitonin, sCD14, IL-6, IL-8, IL-10, sTREM-1, sWNT5a, sLBP, sTNFα and sTNFβ were measured in serum in duplicate by ELISA. <h3>Results</h3> A significant increase in the level of procalcitonin, sLBP, sCD14, IL-6, IL-8 and IL-10 was found in patients with bacterial sepsis compared with patients who underwent Covid-19 infection or were Sputnik-V vaccinated (p<0.0001). Levels of sTREM-1, sWnt5a, TNFα and TNFβ in patients with sepsis, demonstrated no significant change in indicators compared with patients who underwent Covid-19 infection or were Sputnik-V vaccinated. There was a decrease in the concentration of sCD14, sLBP and an increase in procalcitonin in the serum of vaccinated individuals compared with those who had had an infection (p <0.05). High levels of sTREM-1 were seen in patients who have undergone COVID-19 and vaccinated individuals. <h3>Conclusions</h3> Levels of sTREM-1 can serve as both a marker of the immune response and a marker of the prognosis of recovery from COVID-19.

THE ROLE OF PRESEPSIN IN IMMUNOSUPPRESSION IN SEPSIS AND SEPTIC SHOCK PATIENTS

<h3>Introduction</h3> The role of presepsin (soluble CD14-ST) a 13-kDa cleavage product of DC14 receptor- is well described in the initial stage of the septic patients with little data on its role in immunosuppression. <h3>Methods</h3> 33 patients with sepsis (19 men and 14 women, age 57.1±19.9 years) and 6 patients with septic shock (2 men and 4 women, age 49.3±19.6 years) were assessed. Blood was obtained 3-4 days from diagnosis. The expression level of CD14 on monocytes was determined by flow cytometry. sCD14 was measured in serum in duplicate by ELISA. Expression of the CD14 gene was determined by real-time PCR. <h3>Results</h3> A significant decrease in the percentage of CD14-positive monocytes was revealed both in the group of patients with sepsis and in the group with septic shock (p<0.05) compared with normal donors. A significant increase in the level of sCD14 in the blood serum of patients with sepsis and septic shock was shown. The levels of sCD14 in patients with sepsis were inversely correlated with the percentage of CD14 on monocytes (R = -0.4588), indicating a weak inverse relationship. A significant decrease in the level of CD14 gene expression by monocytes was shown by 3.1 fold in patients with sepsis and by 10.2 fold in patients with septic shock compared with the control group. <h3>Conclusion</h3> The percentage of CD14 on monocytes, gene expression and the concentration of sCD14 in serum of patients with sepsis can serve as an indicator of the activity, severity and prognosis of sepsis.

CD14+ monocytes and soluble CD14 of synovial fluid are associated with osteoarthritis progression.

This study aims to investigate the role of cluster of differentiation 14 (CD14) expressed monocytes and soluble CD14-mediated pathway in the synovial inflammation of knee osteoarthritis (OA). Between May 2012 and July 2013, a total of 35 patients with knee OA (9 males, 26 females; mean age: 66.3±8.8 years; range, 52 to 79 years) were included in this cross-sectional study. Synovial fluid was obtained from knee joints of 35 OA patients. The CD14+ monocytes from synovial fluid mononuclear cells (SFMCs) were isolated using the MACS. The fibroblast-like synoviocytes (FLSs) isolated from knee joint tissue were incubated with recombinant CD14 and lipopolysaccharide (LPS) for 24 h. Cytokine profiling was performed with the Luminex® Performance Assay or magnetic bead panel kit. The expression of CD14 and CD16 was analyzed by immunohistochemistry and flow cytometry. The concentration of sCD14 in synovial fluid was correlated with the interleukin-6 (IL-6) level (n=35) (ρ=0.654, p<0.001). The culture supernatants of CD14+ monocytes isolated from SFMC (n=15) showed a correlation between sCD14 and IL-6 (ρ=0.784, p=0.001), along with complement component 3 (ρ=0.756, p=0.010), IL-1b (ρ=0.652, p=0.012), and tumor necrosis factor-alpha (ρ=0.806, p=0.001). Following recombinant CD14 and LPS treatment, OA FLS synergistically enhanced the secretion of IL-6, IL-8, and matrix metalloproteinase 3 (n=3, p<0.05). In five paired-samples from identical patients, the proportions of CD14+ monocytes were significantly elevated in recurred synovial fluid compared to those in initial synovial fluid (p=0.043). When monocyte subsets were analyzed in SFMC (n=26), CD14+CD16+monocytes were abundant (p=0.019) and had higher toll-like receptor 4 expression than CD14+CD16- (p<0.001). Our study results suggest that CD14+ monocytes and the sCD14-mediated pathway play an important role in OA aggravation through inflammatory cytokine secretion.

The Effect of Uterine Lavage on Soluble CD14, Chemokine Ligand 2, and Interleukin 10 Levels in Mares With Postpartum Metritis

Postpartum metritis in mares is a life-threatening condition associated with severe clinical signs due to endotoxemia, and it is often followed by complications such as laminitis. Repeated large-volume uterine lavages are commonly recommended as a part of the treatment protocol to remove endotoxin-laden contents from the uterus. It has, however, also been suggested that lavages may increase the uptake of endotoxin into the circulation, leading to a deterioration of clinical signs. Endotoxemia is associated with the release of a multitude of inflammatory mediators regulating the immune response. The aim of this study was to evaluate if uterine lavage influences serum levels of the inflammation markers soluble CD14 (sCD14), chemokine (C-C motif) ligand 2 (CCL2), and interleukin (IL)-10 in mares with postpartum metritis. Serum samples were collected from eight mares treated for metritis at a university teaching hospital. Mares with fever, tachycardia, and/or leukopenia and hemosanguineous or purulent intrauterine fluid within 1 week of foaling were included in the study. Serum samples were taken before uterine lavage and 15 and 30 minutes after starting the lavage. The concentrations of sCD14, CCL2, and IL-10 were determined with a fluorescent bead–based immunoassay. There were no significant differences between sCD14, CCL2, or IL-10 levels at different sampling times. Heart rate was significantly lower after uterine lavage than before. The differences in body temperature and leukocyte count before and after lavage were not significant. In conclusion, uterine lavage had no immediate effect on the serum concentration of sCD14, CCL2, or IL-10, nor did it affect clinical parameters negatively.

No evidence of a synergistic effect of HIV infection and diabetes mellitus type 2 on fat distribution, plasma adiponectin or inflammatory markers

BackgroundAltered fat distribution and chronic inflammation are found in both persons living with HIV (PLWH) and persons with diabetes mellitus type 2 (DM2) and are known risk factors for cardiovascular diseases (CVD). We aimed to investigate if a synergistic effect of HIV infection and DM2 was found on fat distribution and inflammation.MethodsA cross-sectional study was performed including PLWH with HIV RNA < 200 copies/mL (18 with DM2 (HIV + DM2+), 18 without DM2 (HIV + DM2-)) and controls (19 with DM2 (controls with DM2) and 25 without DM2 (healthy controls). We measured fat distribution using dual-energy X-ray absorptiometry scan. Plasma concentrations of adiponectin, interleukin-6 (IL-6), tumor necrosis factor-alfa (TNF- α) and soluble CD14 (sCD14) was measured using snap-frozen plasma.ResultsHIV + DM2+ and HIV + DM2- had comparable trunk/limb fat ratio. In contrast, HIV + DM2+ had a higher trunk/ limb fat ratio than controls with DM2 and healthy controls (p = 0.013 and p < 0.001, respectively). However, HIV + DM2+ and controls with DM2 had comparable amount of trunk fat mass (kg) (p = 0.254). A lower concentration of plasma adiponectin and higher concentration of IL-6 was found in HIV + DM2+ than in HIV + DM2-(p = 0.037 and p = 0.039) and in healthy controls (p = 0.001 and p = 0.012). In contrast, plasma adiponectin and IL-6 concentrations were comparable in HIV + DM2+ and controls with DM2 (p = 0.345 and p = 0.825). Concentration of sCD14 was comparable in HIV + DM2+ and HIV + DM2–(p = 0.850), but elevated in HIV + DM2+ compared to controls with DM2 (p < 0.001) and healthy controls (p = 0.007). No statistical interactions were found between HIV infection and DM2 for any of the depending variables.ConclusionA synergistic effect of HIV and DM2 was not found for any of the outcomes. However, HIV + DM2+ had features related to both HIV infection and DM2 with a high trunk/limb ratio, high trunk fat mass, low concentration of plasma adiponectin and elevated concentrations of IL-6 and sCD14. This could contribute to elevated risk of CVD.

Lipids, biomarkers, and subclinical atherosclerosis in treatment-naive HIV patients starting or not starting antiretroviral therapy: Comparison with a healthy control group in a 2-year prospective study.

ObjectiveTo assess the effect of HIV infection and combined antiretroviral therapy (c-ART) on various proatherogenic biomarkers and lipids and to investigate their relationship with subclinical atherosclerosis in a cohort of treatment-naive HIV-infected patients.MethodsWe performed a prospective, comparative, multicenter study of 2 groups of treatment-naive HIV-infected patients (group A, CD4>500 cells/μL, not starting c-ART; and group B, CD4<500 cells/μL, starting c-ART at baseline) and a healthy control group. Laboratory analyses and carotid ultrasound were performed at baseline and at months 12 and 24. The parameters measured were low-density lipoprotein (LDL) particle phenotype, lipoprotein-associated phospholipase A2 (Lp-PLA2), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), sCD14, sCD163, monocyte chemoattractant protein-1(MCP-1), and asymmetric dimethylarginine (ADMA). A linear mixed model based on patient clusters was used to assess differences in biomarkers between the study groups and over time.ResultsThe study population comprised 62 HIV-infected patients (group A, n = 31; group B, n = 31) and 22 controls. Age was 37 (30–43) years, and 81% were men. At baseline, the HIV-infected patients had a worse LDL particle phenotype and higher plasma concentration of sCD14, sCD163, hs-CRP, and LDL-Lp-PLA2 than the controls. At month 12, there was an increase in total cholesterol (p = 0.002), HDL-c (p = 0.003), and Apo A-I (p = 0.049) and a decrease in sCD14 (p = <0.001) and sCD163 (p<0.001), although only in group B. LDL particle size increased in group B at month 24 (p = 0.038). No changes were observed in group A or in the healthy controls. Common carotid intima-media thickness increased in HIV-infected patients at month 24 (Group A p = 0.053; group B p = 0.048). Plasma levels of sCD14, sCD163, and hs-CRP correlated with lipid values.ConclusionsIn treatment-naive HIV-infected patients, initiation of c-ART was associated with an improvement in LDL particle phenotype and inflammatory/immune biomarkers, reaching values similar to those of the controls. HIV infection was associated with progression of carotid intima-media thickness.

Estimation of soluble CD14 levels in gingival crevicular fluid and serum in diseased and healthy periodontium

ObjectiveTo estimate the levels of sCD14 in gingival crevicular fluid and serum under periodontally-healthy and diseased conditions. MethodsThe subjects were divided into three groups of 15, each as follows: healthy, gingivitis, and periodontitis. Periodontal parameters including Probing pocket depth, Clinical attachment level, Bleeding index, and Plaque index. Gingival crevicular fluid and serum samples were collected and analyzed for sCD14 levels using commercially-available ELISA kits. ResultsThe mean concentration of sCD14 in GCF was significantly lower in the gingivitis (134.5 ± 26.85 ng/mL) and periodontitis (103.23 ± 20.36 ng/mL) groups than in the healthy group (172.77 ± 46.33 ng/mL); p < 0.001. The mean serum concentration of sCD14 in the healthy group was 1528.13 ± 387.37 ng/mL, which was significantly less than that of the periodontitis group (2051.50 ± 381.10 ng/mL); p = 0.011. ConclusionsThe serum sCD14 levels in the periodontitis groups were significantly higher than those in the healthy controls. The levels of sCD14 in GCF were significantly lower in the gingivitis and periodontitis groups than in the healthy group.

Changes in salivary microbial sensing proteins CD14 and TLR2 with aging.

Soluble toll-like receptor-2 (sTLR2) and soluble CD14 (sCD14) in saliva are defense proteins that bind specific microbe-associated molecular patterns. Since the oral flora changes with aging, the objective of this study is to determine and compare the concentration of sTLR2 and sCD14 in the saliva of healthy individuals in age groups from the first to the sixth decade of life. Unstimulated whole saliva was collected after obtaining informed consent. The concentration of sCD14 and sTLR-2 was measured by enzyme-linked immunosorbent assay. Statistical differences between the age groups were determined by analysis of variance. The relationship between the two markers in each age group was evaluated by Pearson's correlation coefficient and linear regression analyses. The concentration of salivary sTLR2 was highest in the youngest, and that of the sCD14 was highest in the oldest age group. While the salivary sCD14 and the sTLR2 exhibited a moderate negative correlation in the youngest, the relationship between the two markers was inversed in the oldest age group. The results of our exploratory study suggest a need to adjust for age-dependent changes in sCD14 and sTLR2 in healthy saliva while assessing the two proteins as biomarkers.

Increased expression of caspase 1 during active phase of connective tissue disease.

Key factors of pyroptosis play an important role in the inflammatory response to connective tissue disease (CTD). However, information on active and stable stages of CTD is scarce. To distinguish the differences of concentrations of C-reactive protein (CRP), caspase 1, caspase 4, caspase 5 and sCD14 in plasma between the patients with active and stable stages of CTD. A cohort study was conducted to recruit patients diagnosed with CTD of active phase and stable phase as well as health control. These data included the analysis of the concentration of sCD14, caspase 1, caspase 4 and caspase 5 in peripheral plasma by ELISA. The Wilcoxon rank-sum test was used to compare the two groups. The sex ratio and ages of the three groups were not different statistically. The concentrations of sCD14, caspase4 and caspase5 of plasma in the CTD of active phase and the stable phase as well as the health control. The concentration of caspase 1 in active phase of CTD (470.19 [422.33–513.14] pmol/L) was significantly higher than that in stable group (203.95 [160.94–236.12] pmol/L) and healthy control (201.65 [191.11–240.35] pmol/L] pmol/L) (p < 0.001, both), but there was no significant difference between stable group and healthy control (p = 0.2312). Similarly, the concentration of CRP in the active phase of CTD (8.96 [3.06–20.28] mg/L) was significantly higher than that in the stable group (3.00 [1.30–11.40] mg/L) and the healthy control (3.70 [2.30–4.73] mg/L) (p = 0.0013, p = 0.0006, respectively), but there was no significant difference between the stable group and the healthy control (p = 0.3205). However, there were no significant differences in the concentration of sCD14, caspase 4 and caspase 5 in the active phase of CTD and the stable group as well as the health group. Consequently, the patients of the active phase of CTD showed increased expression of caspase 1.

Diet Quality Is Low and Differs by Sex in People with HIV

People with HIV (PWH) are at risk for developing metabolic comorbidities driven, in part, by immune activation/inflammation. Little is known about diet quality, a potential modifiable factor in PWH. This study aimed to explore diet quality in terms of conformance with US dietary guidelines by calculating Healthy Eating Index-2010 (HEI) scores among adults with and without HIV in Boston, MA, and determine associations with HEI and markers of immune activation/inflammation. One-hundred and three HIV-infected [50 women, 53 men; mean±SD age: 47±7 y; body mass index (BMI, in kg/m2): 26±5] and 38 uninfected adults (17 women, 21 men; age: 46±7 y; BMI: 28±4) were included in this cross-sectional analysis. Participants who completed a 4-d food record from which HEI could be calculated were included. HEI was compared between participants with and without HIV, within HIV-infected participants stratified by sex, and by HIV serostatus and sex. In the HIV group, predictors of HEI were determined in multivariable modeling. Univariate associations with diet quality and inflammation/immune markers were assessed. The HEI score was 51.3 in the HIV-infected participants and 57.3 in the HIV-uninfected participants (P=0.052). In the comparison by HIV serostatus and sex, HIV-infected women had significantly lower HEI (49.2) compared with HIV-infected men (55.7) (P=0.005) and HIV-uninfected men (61.8) (P=0.002). Adjusting for potential confounding factors, sex remained an independent predictor of HEI in HIV (P=0.02). In the HIV group, higher log HEI was associated with lower concentration of the immune activation marker sCD14 (P=0.009). Diet quality tended to be lower in HIV-infected individuals compared with HIV-uninfected individuals and was lower among HIV-infected women compared with HIV-infected men, and HIV-uninfected men. There may also be an association with diet quality and sCD14 in PWH. Future prospective studies are needed to confirm these findings and determine whether improving diet quality is a useful strategy to reduce metabolic abnormalities in this population. This study was registered at clinicaltrials.gov as NCT00455793.

КЛИНИКО-ДИАГНОСТИЧЕСКОЕ ЗНАЧЕНИЕ ЛИПОПОЛИСАХАРИД — СВЯЗЫВАЮЩЕГО ПРОТЕИНА И РАСТВОРИМОГО КЛАСТЕРА ДИФФЕРЕНЦИРОВКИ 14 ПРИ ХРОНИЧЕСКИХ ГЕПАТИТАХ И ЦИРРОЗАХ ПЕЧЕНИ

The aim of the study was to investigate the pathogenetic and diagnostic significance of changes in the concentrations of lipopolysaccharide-binding protein (LBP) and the Soluble Cluster of Differentiation 14 (sCD14) in plasma of the blood in chronic hepatitis (CH) and liver cirrhosis (LC). Materials and methods: 54 patients with CH and 120 with LC was included in the study. Control group (CG) - 30 practically healthy donors. The concentration of LBP and sCD14 was studied in EDTA plasma by enzyme immunoassay using a commercial test - HyCult biotechnology systems (Netherlands). The study of the organs of the abdominal cavity and pulse dopplerography with color flow Doppler mapping of vessels were performed on an Ultrasound Monitor "Logic-500" (USA) with a 3.5-MHz convection sensor. Results: The mean values of LBP and sCD14 in CH and LC were significantly higher than in CG and did not differ significantly depending on the etiology of the disease. The concentration in the blood of LBP and sCD14 was influenced by the activity of CH and LC, the severity of portal hypertension and associated clinical manifestations, hepatic encephalopathy, the Child's Pugh class of severity. Reliable relationships between the studied parameters and a number of diagnostically significant ultrasound parameters of the portal blood flow (PBF) have been established. Conclusion: The study of the blood levels of LBP and sCD14 in CH and LC can be used to diagnose endotoxemia syndrome, the degree of activation of the anti-endotoxin immune response. Determination of the concentration of LBP in combination with the leading ultrasound parameters of the PBF contributes to the clarification of the degree of severity of the pathological process in the liver, allows predicting the transformation of CH to LC.

Effect of systemic long-term, low-dose aspirin on periodontal status and soluble CD14 in gingival crevicular fluid: a case-control study.

In the present study, we evaluated the effect of systemic long-term, low-dose aspirin on the periodontal status and gingival crevicular fluid (GCF) concentrations of aspirin-triggered lipoxins (ATL) and soluble CD14 (sCD14). The study group consisted of 45 patients who were on long-term, low-dose aspirin therapy, and the control group included patients not on aspirin therapy. Mean bleeding index, plaque index (PI), probing depth (PD), and clinical attachment loss (CAL) were recorded. GCF samples were analyzed for concentrations of ATL, and sCD14 using enzyme-linked immunosorbent assay method. The means of PI, PD, and CAL were higher for the control group compared to the study group. The mean concentration of ATL was significantly higher for the study group (49.13±37.39ng/mL). The mean concentration of sCD14 was higher in the control group (5.75±3.91μg/mL). There was a negative correlation in the study group between concentrations of ATL with PD (r=-0.54) and CAL (r=-0.123). There was a positive correlation between sCD14 and CAL (r=0.047) in the study group. A negative correlation was also observed between concentrations of sCD14 and ATL (r=-0.134) in the study group. The results indicate better periodontal status among long-term aspirin users compared to non-aspirin users.

LEVELS OF PLASMA SOLUBLE CD14 IN HIV-INFECTED OPIATE USERS

Chronic immune activation is one of the main causes of HIV disease progression. Bacterial components passed to the bloodstream from the gut as a result of microbial translocation, are known to induce immune activation. Component of Gram-negative bacteria’s cell walls, the lipopolysaccharide (LPS), is considered to be the major marker of microbial translocation. Through the activation of myeloid cells (predominantly monocytes) LPS causes the secretion of soluble CD14, thus making it a marker of LPS bioactivity. Besides sCD14 was shown to correlate with immune status in HIVinfected patients and to be an independent predictor of disease progression. Hypothesis: opiates increase microbial translocation from the gut in HIV-infected patients that is manifested by a higher concentration of sCD14 in plasma. Aim: to estimate the influence of opiate use on the level of sCD14 in plasma of HIV-infected patients. Materials and methods. Longitudinal study of 351 HIV positive individuals. Concentration of sCD14, was evaluated at 3 time points: baseline, after 12 and 24 months. Following groups were studied: 1) current opiate users – opiate use within past 30 days; 2) opiate users, who denied consumption of opiates within past 30 days; 3) people claiming to never have used opiates. Results. In dynamic assessment sCD14 mean was significantly higher in current opiate users (2222,46±39,02 ng/ml) against patients who denied opiates within past 30 days (1930±597 ng/ml) and those, claiming to never have used opiates (1915±577 ng/ml) (p<0,001). Conclusion. Opiate use in the course of HIV disease leads to increase in LPS induced monocyte activation which therefore signifies more intensive microbial translocation.

CD14-159C/T polymorphism in the development of delayed skin hypersensitivity to tuberculin.

The skin tuberculin test (TST), an example of a delayed-type hypersensitivity (DTH) reaction, is based on measuring the extent of skin induration to mycobacterial tuberculin (PPD). Little is known about the genetic basis of TST reactivity, widely used for diagnosing TB infection. The study investigated the relationship of the single base change polymorphic variants in CD14 gene (CD14(-159C/T)) with the development of DTH to PPD in BCG-vaccinated Polish Caucasian individuals. We found persistent lack of TST reactivity in about 40% of healthy subjects despite receiving more than one dose of BCG. The TST size was negatively correlated with the number of BCG inoculations. The distribution of C/T genotype was significantly more frequent among TST-negative compared with TST-positive individuals. The concentration of serum sCD14 was positively associated with mCD14 expression, but not with the TST status or CD14(-159C/T) polymorphism. A significant increase in mCD14 expression and serum sCD14 levels was found in TB group. We hypothesize that CD14(-159C/T) polymorphic variants might be one of genetic components in the response to attenuated M. bovis BCG bacilli.

СТАН СПЕЦИФІЧНОГО ІМУНІТЕТУ ДО ЕНДОТОКСИНУ У ХВОРИХ НА БРОНХІАЛЬНУ АСТМУ З ФІКСОВАНОЮ/ЗВОРОТНОЮ ОБСТРУКЦІЄЮ

&lt;p&gt;У дослідження було включено 331 хворого на&lt;br /&gt;бронхіальну астму. Залежно від ступеня пост-бронходілятаційного&lt;br /&gt;співвідношення ОФВ1/ФЖЄЛ було вияв-&lt;br /&gt;лено 151 пацієнта з фіксованою та 180 зі зворотною&lt;br /&gt;обструкцією. Рівні антиендотоксинових антитіл&lt;br /&gt;класів А, М, G та sCD14 визначали методом твер-&lt;br /&gt;дофазного імуноферментного аналізу. Результати&lt;br /&gt;дослідження показали, що вміст антиендотоксинових&lt;br /&gt;антитіл класу G був вище (р&amp;lt;0,001) контролю в обох&lt;br /&gt;групах, при цьому рівень цього імуноглобуліну був&lt;br /&gt;вище (р&amp;lt;0,05) у пацієнтів з фіксованою обструкцією.&lt;br /&gt;Концентрація sCD14 в індукованому мокротинні була&lt;br /&gt;вище (р&amp;lt;0,001) контролю в обох досліджуваних групах,&lt;br /&gt;хоча вміст цього медіатору в сироватці був вище&lt;br /&gt;(р&amp;lt;0,05) контролю тільки в пацієнтів зі зворотною&lt;br /&gt;обструкцією.&lt;br /&gt;Ключові слова: бронхіальна астма, ендотоксин,&lt;br /&gt;імунітет.&lt;/p&gt;

Dysregulated Immune Activation in Second-Line HAART HIV+ Patients Is Similar to That of Untreated Patients.

BackgroundSuccessful highly active antiretroviral therapy (HAART) has changed the outcome of AIDS patients worldwide because the complete suppression of viremia improves health and prolongs life expectancy of HIV-1+ patients. However, little attention has been given to the immunological profile of patients under distinct HAART regimens. This work aimed to investigate the differences in the immunological pattern of HIV-1+ patients under the first- or second-line HAART in Brazil.MethodsCD4+ T cell counts, Viral load, and plasma concentration of sCD14, sCD163, MCP-1, RANTES, IP-10, IL-1β, IL-6, TNF-α, IL-12, IFN-α, IFN-γ, IL-4, IL-5, and IL-10 were assessed for immunological characterization of the following clinical groups: Non-infected individuals (NI; n = 66), HIV-1+ untreated (HIV; n = 46), HIV-1+ treated with first-line HAART (HAART 1; n = 15); and HIV-1+ treated with second-line HAART (HAART 2; n = 15).ResultsWe found that the immunological biosignature pattern of HAART 1 is similar to that of NI individuals, especially in patients presenting slow progression of the disease, while patients under HAART 2 remain in a moderate inflammatory state, which is similar to that of untreated HIV patients pattern. Network correlations revealed that differences in IP-10, TNF-α, IL-6, IFN-α, and IL-10 interactions were primordial in HIV disease and treatment. Heat map and decision tree analysis identified that IP-10>TNF-α>IFN-α were the best respective HAART segregation biomarkers.ConclusionHIV patients in different HAART regimens develop distinct immunological biosignature, introducing a novel perspective into disease outcome and potential new therapies that consider HAART patients as a heterogeneous group.

Soluble toll like receptor 2 (TLR-2) is increased in saliva of children with dental caries.

BackgroundDental caries is the most common microbial disease affecting mankind. Caries risk assessment methods, identification of biomarkers and vaccine development strategies are being emphasized to control the incidence of the largely preventable disease. Pattern recognition receptors such as the toll like receptors (TLR) have been implicated as modulators of host-microbial interactions. Soluble TLR-2 and its co-receptor, CD14 identified in saliva can bind the cell wall components of cariogenic bacteria and modulate the disease process. The objective of this study is to determine the potential of salivary sTLR-2 and sCD14 as biomarkers of caries activity and indirect measures of the cariogenic bacterial burden.MethodsUnstimulated whole saliva was collected from twenty caries free and twenty caries active children between the ages of 5 and 13 years. The concentration of sCD14 and sTLR-2 together with that of the cytokine IL-8 reported to be increased in dental caries was assessed by the enzyme linked immunosorbent assay.ResultsWhile the level of sCD14 and that of IL-8 was equivocal between the two groups, the sTLR-2 concentration in caries active saliva was significantly higher than that in caries free saliva.ConclusionsThe sTLR-2 in saliva could serve as a potential biomarker for caries activity.

Role of adjuvant therapy in the treatment of helicobacter pylori infection in children.

The aim was to study the effect of combined probiotic containing Lactobacillus acidophilus, Bifidobacterium infantis, Enterococcus faecium, on H.pylori eradication efficacy in the treatment of children with chronic H.pylori- associated gastroduodenitis in the scheme of triple therapy of H.pylori eradication. Determination of total serum Ig M , A, G protein to Ag SagA H. pylori, breathing Helik test, rapid urease Helpil test ; that of concentration of serum sCD14 was conducted. The study group included 20 children who received standard triple eradication therapy for 7 days and 1 caps. of probiotic 3 times a day for 4 weeks, control group (20 children) – who received only standard eradication therapy. It is shown that combined use of probiotics in the treatment of Helicobacter pylori infection enhances effectiveness of eradication of H.pylori. In the basis of action of probiotic strains of the drug is an anti-inflammatory effect mediated by the impact on non-specific mechanisms of innate immunity, provided by molecular mechanism responsible for induction of sCD14 synthesis.