Salivary and serum procalcitonin and C-reactive protein as biomarkers of periodontitis in United States veterans with osteoarthritis or rheumatoid arthritis

Serum procalcitonin (ProCT) is elevated in response to bacterial infections, whereas high sensitivity C-reactive protein (hsCRP) is a nonspecific inflammatory marker that is increased by excess adipose tissue. We examined the efficacy of ProCT and hsCRP as biomarkers of periodontitis in the saliva and serum of patients with arthritis, which is characterized by variable levels of systemic inflammation that potentially can confound the interpretation of inflammatory biomarkers. Blood and unstimulated whole saliva were collected from 33 patients with rheumatoid arthritis (RA) and 50 with osteoarthritis (OA). Periodontal status was assessed by full mouth examination and patients were categorized as having no/mild, moderate or severe periodontitis by standard parameters. Salivary and serum ProCT and hsCRP concentrations were compared. BMI, diabetes, anti-inflammatory medications and smoking status were ascertained from the patient records. Differences between OA and RA in proportionate numbers of patients were compared for race, gender, diabetes, adiposity and smoking status. Serum ProCT was significantly higher in arthritis patients with moderate to severe and severe periodontitis compared with no/mild periodontitis patients. There were no significant differences in salivary ProCT or salivary or serum hsCRP in RA patients related to periodontitis category. Most of the OA and RA patients were middle aged or older, 28.9% were diabetic, 78.3% were overweight or obese, and slightly more than half were either current or past smokers. The OA and RA groups differed by race, but not gender; blacks and males were predominant in both groups. The OA and RA groups did not differ in terms of controlled or uncontrolled diabetes, smoking status or BMI. The RA patients had been prescribed more anti-inflammatory medication than the OA patients. Our results demonstrate that circulating ProCT is a more discriminative biomarker for periodontitis than serum hsCRP in patients with underlying arthritis. Any elevation in salivary and serum hsCRP due to periodontitis apparently was overshadowed by differences among these patients in factors that influence CRP, such as the extent of inflammation between RA and OA, the extent of adipose tissue, the use of anti- inflammatory medications and smoking status. Although our study showed no differences in salivary ProCT related to severity of periodontitis, this biomarker also may be useful with further refinement.     

A study of C-reactive protein,lipid metabolism and peripheral blood to identify a link between periodontitis and cardiovascular disease

Periodontitis is characterized by systemic inflammatory host responses that may contribute to a higher risk for cardiovascular disease. We hypothesized that periodontitis may be associated with altered C-reactive protein levels, serum levels of lipids and peripheral blood counts, and that these characteristics may serve as markers for a link between periodontitis and cardiovascular disease. Sixty subjects, 25–60 years old, were divided into three groups of 20 subjects each. Group 1, age and sex matched healthy controls; group 2, patients diagnosed with chronic periodontitis; group 3, patients diagnosed with acute periodontal lesions including periodontal abscess and pericoronal abscesses. Serum C-reactive protein levels, lipid levels and peripheral blood counts were obtained for all three groups. Significant increases in C-reactive protein and serum lipid levels, and altered peripheral blood counts were observed between the experimental groups; these factors were correlated with chronic periodontitis and cardiovascular disease. These simple, economical clinical measurements can be used to assess periodontal tissue damage and may be useful for predicting risk of cardiovascular disease in these subjects.     

C-reactive protein as an early predictor of COVID-19 severity

BackgroundData for predicting severity of patients with COVID-19 infection are sparse and still under investigation. We retrospectively studied whether the admission serum C-reactive protein level (CRP) can serve as nearly predictor of disease severity during COVID-19 infection in comparison with other hematologic and inflammatory markers.MethodsWe included all consecutive patients who were admitted in Cheikh Khalifa International University Hospital, Casablanca, Morocco, between February to April 2020, with a confirmed diagnosis of COVID-19 infection using SARS-CoV-2 viral nucleic acid via RT-PCR. The complete blood count and serum CRP level were routinely measured on admission. All clinical and laboratory data of patients were collected and analyzed. The classification of the disease severity was in accordance with the clinical classification of the WHO interim guidance, and the management of patients were adapted to the national management guideline. We estimated receiver operating characteristic (ROC) curves of blood routine parameters as well as their association with COVID-19 disease severity.Results145 COVID-19 patients were included in the study. The median age (range) was 50 (32-63) years, and 75 (51.7%) were men. 101 patients were classified in the non-severe group and 44 patients in the severe group. Based on disease severity, significant differences were observed in the age, gender, comorbidities, and respiratory symptom. Similarly, the biological analysis found significant differences for the neutrophil count, lymphocyte count, eosinophil count, and CRP level. However, according to ROC curves of these laboratory biomarkers, the AUC of CRP at 0.872 was significantly higher than all other parameters. Further, CRP was independently associated with severity of COVID-19 disease (OR = 1.11, 95% IC (1.01-1.22) and or = 1.13, 95% IC (1.04-1.23)).ConclusionsThis study found that the CRP level at admission represent a simple and independent factor that can be useful for early detection of severity during COVID-19 and the easy guidance of primary care.     

C-反应蛋白对脂肪细胞脂联素表达的影响

通过体外培养脂肪细胞,研究C-反应蛋白（CRP）对大鼠脂肪细胞脂联素蛋白分泌及mRNA基因表达的影响。取大鼠附睾脂肪垫培养脂肪细胞。用0、10、50ug／mL的CRP刺激脂肪细胞6h,提取细胞RNA,用实时荧光定量RT-PCR技术检测脂联素mRNA表达的变化;收集细胞培养液,运用Western blot技术检测脂联素蛋白分泌的变化。结果显示0、10、50ug／mL的CRP对大鼠脂肪细胞脂联素mRNA表达的影响无差异（P〉0．05）。50、10ug／mL的CRP均可减少大鼠脂肪细胞培养液中脂联素蛋白的分泌量（P〈0．05）。CRP可呈剂量依赖性的降低脂肪细胞脂联素蛋白分泌的水平。而各组CRP未能影响脂肪细胞脂联素mRNA的表达。CRP对脂肪细胞脂联素基因表达和蛋白分泌的研究可以揭示转录后的控制决定了CRP对脂联素的影响。     

阿维菌素中毒患者血清C反应蛋白的浓度变化及意义

目的探讨口服阿维菌素中毒患者血清C反应蛋白浓度变化与病情严重程度及预后的关系。方法将39例口服阿维菌素中毒患者分为轻度中毒组和中重度中毒组,42例健康体检者为对照组。轻、中重度中毒组患者分别于入院时及入院第3、5天检测血清C反应蛋白浓度,并进行组间比较。结果中毒组血清CRP水平明显高于对照组,差异有统计学意义（P〈0.05）;轻度中毒组血清CRP水平在入院时及入院第3、5天变化较小,各时点血清CRP水平比较无显著统计学意义（P〉0.05）;中重度中毒组血清CRP水平在入院时即显著升高,入院第3天达最高值,各时点血清CRP水平比较差异有统计学意义（P〈0.05）。结论血清C反应蛋白浓度可作为判断口服阿维菌素中毒患者病情严重程度及预后的敏感指标。     

Cigarette smoking and serum soluble Fas levels: Findings from the JACC study

Cigarette smoking enhances low-grade systemic inflammation in the lung and other organs. Activated immune cells play an important role at early and late stages of inflammation, and in recent years, soluble Fas (sFas), an isoform of death molecule Fas, was found to interfere with the apoptotic pathways of these activated immune cells. The aim of this study was to confirm the association between cigarette smoking and sFas levels in healthy male subjects. We measured serum sFas levels of 4415 male subjects selected as controls for a nested case-control study within the large-scale cohort study conducted in Japan, called the JACC Study. Smoking status at baseline was evaluated by a self-administered questionnaire. Least square means of sFas according to smoking status and numbers of cigarettes smoked per day among smokers were calculated and adjusted for possible confounding factors. Mean sFas levels showed an increasing trend across never smokers, past smokers and current smokers, as 2.21 (95% CI: 2.14–2.27) ng/ml, 2.29 (2.22–2.36) ng/ml, and 2.36 (2.30–2.43) ng/ml, respectively. However, no dose-response relationship was observed between the number of cigarettes smoked per day and sFas levels among smokers.     

地衣芽孢杆菌活菌胶囊对肝炎后肝硬化患者 血清内毒素、超敏C反应蛋白及前降钙素水平的影响

目的探讨地衣芽孢杆菌活菌胶囊对肝炎后肝硬化患者血清内毒素、超敏C反应蛋白（hs-CRP）及前降钙素（PCT）水平的影响。方法将90例乙肝后肝硬化患者随机分为观察组和对照组。两组均予以低盐饮食、保肝利尿和营养支持等基础治疗。观察组加用地衣芽孢杆菌活菌胶囊0.5 g/次,3次/d,连用6周。观察两组治疗前后血氨、血清内毒素、hs-CRP和PCT水平变化。结果治疗6周后,两组血氨和血清内毒素水平较治疗前均明显下降（P〈0.05或P〈0.01）,且观察组患者下降程度与对照组比较更明显（P〈0.05）;同时两组血清hs-CRP和PCT水平较前明显下降（P〈0.05或P〈0.01）,且观察组患者下降程度与对照组比较更明显（P〈0.05）。结论地衣芽孢杆菌活菌胶囊辅助治疗乙肝后肝硬化能明显降低患者血氨和血清内毒素水平,并能下调血清hs-CRP和PCT水平,从而有利于抑制肝内局部炎症反应及降低肠黏膜的通透性。     

Altered serum and salivary C-reactive protein levels in patients with oral premalignant lesions and oral squamous cell carcinoma

Chronic inflammation is associated with cancer development. C-reactive protein (CRP), an acute phase protein synthesized primarily in the liver, is a marker for inflammation and for the progression of many cancers. We compared serum and salivary CRP levels in 20 normal individuals, 20 patients with oral premalignant lesions and 20 patients with oral squamous cell carcinoma (OSCC) to assess its efficacy as a prognostic indicator for OSCC. Saliva and blood samples were obtained and evaluated for CRP levels. Mean CRP levels were higher in patients with oral premalignant lesions compared to controls. CRP levels in OSCC patients were elevated and were associated with advanced tumor stages.     

Relationship between the tumor necrosis factor alpha polymorphism and the serum C-reactive protein levels in inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, including ulcerative colitis (UC) and Crohn's disease (CD). The aim of the study was to determine the prevalence of the tumor necrosis factor alpha (TNF-) promoter polymorphisms at positions –238 and –308, and to measure the serum CRP levels in CD and UC patients and in a healthy population. The TNF- gene polymorphisms were determined by the PCR-RFLP method. Samples of 74 CD and 50 UC patients and 138 healthy Hungarian volunteers were examined. The GA substitution at position –308 (designated the TNF2 allele) was significantly less frequent among IBD patients than in the control group (P=0.0009); 15% of the CD patients and 18% of the UC patients carried the mentioned allele, which was significantly less frequent compared with the healthy population (33%, P=0.0035 and P=0.036, respectively). No difference in the GA substitution at position –238 was observed. We found the median CRP levels to be significantly higher in the active phase of the disease than in the inactive phase among the –308A allele carriers (P=0.002), while this difference was not significant when the CRP levels in the active and inactive phases were compared among the –308GG homozygous patients (P=0.084). The decreased frequency of the TNF2 allele (known to be associated with elevated TNF- production) in IBD may determine the severity of IBD through its interaction with plasma CRP levels, and may modify the pathogenesis of this chronic inflammatory disease.     

Effects of interleukin-2 (IL-2) on human plasma lipid,lipoprotein, and C-reactive protein

Six patients with confirmed malignant disease received four consecutive weekly cycles of human recombinant interleukin-2 (IL-2) 4 days/week, continuous iv. infusion, 3 × 10⁶ U/m²/day. Plasma cholesterol decreased a mean of 7% within 24 hours after IL-2 infusion and decreased by 33% within 4 days. Plasma cholesterol was significantly lower than baseline concentration by day 21 (–21%), and day 25 (–41%) was significantly lower than day 21. Decreased plasma cholesterol was the result of decreased HDL and LDL cholesterol concentrations. Plasma triglyceride demonstrated a mean increase of 46% after 4 days of therapy and remained greater than baseline concentrations at all time points analyzed. Apolipoprotein AI and AII decreased concomitantly with HDL-cholesterol concentrations, whereas apolipoprotein B after an initial mean decrease of 17% during the first cycle was not significantly different from baseline during the fourth cycle. Apolipoprotein E and Lp(a) were not significantly affected by IL-2 treatment. Plasma C-reactive protein (CRP) increased by 79% within 24 hours of therapy, increased by 254% on day 4, then decreased to baseline concentrations by day 21 after 3 days off of IL-2. Day 25 CRP was elevated compared to both baseline and day 21 concentrations. IL-2 induced plasma lipoprotein changes may be due in part to the induction of interferon gamma.     

The interaction of C-reactive protein and serum amyloid P component with nuclear antigens

The pentraxins are a family of proteins characterized by cyclic pentameric structure, calcium-dependent ligand binding and sequence homology. The two main representatives of this family are the serum proteins, C-reactive protein (CRP) and serum amyloid P component (SAP). In man CRP is an acute phase reactant which increases up to 1000 fold during the acute phase response whereas SAP is a constitutive protein expressed at about 30 g/ml. These proteins activate complement through the classical pathway and participate in opsonization of particulate antigens and bacteria. In the past several years it has been determined that both of these pentraxins interact with nuclear antigens including chromatin and small nuclear ribonucleoproteins (snRNPs). Both CRP and SAP have nuclear transport signals which facilitate their entry into the nuclei of intact cells. Furthermore, these pentraxins have been shown to affect the clearance of nuclear antigens in vivo. It is now believed that one of the major functions of the pentraxins could be to interact with the nuclear antigens released from apoptotic or necrotic cells. This interaction could mitigate against deposition of these antigens in tissue and autoimmune reactivity.Abbreviations CRP C-reactive protein - HSA human serum albumin - PC phosphocholine - SAP serum amyloid P component - snRNP small nuclear ribonucleoprotein - SLE systemic lupus erythematosus     

Very low C-reactive protein in apparently healthy individuals: physiological status or just a reflection of an improved health profile

The objective of our study was to determine whether the very low concentrations of C-reactive protein (CRP) detected by high-sensitivity CRP (hs-CRP) assays that one encounters from time to time in apparently healthy individual represent a physiological status or are just a reflection of an improved general health profile. The concentration of hs-CRP was determined by using the Behring BN II nephelometer. The arbitrary cut-off point of hs-CRP (≤0.16mgl^-1) was determined at the lower detection level of the assay. A total of 6588 apparently healthy individuals were screened following exclusion of recent infection/inflammation by using a detailed questionnaire. One hundred and sixty (2.4%) individuals out of the above-mentioned cohort presented hs-CRP concentrations of ≤0.16mgl^-1. They were found to be significantly younger and lean, had an improved lipid profile and an attenuated acute-phase response in terms of lower erythrocyte sedimentation rate and fibrinogen concentration as well as white blood cell count. In addition, these individuals had less atherothrombotic risk factors, except for smoking habits which were as frequent as in those of individuals with a higher hs-CRP concentration. After calculating the concentration of this biomarker following multiple adjustments, the individuals with very low CRP remained with a very low value despite the multiplicity of the adjustments. We raise the possibility that this particular low concentration might represent a physiological status and is not necessarily a result of the improved general health profile per se.     

Very low C-reactive protein in apparently healthy individuals: physiological status or just a reflection of an improved health profile

Abstract

The objective of our study was to determine whether the very low concentrations of C-reactive protein (CRP) detected by high-sensitivity CRP (hs-CRP) assays that one encounters from time to time in apparently healthy individual represent a physiological status or are just a reflection of an improved general health profile. The concentration of hs-CRP was determined by using the Behring BN II nephelometer. The arbitrary cut-off point of hs-CRP (≤0.16mgl^?1) was determined at the lower detection level of the assay. A total of 6588 apparently healthy individuals were screened following exclusion of recent infection/inflammation by using a detailed questionnaire. One hundred and sixty (2.4%) individuals out of the above-mentioned cohort presented hs-CRP concentrations of ≤0.16mgl^?1. They were found to be significantly younger and lean, had an improved lipid profile and an attenuated acute-phase response in terms of lower erythrocyte sedimentation rate and fibrinogen concentration as well as white blood cell count. In addition, these individuals had less atherothrombotic risk factors, except for smoking habits which were as frequent as in those of individuals with a higher hs-CRP concentration. After calculating the concentration of this biomarker following multiple adjustments, the individuals with very low CRP remained with a very low value despite the multiplicity of the adjustments. We raise the possibility that this particular low concentration might represent a physiological status and is not necessarily a result of the improved general health profile per se.     

Association of serum amyloid A levels with adipocyte size and serum levels of adipokines: Differences between men and women

The aim of this study was to characterize the association between adipocyte enlargement and circulating levels of serum amyloid A (SAA). Furthermore, we wanted to search for possible associations with measures of glycemic control and levels of circulating adipokines and/or inflammatory markers in men and women with a large range in body mass index. The study cohort consisted of 167 subjects, 114 non-diabetic and 53 with Type 2 diabetes. Adipocyte diameter as well as circulating levels of SAA, C-reactive protein (CRP), adiponectin, leptin, interleukin-6, tumor necrosis factor alpha, glucose and insulin were measured. Women had higher serum levels of SAA than men (p = 0.044). SAA levels were weakly but positively correlated with BMI (p = 0.043) and % body fat (p = 0.027) in all subjects as well as subcutaneous adipocyte diameter (p = 0.034) in women. Furthermore, in all subjects we found correlations between SAA levels and levels of CRP (p < 0.001), interleukin-6 (p < 0.001), leptin (p = 0.003), insulin (p = 0.006), HbA1c (p = 0.02) and HOMA-IR (p = 0.002). A majority of the correlations were strongest in women. In conclusion, serum levels of SAA are strongly correlated with serum levels of inflammatory markers as well as measures of glycemic control. There seems to be large sex differences in these associations suggesting that sex-specific factors need to be considered when analyzing SAA levels in relation to metabolic disease.     

Interleukin-6 as an independent predictor of future cardiovascular events in high-risk Japanese patients: comparison with C-reactive protein

Inflammation is associated with the development of atherosclerotic vascular lesions and some inflammatory parameters are used as cardiovascular (CV) risk markers. The present study was designed to assess the predictive power of interleukin (IL)-6 for future CV events. In 121 Japanese patients with multiple CV risk factors and/or disease, serum concentrations of IL-6 and high sensitive C-reactive protein (hs-CRP) were measured. During follow-up periods (mean, 2.9 years) after the baseline assessment, 50 patients newly experienced CV events such as stroke/transient ischemic attack (n=10), heart failure hospitalization (n=6), acute coronary syndrome (n=7), and revascularization for coronary artery disease (n=15) and peripheral arterial disease (n=12). The serum level of IL-6, but not hs-CRP, was significantly higher in patients who had CV events than in event-free subjects (3.9±2.6 and 3.0±2.2 pg/mL, P=0.04). When the patients were divided into three groups by tertiles of basal levels of IL-6 (<1.85, 1.85-3.77, and ≥3.77 pg/mL), cumulative event-free rates by the Kaplan-Meier method were decreased according to the increase in basal IL-6 levels (65%, 50%, and 19% in the lowest, middle, and highest tertiles of IL-6, respectively; log-rank test, P=0.002). By univariate Cox regression analysis, previous CV disease, creatinine clearance, and serum IL-6 levels were significantly associated with CV events during follow-up. Among these possible predictors, the highest tertile of IL-6 was only an independent determinant for the morbidity in the multivariate analysis (hazard ratio 2.80 vs. lowest tertile, P=0.006). These findings indicate that IL-6 is a powerful independent predictor of future CV events in high-risk Japanese patients, suggesting its predictive value is superior to that of hs-CRP.     

Carbohydrate ligands of human C-reactive protein: Binding of neoglycoproteins containing galactose-6-phosphate and galactose-terminated disaccharide

Binding of carbohydrate ligand by human C-reactive protein (CRP), in both native form and structurally deviated form (neoCRP or mCRP), was investigated using galactose-6-phosphate (Gal6P)- and Galβ3GalNAc-containing bovine serum albumin (BSA) derivatives. To this end, we synthesized glycosides of Gal6P and Galβ3GalNAc that can potentially generate a terminal aldehyde group. ω-Aldehydo glycosides were then conjugated to BSA via reductive amination. Using these neoglycoproteins, we showed that: (1) Gal6P-BSA and Galβ3GalNAc-BSA bound to both forms of CRP, the former with or without calcium and the latter only in the absence of calcium; (2) phosphate-containing ligands can be bound with or without calcium, but the binding is much stronger in the presence of calcium than in the absence, underscoring the importance of direct coordination of phosphate to two calcium ions observed in the X-ray structure of phosphorylcholine (PC)–CRP complex; (3) cross-inhibition studies further corroborated the hypothesis that binding sites of PC and sugar are contiguous; (4) while PC-BSA bound to the native CRP over a wide pH range of 4.5 to 9, all the carbohydrate ligands and protamine-BSA (poly-cation-based ligand) exhibited optimal binding at around pH 6 to 6.5; and (5) ligand-binding conformation of mCRP appears to be more fragile than that of the native CRP in the acidic media (pH < 6).     

Associations of serum high-sensitivity C-reactive protein and prealbumin with coronary vessels stenosis determined by coronary angiography and heart failure in patients with myocardial infarction

BackgroundTo explore the associations of serum high-sensitivity C-reactive protein (hs-CRP) and prealbumin (PAB) with the number of diseased coronary vessels, degree of stenosis and heart failure in patients with myocardial infarction (MI).MethodsA total of 39 MI patients treated in the Cardiology were selected as the observation group, and another 41 patients with normal results of coronary angiography during the same period were selected as the control group. The general data of patients were recorded in detail, the content of serum hs-CRP and PAB in the peripheral blood was detected, and the number of diseased coronary vessels and the degree of stenosis were detected via coronary angiography.ResultsCompared with those in control group, the blood pressure and heart rate significantly rose, the content of indexes related to the severity of MI were significantly increased, the content of hs-CRP was significantly increased, and the content of PAB was significantly decreased in observation group. Hs-CRP was positively correlated with the number of diseased coronary vessels, degree of stenosis and heart failure in patients, but PAB was negatively correlated with the above factors. The survival rate of MI patients with high content of hs-CRP was obviously lower than that of patients with low content of hsCRPConclusionsSerum hs-CRP and PAB are closely associated with the number of diseased coronary vessels, degree of stenosis and heart failure in MI patients.     

The effects of rose hip (Rosa canina) on plasma antioxidative activity and C-reactive protein in patients with rheumatoid arthritis and normal controls: A prospective cohort study

Objectives

Rose hip (Rosa canina) has been used as an herbal remedy against a wide range of ailments including inflammatory disorders. The anti-inflammatory and antioxidant properties of rose hips have been evaluated in vitro and active constituents have been isolated. Rose hip contains antioxidant nutrients and an anti-inflammatory galactolipid. Rheumatoid arthritis (RA) is an inflammatory disease where activated cells release reactive oxygen substances. Thus it could be relevant to investigate if rose hip had an anti-inflammatory and/or antioxidant effect in this situation.

Methods

In this open case-control study 20 female patients with RA and 10 female controls were given 10.5 g rose hip powder daily (Litozin^®) for 28 days. Blood samples were analysed at baseline and follow-up for the capacity of the antioxidant enzymes superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase and the inflammatory marker C-reactive protein (CRP). The participants kept a food diary for the first 3 days and the last 3 days of the intervention period. The RA-patients completed The Stanford Health Assessment Questionnaire at baseline and follow-up.

Results

CRP-concentrations of both patients and healthy controls did not change. Nor was any effect found on the activity of antioxidant enzymes. There was no difference in food intake at baseline, but in the last week the RA-group reduced their energy intake.

Conclusions

10.5 g Litozin^® in 28 days had neither effect on clinical symptoms or laboratory measurements in patients with RA or healthy controls. This is in contrast to previous intervention studies with rose hip powder that found a reduction in the concentration of CRP. The results of the present study indicate that a daily amount of approximately 10 g rose hip powder for one month has no anti-inflammatory and/or antioxidant effect.