Tanja Pessi

Plasma level of soluble urokinase-type plasminogen activator receptor as a predictor of disease severity and case fatality in patients with bacteraemia: a prospective cohort study.

Huttunen R, Syrjänen J, Vuento R, Hurme M, Huhtala H, Laine J, Pessi T, Aittoniemi J (Tampere University Hospital; University of Tampere Medical School, University of Tampere; Centre for Laboratory Medicine, Pirkanmaa Hospital District; University of Tampere Medical School; School of Health Sciences, University of Tampere; and Medical School, University of Tampere; Tampere, Finland) Plasma level of soluble urokinase‐type plasminogen activator receptor as a predictor of disease severity and case fatality in patients with bacteraemia: a prospective cohort study. J Intern Med 2011; 270: 32–40.

Bacterial Signatures in Thrombus Aspirates of Patients With Myocardial Infarction

Background— Infectious agents, especially bacteria and their components originating from the oral cavity or respiratory tract, have been suggested to contribute to inflammation in the coronary plaque, leading to rupture and the subsequent development of coronary thrombus. We aimed to measure bacterial DNA in thrombus aspirates of patients with ST-segment–elevation myocardial infarction and to check for a possible association between bacteria findings and oral pathology in the same cohort. Methods and Results— Thrombus aspirates and arterial blood from patients with ST-segment–elevation myocardial infarction undergoing primary percutaneous coronary intervention (n=101; 76% male; mean age, 63.3 years) were analyzed with real-time quantitative polymerase chain reaction with specific primers and probes to detect bacterial DNA from several oral species and Chlamydia pneumoniae. The median value for the total amount of bacterial DNA in thrombi was 16 times higher than that found in their blood samples. Bacterial DNA typical for endodontic infection, mainly oral viridans streptococci, was measured in 78.2% of thrombi, and periodontal pathogens were measured in 34.7%. Bacteria-like structures were detected by transmission electron microscopy in all 9 thrombus samples analyzed; whole bacteria were detected in 3 of 9 cases. Monocyte/macrophage markers for bacteria recognition (CD14) and inflammation (CD68) were detected in thrombi (8 of 8) by immunohistochemistry. Among the subgroup of 30 patients with myocardial infarction examined by panoramic tomography, a significant association between the presence of periapical abscesses and oral viridans streptococci DNA–positive thrombi was found (odds ratio, 13.2; 95% confidence interval, 2.11–82.5; P=0.004). Conclusions— Dental infection and oral bacteria, especially viridans streptococci, may be associated with the development of acute coronary thrombosis.

Epistatic Effect of TLR4 and IL4 Genes on the Risk of Asthma in Females

Background: Many studies have demonstrated a connection between asthma and T-cell cytokine genes, such as genes coding for interleukin-4 (IL4) and IL-13, which are involved in the regulation of the TH1/TH2 balance. The toll-like receptor 4 (TLR4), the principal receptor for bacterial endotoxin, has attracted attention as a potential risk factor for asthma. We examined whether the polymorphisms of the TLR4 (A/G at +896) and IL4 (C/T at –590) showed an epistatic effect on the risk of asthma or atopy. Methods: Gene polymorphism analyses and skin prick tests were performed on asthmatic and nonasthmatic adult subjects of a Finnish population-based case-control study. The phenotype studied was persistent asthma. Results: The results showed that genotypes of neither the TLR4 SNP at +896 nor IL4 SNP at –590 were separately found to be associated with asthma. However, the female carriers of allele G (i.e. genotype AG or GG) of TLR4 and allele T (genotype CT or TT) of IL4 had a significantly increased risk for asthma. No association of these genes and atopy was found. Conclusions: Our results indicate that in females the TLR4 and IL4 genes show an epistatic effect on the risk of asthma. The low LPS-responsive allele G of TLR4 and high IgE production allele T of IL4 were found to be the predisposing combination. However, there was no epistatic effect on the risk of atopy.

The IL1A genotype is associated with nasal polyposis in asthmatic adults

Background: Nasal polyposis (NP) is a chronic inflammatory disease often found coexisting with asthma. As this disorder tends to cluster in families, a genetic predisposition has been suggested. Interleukin‐1 (IL‐1) has been proposed to play a role in the pathogenesis of NP.

Changes in gut bacterial populations and their translocation into liver and ascites in alcoholic liver cirrhotics

BackgroundThe liver is the first line of defence against continuously occurring influx of microbial-derived products and bacteria from the gut. Intestinal bacteria have been implicated in the pathogenesis of alcoholic liver cirrhosis. Escape of intestinal bacteria into the ascites is involved in the pathogenesis of spontaneous bacterial peritonitis, which is a common complication of liver cirrhosis. The association between faecal bacterial populations and alcoholic liver cirrhosis has not been resolved.MethodsRelative ratios of major commensal bacterial communities (Bacteroides spp., Bifidobacterium spp., Clostridium leptum group, Enterobactericaea and Lactobacillus spp.) were determined in faecal samples from post mortem examinations performed on 42 males, including cirrhotic alcoholics (n = 13), non-cirrhotic alcoholics (n = 15), non-alcoholic controls (n = 14) and in 7 healthy male volunteers using real-time quantitative PCR (RT-qPCR). Translocation of bacteria into liver in the autopsy cases and into the ascites of 12 volunteers with liver cirrhosis was also studied with RT-qPCR. CD14 immunostaining was performed for the autopsy liver samples.ResultsRelative ratios of faecal bacteria in autopsy controls were comparable to those of healthy volunteers. Cirrhotics had in median 27 times more bacterial DNA of Enterobactericaea in faeces compared to the healthy volunteers (p = 0.011). Enterobactericaea were also the most common bacteria translocated into cirrhotic liver, although there were no statistically significant differences between the study groups. Of the ascites samples from the volunteers with liver cirrhosis, 50% contained bacterial DNA from Enterobactericaea, Clostridium leptum group or Lactobacillus spp.. The total bacterial DNA in autopsy liver was associated with the percentage of CD14 expression (p = 0.045). CD14 expression percentage in cirrhotics was significantly higher than in the autopsy controls (p = 0.004).ConclusionsOur results suggest that translocation of intestinal bacteria into liver may be involved as a one factor in the pathogenesis of alcoholic liver cirrhosis.

Genetic and Environmental Factors in the Immunopathogenesis of Atopy: Interaction of Helicobacter pylori Infection and IL4 Genetics

Background: Both genetic and environmental factors, e.g. early childhood infections, have a role in the pathogenesis of atopic diseases. Objective: To examine simultaneously the strength and possible interactions of two known such factors, IL4 genetics and Helicobacter pylori infection, on the risk of atopy and asthma. Methods: Gene polymorphism analyses and skin prick tests (SPT) were determinedin 245 adult asthmatics and 405 nonasthmatic controls of population-based case-control study. SPTs were used as an indicator of atopy. H. pylori infection was verified by detecting anti-H. pylori IgG antibodies in sera. Results: A significant negative association was seen between the presence H. pylori antibodies and SPT positivity (≧1 positive reactions) in both asthmatics and controls (p = 0.002 and p = 0.025, respectively) but the effect of IL-4 polymorphism (SNP –590C/T) was nonsignificant in both groups (p = 0.071 and p = 0.072, respectively). However, IL4 genetics had an effect on susceptibility to H. pylori: asthmatics carrying the IL4 –590 allele T had a diminished risk to be H. pylori infected (OR 0.485 95%CI 0.287–0.819). This effect was not seen in controls. Logistic regression analysis indicated that H. pylori and IL4 effects on atopy risk are not interdependent. Conclusions: This study showed that the effect of H. pylori infection on atopy risk is stronger than that of IL4 genetics. There is no interaction between these factors on the pathogenesis of atopy suggesting that these factors have distinct immunopathogenetic mechanisms. However, the genetic effect may modify the role of infective agents by effecting on susceptibility to disease.

Mannose-binding lectin 2 (MBL2) gene polymorphism in asthma and atopy among adults.

Mannose‐binding lectin (MBL) insufficiency due to polymorphisms in the MBL2 gene causes an opsonization defect, which has been connected to infections and atopy. We investigated the significance of MBL2 genotypes with regard to persistent asthma and atopy among adults. The genotypes were determined in 243 adults with persistent asthma and 400 controls. Atopy was determined by skin‐prick test. As a result, the carriage of −221 base pairs (bp) promoter region variant allele X (nucleotide change G→C; alleles Y→X, respectively) causing low MBL expression proved to be a significant risk factor for asthma in non‐atopic males [odds ratio (OR) = 2·52, 95% confidence interval (CI) = 1·23–5·15; P = 0·01]. Furthermore, the X‐allele carriage was associated with the decrease in lung function (forced expiratory volume at 1 s, FEV1) during follow‐up in the patients with asthma (P = 0·033), the effect being strongest for non‐atopic asthmatics (P = 0·042). The MBL2 genotype had no clear effect on the occurrence of atopy in adults. In conclusion, our results abrogate the previously suggested predisposing effect of MBL insufficiency on atopy at least in adults. However, as MBL is a complement component participating in immune defence against microbes, and as in the pathogenesis of non‐atopic asthma infectious agents are probably involved, the gene–environment interactions between MBL and infections should be assessed further with regard to asthma.

Allergic rhinitis and polymorphisms of the interleukin 1 gene complex.

BACKGROUND Allergic rhinitis is a chronic inflammatory disease with a genetic background. Inflammatory reactions are regulated by cytokines. Cytokine genes are polymorphic and have been implicated as candidate genes in allergy. OBJECTIVES To study the significance of the interleukin 1 (IL-1) gene complex in allergic rhinitis. METHODS Population-based, cross-sectional study. We studied the polymorphisms of 3 IL-1 gene complex genes, IL1A (+4845G>T), IL1B (-511 degrees C>T), and IL1RN (variable number of tandem repeats; IVS2, 86 bp, duplicates 2 to 5), in patients with allergic rhinitis. The study group consisted of 405 nonasthmatic individuals of whom 56 had allergic rhinitis. RESULTS The genotype distribution differed significantly in all cytokine genes studied between subjects with and without allergic rhinitis. The difference was mainly due to an increased number of IL1A allele G homozygotes (67.9% vs 43.2%; odds ratio [OR], 2.8; 95% confidence interval [CI], 1.5-5.1), IL1B heterozygotes (72.2% vs 47.4%; OR, 2.8; 95% CI, 1.5-5.3), and IL1RN allele 2 homozygotes (18.5% vs 7.5%; OR, 2.8; 95% CI, 1.3-6.2) in allergic rhinitis. Haplotype analysis revealed a significant difference in the distribution of IL-1 gene complex haplotypes between subjects with and without allergic rhinitis (P = 0.005, 10 df). CONCLUSIONS The IL-1 gene complex polymorphism is strongly associated with allergic rhinitis in nonasthmatic individuals.

Evaluation of Postmortem Bacterial Migration Using Culturing and Real‐Time Quantitative PCR

Postmortem bacteriology can be a valuable tool for evaluating deaths due to bacterial infection or for researching the involvement of bacteria in various diseases. In this study, time‐dependent postmortem bacterial migration into liver, mesenteric lymph node, pericardial fluid, portal, and peripheral vein was analyzed in 33 autopsy cases by bacterial culturing and real‐time quantitative polymerase chain reaction (RT‐qPCR). None suffered or died from bacterial infection. According to culturing, pericardial fluid and liver were the most sterile samples up to 5 days postmortem. In these samples, multigrowth and staphylococci were not or rarely detected. RT‐qPCR was more sensitive and showed higher bacterial positivity in all samples. Relative amounts of intestinal bacterial DNA (bifidobacteria, bacteroides, enterobacter, clostridia) increased with time. Sterility of blood samples was low during the studied time periods (1–7 days). The best postmortem microbiological sampling sites were pericardial fluid and liver up to 5 days after death.

Polymorphisms of PAI-1 and platelet GP Ia may associate with impairment of renal function and thrombocytopenia in Puumala hantavirus infection

INTRODUCTION Puumala virus (PUUV) infection is a viral hemorrhagic fever with renal syndrome (HFRS) characterized by thrombocytopenia and acute impairment of renal function. We aimed to assess whether genetic polymorphisms of platelet antigens together with those of von Willebrand factor (VWF) and plasminogen activator inhibitor (PAI-1) correlate with disease severity. Patients and methods 172 consecutive hospital-treated patients with serologically confirmed acute PUUV infection were included. Platelet glycoprotein (GP) IIIa T>C (rs5918), GP Ia T>C (rs1126643), GP Ib C>T (rs6065), GP VI T>C (rs1613662), VWF A>G (rs1063856) and PAI-1 A>G (rs2227631) were genotyped. The associations of the rarer alleles with variables reflecting the severity of the disease were analyzed. RESULTS PAI-1G-carriers had higher maximum creatinine level compared with the non-carriers (median 213 μmol/l, range 60-1499 μmol/l vs. median 122 μmol/l, range 51-1156 μmol/l, p = 0.01). The GG-genotypes had higher creatinine levels than GA- and AA-genotypes (medians 249 μmol/l, 204 μmol/l and 122 μmol/l, respectively, p = 0.03). Polymorphisms of GP VI and VWF associated with lower creatinine levels during PUUV infection. The minor C-allele of GP Ia associated with lower platelet counts (median 44 × 10(9)/l, range 20-90 × 10(9)/l vs median 64 × 10(9)/l, range 3-238 × 10(9)/l; p = 0.02). CONCLUSIONS Polymorphism of PAI-1, a major regulator of fibrinolysis, has an adverse impact on the outcome of kidney function in PUUV-HFRS. Platelet collagen receptor GP Ia polymorphism associates with lower platelet count.