Biomedical subjects

Timo Palosuo

Publications and source records attributed to Timo Palosuo.

At least 19 recordsLinked to original sources

PubMed2006

Murine model of food allergy after epicutaneous sensitization: role of mucosal mast cell protease-1.

OBJECTIVE: Studies of the pathological mechanisms of food allergy have been impeded by the lack of relevant animal models. The purpose of this study was to develop a physiological model of food allergy that was not dependent on immunostimulatory adjuvants. MATERIAL AND METHODS: Balb/c mice were epicutaneously sensitized four times at varying intervals over a 22-day period, and challenged orally from day 40, 6 times every 1-3 days with either saline or ovalbumin. RESULTS: After sensitization (day 35) but before the oral challenges, the ovalbumin-sensitized groups showed increased specific IgE and IgG1 production when compared with the sham-sensitized groups. Mucosal mast cell protease-1 (MMCP-1) was undetectable in serum before the intragastric challenge. MMCP-1 concentrations were increased after the first ovalbumin dose, solely in the ovalbumin-sensitized and -challenged group. After the challenge period, the mean serum MMCP-1 concentration increased from an undetectable level in controls to an over 44-fold level in the ovalbumin-sensitized and -challenged mice. In this group, MMCP-1-positive cells were present in the small intestine and expressions of IFN-gamma and CXCL-9 mRNA were decreased in the ileum, suggesting an impaired Th-1-type response. Within one hour of the last ovalbumin challenge, 5 out of 6 mice developed diarrhea in the ovalbumin-sensitized and -challenged group, but there was no diarrhea in the other groups. CONCLUSIONS: A murine model of food allergy based on sensitization via epicutaneous exposure to allergen without immunostimulatory adjuvants was developed. Effective production of MMCP-1 together with specific IgE and IgG1 suggests a breakdown in oral tolerance to the allergen. Intragastric challenges were accompanied by mast cell-dependent immunopathological changes and diarrhea.

Animals↗

PubMed2005

Napins, 2S albumins, are major allergens in oilseed rape and turnip rape.

BACKGROUND: Children with IgE-mediated allergy to foods frequently react to seeds of oilseed rape (Brassica napus ssp. oleifera) and turnip rape (Brassica rapa ssp. oleifera) in skin prick tests (SPTs). Sensitization pathways are not known. OBJECTIVE: We identified possible major allergens in oilseed rape and turnip rape using sera from 72 atopic children (mean age, 3.3 years) with positive SPT responses to oilseed rape and turnip rape. METHODS: Allergens from oilseed rape and turnip rape seed extracts were purified by using gel filtration and cation exchange chromatography and characterized by means of reversed-phase chromatography, N-terminal amino acid sequencing, and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. IgE binding of sera from 72 children with positive SPT reactions to oilseed rape and turnip rape and 72 age- and sex-matched atopic control subjects with negative SPT responses were analyzed by means of IgE ELISA and immunoblotting. In vivo reactivity of the purified allergens was tested with SPTs in 6 children. RESULTS: In IgE immunoblotting and IgE ELISA major reactivity was to a group of homologous, approximately 9.5- to 14.5-kd proteins. These allergens were identified as 2S albumins, also known as napins, by means of N-terminal amino acid sequencing. In ELISA approximately 80% of the patients had IgE to purified napins from both plants. In SPTs purified napins caused positive reactions in all 6 children tested. CONCLUSIONS: This study shows that 2S albumins in oilseed rape and turnip rape are new potential food allergens. Further studies are needed to clarify the routes of exposure and mechanisms of sensitization.

2S Albumins, Plant↗

PubMed2005

Serum tryptase levels in acute coronary syndromes.

BACKGROUND: Mast cell accumulation and activation have been demonstrated in the vulnerable shoulder regions of atherosclerotic plaques and at the actual sites of plaque erosion and rupture. When activated and degranulated, mast cells release tryptase, a neutral protease, capable of activating matrix metalloproteinases and predisposing to plaque rupture. We tested the hypothesis that in acute coronary syndromes the levels of serum tryptase would reflect mast cell activation. METHODS AND RESULTS: The study population consisted of 183 patients admitted to the emergency room of 3 general hospitals because of acute chest pain of ischemic origin. Of these patients, 64 suffered from exertional angina presenting with acute chest pain, 60 had unstable angina, and 59 had acute myocardial infarction. Serum tryptase levels were analyzed from samples drawn, on average at 7 h, and also at 24 h after the onset of the chest pain. As controls served 41 patients admitted for surgical treatment of inguinal hernia or varicose veins. Serum tryptase levels remained stable within the observation period, and no differences were detected between the patient groups and controls. On the other hand, the differences in C-reactive protein levels reflected the extent of myocardial injury. CONCLUSIONS: In ACS, serum tryptase levels are normal and remain stable. Our results do not exclude the possibility of local activation of coronary mast cells, but suggest that the excess quantity of tryptase acutely released from mast cells in ACS, if any, is not sufficient to be detected by measuring tryptase concentration in the systemic circulation.

Acute Disease↗

PubMed2005

Isolated hevein-like domains, but not 31-kd endochitinases, are responsible for IgE-mediated in vitro and in vivo reactions in latex-fruit syndrome.

BACKGROUND: Individuals with natural rubber latex allergy often have immediate reactions to plant-derived foods and fresh fruits, such as avocado and banana. IgE of these patients has been shown to bind endochitinases containing an N-terminal hevein-like domain (HLD). However, evidence on 31-kd endochitinase-induced reactions in vivo is lacking. OBJECTIVE: We sought to assess the clinical significance of 31-kd endochitinases and isolated HLDs in latex-fruit syndrome. METHODS: The 31-kd endochitinases and corresponding HLDs were purified or produced from avocado, banana, latex, and wheat germ. Skin prick test reactivities against purified proteins were examined in 15 patients with natural rubber latex allergy. The binding efficiency of IgE to purified proteins was studied by using an inhibition ELISA. Experimentally resolved or modeled structures of the proteins were compared to clarify the molecular basis of clinical reactions. RESULTS: Eleven (73%) patients had skin prick test reactions to isolated HLDs of avocado and banana, but only 1 (7%) patient reacted to their corresponding 31-kd endochitinases. HLDs from avocado and banana inhibited binding of IgE to prohevein (Hev b 6.01) in 59% and 38% of patients, respectively, whereas corresponding percentages for 31-kd endochitinases were 17% and 20%, respectively. Isolated HLDs of wheat germ agglutinin and 18-kd wheat germ agglutinin did not significantly inhibit IgE binding to hevein. CONCLUSION: The isolated HLD molecules alone, but not when linked to endochitinases, seem to be responsible for IgE-mediated clinical reactions in latex-fruit syndrome. Careful selection of relevant allergens in their proper molecular form is therefore crucial in forming a reliable diagnosis of latex-fruit syndrome.

Adult↗

PubMed2005

Cutaneous, but not airway, latex exposure induces allergic lung inflammation and airway hyperreactivity in mice.

As respiratory symptoms are common in addition to skin reactions in natural rubber latex allergy, we investigated the significance of different allergen exposure routes in the development of lung inflammation and airway hyperreactivity (AHR). Both intracutaneous (IC) and intraperitoneal (IP) exposure followed by airway challenge with latex proteins induced an influx of mononuclear cells and eosinophils to the lungs. AHR and lung mucus production increased significantly after IC and IP but not after intranasal (IN) exposure. Infiltration of inflammatory cells was associated with the induction of T-helper type 2 (Th2) cytokines and several CC chemokines. Only a marginal induction of these mediators was found after IN exposure. On the contrary, increased levels of transforming growth factor-beta1 and forkhead box 3 mRNA, markers of regulatory activities, were found in the lungs after IN but not after IC exposure. Finally, IC and IP, but not IN, latex exposure induced a striking increase in specific immunoglobulin E (IgE) levels. Cutaneous latex exposure in the absence of adjuvant followed by airway challenge induces a local Th2-dominated lung inflammation and a systemic IgE response. Cutaneous exposure to proteins eluting from latex products may therefore profoundly contribute to the development of asthma in latex allergy.

Administration, Cutaneous↗

PubMed2004

Prognostic usefulness of plasma monocyte/macrophage and T-lymphocyte activation markers in patients with acute coronary syndromes.

Macrophages and T lymphocytes accumulate and are activated in atherosclerotic plaques. We tested the hypothesis that plasma levels of the monocyte/macrophage and T-lymphocyte activation markers, monocyte chemoattractant protein-1 (MCP-1) and soluble interleukin-2 receptor (sIL-2r), respectively, can be used in acute coronary syndrome classification and risk prediction. Blood samples were collected at hospital admissions of 183 patients who had ischemic chest pain. Of these, 59 had acute myocardial infarction, 60 had unstable angina, and 64 had angina pectoris. No significant differences in the levels or proportions of subjects with increased levels of MCP-1 or sIL-2r were found across groups. During a mean follow-up of 13 months, 117 patients (64%) had a study end point (i.e., cardiac death, recurrent myocardial infarction, unstable angina, or revascularization). Increased levels (above median) of MCP-1 and sIL-2r were associated with increased risk, with odds ratios of 1.85 (95% confidence interval 0.92 to 3.73, p = 0.08) and 2.34 (95% confidence interval 1.16 to 4.71, p <0.02), respectively. In summary, in this unselected patient population with a very high rate of coronary events during follow-up, increased plasma levels of MCP-1 and sIL-2r were helpful for predicting new coronary events.

Acute Disease↗

PubMed2004

Severe periodontitis enhances macrophage activation via increased serum lipopolysaccharide.

OBJECTIVE: In periodontitis, overgrowth of Gram-negative bacteria and access of lipopolysaccharide (LPS) to circulation may activate macrophages leading to foam cell formation. We investigated whether periodontal treatment affects proatherogenic properties of low-density lipoprotein (LDL) and, thus, macrophage activation. METHODS AND RESULTS: LDL was isolated and characterized before and after treatment from 30 systemically healthy patients with periodontitis. Production of cytokines and LDL cholesteryl ester (LDL-CE) uptake by macrophages (RAW 264.7) was determined. Baseline periodontal variables correlated positively with serum LPS and C-reactive protein concentrations, as well as macrophage cytokine production and LDL-CE uptake. LPS concentration correlated positively with serum concentration of oxidized LDL and cytokine production. Higher cytokine production and LDL-CE uptake were induced by LDL isolated from patients with elevated number of affected teeth before treatment. Patients with serum LPS concentrations above the median (0.87 ng/mL) at baseline had higher serum high-density lipoprotein (HDL) cholesterol (baseline versus after treatment, 1.30+/-0.19 versus 1.48+/-0.28 mmol/L; P=0.002) and HDL/LDL ratio (0.31+/-0.01 versus 0.34+/-0.10; P=0.048), but lower serum LPS concentration (1.70+/-0.49 versus 0.98+/-0.50 ng/mL; P=0.004) and autoantibodies to beta2-glycoprotein I (0.11+/-0.06 versus 0.09+/-0.04 ELISA units; P=0.022) after treatment. CONCLUSIONS: Our results suggest that in systemically healthy patients, the infected/inflamed area in periodontitis is associated with macrophage activation via increased serum LPS concentration.

Animals↗

PubMed2004

Construction of hevein (Hev b 6.02) with reduced allergenicity for immunotherapy of latex allergy by comutation of six amino acid residues on the conformational IgE epitopes.

Recently we have established that IgE Abs bind to conformational epitopes in the N- and C-terminal regions of the major natural rubber latex allergen, hevein (Hev b 6.02). To identify the critical amino acid residues that interact with IgE, the hevein sequence was scanned by using site-specific mutations. Twenty-nine hevein mutants were designed and produced by a baculovirus expression system in insect cells and tested by IgE inhibition-ELISA using sera from 26 latex allergic patients. Six potential IgE-interacting residues of hevein (Arg(5), Lys(10), Glu(29), Tyr(30), His(35), and Gln(38)) were identified and characterized further in detail. Based on these six residues, two triple mutants (Hdelta3A, Hdelta3B) and hevein mutant where all six residues were mutated (Hdelta6), were designed, modeled, and produced. Structural and functional properties of these combinatory mutants were compared experimentally and in silico with those of recombinant hevein. The IgE-binding affinity of the mutants decreased by three to five orders of magnitude as compared with that of recombinant hevein. Skin prick test reactivity of the triple mutant HDelta3A was drastically reduced and that of the six-residue mutant Hdelta6 was completely abolished in all patients examined in this study. The approach presented in this paper offers tools for identification and modification of amino acid residues on conformational epitopes of allergens that interact with IgE. Hevein with a highly reduced ability to bind IgE should provide a valuable candidate molecule for immunotherapy of latex allergy and is anticipated to have a low risk of systemic side effects.

Adolescent↗

PubMed2004

Serum iron, infection and inflammation; effects on coronary risk.

OBJECTIVES: To explore the potential pathways of association between serum iron and coronary heart disease, with major emphasis on factors related to infections and inflammation. DESIGN: A nested case-control study with 215 cases (myocardial infarction or coronary death) and 215 matched controls over 8.5 years. Logistic regression analyses were used to compare relative risks in various serum iron-high sensitive CRP-total leucocyte count-herpes simplex virus-1 antibody categories. RESULTS: Participants with low iron (< 17 micromol/l) had increased coronary risk with Odds Ratio (OR) of 2.1 (95% CI 1.1-3.8). Simultaneous elevation of hs-CRP and leucocyte count increased the risk substantially in those with low iron, OR 9.8 (95% CI 3.9-24.4). A combination of high herpes simplex virus-1 antibody level and low iron increased the risk modestly (OR 1.2), but when hs-CRP level was high simultaneously, the OR was 13.1 (95% CI 2.9-60.1). CONCLUSIONS: Our data suggest an association between low serum iron level and coronary risk. The association is not independent, but is related to the fact that chronic infections and inflammation are accompanied with low serum iron.

Adult↗

PubMed2004

Latex allergy and skin.

PURPOSE OF REVIEW: In this review we address the prevalence and outcome of latex allergy in health care workers (HCWs). Recent findings in natural rubber latex (NRL) allergens and trials of specific immunotherapy (SIT) are also of interest. RECENT FINDINGS: A study involving skin prick test (SPT) screening in HCWs in Russia and adjacent countries found a prevalence of latex allergy of 1.9%. Questionnaire studies performed in Wales and in the USA identified prevalence rates of about 0.6%. An intervention undertaken at the Mayo Clinic, in which only gloves with low or undetectable allergen levels were allowed, reduced markedly the incidence of NRL allergy. Two studies, one from Finland and another from Ohio, showed that outcomes in latex-allergic HCWs are generally good. A study involving SPT screening showed that 6% of construction workers had latex allergy. A questionnaire study among allergists practicing in the USA showed that 62% performed latex SPT and 6% reported anaphylaxis, which mostly occurred while using a homemade SPT solution. Hev b 2, Hev b 5, Hev b 6.01 and Hev b 13 produced positive SPT reactions in over 60% of latex-allergic individuals. Topical application of NRL in a murine model of protein contact dermatitis caused a striking increase in prohevein-specific (Hev b 6.01) immunoglobulin E levels, together with a T-helper-2 type dermatitis. A placebo-controlled SIT trial with NRL extract alleviated cutaneous symptoms but caused some systemic reactions in latex-allergic patients. SUMMARY: Low prevalence rates suggest that the peak of the latex allergy epidemic has already passed in HCWs. Hospital-wide interventions requiring use of low-allergen gloves reduce sensitization and changing gloves to nonlatex ones, or even using low-allergen latex gloves, in the affected individuals appears to confer adequate secondary prevention. In the USA there is an urgent need for standardized latex SPT reagent. Hev b 5 and Hev b 6.01 are major in vivo NRL allergens. Findings in mice suggest that NRL proteins eluting from latex gloves may also cause hand eczema in humans. SIT with NRL extract must still be considered an experimental treatment.

Allergens↗

PubMed2003

Periodontitis decreases the antiatherogenic potency of high density lipoprotein.

Periodontitis, a consequence of persistent bacterial infection and chronic inflammation, has been suggested to predict coronary heart disease (CHD). The aim of this study was to investigate the impact of periodontitis on HDL structure and antiatherogenic function in cholesterol efflux in vitro. HDL was isolated from 30 patients (age 43.6 +/- 6.1 years, mean +/- SD) with periodontitis before and after (3.2 +/- 1.4 months) periodontal treatment. The capacity of HDL for cholesterol efflux from macrophages (RAW 264.7), HDL composition, and key proteins of HDL metabolism were determined. After periodontal treatment, phospholipid transfer protein (PLTP) activity was 6.2% (P<0.05) lower, and serum HDL cholesterol concentration, PLTP mass, and cholesteryl ester transfer protein activity were 10.7% (P<0.001), 7.1% (P=0.078), and 19.4% (P<0.001) higher, respectively. The mean HDL2/HDL3 ratio increased from 2.16 +/- 0.87 to 3.56 +/- 0.48 (P<0.05). HDL total phospholipid mass and sphingomyelin-phosphatidylcholine ratio were 7.4% (P<0.05) and 36.8% (P<0.001) higher, respectively. The HDL-mediated cholesterol efflux tended to be higher after periodontal treatment; interestingly, this increase was significant (P<0.05) among patients whose C-reactive protein decreased (53.7% reduction, P=0.015) and who were positive by PCR for Actinobacillus actinomycetemcomitans. These results suggest that periodontitis causes similar, but milder, changes in HDL metabolism than those that occur during the acute-phase response and that periodontitis may diminish the antiatherogenic potency of HDL, thus increasing the risk for CHD.

C-Reactive Protein↗

PubMed2003

Synergistic effect of persistent Chlamydia pneumoniae infection, autoimmunity, and inflammation on coronary risk.

BACKGROUND: Given the role of chronic infections, autoimmunity, and inflammation in atherosclerosis, we studied the joint effect of chronic Chlamydia pneumoniae infection, persistently elevated human heat-shock protein 60 (hHsp60) antibodies, and C-reactive protein (CRP) on coronary risk. METHODS AND RESULTS: The participants for this prospective nested case-control study were obtained from the Helsinki Heart Study, during which 241 nonfatal myocardial infarctions or coronary deaths occurred among 4081 dyslipidemic middle-aged men. Serum samples taken at baseline and 3 to 6 months before the coronary events that occurred during the 8.5-year period were analyzed for antibodies to C pneumoniae and hHsp60 and the CRP concentration. Compared with persistently low levels, the risk of coronary events was 2-fold for persistently elevated immunocomplex (IC)-bound and/or serum IgA antibodies to C pneumoniae (OR, 1.96; 95% CI, 1.14 to 3.36) and also for serum IgA antibodies to hHsp60 (OR, 2.11; 95% CI, 1.08 to 4.13). The risks associated with elevated antibodies were much higher when CRP was also elevated. Compared with low or transiently elevated levels, the risk of coronary events, with adjustment for age and smoking, was 4.5-fold for persistently elevated CRP and C pneumoniae IC/IgA antibodies together (OR, 4.47; 95% CI, 1.84 to 10.83) and was similar for CRP and hHsp60 IgA antibodies together (OR, 4.36; 95% CI, 1.53 to 12.39). CONCLUSIONS: Persistently but not transiently elevated C pneumoniae IC/IgA and hHsp60 IgA antibodies, especially when present together with an elevated CRP level, predicted coronary events.

Autoantibodies↗

PubMed2003

Antibodies to periodontal pathogens are associated with coronary heart disease.

OBJECTIVE: We analyzed the association of coronary heart disease (CHD) and serology of periodontitis in a random sample (n=1163) of men (aged 45 to 74 years) by determining serum IgG-antibodies to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. METHODS AND RESULTS: CHD (n=159) was more prevalent among edentulous than dentate subjects (19.8% and 12.1%, P=0.003). In the dentate population, CHD was more common among subjects seropositive for P. gingivalis compared with those seronegative (14.0% and 9.7%, P=0.029). Accordingly, CHD was more prevalent in subjects with a high combined antibody response than those with a low response (17.4% and 11.1%, P=0.026). When adjusted for age and several CHD risk factors, the subjects with a high combined antibody response had an odds ratio of 1.5 (95% CI, 0.95 to 2.50, P=0.077) for prevalent CHD. In a linear regression model, the combined antibody response was directly associated with prevalent CHD (P=0.046) and inversely with serum HDL cholesterol concentration (P=0.050). CONCLUSIONS: In conclusion, edentulousness and serum antibodies to major periodontal pathogens were associated with CHD. This suggests that periodontal infection or response of the host against the infection may play a role in the pathogenesis of CHD.

Aged↗

PubMed2003

Epicutaneous natural rubber latex sensitization induces T helper 2-type dermatitis and strong prohevein-specific IgE response.

In addition to immediate type I allergy symptoms, natural rubber latex allergy may manifest as protein contact dermatitis on the hands of health-care workers and other natural rubber latex glove users. We examined whether repeated application of natural rubber latex on mouse skin causes sensitization to natural rubber latex and dermatitis. Epicutaneous sensitization with natural rubber latex produced a significant influx of mononuclear cells, CD4+ CD3+ cells, and eosinophils to the sensitized skin sites. The number of degranulated mast cells in natural rubber latex-sensitized skin sites was significantly higher compared with control sites treated with phosphate-buffered saline. The expression of interleukin-1beta and interleukin-4 mRNA was markedly increased in natural rubber latex-sensitized skin sites. Moreover, significant increases in the mRNA expression of chemokines CCL2 (monocyte chemoattractant protein-1), CCL11 (eotaxin-1), CCL3 (macrophage inflammatory protein-1alpha), and CCL4 (macrophage inflammatory protein-1beta) were found. In addition to the cutaneous inflammatory response, epicutaneous sensitization with natural rubber latex induced a striking increase in the total and specific immunoglobulin E levels but not in the immunoglobulin G2a levels. Intraperitoneal immunization with natural rubber latex induced a strong natural rubber latex-specific immunoglobulin G2a response, but only a weak immunoglobulin E response. We also studied the role of two major natural rubber latex allergens, the highly hydrophilic prohevein and the hydrophobic rubber elongation factor. Cutaneous application of natural rubber latex elicited a strong immunoglobulin E response against prohevein, but not against rubber elongation factor. On the contrary, intraperitoneal immunization with natural rubber latex elicited strong immunoglobulin G2a production to rubber elongation factor but not to prohevein. These results demonstrate that epicutaneous sensitization with natural rubber latex induces T helper 2-dominated dermal inflammation and strong immunoglobulin E response in this murine model of natural rubber latex induced protein contact dermatitis. Epicutaneous sensitization to natural rubber latex proteins eluting from latex gloves may therefore contribute to the development of hand dermatitis and also natural rubber latex-specific immunoglobulin E antibodies.

Allergens↗

PubMed2003

CCR3, CCR5, interleukin 4, and interferon-gamma expression on synovial and peripheral T cells and monocytes in patients with rheumatoid arthritis.

OBJECTIVE: To characterize cytokine and chemokine receptor profiles of T cells and monocytes in inflamed synovium and peripheral blood (PB) in patients with rheumatoid arthritis (RA) and other arthritides. METHODS: We studied PB and synovial fluid (SF) samples taken from 20 patients with RA and 9 patients with other arthritides. PB cells from 8 healthy adults were used as controls. CCR3, CCR5, and intracellular interferon-g (IFN-g) and interleukin 4 (IL-4) expression in CD8+ and CD8- T cell populations and in CD14+ cells were determined with flow cytometry. RESULTS: Expression of CCR5 and CCR3 by CD8-, CD8+ T cells and CD14+ monocytes was increased in SF compared to PB cells in patients with RA and other arthritides. The number of CD8+ T cells spontaneously expressing IL-4 and IFN-g was higher in SF than in PB in RA patients. Spontaneous CCR5 expression was associated with intracellular IFN-g expression in CD8+ T cells derived from SF in RA. In CD8- T cells the ratio of CCR5+/CCR3+ cells was increased in patients with RA compared to patients with other arthritides. The number of PB CD8- T cells expressing IFN-g after mitogen stimulation was higher in controls than in patients. In PB monocytes the ratio of CCR5+/CCR3+ cells was increased in patients with RA compared to patients with other arthritides and controls. CONCLUSION: T cells and monocytes infiltrating joints in RA and in other arthritides showed increased activation of both type 1 and type 2 immune markers. More pronounced type 1 immune response in joints, shown as an increased CCR5/CCR3 ratio, was found in the patients with RA versus those with other arthritides. Monocytes but not T cells in PB showed increased activation in RA.

Adult↗

PubMed2002

Effect of treating periodontitis on C-reactive protein levels: a pilot study.

BACKGROUND: Periodontitis is associated with elevated levels of C-reactive protein and fibrinogen and it may be a coronary heart disease risk factor. We wanted to study if treatment of periodontitis can decrease the levels of these inflammatory markers. METHODS: C-reactive protein and fibrinogen levels were measured in 35 patients (21 M, 14 F, mean age 50 years) with adult periodontitis, before and after treatment. RESULTS: The median baseline C-reactive protein level in the patients was 1.05 mg/l and it decreased to 0.7 mg/l (p = 0.05) after periodontal treatment. Of the 30 patients who could be included in the analyses, 24 patients had a baseline level below 2 mg/l (the 95th percentile limit in Finland); 6 patients had levels higher than this. Elevation of the baseline C-reactive protein level or the magnitude of its decrease were not associated with severe form of periodontitis. The decrease in C-reactive protein levels was at least 50 % in 4/6 of those with elevated baseline levels, as compared with 3/24 of the rest of the patients (p = 0.016). No corresponding effect was observed in fibrinogen levels. CONCLUSIONS: Periodontitis seems to increase C-reactive protein only in some individuals, presumably the ones reacting to it with a systemic inflammatory reaction. Periodontal treatment decreases C-reactive protein levels in these individuals and it may thus decrease their risk of coronary heart disease.

C-Reactive Protein↗

PubMed2002

The major conformational IgE-binding epitopes of hevein (Hev b6.02) are identified by a novel chimera-based allergen epitope mapping strategy.

A novel approach to localize and reconstruct conformational IgE-binding epitope regions of hevein (Hev b6.02), a major natural rubber latex allergen, is described. An antimicrobial protein (AMP) from the amaranth Amaranthus caudatus was used as an immunologically non-IgE-binding adaptor molecule to which terminal or central parts of hevein were fused. Hevein and AMP share a structurally identical core region but have different N-terminal and C-terminal regions. Only 1 of 16 hevein-allergic patients showed weak IgE binding to purified native or recombinant AMP. Chimeric AMP with the hevein N terminus was recognized by IgE from 14 (88%) patients, and chimeric AMP with the hevein C terminus was recognized by IgE from 6 (38%) patients. In contrast, chimeric AMP containing the hevein core region was recognized by IgE from only two patients. When both the N-terminal and C-terminal regions of hevein were fused with the AMP core, IgE from all 16 patients bound to the chimera. This chimera was also able to significantly inhibit (>70%) IgE binding to the native hevein. On the contrary, linear synthetic peptides corresponding to hevein regions in the AMP chimeras showed no significant IgE binding capacity in either enzyme-linked immunosorbent assay or inhibition enzyme-linked immunosorbent assay. These results suggest that the IgE binding ability of hevein is essentially determined by its N-terminal and C-terminal regions and that major IgE-binding epitopes of hevein are conformational. The chimera-based epitope mapping strategy described here provides a valuable tool for defining structural epitopes and creating specific reagents for allergen immunotherapy.

Adenosine Monophosphate↗

PubMed2002

Autoimmunity to human heat shock protein 60, Chlamydia pneumoniae infection, and inflammation in predicting coronary risk.

Heat shock protein 60 (Hsp60) and Chlamydia pneumoniae infection have both been associated with cardiovascular diseases. Our aim was to study the role of Hsp60 antibodies as coronary risk predictors and their association with C pneumoniae infection and inflammation. This was a prospective, nested, case-control study. The cases consisted of 239 middle-aged Finnish men who developed myocardial infarction or coronary death during the follow-up. Baseline levels of IgA and IgG antibodies to human-specific and C pneumoniae-specific Hsp60 were measured by enzyme immunoassay. Human Hsp60 IgA, but not IgG or C pneumoniae Hsp60, antibodies were a significant risk factor for coronary events (odds ratio 2.0, 95% CI 1.1 to 3.6, when the fourth and first quartiles are compared). When an elevated human Hsp60 IgA antibody level (above the second quartile) was present simultaneously with a high C pneumoniae IgA antibody level (the third quartile) and an elevated C-reactive protein level (the second quartile), compared with all factors at low levels, the risk was 7.0 (95% CI 2.6 to 19.1) without adjustment and 5.0 (95% CI 1.8 to 14.2) when adjustment was made for age and smoking. In conclusion, an elevated human Hsp60 IgA antibody level was a risk factor for coronary events, especially when it was present together with C pneumoniae infection and inflammation.

Antibodies, Bacterial↗