T Palosuo

Finnish Institute of Occupational Health, Helsinki, Southern Finland Province, Finland

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Publications (235)1020.51 Total impact

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    ABSTRACT: Asthma and other allergic diseases are continuously increasing, causing considerable economic and sociologic burden to society. The hygiene hypothesis proposes that lack of microbial T helper (Th) 1-like stimulation during early childhood leads to increased Th2-driven allergic disorders later in life. Immunostimulatory cytosine-phosphate-guanosine (CpG)-oligodeoxynucleotide motifs are candidate molecules for immunotherapeutic studies, as they have been shown to shift the Th2 response toward the Th1 direction and reduce allergic symptoms. Using natural rubber latex (NRL)-induced murine model of asthma, we demonstrated that intradermal CpG administration with allergen reduced pulmonary eosinophilia, mucus production, and Th2-type cytokines, but unexpectedly induced airway hyperreactivity (AHR) to inhaled methacholine, one of the hallmarks of asthma. We found that induction in AHR was dependent on STAT4, but independent of STAT6 signaling. CpG treatment increased production of IFN-γ in the airways and shifted the ratio of CD4(+):CD8(+) T cells toward CD8(+) dominance. By blocking soluble IFN-γ with neutralizing antibody, AHR diminished and the CD4(+):CD8(+) ratio returned to CD4(+) dominance. These results indicate that increased production of IFN-γ in the lungs may lead to severe side effects, such as enhancement of bronchial hyperreactivity to inhaled allergen. This finding should be taken into consideration when planning prophylaxis treatment of asthma with intradermal CpG injections.
    American Journal of Respiratory Cell and Molecular Biology 05/2011; 44(5):639-47. · 4.15 Impact Factor
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    ABSTRACT: Turnip rape and oilseed rape 2S albumins are new allergens in children with atopic dermatitis suspected for food allergy. We recently found that 11% (206/1887) of these children had a positive skin prick test to seeds of oilseed rape (Brassica napus) and/or turnip rape (Brassica rapa). In the present case-control study we examined how the children with atopic dermatitis sensitized to turnip rape and oilseed rape had been breast-fed and whether they had some common sensitization pattern to certain foods or pollens. A total of 64 children with atopic dermatitis and a positive skin prick test to turnip rape and/or oilseed rape (>or=5 mm) were examined. Sixty-four age- and sex-matched children with atopic dermatitis but negative skin prick tests to turnip rape and oilseed rape served as case controls. The turnip rape and/or oilseed rape sensitized children with atopic dermatitis had significantly more often positive skin prick tests reactions and IgE antibodies to various foods (cow's milk, egg, wheat, mustard; p < 0.01) and pollens (birch, timothy, mugwort; p < 0.01) than the control children. They had been exclusively breast-fed for a longer period (median 4 months; p < 0.05) and had more often associated asthma (36%) and allergic rhinitis (44%). Children with atopic dermatitis sensitized to oilseed rape and turnip rape had high frequency of associated sensitizations to all foods and pollens tested showing that oilseed plant sensitization affects especially atopic children who have been sensitized to multiple allergens.
    Pediatric Allergy and Immunology 02/2008; 19(5):408-11. · 3.38 Impact Factor
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    ABSTRACT: Hevea brasiliensis (Hev b) 2 and Hev b 13 have recently been identified as major latex allergens by detecting specific IgE antibodies in >50% of sera from Hev b latex-allergic individuals. We assessed the prevalence rates for sensitization to extensively purified latex allergens in patients from three diverse geographical areas. Native Hev b 2, Hev b 5, Hev b 6.01 and Hev b 13 were purified by non-denaturating chromatography and were used in ELISAs to assess sera from 215 latex-allergic patients and 172 atopic non-sensitized controls from Finland, Spain and the United States to detect allergen-specific IgE antibodies. Unexpectedly, even highly purified Hev b 13 contained epitope(s) to which Hev b 6-specific human IgE antibodies bound effectively. Further purification, however, reduced the prevalence of IgE antibody reactivity to low levels: 15%, 5% and 11% for Hev b 2, and 18%, 30% and 27% for Hev b 13 among latex-allergic Finnish, Spanish and American patients, respectively. Interestingly, Finnish patients had a lower prevalence of Hev b 5-specific IgE antibody (28%) as compared with Spanish (49%) and American (71%) patients. The prevalence of Hev b 6.01-specific IgE reactivity was uniformly >50% in all three populations. Neither Hev b 2 nor Hev b 13 appear to be major latex allergens when evaluated in serological assays using highly purified allergens. The reason(s) for the observed differences in published sensitization rates in various geographic regions requires further study. The purity of the allergen preparations has a marked impact on the accuracy of latex-specific IgE antibody detection in epidemiological studies and in the serological diagnosis of latex allergy.
    Clinical & Experimental Allergy 10/2007; 37(10):1502-11. · 4.79 Impact Factor
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    ABSTRACT: Assessment of allergenic potential of medical devices made of natural rubber latex (NRL) requires the measurement of concentrations of specific allergenic proteins or polypeptides eluting from rubber. Four NRL allergens (Hev b 1, 3, 5, and 6.02) were quantified in all medical glove brands marketed in Finland in 1999, 2001, and 2003 (n = 208) by a capture enzyme immunoassay. The results were compared with those obtained from previous nationwide market surveys, using a skin prick test-validated human IgE-based ELISA-inhibition method. A high overall correlation (r = 0.87, 95% CI 0.83-0.90) emerged between the sum values of the four allergens(microg/g glove) and IgE-ELISA inhibition (allergen units, AU/ml, 1 : 5 diluted glove extract). The sum of four allergens when set at 0.15 microg/g discriminated 'low allergenic' (<10 AU/ml) from 'moderate- to high-allergenic' (>/=10 AU/ml) gloves at a sensitivity of 0.93 (95% CI 0.85-0.98) and specificity of 0.90 (95% CI 0.83-0.94). When the sum was below the detection limit (0.03 microg/g) all gloves belonged to the previously defined low-allergen category. By comparing the sum concentration of four selected NRL allergens with results obtained in human IgE-ELISA inhibition, it was possible set a cut-off level (0.15 microg/g) below which virtually all gloves contain low or insignificant amounts of allergens, and can be considered as low allergenic. At different cut-off-points, one could calculate the likelihood of a given glove to belong to the previously defined low, moderate or high allergen categories.
    Allergy 08/2007; 62(7):781-6. · 5.88 Impact Factor
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    ABSTRACT: Hev b 6.01 (prohevein) and Hev b 5 [acidic natural rubber latex (NRL) protein] are major IgE-binding allergens in NRL allergy. To examine allergen-specific cytokine and chemokine responses in NRL-allergic patients. Fourteen NRL-allergic patients and 10 healthy controls participated in the study. Hev b 6.01 and Hev b 5 were purified under non-denaturating conditions by chromatographic methods. Specific IgE antibodies were measured by ELISA and proliferation of peripheral blood mononuclear cells (PBMC) by (3)H-thymidine incorporation assay. Allergen-specific induction of cytokine and chemokine mRNA in PBMC was measured by real-time PCR and protein levels by ELISA. Surface expression of chemokine receptors was analysed by flow cytometry. Twelve (86%) NRL-allergic patients had positive skin prick test reactions and IgE antibodies against Hev b 6.01, but less than 30% responded to Hev b 5. Cell proliferation against Hev b 6.01, but not against Hev b 5, was significantly increased. Both allergens elicited significantly higher expression of pro-inflammatory and T-helper type 2 cytokines (TNF, IL-12p40, IL-13) and chemokines (CCL3, CCL4, CCL20) in the NRL-allergic patients than in controls. Interestingly, mRNA expression of the regulatory cytokine TGF-beta1 was reduced, whereas IL-10 expression was enhanced after allergen stimulations in patients with NRL allergy. Finally, the NRL-allergic patients showed increased CCR4 expression on CD3(+)CD8(-) T cells and decreased CXCR3 expression on CD3(+)CD8(+) T cells. Allergen-specific induction of cytokines and chemokines in PBMC and chemokine receptor expression on circulating T cells may contribute to the pathogenesis of NRL allergy.
    Clinical & Experimental Allergy 02/2007; 37(1):133-40. · 4.79 Impact Factor
  • World Allergy Organization Journal. 01/2007;
  • Journal of Allergy and Clinical Immunology - J ALLERG CLIN IMMUNOL. 01/2007; 119(1).
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    ABSTRACT: 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. 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. 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. 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.
    Scandinavian Journal of Gastroenterology 01/2007; 41(12):1405-13. · 2.33 Impact Factor
  • Journal of Allergy and Clinical Immunology - J ALLERG CLIN IMMUNOL. 01/2007; 119(1).
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    ABSTRACT: 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. 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. 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. 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. 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.
    Journal of Allergy and Clinical Immunology 03/2006; 117(2):426-32. · 12.05 Impact Factor
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    ABSTRACT: When skin prick testing (SPT) young children with atopic dermatitis (AD) for suspected food allergy, we frequently found positive reactions with turnip rape (Brassica rapa) and oilseed rape (Brassica napus). We performed food challenge to examine whether these children react clinically to turnip rape. A total of 1887 children were screened with SPTs for sensitization to turnip rape and oilseed rape. Twenty-eight children with clearly positive SPT (> or =5 mm) were first subjected to labial challenge with turnip rape seeds followed, if negative, by open oral challenge for up to 7 days. Twenty-five children with AD but negative SPT to turnip rape and oilseed rape served as controls. Two-hundred and six (10.9%) children had positive SPT to turnip rape and/or oilseed rape. Twenty-five (89%) of 28 children showed a positive challenge reaction to turnip rape. Seventeen reacted with labial whealing, and eight in oral challenge with facial urticaria, flare-up of AD or abdominal symptoms. All 25 control children remained negative in the labial challenge. Turnip rape and oilseed rape seem to be new important food allergens in young children with AD. The modes of exposure to these allergens and the possible routes of sensitization remain to be established.
    Allergy 02/2006; 61(1):124-7. · 5.88 Impact Factor
  • Journal of Allergy and Clinical Immunology - J ALLERG CLIN IMMUNOL. 01/2006; 117(2).
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    ABSTRACT: 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.
    Journal of Investigative Dermatology 12/2005; 125(5):962-8. · 6.19 Impact Factor
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    ABSTRACT: Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke. To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data. Relevant studies were identified by computer-assisted searches, hand searches of reference lists, and personal communication with relevant investigators. All identified prospective studies were included with information available on baseline fibrinogen levels and details of subsequent major vascular morbidity and/or cause-specific mortality during at least 1 year of follow-up. Studies were excluded if they recruited participants on the basis of having had a previous history of cardiovascular disease; participants with known preexisting CHD or stroke were excluded. Individual records were provided on each of 154,211 participants in 31 prospective studies. During 1.38 million person-years of follow-up, there were 6944 first nonfatal myocardial infarctions or stroke events and 13,210 deaths. Cause-specific mortality was generally available. Analyses involved proportional hazards modeling with adjustment for confounding by known cardiovascular risk factors and for regression dilution bias. Within each age group considered (40-59, 60-69, and > or =70 years), there was an approximately log-linear association with usual fibrinogen level for the risk of any CHD, any stroke, other vascular (eg, non-CHD, nonstroke) mortality, and nonvascular mortality. There was no evidence of a threshold within the range of usual fibrinogen level studied at any age. The age- and sex- adjusted hazard ratio per 1-g/L increase in usual fibrinogen level for CHD was 2.42 (95% confidence interval [CI], 2.24-2.60); stroke, 2.06 (95% CI, 1.83-2.33); other vascular mortality, 2.76 (95% CI, 2.28-3.35); and nonvascular mortality, 2.03 (95% CI, 1.90-2.18). The hazard ratios for CHD and stroke were reduced to about 1.8 after further adjustment for measured values of several established vascular risk factors. In a subset of 7011 participants with available C-reactive protein values, the findings for CHD were essentially unchanged following additional adjustment for C-reactive protein. The associations of fibrinogen level with CHD or stroke did not differ substantially according to sex, smoking, blood pressure, blood lipid levels, or several features of study design. In this large individual participant meta-analysis, moderately strong associations were found between usual plasma fibrinogen level and the risks of CHD, stroke, other vascular mortality, and nonvascular mortality in a wide range of circumstances in healthy middle-aged adults. Assessment of any causal relevance of elevated fibrinogen levels to disease requires additional research.
    JAMA The Journal of the American Medical Association 10/2005; 294(14):1799-809. · 29.98 Impact Factor
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    ABSTRACT: 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. 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. 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.
    International Journal of Cardiology 10/2005; 104(2):138-43. · 6.18 Impact Factor
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    ABSTRACT: 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. We sought to assess the clinical significance of 31-kd endochitinases and isolated HLDs in latex-fruit syndrome. 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. 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. 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.
    Journal of Allergy and Clinical Immunology 04/2005; 115(3):598-605. · 12.05 Impact Factor
  • Journal of Allergy and Clinical Immunology - J ALLERG CLIN IMMUNOL. 01/2005; 115(2).
  • Journal of Allergy and Clinical Immunology - J ALLERG CLIN IMMUNOL. 01/2005; 115(2).
  • Journal of Allergy and Clinical Immunology - J ALLERG CLIN IMMUNOL. 01/2005; 115(2).
  • Journal of Allergy and Clinical Immunology - J ALLERG CLIN IMMUNOL. 01/2005; 115(2).

Publication Stats

6k Citations
1,020.51 Total Impact Points

Institutions

  • 2000–2011
    • Finnish Institute of Occupational Health
      • Centre of Expertise for Health and Work Ability
      Helsinki, Southern Finland Province, Finland
  • 1990–2008
    • University of Tampere
      • • Department of Dermatology
      • • Medical School
      Tampere, Western Finland, Finland
    • Turku University Hospital
      Turku, Province of Western Finland, Finland
  • 1983–2008
    • National Public Health Institute
      Helsinki, Southern Finland Province, Finland
  • 2002–2005
    • University of Jyväskylä
      • Department of Biological and Environmental Science
      Jyväskylä, Western Finland, Finland
  • 1975–2004
    • University of Helsinki
      • • Institute of Dentistry
      • • Department of Dental Public Health
      • • Institute of Biotechnology
      • • Department of Bacteriology and Immunology
      • • Department of Dermatology
      • • Department of Virology
      Helsinki, Province of Southern Finland, Finland
  • 1979–2003
    • Helsinki University Central Hospital
      • • Department of Medicine
      • • Division of Cardiology
      • • Division of Dermatology and Venereology
      • • Division of Allergology
      Helsinki, Province of Southern Finland, Finland
  • 1992–2001
    • ORTON Foundation, Helsinki, Finland
      Helsinki, Southern Finland Province, Finland
  • 1985–2000
    • Kela - The Social Insurance Institution of Finland
      • Research Department
      Helsinki, Southern Finland Province, Finland
  • 1998
    • Kanta-Häme Central Hospital, Finland
      Tavastehus, Southern Finland Province, Finland
    • Wihuri Research Institute
      Helsinki, Southern Finland Province, Finland
  • 1996
    • City of Helsinki
      Helsinki, Southern Finland Province, Finland
  • 1988
    • Central Hospital Central Finland
      Jyväskylä, Province of Western Finland, Finland
  • 1986
    • Finnish Red Cross Blood Service
      Helsinki, Southern Finland Province, Finland
  • 1978–1981
    • University at Buffalo, The State University of New York
      • Department of Medicine
      Buffalo, NY, United States