Lena Elfman

Development of new IgE specificities to allergenic components in birch pollen extract during specific immunotherapy studied with immunoblotting and Pharmacia CAP system

Background: New IgE sensitizations to proteins in allergen extracts have been shown to occur during allergen‐specific immunotherapy (IT). However little is known about the kinetics of the changes in antibody reactivities.

Different IgE Reactivity Profiles in Birch Pollen-Sensitive Patients from Six European Populations Revealed by Recombinant Allergens: An Imprint of Local Sensitization

Background: Sensitivity to birch pollen allergens is a common feature among European patients with seasonal pollen allergy. In this in vitro study, we examined the specific serum IgE binding profiles to individual birch pollen allergens in birch-sensitive patients from six European populations. Methods: The study included 242 patients from Finland, Sweden, Austria, France, Switzerland and Italy. All suffered from seasonal rhinoconjunctivitis and/or asthma. Their sera were analyzed for specific IgE reactivity to individual birch pollen allergens (recombinant Bet v 1, Bet v 2 and Bet v 4) and natural birch pollen extract using Pharmacia CAP System™ and immunoblotting. Results: Almost all Finnish, Swedish and Austrian sera contained IgE specific for Bet v 1 (≧98%). Bet v 1-specific IgE antibodies were found in 90% of the French sera, and in 65 and 62% of the sera from Switzerland and Italy, respectively. Few Finnish (2%) and Swedish (12%) patients had IgE to Bet v 2, while Bet v 2 reactivity was more common in the other populations (20–43%). Reactivity to Bet v 4 was rare in all populations (5–11%) except for the Italian patients, in whom 3 of 11 sera were positive (27%). The immunoblot results supported the specific IgE profiles obtained with Pharmacia CAP System showing a broader IgE reactivity profile in patients from central and southern Europe as compared to northern Europe. Conclusion: Component-resolved allergy diagnosis with recombinant allergens reveals that the IgE reactivity profiles to individual birch pollen allergens vary between European populations. This observation may be explained by sensitization to different allergen sources and will have an impact on allergen-specific prevention and therapy strategies.

Study of the Th1/Th2 balance, including IL‐10 production,in cultures of peripheral blood mononuclear cells frombirch‐pollen‐allergic patients

Background: Excessive production of interleukin (IL)‐4, IL‐5, IL‐10, and IL‐13 is thought to be important in the development of allergy and asthma. The objective of this investigation was to study Th1/Th2‐like cytokine profiles in vitro in seven patients allergic to birch pollen and six nonallergic controls during the birch‐pollen season.

Serum levels of granulocyte-colony stimulating factor (G-CSF) in bacterial and viral infections, and in atypical pneumonia

Summary. Serum granulocyte‐colony stimulating factor (G‐CSF) was measured with an ELISA method in patients with acute bacterial and viral infections, or with and atypical pneumonia. Before initiation of antibiotic treatment, G‐CSF was found to be significantly increased (799 ± 1501 ng/1) in sera from 34 patients with and acute bacterial infection compared with the 27 patients with the 27 patients with viral infection (58 ± 34 ng/1; P < 0.001) and with the eight patients with an atypical pneumonia (60 ± 33) ng/1; P < 0.001). No significant difference in G‐CSF levels was seen between gram‐positive and gram‐negative bacterial infections. In septic shock, increased G‐CSF levels were seen both in patients with leucocytosis and leucopenia. In uncomplicated bacterial infections, both G‐CSF and IL‐6 were increased on day 0, and decreased rapidly after initiation of antibacterial therapy and before the patients became afebrile. In bacterial infections on day 0, G‐CSF levels correlated with mononuclear cells (rs=−0.62, p < 0.001), IL‐6 (rs= 0.40, P < 0.05 and S‐MPO (rs=−0.5, P < 0.01). In viral infections, G‐CSF was correlated with mononuclear cells (rs= 0.041, P < 0.05), White blood cell counts (rs= 0.56, P < 0.01), neutorphils (rs= 0.41, P < 0.05) and CRP (rs= 0.47, P < 0.05). We conclude that G‐CSF is rapidly rised in the blood in acute baterica infections but not in acute viral infections or in infections with Mycoplasma pneumonia. Our results also support the theory that G‐CSF is involved in the mechanisms of mobilization of neutrophils into the peripheral circulation.

Different Profiles in Specific IgE to rBet v 1 and rBet v 2 in Patients Allergic to Birch Pollen from Six Countries

There are differences in IgE reactivity to rBet v 1 and rBet v 2 among allergic patients from the six countries studied. The complexity of the reactivity profile tends to be greater in individuals from the central/southern parts of Europe compared to Sweden and Finland. There is a good agreement between in vitro diagnosis with Pharmacia CAP System and Skin prick testing when using the same reagents, rBet v 1 and rBet v 2.

Systematic Review of Respiratory Health Among Dairy Workers

ABSTRACT The dairy industry is changing on a global scale with larger, more efficient operations. The impact of this change on worker health and safety, specifically, associations between occupational lung disease and inhalation exposures, has yet to be reported in a comprehensive review of the scientific literature. Therefore, a three-tier process was used to identify information using a keyword search of online databases of scientific literature. Of the 147 citations reviewed, 52 met initial screening criteria, and 30 were included in this review. Dairy workers experience lung conditions such as asthma, chronic obstructive pulmonary disease, hypersensitivity pneumonitis, chronic bronchitis, and cancer. Recent pulmonary function studies have identified obstructive lung changes among dairy farm workers. The increased scale of dairy production with significant changes in technology and work practices has altered inhalation exposure patterns among dairy workers. The inhalation exposure in the dairy work environment may elicit differing inflammatory responses in relation to timing of initial exposure as well as to repeated exposures. Few studies have measured inhalation exposure while simultaneously assessing the impact of the exposure on lung function of dairy farm workers. Even fewer studies have been implemented to assess the impact of aerosol control technology to reduce inhalation exposure. Future research should evaluate worker exposure to aerosols through a task-based approach while utilizing novel methods to assess inhalation exposure and associated inflammatory responses. Finally, potential solutions should be developed and tested to reduce inhalation exposure to inflammatory agents and respiratory diseases in the dairy farm work environment.

Pollen-specific rush immunotherapy: clinical efficacy and effects on antibody concentrations

BACKGROUND Studies of rush immunotherapy (RIT) with standardized extracts for the treatment of seasonal pollen allergy are few, especially for birch-pollen RIT. OBJECTIVE The study was performed to investigate the efficacy of RIT with standardized birch- or timothy-pollen extracts. Further, the serum antibody levels were evaluated for correlation with clinical efficacy. METHODS This open, longitudinal study included 30 allergic patients treated with RIT and 16 allergic patients serving as a control group. The therapy was continued for 3 years and blood samples were collected at regular intervals for antibody measurements using the Pharmacia CAP System. RESULTS The RIT was generally well tolerated. An increase in the total and specific IgE concentrations during the early months of RIT was observed, followed by decreased levels. Specific IgG and IgG4 increased continuously for 2 years. The symptom and medication scores were significantly decreased, compared with preRIT, at both the first and third pollen seasons after the start of RIT treatment (P < .0001 and P < .001, respectively). The clinical improvement during RIT was significantly greater compared with the control group (P < .05). The decreased medication and the symptom improvement during the third year of RIT correlated with the relative decrease in specific IgE (rs = .52, P < .05) and with the specific IgG4 level before the start of RIT (rs= -.68, P < .01), respectively. CONCLUSIONS Our study indicates that RIT with standardized birch- or timothypollen extracts is clinically effective and safe. Measurements of specific antibody levels during treatment may be helpful in monitoring RIT.

Cytokine production by peripheral blood mononuclear cells following birch-pollen immunotherapy

We studied the Th2/Th1 balance by short-term stimulation of peripheral blood mononuclear cells (PBMC) isolated during the pollen season from seven allergic patients treated with conventional birch-pollen immunotherapy (IT) for 18 months, eight matched allergic control patients and 10 non-atopic individuals. The PBMC were cultured for 7 days with birch-pollen extract (BPE) or tetanus toxoid (TT), and then restimulated with PHA and PMA to induce high IL-5, IL-10 and IFN-gamma production. The serum levels of birch-pollen-specific IgG and IgG4 were significantly elevated after IT treatment. The proliferative response to BPE was significantly enhanced in the allergic control group, but not in the IT-treated group, compared to the non-atopic group (P<0.05). Birch-pollen-specific IL-5 production was significantly enhanced in both the IT-treated group and the allergic control group (P<0.01-0. 05). Furthermore, both the IT-treated group and the allergic control group had a cytokine profile to BPE significantly more Th2 polarized (high IL-5/IFN-gamma ratio) than to TT (P<0.05 and P<0.01, respectively). No differences in IL-10 production between the three study groups were observed. The Th2/Th1 balance in vitro correlated with the serum concentrations of birch-pollen-specific IgE (r=0.60, P<0.05), and in the IT-treated group, also with the IgG and IgG4 levels (r=0.79, P<0.05 and r=0.86, P<0.05, respectively). We conclude that conventional birch-pollen IT does not lead to changes in the cytokine profile of the circulating pool of allergen-specific T cells during birch-pollen season. However, induction of peripheral T-cell tolerance and increased production of specific IgG and IgG4 might be part of the mechanisms of IT.

IgA cross-reactivity between a nuclear autoantigen and wheat proteins suggests molecular mimicry as a possible pathomechanism in celiac disease.

Celiac disease patients display IgA antibody reactivity to wheat as well as to human proteins. We used serum IgA from celiac patients and, for control purposes, from patients with Crohn′s disease, ulcerative colitis and from healthy individuals to identify celiac disease‐specific IgA autoantigens in nitrocellulose‐blotted extracts from various human cell types (epithelial, endothelial, intestinal cells, fibroblasts). The pattern, recognition intensity and time course of IgA autoreactivity was monitored using serial serum samples obtained from celiac children before and under gluten‐free diet. By immunoblot inhibition and subcellular (cytosolic, nuclear) cell fractionation we identified a 55 kDa nuclear autoantigen expressed in intestinal, endothelial cells and in fibroblasts which was recognized by IgA antibodies of approximately half of the celiac disease patients and cross‐reacted with wheat proteins. IgA reactivity to the 55 kDa autoantigen disappeared during gluten‐free diet and was inhibited after pre‐absorption of sera with wheat proteins but not with tissue transglutaminase, previously reported as the unique celiac disease‐specific autoantigen. In conclusion, we defined a novel 55 kDa celiac disease‐specific nuclear IgA autoantigen which shares epitopes with wheat proteins and which is different from tissue transglutaminase and calreticulin. Although the newly defined autoantigen was recognized much less frequently than tissue transglutaminase, our data suggest molecular mimicry between wheat and human proteins as a possible pathomechanism for the induction and/or maintenance of mucosal tissue damage in celiac disease.

IL-8 and the Activation of Eosinophils and Neutrophils following Nasal Allergen Challenge

Background: A growing body of evidence suggests that proinflammatory cytokines play a role in allergic inflammation by attracting and activating inflammatory cells. In this study, we have investigated the relationship between interleukin-8 (IL-8) in nasal lavage fluid and the local activation of eosinophils and neutrophils following nasal allergen challenge of allergic patients. Methods: Nasal challenges were performed with grass pollen extract in 14 allergic patients and 5 nonallergic controls. Nasal lavage fluid was collected repeatedly for 10 h, and the levels of eosinophil cationic protein (ECP) and myeloperoxidase (MPO) were used as markers of eosinophil and neutrophil activation, respectively. The levels of these molecules were compared with that of IL-8 in nasal lavage fluid. Results: Allergen challenge of allergic patients produced a significant late-phase increase in the levels of ECP and MPO. Furthermore, the level of MPO showed a highly significant correlation with the level of IL-8 in lavage fluid (r = 0.8, p < 0.0001), whereas there was no significant relationship between the levels of ECP and IL-8. Conclusion: Interestingly, our findings suggest that both eosinophils and neutrophils are activated following nasal allergen challenge. In addition, our results are consistent with the hypothesis that IL-8 acts as a chemoattractant/activator of neutrophils during the late phase of the allergic inflammation. In contrast, we were not able to demonstrate any significant relationship between the level of IL-8 in lavage fluid and the activation of eosinophils.