| 31. |
- Franciskovic, Eric, et al.
(författare)
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Linear epitopes of bony fish β-parvalbumins
- 2024
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Ingår i: Frontiers in Immunology. - 1664-3224. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Fish β-parvalbumins are common targets of allergy-causing immunity. The nature of antibody responses to such allergens determines the biological outcome following exposure to fish. Specific epitopes on these allergens recognised by antibodies are incompletely characterised. Methods: High-content peptide microarrays offer a solution to the identification of linear epitopes recognised by antibodies. We characterized IgG and IgG4 recognition of linear epitopes of fish β-parvalbumins defined in the WHO/IUIS allergen database as such responses hold the potential to counter an allergic reaction to these allergens. Peripheral blood samples, collected over three years, of 15 atopic but not fish-allergic subjects were investigated using a microarray platform that carried every possible 16-mer peptide of known isoforms and isoallergens of these and other allergens. Results: Interindividual differences in epitope recognition patterns were observed. In contrast, reactivity patterns in a given individual were by comparison more stable during the 3 years-course of the study. Nevertheless, evidence of the induction of novel specificities over time was identified across multiple regions of the allergens. Particularly reactive epitopes were identified in the D helix of Cyp c 1 and in the C-terminus of Gad c 1 and Gad m 1.02. Residues important for the recognition of certain linear epitopes were identified. Patterns of differential recognition of isoallergens were observed in some subjects. Conclusions: Altogether, comprehensive analysis of antibody recognition of linear epitopes of multiple allergens enables characterisation of the nature of the antibody responses targeting this important set of food allergens.
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| 32. |
- Gomez Jimenez, David, et al.
(författare)
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Single-cell analysis of myeloid cells in HPV+ tonsillar cancer
- 2022
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The incidence of Human Papillomavirus positive (HPV+) tonsillar cancer has been sharply rising during the last two decades. Myeloid cells represent an appropriate therapeutic target due to their ability to orchestrate antigen-specific immunity within the tonsil, the availability of viral antigens, and the proximity of the tumor and the underlying lymphoid tissue. However, the interrelationship of steady-state and inflammatory myeloid cell subsets, and their impact on patient survival remains unexplored. Here, we used single-cell RNA-sequencing to map the myeloid compartment in HPV+ tonsillar cancer. Our analysis unveiled the existence of four dendritic cell lineages, two macrophage polarization processes, and their sequential maturation profiles. We observed an expansion of the myeloid compartment in HPV+ tonsillar cancer, accompanied by interferon-induced cellular responses both in DCs and monocyte-macrophages. Within the DC lineages, we describe a balance shift in the frequency of progenitor and mature cDC favoring the cDC1 lineage in detriment of cDC2s, in HPV+ lesions. Furthermore, we observed that all DC lineages apart from DC5s matured into a common activated DC profile. In turn, the monocyte-macrophage lineage was subjected to early monocyte polarization events, which gave raise to inflammatory-activated, and chemokine-producing macrophages. We validated the existence of most of the single-cell RNA-seq clusters using 26-plex flow cytometry, and described a positive impact of cDC1, activated DCs and macrophages in patient survival using signature scoring. The current study contributes towards the understanding of myeloid ontogeny and dynamics in human papilloma driven tonsillar cancer, and details myeloid biomarkers that can be used to predict therapy effects and assess patient prognosis.
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| 33. |
- Greiff, Lennart, et al.
(författare)
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Absorption across the nasal airway mucosa in house dust mite perennial allergic rhinitis.
- 2002
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Ingår i: Clinical Physiology and Functional Imaging. - 1475-0961. ; 22:1, s. 55-57
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Tidskriftsartikel (refereegranskat)abstract
- House dust mite allergens express protease activity and it has been suggested that this property has pathogenic effects by increasing airway absorption. In accordance, house dust mite allergens may increase mucosal permeability in vitro. The objective of the present study was to examine nasal absorption of desmopressin (1-deamino-8-D-arginine vasopressin) in patients with perennial house dust mite allergic rhinitis and in healthy subjects in vivo. Patients with perennial allergic rhinitis were examined after a 4-week treatment withdrawal period, when symptoms of allergic rhinitis occurred, and healthy subjects were examined together with the patients. Desmopressin (20 microg ml(-1)) was moved into the nasal cavity using a nasal pool-device that contained 15 ml fluid. The fluid was kept in the nasal cavity for 15 min and then recovered. Urine was collected for 24 h after the nasal administration and the urinary excretion of desmopressin was determined as an index of nasal absorption. The urinary excretion of desmopressin was 1148+/-535 pmol 24 h(-1) in patients with perennial house dust mite allergic rhinitis and 1012+/-291 pmol 24 h(-1) in healthy subjects. We conclude that nasal airway absorption of the 1067 Da peptide desmopressin is unaffected in perennial house dust mite allergic rhinitis compared with healthy subjects.
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| 34. |
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| 35. |
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| 36. |
- Greiff, Lennart, et al.
(författare)
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Challenge-induced plasma exudation and mucinous secretion in human airways
- 2005
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Ingår i: Clinical Physiology and Functional Imaging. - 1475-0961. ; 25:4, s. 241-245
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Tidskriftsartikel (refereegranskat)abstract
- Secretion of mucins and exudation of plasma are distinct processes of importance to innate immunity and inflammatory disease. Yet, little is known about their relation in human airways. The objective of the present study was to use the human nasal airway to determine mucinous secretion and plasma exudation in response to common challenge agents and mediators. Ten healthy volunteers were subjected to nasal challenge-lavage procedures. Thus, the nasal mucosa was exposed to increasing doses of histamine (40 and 400 microg ml(-1)), methacholine (12.5 and 25 mg) and capsaicin (30 and 300 ng ml(-1)). Fucose was selected as a global marker of mucinous secretion and alpha(2)-macroglobulin as an index of exudation of bulk plasma. All challenge agents increased the mucosal output of fucose to about the same level (P<0.01-0.05). Once significant secretion had been induced the subsequently increased dose of the challenge agent, in the case of histamine and methacholine, failed to further increase the response. Only histamine increased the mucosal output of alpha(2)-macroglobulin (P<0.01). We conclude that prompt but potentially rapidly depleted mucinous secretion is common to different kinds of airway challenges, whereas inflammatory histamine-type mediators are required to produce plasma exudation. Along with the acknowledged secretion of mucins, a practically non-depletable, pluripotent mucosal output of plasma emerges as an important component of the innate immunity of human airways.
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| 37. |
- Greiff, Lennart, et al.
(författare)
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Desloratadine reduces allergen challenge-induced mucinous secretion and plasma exudation in allergic rhinitis.
- 2002
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Ingår i: Annals of Allergy, Asthma & Immunology. - 1081-1206. ; 89:4, s. 413-418
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Rhinorrhea is a key symptom of allergic rhinitis and this disease feature is reduced by antihistamine treatment. The nasal output of fluid in allergic rhinitis is associated with luminal appearance of bioactive molecules emanating from the microcirculation as well as the secretory apparatus. OBJECTIVE: In the present study, we examined the effects of antihistamine treatment on nasal symptoms and output of mucinous secretions and plasma. METHODS: Desloratadine (5 mg) was administered orally once daily for 5 days in a placebo-controlled, crossover design to 24 patients with allergic rhinitis. Nasal challenges with diluent and allergen (100 to 10,000 SQ-U) were carried out on day 5 of the treatment. The nasal mucosa was lavaged with saline, and symptoms were scored 10 minutes after each allergen challenge and 1 to 4 hours after the challenge series. Nasal lavage fluid levels of fucose and alpha2-macroglobulin were determined as indices of mucinous secretion and plasma exudation, respectively. RESULTS: The allergen challenges produced nasal symptoms, including rhinorrhea, and increased nasal output of fucose and alpha2-macroglobulin. Desloratadine reduced the nasal symptoms (P < 0.05 to 0.001) and output of fucose (P < 0.05 at 100 and 1,000 SQ-U) and alpha2-macroglobulin (P < 0.05 at 1,000 SQ-U). In both treatment groups, symptoms and nasal lavage fluid levels of fucose and alpha2-macroglobulin returned toward prechallenge levels 1 to 4 hours after the allergen challenge series. CONCLUSION: We conclude that the antihistamine desloratadine, in addition to a symptom-reducing effect, also reduces acute allergen challenge-induced mucinous secretion and plasma exudation in allergic rhinitis.
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| 38. |
- Greiff, Lennart, et al.
(författare)
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Effects of a dual CCR3 and H-1-antagonist on symptoms and eosinophilic inflammation in allergic rhinitis
- 2010
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Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: The CC-chemokine receptor-3 (CCR3) has emerged as a target molecule for pharmacological intervention in allergic inflammation. Objective: To examine whether a dual CCR3 and H-1-receptor antagonist (AZD3778) affects allergic inflammation and symptoms in allergic rhinitis. Methods: Patients with seasonal allergic rhinitis were subjected to three seven days' allergen challenge series. Treatment with AZD3778 was given in a placebo and antihistamine-controlled design. Symptoms and nasal peak inspiratory flow (PIF) were monitored in the morning, ten minutes post challenge, and in the evening. Nasal lavages were carried out at the end of each challenge series and alpha(2)-macroglobulin, ECP, and tryptase were monitored as indices of allergic inflammation. Results: Plasma levels of AZD3778 were stable throughout the treatment series. AZD3778 and the antihistamine (loratadine) reduced rhinitis symptoms recorded ten minutes post challenge during this period. AZD3778, but not the anti-histamine, also improved nasal PIF ten minutes post challenge. Furthermore, scores for morning and evening nasal symptoms from the last five days of the allergen challenge series showed statistically significant reductions for AZD3778, but not for loratadine. ECP was reduced by AZD3778, but not by loratadine. Conclusions: AZD3778 exerts anti-eosinophil and symptom-reducing effects in allergic rhinitis and part of this effect can likely be attributed to CCR3-antagonism. The present data are of interest with regard to the potential use of AZD3778 in allergic rhinitis and to the relative importance of eosinophil actions to the symptomatology of allergic rhinitis.
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| 39. |
- Greiff, Lennart, et al.
(författare)
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Effects of hydrogen peroxide on the guinea-pig tracheobronchial mucosa in vivo
- 1999
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Ingår i: Acta Physiologica Scandinavica. - : Wiley. - 0001-6772 .- 1365-201X. ; 165:4, s. 415-420
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Tidskriftsartikel (refereegranskat)abstract
- Lumenal entry of plasma (mucosal exudation) is a key feature of airway inflammation. In airways challenged with histamine-type mediators and allergen the mucosal exudation response occurs without causing epithelial derangement and without increased airway absorption. In contrast, reactive oxygen metabolites may cause mucosal damage. In this study, involving guinea-pig airways, we have examined effects of H2O2 on airway exudation and absorption in vivo. Vehicle or H2O2 (0.1 and 0.5 M) was superfused onto the tracheobronchial mucosal surface through an oro-tracheal catheter. 125I-albumin, given intravenously, was determined in tracheobronchial tissue and in lavage fluids 10 min after challenge as an index of mucosal exudation of plasma. The tracheobronchial mucosa was also examined by scanning electron microscopy. In separate animals, 99mTc-DTPA was superfused 20 min after vehicle or H2O2 (0.1 and 0.5 M) had been given. A gamma camera determined the disappearance rate of 99mTc-DTPA from the airways as an index of airway absorption. The high dose of H2O2 (0.5 M) produced epithelial damage, increased the absorption of 99mTc-DTPA (P < 0.001), and increased the exudation of plasma (P < 0.001). Notably, it appeared that all extravasated plasma had entered the airway lumen within 10 min. These data demonstrate that H2O2 differs from exudative autacoids such as histamine by causing both epithelial damage and plasma exudation responses. These data also agree with the view that the epithelial lining determines the rate of absorption and is responsible for the valve-like function that allows lumenal entry of extravasated bulk plasma without any increased inward perviousness.
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| 40. |
- Greiff, Lennart, et al.
(författare)
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Effects of rhinovirus-induced common colds on granulocyte activity in allergic rhinitis
- 2002
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Ingår i: Journal of Infection. - : Elsevier BV. - 0163-4453 .- 1532-2742. ; 45:4, s. 227-232
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To explore the activities of mast cells, eosinophils, and neutrophils in patients with allergic rhinitis developing common colds and increased responsiveness to allergen following nasal rhinovirus inoculation. METHODS: We have revisited a nasal lavage material obtained from 17 patients who were successfully inoculated with rhinovirus outside the pollen season and received nasal allergen challenges before and after inoculation. We have examined indices of mast cell activity (tryptase), eosinophil degranulation (eosinophil peroxidase; EPO), and neutrophil activation (myeloperoxidase; MPO). RESULTS: Allergen challenges performed before rhinovirus inoculation increased the nasal output of EPO. Notably, this response was significantly greater after rhinovirus inoculation (cf. before inoculation). The output of MPO was also increased following allergen challenge after, but not before, rhinovirus inoculation. Nasal lavage fluid levels of tryptase were increased following allergen challenge similarly before and after rhinovirus inoculation. Also, the viral infection did not affect the baseline levels of tryptase. CONCLUSIONS: The present data demonstrate that rhinovirus infections activate both eosinophils and neutrophils, but that they may not affect mast cell activity. We suggest that common colds in part through stimulation of granulocyte activity potentiate the airway inflammation in allergic diseases.
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