Hans Grönlund - Academia.edu (original) (raw)

Papers by Hans Grönlund

Research paper thumbnail of Cross-reactive EBNA1 immunity targets alpha-crystallin B and is associated with multiple sclerosis

Science Advances

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system, for which Epste... more Multiple sclerosis (MS) is an inflammatory disease of the central nervous system, for which Epstein-Barr virus (EBV) infection is a likely prerequisite. Due to the homology between Epstein-Barr nuclear antigen 1 (EBNA1) and alpha-crystallin B (CRYAB), we examined antibody reactivity to EBNA1 and CRYAB peptide libraries in 713 persons with MS (pwMS) and 722 matched controls (Con). Antibody response to CRYAB amino acids 7 to 16 was associated with MS (OR = 2.0), and combination of high EBNA1 responses with CRYAB positivity markedly increased disease risk (OR = 9.0). Blocking experiments revealed antibody cross-reactivity between the homologous EBNA1 and CRYAB epitopes. Evidence for T cell cross-reactivity was obtained in mice between EBNA1 and CRYAB, and increased CRYAB and EBNA1 CD4 + T cell responses were detected in natalizumab-treated pwMS. This study provides evidence for antibody cross-reactivity between EBNA1 and CRYAB and points to a similar cross-reactivity in T cells, furthe...

Research paper thumbnail of 654 Personalised tumour-trained lymphocytes derived from regional lymph nodes for treatment of colorectal cancer

Regular and Young Investigator Award Abstracts

Research paper thumbnail of Diagnosis of IgE-mediated allergy : New approaches using recombnant allergens

More than 10% of the population in industrialized countries suffer from lgE-mediated cat allergy.... more More than 10% of the population in industrialized countries suffer from lgE-mediated cat allergy. Allergens produced by recombinant techniques offer new possibilites to diagnose and treat allergic patients but will also help to uncover the mechanisms behind the sensitisation. The aim of this thesis was to investigate the clinical usefulness of a recombinant form of the major cat allergen, Fel d 1, from construction of genes and characterisation to diagnosis of cat allergic patients. Furthermore, tools for treatment were developed using the Fel d 1 structure and the major allergen in timothy, Phl p 5. Although Fel d 1 was cloned more than a decade ago, attempts to produce a tetrameric allergen by recombinant methods with structural features similar to the natural allergen have been only partially successful. A synthetic gene coding for direct fusion of the two chains of Fel d 1 was constructed. Expression resulted in a 30 kDa non-covalently associated homodimer. Biochemical and biolo...

Research paper thumbnail of Assessments of asthma control in the BAMSE birth cohort up to 12 years

Research paper thumbnail of Diagnostic and therapeutic concepts based on recombinant allergens

Research paper thumbnail of The Enigma of a Human Tumor Marker: Tpa Revisited

Human Tumor Markers, 1987

Research paper thumbnail of Cutting Edge: Marginal Zone Macrophages Regulate Antigen Transport by B Cells to the Follicle in the Spleen via CD21

Journal of immunology (Baltimore, Md. : 1950), Sep 15, 2016

Marginal zone macrophages (MZM) are strategically located in the spleen, lining the marginal sinu... more Marginal zone macrophages (MZM) are strategically located in the spleen, lining the marginal sinus where they sense inflammation and capture Ag from the circulation. One of the receptors expressed by MZM is scavenger receptor macrophage receptor with collagenous structure (MARCO), which has affinity for modified self-antigens. In this article, we show that engagement of MARCO on murine macrophages induces extracellular ATP and loss of CD21 and CD62L on marginal zone B cells. Engagement of MARCO also leads to reduction of Ag transport by marginal zone B cells and affects the subsequent immune response. This study highlights a novel function for MZM in regulating Ag transport and activation, and we suggest that MARCO-dependent ATP release regulates this through shedding of CD21 and CD62L. Because systemic lupus erythematosus patients were shown to acquire autoantibodies against MARCO, this highlights a mechanism that could affect a patient's ability to combat infections.

Research paper thumbnail of Compound for treatment of allergy and asthma

Research paper thumbnail of Diagnostic and Therapeutic Methods and Compositions for Cardiovascular Disease

Research paper thumbnail of Novel Compound for Treatment of Allergy and Asthma

Research paper thumbnail of Inflammatory cytokines in serum from children with severe asthma compared to controlled asthmatics

European Respiratory Journal, Sep 1, 2012

Research paper thumbnail of Non-anaphylactic Forms of Grass Pollen Ph1 p 6 Allergen and Their Use

Research paper thumbnail of Non-anaphylactic forms of grass pollen Phl p 6 allergen and their use

Research paper thumbnail of Non-anaphylactic forms of allergens and their use

Research paper thumbnail of Microparticles comprising carbohydrate beads covalently linked with allergen

Research paper thumbnail of Dendritic cell‐derived exosomes carry the major cat allergen Fel d 1 and induce an allergic immune response

Allergy, 2015

Exosomes are nano‐sized membrane vesicles (50–120 nm), which are released from a wide variety of ... more Exosomes are nano‐sized membrane vesicles (50–120 nm), which are released from a wide variety of cells. Depending on their cellular origin, they can induce immune stimulatory‐, inhibitory‐, or tolerance‐inducing effects. However, it is still unclear what role exosomes play during human inflammatory diseases. It has not been studied whether exosomes derived from human dendritic cells (DCs), the first cells to encounter allergens in the mucosa, can carry aeroallergens and contribute to allergic immune responses. We therefore explored whether DC‐derived exosomes can present the major cat allergen Fel d 1 and whether they thereby contribute to the pathogenesis of allergic disease. Our results demonstrate that exosomes are able to present aeroallergens and thereby induce T‐cell T(H)2‐like cytokine production in allergic donors. Thus, these exosomes may be important immune‐stimulatory factors in allergic immune responses and important targets or engineered tools in immunotherapy.

Research paper thumbnail of A Novel Adjuvant Allergen Complex, CBP-Fel d 1, Induces Upregulation of CD86 and Cytokine Release in Human Dendritic Cells

Scandinavian Journal of Immunology, 2008

ABSTRACT Allergen-specific immunotherapy (SIT) is commonly conducted with allergen extracts adsor... more ABSTRACT Allergen-specific immunotherapy (SIT) is commonly conducted with allergen extracts adsorbed to aluminium hydroxide (alum). Drawbacks linked to the use of alum, such as the formation of granuloma at the site of injection, have led to suggestions of novel allergen carriers. An alternative carrier is 2 μm carbohydrate-based particles (CBPs). In mouse, allergen-coupled CBPs have been demonstrated to skew the allergen-specific immune response towards a Th1-like activity (Grönlund et al. Immunology, 2002). We here coupled the recombinant major cat allergen Fel d 1 to CBPs (CBP-Fel d 1) by cyanogen-bromide activation, resulting in covalent binding. The effect of CBP-Fel d 1 on monocyte-derived dendritic cells (MDDCs) from healthy human blood donors was studied. We found that the majority of the CD1a+ MDDCs were capable of taking up FITC-labelled CBP-Fel d 1, as demonstrated by flow cytometry and confocal laser scanning microscopy. Furthermore, incubation with CBP-Fel d 1 resulted in an upregulation of the costimulatory molecule CD86 on the MDDCs, which was not observed with Fel d 1 or CBPs alone. Finally, CBP-Fel d 1 induced a fivefold increase in the release of the pro-inflammatory cytokine tumour necrosis factor (TNF)-α and a fourfold increase in the release of the chemokine interleukin-8 from MDDCs. Taken together, the effects CBPs possess make them interesting as novel allergen carriers for SIT.

Research paper thumbnail of Cellular responses to animal dander allergens are mediated by interactions between Allergen, Lipid and Toll-Like Receptors

Research paper thumbnail of Recombinant allergens. Steps on the way to diagnosis and therapy of type I allergy

Advances in experimental medicine and biology, 1996

Research paper thumbnail of The non-proteolytic major house dust mite allergen Der p 2 induce proasthmatic responses in bronchial epithelial cells partly through NF-??B and MAPK pathways

World Allergy Organization Journal, 2007

Aim: To evaluate the efficacity of educational activity from School of Asthma in children with as... more Aim: To evaluate the efficacity of educational activity from School of Asthma in children with asthma and/or their family. Methods and Materials: In the school of asthma children the specialists have performed educational activities in 172 children with different forms of asthma and their parents. Educational seminars consisted of 5 sessions which approached the following subjects: triggers, asthma symptoms, prophylaxis and asthma medicines. Each session also included individual interrogation of the trained to estimate their knowledge of asthma before and after the education session according to the theme of the working day. The quality of knowledge of some children with asthma and/or their parents was also tested after 3Y12 months and afterwards visits. Results: It was found that the knowledge-of children and parents before the training at the School of Asthma Children was incomplete and incorrect. Children with severe asthma had wrong knowledge about triggers (47,73%), about prophylaxis (52,76%) comparatively with those who suffer of mild asthma (58,06% and 60,76% respectively) and moderate (51,81% and 55,94% respectively). Knowledge of children with mild asthma referring in triggers has grown to 90,77%, of children with moderate asthma to 83,72% and those with severe asthma to 80%. Also was established a growth in knowledge about prophylaxis in all groups of children: mild asthma-83,82%, moderate asthma-85,72%, severe asthma-79,26%. Knowledge of children regarding clinic manifestations constituted: mild asthma-5,5%, moderate asthma-74,79%, severe asthma-78,28%. Knowledge level under the subject "treatment" is the most incomplete in all groups of the questioned persons: mild asthma-37,93%, moderate asthma-36,96%, severe asthma-38,78%. Towards the end of the course they were appreciated as follows: mild asthma-63,17%, moderate asthma-72,67%, severe asthma-73,0%. The average of knowledge in all groups of children after 3Y12 month referring triggers was 79,72%, about prophylaxis 79,01%, regarding clinic manifestations-69,75% and referring treatment-52,44%. For compare, the average of knowledge before educational activity was: referring triggers-52,43%, prophylactic measures-56,32%, clinic manifestations-45,95% and treatment-37,89%. Conclusion: The knowledge of those questioned has little decreased during 3Y12 months, but it remained net superior to the level before the seminars.

Research paper thumbnail of Cross-reactive EBNA1 immunity targets alpha-crystallin B and is associated with multiple sclerosis

Science Advances

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system, for which Epste... more Multiple sclerosis (MS) is an inflammatory disease of the central nervous system, for which Epstein-Barr virus (EBV) infection is a likely prerequisite. Due to the homology between Epstein-Barr nuclear antigen 1 (EBNA1) and alpha-crystallin B (CRYAB), we examined antibody reactivity to EBNA1 and CRYAB peptide libraries in 713 persons with MS (pwMS) and 722 matched controls (Con). Antibody response to CRYAB amino acids 7 to 16 was associated with MS (OR = 2.0), and combination of high EBNA1 responses with CRYAB positivity markedly increased disease risk (OR = 9.0). Blocking experiments revealed antibody cross-reactivity between the homologous EBNA1 and CRYAB epitopes. Evidence for T cell cross-reactivity was obtained in mice between EBNA1 and CRYAB, and increased CRYAB and EBNA1 CD4 + T cell responses were detected in natalizumab-treated pwMS. This study provides evidence for antibody cross-reactivity between EBNA1 and CRYAB and points to a similar cross-reactivity in T cells, furthe...

Research paper thumbnail of 654 Personalised tumour-trained lymphocytes derived from regional lymph nodes for treatment of colorectal cancer

Regular and Young Investigator Award Abstracts

Research paper thumbnail of Diagnosis of IgE-mediated allergy : New approaches using recombnant allergens

More than 10% of the population in industrialized countries suffer from lgE-mediated cat allergy.... more More than 10% of the population in industrialized countries suffer from lgE-mediated cat allergy. Allergens produced by recombinant techniques offer new possibilites to diagnose and treat allergic patients but will also help to uncover the mechanisms behind the sensitisation. The aim of this thesis was to investigate the clinical usefulness of a recombinant form of the major cat allergen, Fel d 1, from construction of genes and characterisation to diagnosis of cat allergic patients. Furthermore, tools for treatment were developed using the Fel d 1 structure and the major allergen in timothy, Phl p 5. Although Fel d 1 was cloned more than a decade ago, attempts to produce a tetrameric allergen by recombinant methods with structural features similar to the natural allergen have been only partially successful. A synthetic gene coding for direct fusion of the two chains of Fel d 1 was constructed. Expression resulted in a 30 kDa non-covalently associated homodimer. Biochemical and biolo...

Research paper thumbnail of Assessments of asthma control in the BAMSE birth cohort up to 12 years

Research paper thumbnail of Diagnostic and therapeutic concepts based on recombinant allergens

Research paper thumbnail of The Enigma of a Human Tumor Marker: Tpa Revisited

Human Tumor Markers, 1987

Research paper thumbnail of Cutting Edge: Marginal Zone Macrophages Regulate Antigen Transport by B Cells to the Follicle in the Spleen via CD21

Journal of immunology (Baltimore, Md. : 1950), Sep 15, 2016

Marginal zone macrophages (MZM) are strategically located in the spleen, lining the marginal sinu... more Marginal zone macrophages (MZM) are strategically located in the spleen, lining the marginal sinus where they sense inflammation and capture Ag from the circulation. One of the receptors expressed by MZM is scavenger receptor macrophage receptor with collagenous structure (MARCO), which has affinity for modified self-antigens. In this article, we show that engagement of MARCO on murine macrophages induces extracellular ATP and loss of CD21 and CD62L on marginal zone B cells. Engagement of MARCO also leads to reduction of Ag transport by marginal zone B cells and affects the subsequent immune response. This study highlights a novel function for MZM in regulating Ag transport and activation, and we suggest that MARCO-dependent ATP release regulates this through shedding of CD21 and CD62L. Because systemic lupus erythematosus patients were shown to acquire autoantibodies against MARCO, this highlights a mechanism that could affect a patient's ability to combat infections.

Research paper thumbnail of Compound for treatment of allergy and asthma

Research paper thumbnail of Diagnostic and Therapeutic Methods and Compositions for Cardiovascular Disease

Research paper thumbnail of Novel Compound for Treatment of Allergy and Asthma

Research paper thumbnail of Inflammatory cytokines in serum from children with severe asthma compared to controlled asthmatics

European Respiratory Journal, Sep 1, 2012

Research paper thumbnail of Non-anaphylactic Forms of Grass Pollen Ph1 p 6 Allergen and Their Use

Research paper thumbnail of Non-anaphylactic forms of grass pollen Phl p 6 allergen and their use

Research paper thumbnail of Non-anaphylactic forms of allergens and their use

Research paper thumbnail of Microparticles comprising carbohydrate beads covalently linked with allergen

Research paper thumbnail of Dendritic cell‐derived exosomes carry the major cat allergen Fel d 1 and induce an allergic immune response

Allergy, 2015

Exosomes are nano‐sized membrane vesicles (50–120 nm), which are released from a wide variety of ... more Exosomes are nano‐sized membrane vesicles (50–120 nm), which are released from a wide variety of cells. Depending on their cellular origin, they can induce immune stimulatory‐, inhibitory‐, or tolerance‐inducing effects. However, it is still unclear what role exosomes play during human inflammatory diseases. It has not been studied whether exosomes derived from human dendritic cells (DCs), the first cells to encounter allergens in the mucosa, can carry aeroallergens and contribute to allergic immune responses. We therefore explored whether DC‐derived exosomes can present the major cat allergen Fel d 1 and whether they thereby contribute to the pathogenesis of allergic disease. Our results demonstrate that exosomes are able to present aeroallergens and thereby induce T‐cell T(H)2‐like cytokine production in allergic donors. Thus, these exosomes may be important immune‐stimulatory factors in allergic immune responses and important targets or engineered tools in immunotherapy.

Research paper thumbnail of A Novel Adjuvant Allergen Complex, CBP-Fel d 1, Induces Upregulation of CD86 and Cytokine Release in Human Dendritic Cells

Scandinavian Journal of Immunology, 2008

ABSTRACT Allergen-specific immunotherapy (SIT) is commonly conducted with allergen extracts adsor... more ABSTRACT Allergen-specific immunotherapy (SIT) is commonly conducted with allergen extracts adsorbed to aluminium hydroxide (alum). Drawbacks linked to the use of alum, such as the formation of granuloma at the site of injection, have led to suggestions of novel allergen carriers. An alternative carrier is 2 μm carbohydrate-based particles (CBPs). In mouse, allergen-coupled CBPs have been demonstrated to skew the allergen-specific immune response towards a Th1-like activity (Grönlund et al. Immunology, 2002). We here coupled the recombinant major cat allergen Fel d 1 to CBPs (CBP-Fel d 1) by cyanogen-bromide activation, resulting in covalent binding. The effect of CBP-Fel d 1 on monocyte-derived dendritic cells (MDDCs) from healthy human blood donors was studied. We found that the majority of the CD1a+ MDDCs were capable of taking up FITC-labelled CBP-Fel d 1, as demonstrated by flow cytometry and confocal laser scanning microscopy. Furthermore, incubation with CBP-Fel d 1 resulted in an upregulation of the costimulatory molecule CD86 on the MDDCs, which was not observed with Fel d 1 or CBPs alone. Finally, CBP-Fel d 1 induced a fivefold increase in the release of the pro-inflammatory cytokine tumour necrosis factor (TNF)-α and a fourfold increase in the release of the chemokine interleukin-8 from MDDCs. Taken together, the effects CBPs possess make them interesting as novel allergen carriers for SIT.

Research paper thumbnail of Cellular responses to animal dander allergens are mediated by interactions between Allergen, Lipid and Toll-Like Receptors

Research paper thumbnail of Recombinant allergens. Steps on the way to diagnosis and therapy of type I allergy

Advances in experimental medicine and biology, 1996

Research paper thumbnail of The non-proteolytic major house dust mite allergen Der p 2 induce proasthmatic responses in bronchial epithelial cells partly through NF-??B and MAPK pathways

World Allergy Organization Journal, 2007

Aim: To evaluate the efficacity of educational activity from School of Asthma in children with as... more Aim: To evaluate the efficacity of educational activity from School of Asthma in children with asthma and/or their family. Methods and Materials: In the school of asthma children the specialists have performed educational activities in 172 children with different forms of asthma and their parents. Educational seminars consisted of 5 sessions which approached the following subjects: triggers, asthma symptoms, prophylaxis and asthma medicines. Each session also included individual interrogation of the trained to estimate their knowledge of asthma before and after the education session according to the theme of the working day. The quality of knowledge of some children with asthma and/or their parents was also tested after 3Y12 months and afterwards visits. Results: It was found that the knowledge-of children and parents before the training at the School of Asthma Children was incomplete and incorrect. Children with severe asthma had wrong knowledge about triggers (47,73%), about prophylaxis (52,76%) comparatively with those who suffer of mild asthma (58,06% and 60,76% respectively) and moderate (51,81% and 55,94% respectively). Knowledge of children with mild asthma referring in triggers has grown to 90,77%, of children with moderate asthma to 83,72% and those with severe asthma to 80%. Also was established a growth in knowledge about prophylaxis in all groups of children: mild asthma-83,82%, moderate asthma-85,72%, severe asthma-79,26%. Knowledge of children regarding clinic manifestations constituted: mild asthma-5,5%, moderate asthma-74,79%, severe asthma-78,28%. Knowledge level under the subject "treatment" is the most incomplete in all groups of the questioned persons: mild asthma-37,93%, moderate asthma-36,96%, severe asthma-38,78%. Towards the end of the course they were appreciated as follows: mild asthma-63,17%, moderate asthma-72,67%, severe asthma-73,0%. The average of knowledge in all groups of children after 3Y12 month referring triggers was 79,72%, about prophylaxis 79,01%, regarding clinic manifestations-69,75% and referring treatment-52,44%. For compare, the average of knowledge before educational activity was: referring triggers-52,43%, prophylactic measures-56,32%, clinic manifestations-45,95% and treatment-37,89%. Conclusion: The knowledge of those questioned has little decreased during 3Y12 months, but it remained net superior to the level before the seminars.