The Experts below are selected from a list of 2781 Experts worldwide ranked by ideXlab platform

E Marti - One of the best experts on this subject based on the ideXlab platform.

  • comparison of recombinant culicoides allergens produced in different expression systems for ige serology of Insect Bite hypersensitivity in horses of different origins
    Veterinary Immunology and Immunopathology, 2021
    Co-Authors: Sigridur Jonsdottir, Sigurbjörg Torsteinsdóttir, Vilhjálmur Svansson, Johannes Gudbrandsson, Sara Bjork Stefansdottir, Jon Mar Bjornsson, Arna Runarsdottir, E Marti
    Abstract:

    Abstract Insect Bite hypersensitivity (IBH) is an allergic dermatitis of horses, an IgE-mediated reaction to Culicoides midges. Causative Culicoides spp. are not indigenous in Iceland resulting in high prevalence of IBH in horses born in Iceland and exported as compared to Icelandic horses born in a Culicoides rich environment. The aims were (i) to compare IgE levels in sera of IBH-affected horses born in Iceland (n = 47) with horses of the Icelandic breed (n = 23) and of other breeds (n = 27) born in Culicoides infested area; (ii) to investigate if barley could be a useful production system of allergens for IBH immunoassays. IgE binding in sera was tested by ELISA on two recombinant Culicoides allergens, rCul n 3 and rCul n 4, each produced in E. coli, Insect cells and barley. Significantly more IgE was detected against all allergens in sera from IBH-affected compared to healthy horses. Icelandic-born Icelandic horses stand out with higher IgE levels against the allergens and higher area under the curve (AUC) on rCul n 4 as compared to the European-born horses. The barley and E.coli produced allergens had very similar performance in distinguishing between IBH-affected and healthy horses.

  • new strategies for prevention and treatment of Insect Bite hypersensitivity in horses
    Current Dermatology Reports, 2019
    Co-Authors: Sigridur Jonsdottir, Sigurbjörg Torsteinsdóttir, Vilhjálmur Svansson, Iva Cvitas, Antonia Fettelschlossgabriel, E Marti
    Abstract:

    Treatment of equine Insect Bite hypersensitivity (IBH) needs to be improved. Allergen-specific immunotherapy (ASIT), the only curative treatment of allergy, currently has only a limited efficacy for treatment of IBH. This review highlights the latest findings in prophylactic and therapeutic strategies. Prophylactic vaccination against IBH using recombinant Culicoides allergen has been developed in unexposed Icelandic horses and is ready to be tested. Therapeutic virus-like particle (VLP)–based vaccines targeting equine interleukin- (IL-) 5 or IL-31 improved clinical signs of IBH by induction of anti-cytokine antibodies thus reducing eosinophil counts or allergic pruritus, respectively. First studies for development of ASIT using pure r-Culicoides allergens have yielded promising results and need now to be tested in clinical studies for both prevention and treatment of IBH. Therapeutic vaccines inducing neutralizing antibodies against IL-5 or IL-31 will be valuable future treatments for reduction of clinical signs of IBH.

  • allergen specific immunoglobulin e in sera of horses affected with Insect Bite hypersensitivity severe equine asthma or both conditions
    Journal of Veterinary Internal Medicine, 2019
    Co-Authors: Maëva Verdon, Claudio Rhyner, Vinzenz Gerber, Simone Lanz, E Marti
    Abstract:

    BACKGROUND Genetic, epidemiologic, and clinical evidence suggests that, in horses, there are manifestations of hypersensitivity that can occur together. OBJECTIVES To investigate whether concurrent Insect Bite hypersensitivity (IBH) and severe equine asthma (EA) is associated with higher allergen-specific and total serum immunoglobulin E (IgE) concentrations than only EA or IBH. ANIMALS Healthy control horses (C, n = 40), horses with IBH (IBH, n = 24), severe EA (EA, n = 18), and both conditions (IBH/EA, n = 23) were included. METHODS In our retrospective comparative study, sera from horses with signs of severe EA, IBH, and control animals were used. IgE specific for 15 recombinant (r) allergens as well as total serum IgE concentrations were measured by enzyme-linked immunosorbent assay. RESULTS Group IBH (median sum r-Culicoides IgE: optical density at 405 nm [OD ] = 3.54 [0.48-15.07]) and group IBH/EA (OD  = 4.55 [0.46-17.15]) had significantly (P   .05) differences between group IBH and group IBH/EA. No significant differences among the groups were found for the other r-allergens or total serum IgE concentration. Compared to controls, horses with severe IBH had significantly increased IgE concentration to 5 Culicoides r-allergens (P < .05), whereas horses with moderate IBH had significantly increased IgE concentration to only 3 Culicoides r-allergens (P < .05). CONCLUSIONS AND CLINICAL IMPORTANCE Susceptibility of IBH-affected horses to develop EA is likely not associated with IgE-mediated immune reactions but with other immunopathological mechanisms.

  • a prospective study on Insect Bite hypersensitivity in horses exported from iceland into switzerland
    Acta Veterinaria Scandinavica, 2018
    Co-Authors: Sigurbjörg Torsteinsdóttir, Sigridur Jonsdottir, Vilhjálmur Svansson, Stephan Scheidegger, Silvia Baselgia, Sigridur Björnsdottir, E Marti
    Abstract:

    Insect Bite hypersensitivity (IBH) is an IgE-mediated dermatitis caused by Bites of Culicoides spp., which occurs frequently in horses imported from Iceland to continental Europe. IBH does not occur in Iceland because Culicoides species that Bite horses are not present. However, Simulium vittatum (S. vittatum) are found in Iceland. In Europe, blood basophils from IBH-affected horses release significantly more sulfidoleukotrienes (sLT) than those from healthy controls after in vitro stimulation with Culicoides nubeculosus (C. nubeculosus) and S. vittatum. Aims of the study were: (I) using the sLT release assay, to test if horses living in Iceland were sensitized to S. vittatum and (II) to determine in a longitudinal study in horses imported from Iceland to Switzerland whether the sLT release assay would allow to predict which horses would develop IBH. Horses in Iceland, even when living in high S. vittatum areas, were usually not sensitized to S. vittatum or C. nubeculosus. Incidence of IBH in the 145 horses from the longitudinal study was 51% and mean time until IBH developed was 2.5 ± 1 year. Before import and after the first summer following import, there were no significant differences in sLT release between the endpoint healthy (H) and IBH groups. After the 2nd summer, when the number of clinically affected horses increased in the endpoint IBH group, a significantly higher sLT release after stimulation with C. nubeculosus but not with S. vittatum was observed. After the 3rd and 4th summer, the endpoint IBH group had a significantly higher sLT release with C. nubeculosus and S. vittatum than the endpoint H group. Some of the horses that remained healthy became transiently positive in the sLT release assay upon stimulation of their peripheral blood leucocytes with C. nubeculosus. Horses in Iceland are not sensitized to S. vittatum. In horses that develop IBH, sensitization to S. vittatum is secondary to sensitization to C. nubeculosus and probably a result of an immunological cross-reactivity. A sLT release assay cannot be used to predict which horses will develop IBH. A transient positive reaction in the sLT release assay observed in horses that remained healthy suggests that immunoregulatory mechanisms may control an initial sensitization of the healthy horses.

  • longitudinal analysis of allergen specific ige and igg subclasses as potential predictors of Insect Bite hypersensitivity following first exposure to culicoides in icelandic horses
    Veterinary Dermatology, 2018
    Co-Authors: Anja Ziegler, Sigridur Jonsdottir, Claudio Rhyner, Eman Hamza, Sigurbjörg Torsteinsdóttir, Vilhjálmur Svansson, Bettina Wagner, Gertraud Schupbach, E Marti
    Abstract:

    BACKGROUND: Insect Bite hypersensitivity (IBH) is an allergic dermatitis of horses caused by Bites of Culicoides spp. IBH does not occur in Iceland because of the absence of Culicoides, but the prevalence is high in horses imported from Iceland to environments where Culicoides are present. HYPOTHESIS/OBJECTIVE: Test, in a longitudinal study before and after Culicoides exposure, whether a primary sensitizing Culicoides allergen can be identified and if an increase of allergen-specific immunoglobulin (Ig)E or IgG subclasses precedes clinical signs of IBH. ANIMALS: Thirty two horses imported from Iceland to Europe; 16 developed IBH and 16 remained healthy. METHODS: Determination of IgE and IgG subclasses against recombinant (r)-Culicoides allergens and Culicoides extract in sera taken before first exposure to Culicoides and yearly over a period of 3-4 years. RESULTS: Before Culicoides exposure, there were no significant differences in Culicoides-specific serum IgE levels between horse that developed IBH or remained healthy. Culicoides exposure induced an individual IgE response pattern (to a median of 4.5 r-allergens) in the IBH but not in the healthy end-point group. The increase in serum IgE levels to Culicoides r-allergens was concurrent with the initial onset of clinical signs of IBH. IBH-affected horses displayed significantly higher allergen-specific IgG1 and IgG5 levels than healthy controls. Recombinant Culicoides obsoletus 1 (Cul o1) and Cul o3-specific IgG5 was significantly higher in the IBH compared to the healthy end-point group, before clinical signs of IBH. CONCLUSION/CLINICAL RELEVANCE: Allergen-specific serum IgE cannot be used as predictor for IBH, whereas allergen-specific IgG5 levels may have a predictive value.

Claudio Rhyner - One of the best experts on this subject based on the ideXlab platform.

  • component resolved microarray analysis of ige sensitization profiles to culicoides recombinant allergens in horses with Insect Bite hypersensitivity
    Allergy, 2021
    Co-Authors: Ella N Novotny, Sigridur Jonsdottir, A D Wilson, Edwin Tijhaar, Sara Bjork Stefansdottir, Samuel White, Rebekka Frey, Dania Birte Reiche, Horst Rose, Claudio Rhyner
    Abstract:

    Background Allergy to Bites of blood‐sucking Insects, including biting midges, can affect both human and veterinary patients. Horses are often suffering from an IgE‐mediated allergic dermatitis caused by Bites of midges (Culicoides spp). With the aim to improve allergen immunotherapy (AIT), numerous Culicoides allergens have been produced as recombinant (r‐) proteins. This study aimed to test a comprehensive panel of differently expressed Culicoides r‐allergens on a cohort of IBH‐affected and control horses using an allergen microarray. Methods IgE levels to 27 Culicoides r‐allergens, including 8 previously unpublished allergens, of which 11 were expressed in more than one expression system, were determined in sera from 347 horses. ROC analyses were carried out, cut‐offs selected using a specificity of 95% and seropositivity rates compared between horses affected with Insect Bite hypersensitivity (IBH) and control horses. The combination of r‐allergens giving the best performing test was determined using logistic regression analysis. Results Seropositivity was significantly higher in IBH horses compared with controls for 25 r‐allergens. Nine Culicoides r‐allergens were major allergens for IBH with seven of them binding IgE in sera from > 70% of the IBH‐affected horses. Combination of these top seven r‐allergens could diagnose > 90% of IBH‐affected horses with a specificity of > 95%. Correlation between differently expressed r‐allergens was usually high (mean = 0.69, range: 0.28‐0.91). Conclusion This microarray will be a powerful tool for the development of component‐resolved, patient‐tailored AIT for IBH and could be useful for the study of allergy to biting midges in humans and other species.

  • Allergen‐specific immunoglobulin E in sera of horses affected with Insect Bite hypersensitivity, severe equine asthma or both conditions
    Wiley, 2019
    Co-Authors: Maëva Verdon, Vinzenz Gerber, Claudio Rhyner, Simone Lanz, Eliane Marti
    Abstract:

    Background Genetic, epidemiologic, and clinical evidence suggests that, in horses, there are manifestations of hypersensitivity that can occur together. Objectives To investigate whether concurrent Insect Bite hypersensitivity (IBH) and severe equine asthma (EA) is associated with higher allergen‐specific and total serum immunoglobulin E (IgE) concentrations than only EA or IBH. Animals Healthy control horses (C, n = 40), horses with IBH (IBH, n = 24), severe EA (EA, n = 18), and both conditions (IBH/EA, n = 23) were included. Methods In our retrospective comparative study, sera from horses with signs of severe EA, IBH, and control animals were used. IgE specific for 15 recombinant (r) allergens as well as total serum IgE concentrations were measured by enzyme‐linked immunosorbent assay. Results Group IBH (median sum r‐Culicoides IgE: optical density at 405 nm [OD405] = 3.54 [0.48‐15.07]) and group IBH/EA (OD405 = 4.55 [0.46‐17.15]) had significantly (P  .05) differences between group IBH and group IBH/EA. No significant differences among the groups were found for the other r‐allergens or total serum IgE concentration. Compared to controls, horses with severe IBH had significantly increased IgE concentration to 5 Culicoides r‐allergens (P 

  • allergen specific immunoglobulin e in sera of horses affected with Insect Bite hypersensitivity severe equine asthma or both conditions
    Journal of Veterinary Internal Medicine, 2019
    Co-Authors: Maëva Verdon, Claudio Rhyner, Vinzenz Gerber, Simone Lanz, E Marti
    Abstract:

    BACKGROUND Genetic, epidemiologic, and clinical evidence suggests that, in horses, there are manifestations of hypersensitivity that can occur together. OBJECTIVES To investigate whether concurrent Insect Bite hypersensitivity (IBH) and severe equine asthma (EA) is associated with higher allergen-specific and total serum immunoglobulin E (IgE) concentrations than only EA or IBH. ANIMALS Healthy control horses (C, n = 40), horses with IBH (IBH, n = 24), severe EA (EA, n = 18), and both conditions (IBH/EA, n = 23) were included. METHODS In our retrospective comparative study, sera from horses with signs of severe EA, IBH, and control animals were used. IgE specific for 15 recombinant (r) allergens as well as total serum IgE concentrations were measured by enzyme-linked immunosorbent assay. RESULTS Group IBH (median sum r-Culicoides IgE: optical density at 405 nm [OD ] = 3.54 [0.48-15.07]) and group IBH/EA (OD  = 4.55 [0.46-17.15]) had significantly (P   .05) differences between group IBH and group IBH/EA. No significant differences among the groups were found for the other r-allergens or total serum IgE concentration. Compared to controls, horses with severe IBH had significantly increased IgE concentration to 5 Culicoides r-allergens (P < .05), whereas horses with moderate IBH had significantly increased IgE concentration to only 3 Culicoides r-allergens (P < .05). CONCLUSIONS AND CLINICAL IMPORTANCE Susceptibility of IBH-affected horses to develop EA is likely not associated with IgE-mediated immune reactions but with other immunopathological mechanisms.

  • longitudinal analysis of allergen specific ige and igg subclasses as potential predictors of Insect Bite hypersensitivity following first exposure to culicoides in icelandic horses
    Veterinary Dermatology, 2018
    Co-Authors: Anja Ziegler, Sigridur Jonsdottir, Claudio Rhyner, Eman Hamza, Sigurbjörg Torsteinsdóttir, Vilhjálmur Svansson, Bettina Wagner, Gertraud Schupbach, E Marti
    Abstract:

    BACKGROUND: Insect Bite hypersensitivity (IBH) is an allergic dermatitis of horses caused by Bites of Culicoides spp. IBH does not occur in Iceland because of the absence of Culicoides, but the prevalence is high in horses imported from Iceland to environments where Culicoides are present. HYPOTHESIS/OBJECTIVE: Test, in a longitudinal study before and after Culicoides exposure, whether a primary sensitizing Culicoides allergen can be identified and if an increase of allergen-specific immunoglobulin (Ig)E or IgG subclasses precedes clinical signs of IBH. ANIMALS: Thirty two horses imported from Iceland to Europe; 16 developed IBH and 16 remained healthy. METHODS: Determination of IgE and IgG subclasses against recombinant (r)-Culicoides allergens and Culicoides extract in sera taken before first exposure to Culicoides and yearly over a period of 3-4 years. RESULTS: Before Culicoides exposure, there were no significant differences in Culicoides-specific serum IgE levels between horse that developed IBH or remained healthy. Culicoides exposure induced an individual IgE response pattern (to a median of 4.5 r-allergens) in the IBH but not in the healthy end-point group. The increase in serum IgE levels to Culicoides r-allergens was concurrent with the initial onset of clinical signs of IBH. IBH-affected horses displayed significantly higher allergen-specific IgG1 and IgG5 levels than healthy controls. Recombinant Culicoides obsoletus 1 (Cul o1) and Cul o3-specific IgG5 was significantly higher in the IBH compared to the healthy end-point group, before clinical signs of IBH. CONCLUSION/CLINICAL RELEVANCE: Allergen-specific serum IgE cannot be used as predictor for IBH, whereas allergen-specific IgG5 levels may have a predictive value.

  • a preventive immunization approach against Insect Bite hypersensitivity intralymphatic injection with recombinant allergens in alum or alum and monophosphoryl lipid a
    Veterinary Immunology and Immunopathology, 2016
    Co-Authors: Sigridur Jonsdottir, Claudio Rhyner, Vilhjálmur Svansson, E Marti, Gertraud Schupbach, Sara Bjork Stefansdottir, Sigurbjörg Torsteinsdóttir
    Abstract:

    Insect Bite hypersensitivity (IBH) is an IgE-mediated dermatitis of horses caused by Bites of Culicoides Insects, not indigenous to Iceland. Horses born in Iceland and exported to Culicoides-rich areas are frequently affected with IBH. The aims of the study were to compare immunization with recombinant allergens using the adjuvant aluminum hydroxide (Alum) alone or combined with monophosphoryl lipid A (MPLA) for development of a preventive immunization against IBH. Twelve healthy Icelandic horses were vaccinated intralymphatically three times with 10 μg each of four recombinant Culicoides nubeculosus allergens in Alum or in Alum/MPLA. Injection with allergens in both Alum and Alum/MPLA resulted in significant increase in specific IgG subclasses and IgA against all r-allergens with no significant differences between the adjuvant groups. The induced antibodies from both groups could block binding of allergen specific IgE from IBH affected horses to a similar extent. No IgE-mediated reactions were induced. Allergen-stimulated PBMC from Alum/MPLA horses but not from Alum only horses produced significantly more IFNγ and IL-10 than PBMC from non-vaccinated control horses. In conclusion, intralymphatic administration of small amounts of pure allergens in Alum/MPLA induces high IgG antibody levels and Th1/Treg immune response and is a promising approach for immunoprophylaxis and immunotherapy against IBH.

A. Schurink - One of the best experts on this subject based on the ideXlab platform.

  • copy number variations in friesian horses and genetic risk factors for Insect Bite hypersensitivity
    BMC Genetics, 2018
    Co-Authors: A. Schurink, Steven Janssens, Brandon D Velie, Liesbeth Franҫois, Anneleen Stinckens, Vinicius Henrique Da Silva, Bert Dibbits, Richard P M A Crooijmans, Sarah C Blott
    Abstract:

    Many common and relevant diseases affecting equine welfare have yet to be tested regarding structural variants such as copy number variations (CNVs). CNVs make up a substantial proportion of total genetic variability in populations of many species, resulting in more sequence differences between individuals than SNPs. Associations between CNVs and disease phenotypes have been established in several species, but equine CNV studies have been limited. Aim of this study was to identify CNVs and to perform a genome-wide association (GWA) study in Friesian horses to identify genomic loci associated with Insect Bite hypersensitivity (IBH), a common seasonal allergic dermatitis observed in many horse breeds worldwide. Genotypes were obtained using the Axiom® Equine Genotyping Array containing 670,796 SNPs. After quality control of genotypes, 15,041 CNVs and 5350 CNV regions (CNVRs) were identified in 222 Friesian horses. Coverage of the total genome by CNVRs was 11.2% with 49.2% of CNVRs containing genes. 58.0% of CNVRs were novel (i.e. so far only identified in Friesian horses). A SNP- and CNV-based GWA analysis was performed, where about half of the horses were affected by IBH. The SNP-based analysis showed a highly significant association between the MHC region on ECA20 and IBH in Friesian horses. Associations between the MHC region on ECA20 and IBH were also detected based on the CNV-based analysis. However, CNVs associated with IBH in Friesian horses were not often in close proximity to SNPs identified to be associated with IBH. CNVs were identified in a large sample of the Friesian horse population, thereby contributing to our knowledge on CNVs in horses and facilitating our understanding of the equine genome and its phenotypic expression. A clear association was identified between the MHC region on ECA20 and IBH in Friesian horses based on both SNP- and CNV-based GWA studies. These results imply that MHC contributes to IBH sensitivity in Friesian horses. Although subsequent analyses are needed for verification, nucleotide differences, as well as more complex structural variations like CNVs, seem to contribute to IBH sensitivity. IBH should be considered as a common disease with a complex genomic architecture.

  • using an inbred horse breed in a high density genome wide scan for genetic risk factors of Insect Bite hypersensitivity ibh
    PLOS ONE, 2016
    Co-Authors: Brandon D Velie, A. Schurink, B J Ducro, Sofia Mikko, M. Shrestha, Liesbeth Franҫois, Yohannes G Tesfayonas, Anneleen Stinckens, Sarah C Blott, Ruth E Thomas
    Abstract:

    While susceptibility to hypersensitive reactions is a common problem amongst humans and animals alike, the population structure of certain animal species and breeds provides a more advantageous route to better understanding the biology underpinning these conditions. The current study uses Exmoor ponies, a highly inbred breed of horse known to frequently suffer from Insect Bite hypersensitivity, to identify genomic regions associated with a type I and type IV hypersensitive reaction. A total of 110 cases and 170 controls were genotyped on the 670K Axiom Equine Genotyping Array. Quality control resulted in 452,457 SNPs and 268 individuals being tested for association. Genome-wide association analyses were performed using the GenABEL package in R and resulted in the identification of two regions of interest on Chromosome 8. The first region contained the most significant SNP identified, which was located in an intron of the DCC netrin 1 receptor gene. The second region identified contained multiple top SNPs and encompassed the PIGN, KIAA1468, TNFRSF11A, ZCCHC2, and PHLPP1 genes. Although additional studies will be needed to validate the importance of these regions in horses and the relevance of these regions in other species, the knowledge gained from the current study has the potential to be a step forward in unraveling the complex nature of hypersensitive reactions.

  • Genome-Wide Association Study of Insect Bite Hypersensitivity in Swedish-Born Icelandic Horses
    The Journal of heredity, 2015
    Co-Authors: M. Shrestha, A. Schurink, Bart J. Ducro, Hans Brostrom, Susanne Eriksson, Rebecka Frey, M. Sundquist, Lisa S. Andersson, Tomas F. Bergström, Gabriella Lindgren
    Abstract:

    Insect Bite hypersensitivity (IBH) is the most common allergic skin disease in horses and is caused by biting midges, mainly of the genus Culicoides. The disease predominantly comprises a type I hypersensitivity reaction, causing severe itching and discomfort that reduce the welfare and commercial value of the horse. It is a multifactorial disorder influenced by both genetic and environmental factors, with heritability ranging from 0.16 to 0.27 in various horse breeds. The worldwide prevalence in different horse breeds ranges from 3% to 60%; it is more than 50% in Icelandic horses exported to the European continent and approximately 8% in Swedish-born Icelandic horses. To minimize the influence of environmental effects, we analyzed Swedish-born Icelandic horses to identify genomic regions that regulate susceptibility to IBH. We performed a genome-wide association (GWA) study on 104 affected and 105 unaffected Icelandic horses genotyped using Illumina® EquineSNP50 Genotyping BeadChip. Quality control and population stratification analyses were performed with the GenABEL package in R (λ = 0.81). The association analysis was performed using the Bayesian variable selection method, Bayes C, implemented in GenSel software. The highest percentage of genetic variance was explained by the windows on X chromosomes (0.51% and 0.36% by 73 and 74 mb), 17 (0.34% by 77 mb), and 18 (0.34% by 26 mb). Overlapping regions with previous GWA studies were observed on chromosomes 7, 9, and 17. The windows identified in our study on chromosomes 7, 10, and 17 harbored immune system genes and are priorities for further investigation.

  • Risk factors for Insect Bite hypersensitivity in Friesian horses and Shetland ponies in The Netherlands.
    The Veterinary Journal, 2013
    Co-Authors: A. Schurink, Bart J. Ducro, J.a.m. Van Arendonk, Sabrina C. Podesta, Klaas Frankena
    Abstract:

    Insect Bite hypersensitivity (IBH) is an equine skin allergy caused by Bites of Culicoides spp. and impacts on the welfare of affected horses. The aim of this study was to identify and quantify risk factors for IBH. Data from 3453 Friesian horse mares and 7074 Shetland pony mares scored for IBH by inspectors during obligatory foal inspections were analysed using breed-specific multivariable logistic regression models. The combined effect of month and year of scoring, Province and inspector were significantly associated with IBH in both breeds. In Shetland pony mares, withers height and coat colour were also significantly associated with IBH, while body condition had a nearly significant effect. The outcomes from this study on risk factors might contribute to the development of more efficient measures to reduce the prevalence of IBH.

  • genome wide association study of Insect Bite hypersensitivity in two horse populations in the netherlands
    Genetics Selection Evolution, 2012
    Co-Authors: A. Schurink, Bart J. Ducro, Klaas Frankena, Anna Wolc, D J Garrick, Jack C M Dekkers, J.a.m. Van Arendonk
    Abstract:

    Insect Bite hypersensitivity is a common allergic disease in horse populations worldwide. Insect Bite hypersensitivity is affected by both environmental and genetic factors. However, little is known about genes contributing to the genetic variance associated with Insect Bite hypersensitivity. Therefore, the aim of our study was to identify and quantify genomic associations with Insect Bite hypersensitivity in Shetland pony mares and Icelandic horses in the Netherlands. Data on 200 Shetland pony mares and 146 Icelandic horses were collected according to a matched case–control design. Cases and controls were matched on various factors (e.g. region, sire) to minimize effects of population stratification. Breed-specific genome-wide association studies were performed using 70 k single nucleotide polymorphisms genotypes. Bayesian variable selection method Bayes-C with a threshold model implemented in GenSel software was applied. A 1 Mb non-overlapping window approach that accumulated contributions of adjacent single nucleotide polymorphisms was used to identify associated genomic regions. The percentage of variance explained by all single nucleotide polymorphisms was 13% in Shetland pony mares and 28% in Icelandic horses. The 20 non-overlapping windows explaining the largest percentages of genetic variance were found on nine chromosomes in Shetland pony mares and on 14 chromosomes in Icelandic horses. Overlap in identified associated genomic regions between breeds would suggest interesting candidate regions to follow-up on. Such regions common to both breeds (within 15 Mb) were found on chromosomes 3, 7, 11, 20 and 23. Positional candidate genes within 2 Mb from the associated windows were identified on chromosome 20 in both breeds. Candidate genes are within the equine lymphocyte antigen class II region, which evokes an immune response by recognizing many foreign molecules. The genome-wide association study identified several genomic regions associated with Insect Bite hypersensitivity in Shetland pony mares and Icelandic horses. On chromosome 20, associated genomic regions in both breeds were within 2 Mb from the equine lymphocyte antigen class II region. Increased knowledge on Insect Bite hypersensitivity associated genes will contribute to our understanding of its biology, enabling more efficient selection, therapy and prevention to decrease Insect Bite hypersensitivity prevalence.

Vinzenz Gerber - One of the best experts on this subject based on the ideXlab platform.

  • Allergen‐specific immunoglobulin E in sera of horses affected with Insect Bite hypersensitivity, severe equine asthma or both conditions
    Wiley, 2019
    Co-Authors: Maëva Verdon, Vinzenz Gerber, Claudio Rhyner, Simone Lanz, Eliane Marti
    Abstract:

    Background Genetic, epidemiologic, and clinical evidence suggests that, in horses, there are manifestations of hypersensitivity that can occur together. Objectives To investigate whether concurrent Insect Bite hypersensitivity (IBH) and severe equine asthma (EA) is associated with higher allergen‐specific and total serum immunoglobulin E (IgE) concentrations than only EA or IBH. Animals Healthy control horses (C, n = 40), horses with IBH (IBH, n = 24), severe EA (EA, n = 18), and both conditions (IBH/EA, n = 23) were included. Methods In our retrospective comparative study, sera from horses with signs of severe EA, IBH, and control animals were used. IgE specific for 15 recombinant (r) allergens as well as total serum IgE concentrations were measured by enzyme‐linked immunosorbent assay. Results Group IBH (median sum r‐Culicoides IgE: optical density at 405 nm [OD405] = 3.54 [0.48‐15.07]) and group IBH/EA (OD405 = 4.55 [0.46‐17.15]) had significantly (P  .05) differences between group IBH and group IBH/EA. No significant differences among the groups were found for the other r‐allergens or total serum IgE concentration. Compared to controls, horses with severe IBH had significantly increased IgE concentration to 5 Culicoides r‐allergens (P 

  • allergen specific immunoglobulin e in sera of horses affected with Insect Bite hypersensitivity severe equine asthma or both conditions
    Journal of Veterinary Internal Medicine, 2019
    Co-Authors: Maëva Verdon, Claudio Rhyner, Vinzenz Gerber, Simone Lanz, E Marti
    Abstract:

    BACKGROUND Genetic, epidemiologic, and clinical evidence suggests that, in horses, there are manifestations of hypersensitivity that can occur together. OBJECTIVES To investigate whether concurrent Insect Bite hypersensitivity (IBH) and severe equine asthma (EA) is associated with higher allergen-specific and total serum immunoglobulin E (IgE) concentrations than only EA or IBH. ANIMALS Healthy control horses (C, n = 40), horses with IBH (IBH, n = 24), severe EA (EA, n = 18), and both conditions (IBH/EA, n = 23) were included. METHODS In our retrospective comparative study, sera from horses with signs of severe EA, IBH, and control animals were used. IgE specific for 15 recombinant (r) allergens as well as total serum IgE concentrations were measured by enzyme-linked immunosorbent assay. RESULTS Group IBH (median sum r-Culicoides IgE: optical density at 405 nm [OD ] = 3.54 [0.48-15.07]) and group IBH/EA (OD  = 4.55 [0.46-17.15]) had significantly (P   .05) differences between group IBH and group IBH/EA. No significant differences among the groups were found for the other r-allergens or total serum IgE concentration. Compared to controls, horses with severe IBH had significantly increased IgE concentration to 5 Culicoides r-allergens (P < .05), whereas horses with moderate IBH had significantly increased IgE concentration to only 3 Culicoides r-allergens (P < .05). CONCLUSIONS AND CLINICAL IMPORTANCE Susceptibility of IBH-affected horses to develop EA is likely not associated with IgE-mediated immune reactions but with other immunopathological mechanisms.

  • Insect Bite hypersensitivity in horses is associated with airway hyperreactivity
    Journal of Veterinary Internal Medicine, 2017
    Co-Authors: Simone Lanz, E Marti, A Brunner, Claudia Graubner, Vinzenz Gerber
    Abstract:

    BACKGROUND Genetic and epidemiologic evidence suggests that in horses, as in other species, different manifestations of hypersensitivity may occur together. HYPOTHESIS Horses affected with Insect Bite hypersensitivity (IBH) show airway hyperreactivity (AH) to inhaled histamine, even in the absence of overt clinical signs of equine asthma (EA). ANIMALS Twenty-two healthy controls (group C), 24 horses suffering from IBH alone (group IBH), and 23 horses suffering from IBH and EA (group IBH/EA). METHODS The clinical histories were assessed using 2 standardized questionnaires, the Horse Owner Assessed Respiratory Signs Index (HOARSI), and IBH scoring. Horses were classified as EA-affected if their HOARSI was >1 and as IBH-affected if IBH score was >0. Confounding disorders were excluded by clinical examination. The arterial partial pressure of oxygen (PaO2 ) was measured and flowmetric plethysmography used to assess airway reactivity to increasing doses of inhaled histamine. RESULTS The median histamine provocation concentration (PC) when ∆flow values increased by 35% (PC35) was significantly higher in group C (5.94 [1.11-26.33] mg/mL) compared to group IBH (2.95 [0.23-10.13] mg/mL) and group IBH/EA (2.03 [0.43-10.94] mg/mL; P < 0.01). The PC50 and PC75 showed very similar differences between groups. Furthermore, PaO2 was significantly lower in group IBH (84 ± 8 mmHg) and group IBH/EA (78 ± 11 mmHg) compared to group C (89 ± 6 mmHg; P < 0.01). CONCLUSIONS AND CLINICAL IMPORTANCE IBH is associated with AH and decreased PaO2 , even in the absence of overt respiratory clinical signs.

  • multiple hypersensitivities including recurrent airway obstruction Insect Bite hypersensitivity and urticaria in 2 warmblood horse populations
    Journal of Veterinary Internal Medicine, 2015
    Co-Authors: Dounia Kehrli, Vendula Jandova, Kerstin Fey, P Jahn, Vinzenz Gerber
    Abstract:

    Background Multiple hypersensitivities (MHS) have been described in humans, cats, and dogs, but not horses. Hypotheses Horses suffering from recurrent airway obstruction (RAO), Insect Bite hypersensitivity (IBH), or urticaria (URT) will have an increased risk of also being affected by another one of these hypersensitivities. This predisposition for MHS also will be associated with decreased shedding of strongylid eggs in feces and with a single nucleotide polymorphism (SNP BIEC2-224511), previously shown to be associated with RAO. Animals The first population (P1) included 119 randomly sampled horses representative of the Swiss sporthorse population; the replication population (P2) included 210 RAO-affected Warmblood horses and 264 RAO-unaffected controls. All horses were Warmbloods, 14 years or older. Methods Associations between disease phenotypes (RAO, IBH, URT, MHS) fecal egg counts, the SNP BIEC2-224511 as well as management and environmental factors were investigated. Results In P1, RAO-affected horses had a 13.1 times higher odds ratio (OR) of also suffering from IBH (P = .004). In P2, the respective OR was 7.4 (P = .002) and IBH-affected horses also showed a 7.1 times increased OR of concomitantly suffering from URT (P < .001). IBH, URT, and MHS phenotypes were significantly associated with the absence of nematode eggs in the feces. Conclusions and Clinical Importance This is the first report of MHS in horses. Specifically, an increased risk for IBH should be expected in RAO-affected horses.

Eliane Marti - One of the best experts on this subject based on the ideXlab platform.

  • New Strategies for Prevention and Treatment of Insect Bite Hypersensitivity in Horses
    Current Dermatology Reports, 2019
    Co-Authors: Sigridur Jonsdottir, Sigurbjörg Torsteinsdóttir, Vilhjálmur Svansson, Iva Cvitas, Antonia Fettelschloss-gabriel, Eliane Marti
    Abstract:

    Purpose of Review Treatment of equine Insect Bite hypersensitivity (IBH) needs to be improved. Allergen-specific immunotherapy (ASIT), the only curative treatment of allergy, currently has only a limited efficacy for treatment of IBH. This review highlights the latest findings in prophylactic and therapeutic strategies. Recent Findings Prophylactic vaccination against IBH using recombinant Culicoides allergen has been developed in unexposed Icelandic horses and is ready to be tested. Therapeutic virus-like particle (VLP)–based vaccines targeting equine interleukin- (IL-) 5 or IL-31 improved clinical signs of IBH by induction of anti-cytokine antibodies thus reducing eosinophil counts or allergic pruritus, respectively. Summary First studies for development of ASIT using pure r- Culicoides allergens have yielded promising results and need now to be tested in clinical studies for both prevention and treatment of IBH. Therapeutic vaccines inducing neutralizing antibodies against IL-5 or IL-31 will be valuable future treatments for reduction of clinical signs of IBH.

  • Microarray Feature Selection and Dynamic Selection of Classifiers for Early Detection of Insect Bite Hypersensitivity in Horses
    2019 IEEE Congress on Evolutionary Computation (CEC), 2019
    Co-Authors: Alexandre Maciel-guerra, Eliane Marti, Grazziela P. Figueredo, Fernando J. Von Zuben, Jamie Twycross, Marcos J. C. Alcocer
    Abstract:

    Microarrays can be employed to better characterise allergies, as interactions between antibodies and allergens in mammals can be monitored. Once the joint dynamics of these elements in both healthy and diseased animals are understood, a model to predict the likelihood of an individual having allergic reactions can be defined. We investigate the potential use of Dynamic Selection (DS) methods to classify protein microarray data, with a case study of equine Insect Bite hypersensitivity (IBH) disease. To the best of our knowledge DS has not yet been applied to these data types. Since most microarrays datasets have a low number of samples, we hypothesise that DS models will produce satisfactory results due to their ability to perform better when compared to traditional ensemble techniques for similar data. We focus on three research questions: 1) What is the potential of DS for microarray data classification and how does it compare with existing classical classification methods results? 2) how do DS methods perform for the IBH dataset? and 3) does feature selection improve DS performance for this data? A wrapper using backward elimination and embedded with a regularized extreme learning machine are adopted to identify the more relevant features influencing the onset of the disease. Results from traditional classifiers are compared to 21 different DS methods before and after performing feature selection. Our results indicate that DS methods do not outperform single and static classifiers on this high-dimensional dataset and their performance also does not improved after feature selection.

  • Allergen‐specific immunoglobulin E in sera of horses affected with Insect Bite hypersensitivity, severe equine asthma or both conditions
    Wiley, 2019
    Co-Authors: Maëva Verdon, Vinzenz Gerber, Claudio Rhyner, Simone Lanz, Eliane Marti
    Abstract:

    Background Genetic, epidemiologic, and clinical evidence suggests that, in horses, there are manifestations of hypersensitivity that can occur together. Objectives To investigate whether concurrent Insect Bite hypersensitivity (IBH) and severe equine asthma (EA) is associated with higher allergen‐specific and total serum immunoglobulin E (IgE) concentrations than only EA or IBH. Animals Healthy control horses (C, n = 40), horses with IBH (IBH, n = 24), severe EA (EA, n = 18), and both conditions (IBH/EA, n = 23) were included. Methods In our retrospective comparative study, sera from horses with signs of severe EA, IBH, and control animals were used. IgE specific for 15 recombinant (r) allergens as well as total serum IgE concentrations were measured by enzyme‐linked immunosorbent assay. Results Group IBH (median sum r‐Culicoides IgE: optical density at 405 nm [OD405] = 3.54 [0.48‐15.07]) and group IBH/EA (OD405 = 4.55 [0.46‐17.15]) had significantly (P  .05) differences between group IBH and group IBH/EA. No significant differences among the groups were found for the other r‐allergens or total serum IgE concentration. Compared to controls, horses with severe IBH had significantly increased IgE concentration to 5 Culicoides r‐allergens (P 

  • A prospective study on Insect Bite hypersensitivity in horses exported from Iceland into Switzerland
    Acta Veterinaria Scandinavica, 2018
    Co-Authors: Sigurbjörg Torsteinsdóttir, Sigridur Jonsdottir, Vilhjálmur Svansson, Stephan Scheidegger, Silvia Baselgia, Sigridur Björnsdottir, Eliane Marti
    Abstract:

    Background Insect Bite hypersensitivity (IBH) is an IgE-mediated dermatitis caused by Bites of Culicoides spp., which occurs frequently in horses imported from Iceland to continental Europe. IBH does not occur in Iceland because Culicoides species that Bite horses are not present. However, Simulium vittatum ( S. vittatum ) are found in Iceland. In Europe, blood basophils from IBH-affected horses release significantly more sulfidoleukotrienes (sLT) than those from healthy controls after in vitro stimulation with Culicoides nubeculosus ( C. nubeculosus ) and S. vittatum . Aims of the study were: (I) using the sLT release assay, to test if horses living in Iceland were sensitized to S. vittatum and (II) to determine in a longitudinal study in horses imported from Iceland to Switzerland whether the sLT release assay would allow to predict which horses would develop IBH. Results Horses in Iceland, even when living in high S. vittatum areas, were usually not sensitized to S. vittatum or C. nubeculosus. Incidence of IBH in the 145 horses from the longitudinal study was 51% and mean time until IBH developed was 2.5 ± 1 year. Before import and after the first summer following import, there were no significant differences in sLT release between the endpoint healthy (H) and IBH groups. After the 2nd summer, when the number of clinically affected horses increased in the endpoint IBH group, a significantly higher sLT release after stimulation with C. nubeculosus but not with S. vittatum was observed. After the 3rd and 4th summer, the endpoint IBH group had a significantly higher sLT release with C. nubeculosus and S. vittatum than the endpoint H group. Some of the horses that remained healthy became transiently positive in the sLT release assay upon stimulation of their peripheral blood leucocytes with C. nubeculosus . Conclusions Horses in Iceland are not sensitized to S. vittatum . In horses that develop IBH, sensitization to S. vittatum is secondary to sensitization to C. nubeculosus and probably a result of an immunological cross-reactivity. A sLT release assay cannot be used to predict which horses will develop IBH. A transient positive reaction in the sLT release assay observed in horses that remained healthy suggests that immunoregulatory mechanisms may control an initial sensitization of the healthy horses.

  • Developing a preventive immunization approach against Insect Bite hypersensitivity using recombinant allergens: A pilot study
    Veterinary Immunology and Immunopathology, 2015
    Co-Authors: Sigridur Jonsdottir, Eliane Marti, Claudio Rhyner, Eman Hamza, Vilhjálmur Svansson, Jozef Janda, Andreas Meinke, Sigurbjörg Torsteinsdóttir
    Abstract:

    Insect Bite hypersensitivity (IBH) is an allergic dermatitis of horses caused by Bites of midges (Culicoides spp.). IgE-mediated reactions are often involved in the pathogenesis of this disease. IBH does not occur in Iceland due to the absence of Culicoides, but it occurs with a high frequency in Icelandic horses exported to mainland Europe, where Culicoides are present. We hypothesize that immunization with the Culicoides allergens before export could reduce the incidence of IBH in exported Icelandic horses. The aim of the present study was therefore to compare intradermal and intralymphatic vaccination using four purified recombinant allergens, in combination with a Th1 focusing adjuvant.Twelve horses were vaccinated three times with 10μg of each of the four recombinant Culicoides nubeculosus allergens. Six horses were injected intralymphatically, three with and three without IC31 ® , and six were injected intradermally, in the presence or absence of IC31 ® . Antibody responses were measured by immunoblots and ELISA, potential sensitization in a sulfidoleukotriene release test and an intradermal test, cytokine and FoxP3 expression with real time PCR following in vitro stimulation of PBMC.Immunization with the r-allergens induced a significant increase in levels of r-allergen-specific IgG1, IgG1/3, IgG4/7, IgG5 and IgG(T). Application of the r-allergens in IC31 ® adjuvant resulted in a significantly higher IgG1, IgG1/3, IgG4/7 allergen-specific response. Intralymphatic injection was slightly more efficient than intradermal injection, but the difference did not reach significance.Testing of the blocking activity of the sera from the horses immunized intralymphatically with IC31 ® showed that the generated IgG antibodies were able to partly block binding of serum IgE from an IBH-affected horse to these r-allergens. Furthermore, IgG antibodies bound to protein bands on blots of C. nubeculosus salivary gland extract.No allergen-specific IgE was induced and there was no indication of induction of IgE-mediated reactions, as horses neither responded to Culicoides extract stimulation in a sulfidoleukotriene release test, nor developed a relevant immediate hypersensitivity reaction to the recombinant allergens in skin test. IL-4 expression was significantly higher in horses vaccinated intralymphatically without IC31 ® , as compared to horses intradermally vaccinated with IC31 ® . Both routes gave higher IL-10 expression with IC31 ® .Both intralymphatic and intradermal vaccination of horses with recombinant allergens in IC31 ® adjuvant induced an immune response without adverse effects and without IgE production. The horses were not sensitized and produced IgG that could inhibit allergen-specific IgE binding. We therefore conclude that both the injection routes and the IC31 ® adjuvant are strong candidates for further development of immunoprophylaxis and therapy in horses.