66 results on '"Mike Kulis"'
Search Results
2. Tick salivary gland extract induces alpha‐gal syndrome in alpha‐gal deficient mice
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Shailesh K. Choudhary, Shahid Karim, Onyinye I. Iweala, Shivangi Choudhary, Gary Crispell, Surendra Raj Sharma, Claire T. Addison, Mike Kulis, Brian H. Herrin, Susan E. Little, and Scott P. Commins
- Subjects
alpha‐gal ,alpha‐gal knockout mice ,alpha‐gal syndrome ,Amblyomma americanum ,delayed allergic responses ,food allergy ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract Introduction Alpha‐gal syndrome (AGS) is characterized by delayed hypersensitivity to non‐primate mammalian meat in people having specific immunoglobulin E (sIgE) to the oligosaccharide galactose‐alpha‐1,3‐galactose. AGS has been linked to tick bites from Amblyomma americanum (Aa) in the U.S. A small animal model of meat allergy is needed to study the mechanism of alpha‐gal sensitization, the effector phase leading to delayed allergic responses and potential therapeutics to treat AGS. Methods Eight‐ to ten‐weeks old mice with a targeted inactivation of alpha‐1,3‐galactosyltransferase (AGKO) were injected intradermally with 50 μg of Aa tick salivary gland extract (TSGE) on days 0, 7, 21, 28, 42, and 49. Total IgE and alpha‐gal sIgE were quantitated on Day 56 by enzyme‐linked immunosorbent assay. Mice were challenged orally with 400 mg of cooked pork kidney homogenate or pork fat. Reaction severity was assessed by measuring a drop in core body temperature and scoring allergic signs. Results Compared to control animals, mice treated with TSGE had 190‐fold higher total IgE on Day 56 (0.60 ± 0.12 ng/ml vs. 113.2 ± 24.77 ng/ml; p < 0.001). Alpha‐gal sIgE was also produced in AGKO mice following TSGE sensitization (undetected vs. 158.4 ± 72.43 pg/ml). Further, sensitized mice displayed moderate clinical allergic signs along with a drop in core body temperature of ≥2°C as an objective measure of a systemic allergic reaction. Interestingly, female mice had higher total IgE responses to TSGE treatment but male mice had larger declines in mean body temperature. Conclusion TSGE‐sensitized AGKO mice generate sIgE to alpha‐gal and demonstrate characteristic allergic responses to pork fat and pork kidney. In keeping with the AGS responses documented in humans, mice reacted more rapidly to organ meat than to high fat pork challenge. This mouse model establishes the central role of tick bites in the development of AGS and provides a small animal model to mechanistically study mammalian meat allergy.
- Published
- 2021
- Full Text
- View/download PDF
3. Distinct trajectories distinguish antigen-specific T cells in peanut-allergic individuals undergoing oral immunotherapy
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Justine Calise, Hannah DeBerg, Nahir Garabatos, Sugandhika Khosa, Veronique Bajzik, Lorena Botero Calderon, Kelly Aldridge, Mario Rosasco, Brian C. Ferslew, Tong Zhu, Ronald Smulders, Lisa M. Wheatley, Tanya M. Laidlaw, Tielin Qin, Gurunadh R. Chichili, Daniel C. Adelman, Mary Farrington, David Robinson, David Jeong, Stacie M. Jones, Srinath Sanda, David Larson, William W. Kwok, Carolyn Baloh, Gerald T. Nepom, Erik Wambre, Edwin H. Kim, Kari C. Nadeau, Anna Nowak-Wegrzyn, Robert A. Wood, Hugh A. Sampson, Amy M. Scurlock, Sharon Chinthrajah, Julie Wang, Robert D. Pesek, Sayantani B. Sindher, Mike Kulis, Jacqueline Johnson, Katharine Spain, Denise C. Babineau, Hyunsook Chin, Joy Laurienzo-Panza, null Rachel Yan, null Tielin Qin, Don Whitehouse, Michelle L. Sever, Marshall Plaut, A. Wesley Burks, Gina Marchesini, Kavitha Gilroy, Sylvia Posso, Sabrina Skiba, Thien-Son Nguyen, Adam Wojno, Tuan Nguyen, Vivian Gersuk, Quynh-Anh Nguyen, Jessica Garber, Kimberly O’Brien, Brandon Larson, C. Cousens-Jacobs, and Alex Hu
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Immunology ,Immunology and Allergy - Published
- 2023
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4. Tick salivary gland extract induces alpha‐gal syndrome in alpha‐gal deficient mice
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Shahid Karim, Claire T. Addison, Brian H. Herrin, Susan E. Little, Gary Crispell, Shailesh K. Choudhary, Scott P. Commins, Onyinye I. Iweala, Surendra Raj Sharma, Shivangi Choudhary, and Mike Kulis
- Subjects
Male ,0301 basic medicine ,alpha‐gal syndrome ,delayed allergic responses ,Immunology ,Alpha (ethology) ,alpha‐gal ,Tick ,Salivary Glands ,Amblyomma americanum ,Mice ,03 medical and health sciences ,Ticks ,0302 clinical medicine ,Food allergy ,Animals ,Immunology and Allergy ,Medicine ,alpha‐gal knockout mice ,Sensitization ,food allergy ,mammalian meat ,biology ,Salivary gland ,Plant Extracts ,Effector ,business.industry ,Original Articles ,RC581-607 ,biology.organism_classification ,medicine.disease ,tick ,030104 developmental biology ,medicine.anatomical_structure ,Delayed hypersensitivity ,Female ,Original Article ,Immunologic diseases. Allergy ,business ,Food Hypersensitivity ,030215 immunology - Abstract
Introduction Alpha‐gal syndrome (AGS) is characterized by delayed hypersensitivity to non‐primate mammalian meat in people having specific immunoglobulin E (sIgE) to the oligosaccharide galactose‐alpha‐1,3‐galactose. AGS has been linked to tick bites from Amblyomma americanum (Aa) in the U.S. A small animal model of meat allergy is needed to study the mechanism of alpha‐gal sensitization, the effector phase leading to delayed allergic responses and potential therapeutics to treat AGS. Methods Eight‐ to ten‐weeks old mice with a targeted inactivation of alpha‐1,3‐galactosyltransferase (AGKO) were injected intradermally with 50 μg of Aa tick salivary gland extract (TSGE) on days 0, 7, 21, 28, 42, and 49. Total IgE and alpha‐gal sIgE were quantitated on Day 56 by enzyme‐linked immunosorbent assay. Mice were challenged orally with 400 mg of cooked pork kidney homogenate or pork fat. Reaction severity was assessed by measuring a drop in core body temperature and scoring allergic signs. Results Compared to control animals, mice treated with TSGE had 190‐fold higher total IgE on Day 56 (0.60 ± 0.12 ng/ml vs. 113.2 ± 24.77 ng/ml; p < 0.001). Alpha‐gal sIgE was also produced in AGKO mice following TSGE sensitization (undetected vs. 158.4 ± 72.43 pg/ml). Further, sensitized mice displayed moderate clinical allergic signs along with a drop in core body temperature of ≥2°C as an objective measure of a systemic allergic reaction. Interestingly, female mice had higher total IgE responses to TSGE treatment but male mice had larger declines in mean body temperature. Conclusion TSGE‐sensitized AGKO mice generate sIgE to alpha‐gal and demonstrate characteristic allergic responses to pork fat and pork kidney. In keeping with the AGS responses documented in humans, mice reacted more rapidly to organ meat than to high fat pork challenge. This mouse model establishes the central role of tick bites in the development of AGS and provides a small animal model to mechanistically study mammalian meat allergy., Alpha‐gal syndrome (AGS) is characterized by delayed hypersensitivity to non‐primate mammalian meat in people having specific IgE (sIgE) to the oligosaccharide galactose‐alpha‐1,3‐galactose and has been linked to tick bites from Amblyomma americanum (Aa) in the U.S. We demonstrate that intradermal injection of Aa tick salivary gland extract (TSGE) in alpha‐gal knockout (AGKO) mice induce alpha‐gal sIgE production and mice displayed moderate clinical allergic signs along with a drop in core body temperature as an objective measure of a systemic allergic reaction. Further, this model recapitulates several aspects of red meat allergy seen in the humans and will be used to mechanistically study this novel food allergy and model therapeutic approaches to treat this disease.
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- 2021
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5. Content and Performance of the MiniMUGA Genotyping Array: A New Tool To Improve Rigor and Reproducibility in Mouse Research
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Martin T. Ferris, Sarah A. Schoenrock, Timothy R. Gershon, David B. Darr, Mark J. Zylka, J. Mauro Calabrese, James E. Faber, Laura G. Reinholdt, David W. Threadgill, John R. Shorter, Kathleen M. Caron, Lisa E. Gralinski, Robert S. Hagan, Glenn K. Matsushima, Yuyu Ren, Christopher M. Sassetti, Christiann H. Gaines, Bin Gu, Lori L. O'Brien, Sheryl S. Moy, Timothy A. Bell, Keegan Wardwell, Barbara J. Vilen, Terry Magnuson, Darla R. Miller, Clare M. Smith, Abraham A. Palmer, A. Wesley Burks, Fernando Pardo-Manuel de Villena, Celine L. St. Pierre, William Valdar, Rachel C. McMullan, Pablo Hock, Frank L. Conlon, Kevin C K Lloyd, Gudrun A. Brockmann, Anwica Kashfeen, Ginger D. Shaw, Steve Rockwood, Karen L. Mohlke, Matthew Blanchard, Alessandra Livraghi-Butrico, Benjamin D. Philpot, Rachel M Lynch, Scott H. Randell, J. Brennan, John Sebastian Sigmon, Vivek Kumar, Ralph S. Baric, Leonard McMillan, Mark T. Heise, Ernest G. Heimsath, Richard E. Cheney, Avani Saraswatula, Lucy H. Williams, Allison R. Rogala, Colton L. Linnertz, Caroline E. Y. Murphy, Dominic Ciavatta, Mike Kulis, Tal Kafri, Craig L. Franklin, Jason K. Whitmire, J. Charles Jennette, Maya L. Najarian, Cathleen M. Lutz, Jonathan C. Schisler, Lisa M. Tarantino, and Folami Y. Ideraabdullah
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Male ,Genotype ,Genotyping Techniques ,genetic QC ,Single-nucleotide polymorphism ,diagnostic SNPs ,Computational biology ,genetic constructs ,Biology ,Investigations ,Inbred C57BL ,Genome ,genetic background ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Inbred strain ,Genetic ,Gene duplication ,Methods, Technology, & Resources ,Genetics ,Animals ,Polymorphism ,Genotyping ,030304 developmental biology ,Oligonucleotide Array Sequence Analysis ,0303 health sciences ,substrains ,Polymorphism, Genetic ,Laboratory mouse ,Robustness (evolution) ,Reproducibility of Results ,Sex Determination Processes ,Mice, Inbred C57BL ,Female ,030217 neurology & neurosurgery ,chromosomal sex ,Genome-Wide Association Study - Abstract
The laboratory mouse is the most widely used animal model for biomedical research, due in part to its well-annotated genome, wealth of genetic resources, and the ability to precisely manipulate its genome. Despite the importance of genetics for mouse research, genetic quality control (QC) is not standardized, in part due to the lack of cost-effective, informative, and robust platforms. Genotyping arrays are standard tools for mouse research and remain an attractive alternative even in the era of high-throughput whole-genome sequencing. Here, we describe the content and performance of a new iteration of the Mouse Universal Genotyping Array (MUGA), MiniMUGA, an array-based genetic QC platform with over 11,000 probes. In addition to robust discrimination between most classical and wild-derived laboratory strains, MiniMUGA was designed to contain features not available in other platforms: (1) chromosomal sex determination, (2) discrimination between substrains from multiple commercial vendors, (3) diagnostic SNPs for popular laboratory strains, (4) detection of constructs used in genetically engineered mice, and (5) an easy-to-interpret report summarizing these results. In-depth annotation of all probes should facilitate custom analyses by individual researchers. To determine the performance of MiniMUGA, we genotyped 6899 samples from a wide variety of genetic backgrounds. The performance of MiniMUGA compares favorably with three previous iterations of the MUGA family of arrays, both in discrimination capabilities and robustness. We have generated publicly available consensus genotypes for 241 inbred strains including classical, wild-derived, and recombinant inbred lines. Here, we also report the detection of a substantial number of XO and XXY individuals across a variety of sample types, new markers that expand the utility of reduced complexity crosses to genetic backgrounds other than C57BL/6, and the robust detection of 17 genetic constructs. We provide preliminary evidence that the array can be used to identify both partial sex chromosome duplication and mosaicism, and that diagnostic SNPs can be used to determine how long inbred mice have been bred independently from the relevant main stock. We conclude that MiniMUGA is a valuable platform for genetic QC, and an important new tool to increase the rigor and reproducibility of mouse research.
- Published
- 2020
6. Efficacy and safety of oral immunotherapy in children aged 1-3 years with peanut allergy (the Immune Tolerance Network IMPACT trial): a randomised placebo-controlled study
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Stacie M Jones, Edwin H Kim, Kari C Nadeau, Anna Nowak-Wegrzyn, Robert A Wood, Hugh A Sampson, Amy M Scurlock, Sharon Chinthrajah, Julie Wang, Robert D Pesek, Sayantani B Sindher, Mike Kulis, Jacqueline Johnson, Katharine Spain, Denise C Babineau, Hyunsook Chin, Joy Laurienzo-Panza, Rachel Yan, David Larson, Tielin Qin, Don Whitehouse, Michelle L Sever, Srinath Sanda, Marshall Plaut, Lisa M Wheatley, and A Wesley Burks
- Subjects
Male ,Arachis ,Administration, Oral ,General Medicine ,Allergens ,Treatment Outcome ,Double-Blind Method ,Desensitization, Immunologic ,Child, Preschool ,Immune Tolerance ,Humans ,Female ,Peanut Hypersensitivity ,Child - Abstract
For young children with peanut allergy, dietary avoidance is the current standard of care. We aimed to assess whether peanut oral immunotherapy can induce desensitisation (an increased allergic reaction threshold while on therapy) or remission (a state of non-responsiveness after discontinuation of immunotherapy) in this population.We did a randomised, double-blind, placebo-controlled study in five US academic medical centres. Eligible participants were children aged 12 to younger than 48 months who were reactive to 500 mg or less of peanut protein during a double-blind, placebo-controlled food challenge (DBPCFC). Participants were randomly assigned by use of a computer, in a 2:1 allocation ratio, to receive peanut oral immunotherapy or placebo for 134 weeks (2000 mg peanut protein per day) followed by 26 weeks of avoidance, with participants and study staff and investigators masked to group treatment assignment. The primary outcome was desensitisation at the end of treatment (week 134), and remission after avoidance (week 160), as the key secondary outcome, were assessed by DBPCFC to 5000 mg in the intention-to-treat population. Safety and immunological parameters were assessed in the same population. This trial is registered on ClinicalTrials.gov, NCT03345160.Between Aug 13, 2013, and Oct 1, 2015, 146 children, with a median age of 39·3 months (IQR 30·8-44·7), were randomly assigned to receive peanut oral immunotherapy (96 participants) or placebo (50 participants). At week 134, 68 (71%, 95% CI 61-80) of 96 participants who received peanut oral immunotherapy compared with one (2%, 0·05-11) of 50 who received placebo met the primary outcome of desensitisation (risk difference [RD] 69%, 95% CI 59-79; p0·0001). The median cumulative tolerated dose during the week 134 DBPCFC was 5005 mg (IQR 3755-5005) for peanut oral immunotherapy versus 5 mg (0-105) for placebo (p0·0001). After avoidance, 20 (21%, 95% CI 13-30) of 96 participants receiving peanut oral immunotherapy compared with one (2%, 0·05-11) of 50 receiving placebo met remission criteria (RD 19%, 95% CI 10-28; p=0·0021). The median cumulative tolerated dose during the week 160 DBPCFC was 755 mg (IQR 0-2755) for peanut oral immunotherapy and 0 mg (0-55) for placebo (p0·0001). A significant proportion of participants receiving peanut oral immunotherapy who passed the 5000 mg DBPCFC at week 134 could no longer tolerate 5000 mg at week 160 (p0·001). The participant receiving placebo who was desensitised at week 134 also achieved remission at week 160. Compared with placebo, peanut oral immunotherapy decreased peanut-specific and Ara h2-specific IgE, skin prick test, and basophil activation, and increased peanut-specific and Ara h2-specific IgG4 at weeks 134 and 160. By use of multivariable regression analysis of participants receiving peanut oral immunotherapy, younger age and lower baseline peanut-specific IgE was predictive of remission. Most participants (98% with peanut oral immunotherapy vs 80% with placebo) had at least one oral immunotherapy dosing reaction, predominantly mild to moderate and occurring more frequently in participants receiving peanut oral immunotherapy. 35 oral immunotherapy dosing events with moderate symptoms were treated with epinephrine in 21 participants receiving peanut oral immunotherapy.In children with a peanut allergy, initiation of peanut oral immunotherapy before age 4 years was associated with an increase in both desensitisation and remission. Development of remission correlated with immunological biomarkers. The outcomes suggest a window of opportunity at a young age for intervention to induce remission of peanut allergy.National Institute of Allergy and Infectious Disease, Immune Tolerance Network.
- Published
- 2020
7. Content and performance of the MiniMUGA genotyping array, a new tool to improve rigor and reproducibility in mouse research
- Author
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Christiann H. Gaines, Sheryl S. Moy, Mark T. Heise, Scott H. Randell, Matthew Blanchard, Vivek Kumar, Leonard McMillan, Darla R. Miller, Lucy H. Williams, Timothy A. Bell, Keegan Wardwell, Terry Magnuson, Mark J. Zylka, Christopher M. Sassetti, Craig L. Franklin, Ralph S. Baric, Sarah A. Schoenrock, Glenn K. Matsushima, Cathleen M. Lutz, James E. Faber, Maya L. Najarian, Yuyu Ren, Folami Y. Ideraabdullah, Jason K. Whitmire, Bin Gu, Jonathan C. Schisler, Pablo Hock, J. Charles Jennette, Celine L. St. Pierre, Lisa M. Tarantino, Samir N. P. Kelada, Karen L. Mohlke, Laura G. Reinholdt, Alessandra Livraghi-Butrico, Richard F. Loeser, Abraham A. Palmer, Robert S. Hagan, John R. Shorter, David W. Threadgill, Lori L. O'Brien, Kathleen M. Caron, Steve Rockwood, Kent Lloyd, Fernando Pardo-Manuel de Villena, Caroline E. Y. Murphy, A. Wesley Burks, Tal Kafri, Benjamin D. Philpot, David B. Darr, Avani Saraswatula, Ernest G. Heimsath, Richard E. Cheney, Allison R. Rogala, William Valdar, Dominic Ciavatta, Rachel C. McMullan, Ginger D. Shaw, Clare M. Smith, Frank L. Conlon, Barbara J. Vilen, John Sebastian Sigmon, Gudrun A. Brockmann, Anwica Kashfeen, Martin T. Ferris, Rachel M Lynch, Mauro Calabrese, Colton L. Linnertz, Timothy R. Gershon, J. Brennan, Lisa E. Gralinski, and Mike Kulis
- Subjects
Whole genome sequencing ,Inbred strain ,Genotype ,Laboratory mouse ,Robustness (evolution) ,Single-nucleotide polymorphism ,Computational biology ,Biology ,Genome ,Genotyping - Abstract
The laboratory mouse is the most widely used animal model for biomedical research, due in part to its well annotated genome, wealth of genetic resources and the ability to precisely manipulate its genome. Despite the importance of genetics for mouse research, genetic quality control (QC) is not standardized, in part due to the lack of cost effective, informative and robust platforms. Genotyping arrays are standard tools for mouse research and remain an attractive alternative even in the era of high-throughput whole genome sequencing. Here we describe the content and performance of a new Mouse Universal Genotyping Array (MUGA). MiniMUGA, an array-based genetic QC platform with over 11,000 probes. In addition to robust discrimination between most classical and wild-derived laboratory strains, MiniMUGA was designed to contain features not available in other platforms: 1) chromosomal sex determination, 2) discrimination between substrains from multiple commercial vendors, 3) diagnostic SNPs for popular laboratory strains, 4) detection of constructs used in genetically engineered mice, and 5) an easy to interpret report summarizing these results. In-depth annotation of all probes should facilitate custom analyses by individual researchers. To determine the performance of MiniMUGA we genotyped 6,899 samples from a wide variety of genetic backgrounds. The performance of MiniMUGA compares favorably with three previous iterations of the MUGA family of arrays both in discrimination capabilities and robustness. We have generated publicly available consensus genotypes for 241 inbred strains including classical, wild-derived and recombinant inbred lines. Here we also report the detection of a substantial number of XO and XXY individuals across a variety of sample types, the extension of the utility of reduced complexity crosses to genetic backgrounds other than C57BL/6, and the robust detection of 17 genetic constructs. There is preliminary but striking evidence that the array can be used to identify both partial sex chromosome duplication and mosaicism, and that diagnostic SNPs can be used to determine how long inbred mice have been bred independently from the main stock for a significant action of the genotyped inbred samples. We conclude that MiniMUGA is a valuable platform for genetic QC and important new tool to the increase rigor and reproducibility of mouse research.
- Published
- 2020
- Full Text
- View/download PDF
8. Food allergens
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Anusha Penumarti and Mike Kulis
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- 2020
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9. Characterization of the B-cell receptor repertoires in peanut allergic subjects undergoing oral immunotherapy
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Yusuke Nakamura, A. Wesley Burks, Tu H Mai, Kazuma Kiyotani, Kelly Orgel, Seiya Imoto, Poh Yin Yew, Rui Yamaguchi, Mike Kulis, and Satoru Miyano
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Male ,0301 basic medicine ,Allergy ,medicine.medical_treatment ,B-cell receptor ,Receptors, Antigen, B-Cell ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Antigen ,Genetics ,medicine ,Humans ,Peanut Hypersensitivity ,Child ,Genetics (clinical) ,breakpoint cluster region ,High-Throughput Nucleotide Sequencing ,Immunotherapy ,medicine.disease ,030104 developmental biology ,Child, Preschool ,030220 oncology & carcinogenesis ,Immunology ,biology.protein ,Immunoglobulin heavy chain ,Female ,Antibody - Abstract
B-cell receptors (BCRs) play a critical role in adaptive immunity as they generate highly diverse immunoglobulin repertoires to recognize a wide variety of antigens. To better understand immune responses, it is critically important to establish a quantitative and rapid method to analyze BCR repertoire comprehensively. Here, we developed "Bcrip", a novel approach to characterize BCR repertoire by sequencing millions of BCR cDNA using next-generation sequencer. Using this method and quantitative real-time PCR, we analyzed expression levels and repertoires of BCRs in a total of 17 peanut allergic subjects' peripheral blood samples before and after receiving oral immunotherapy (OIT) or placebo. By our methods, we successfully identified all of variable (V), joining (J), and constant (C) regions, in an average of 79.1% of total reads and 99.6% of these VJC-mapped reads contained the C region corresponding to the isotypes that we aimed to analyze. In the 17 peanut allergic subjects' peripheral blood samples, we observed an oligoclonal enrichment of certain immunoglobulin heavy chain alpha (IGHA) and IGH gamma (IGHG) clones (P = 0.034 and P = 0.027, respectively) in peanut allergic subjects after OIT. This newly developed BCR sequencing and analysis method can be applied to investigate B-cell repertoires in various research areas, including food allergies as well as autoimmune and infectious diseases.
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- 2017
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10. Eosinophilic esophagitis during peanut oral immunotherapy with omalizumab
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Brian P. Vickery, Yamini V. Virkud, Pamela H. Steele, Evan S. Dellon, Caitlin M. Burk, Mike Kulis, and A. Wesley Burks
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0301 basic medicine ,medicine.medical_specialty ,Oral immunotherapy ,business.industry ,Extramural ,MEDLINE ,Omalizumab ,medicine.disease ,Dermatology ,Article ,Clinical trial ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030228 respiratory system ,medicine ,Immunology and Allergy ,Young adult ,Eosinophilic esophagitis ,business ,medicine.drug - Published
- 2017
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11. Hypoallergenic Proteins for the Treatment of Food Allergy
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Luanna Yang and Mike Kulis
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Pulmonary and Respiratory Medicine ,Allergen immunotherapy ,Allergy ,Adolescent ,medicine.medical_treatment ,Immunology ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Allergen ,Food allergy ,medicine ,Humans ,Immunology and Allergy ,Child ,030223 otorhinolaryngology ,Modalities ,business.industry ,Infant ,Hypoallergenic ,Immunotherapy ,Allergens ,medicine.disease ,030228 respiratory system ,Desensitization, Immunologic ,Child, Preschool ,Peptides ,business ,Food Hypersensitivity ,Anaphylaxis - Abstract
Food allergy is a growing health problem worldwide that impacts millions of individuals. Current treatment options are limited and strict dietary avoidance remains the standard of care. Immunotherapy using whole, native allergens is under active clinical investigation but harbors the risk of severe side effects including anaphylaxis. Newer food-specific therapies with hypoallergenic proteins may potentially offer safer treatment alternatives, and this review seeks to investigate the evidence supporting the use of these modalities. The utilization of different methods to alter allergen structure and IgE binding leads to reduced allergenicity and decreases the risk for systemic reactions, making the use of potential therapies including extensively heated egg/milk, peptide immunotherapy, recombinant allergen immunotherapy, and DNA vaccines safe and possibly efficacious forms of treatment in food allergy. However, for the majority of these treatment modalities, limited data currently exists looking at the safety and efficacy in human subjects with food allergy. This review provides a comprehensive overview of the current evidence examining the safety and efficacy of hypoallergenic proteins in the treatment of food allergies.
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- 2019
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12. Food antigen sensitization in genetically-susceptible mice is influenced by fecal IgA, antigen absorption, and gut microbiome composition
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Andrew Hinton, Peter J. Mucha, Herman F. Staats, Erin C. Steinbach, Brandi T. Johnson-Weaver, Robert M. Immormino, Johanna Smeekens, Martin T. Ferris, Janelle Kesselring, Kelly Orgel, A. Wesley Burks, M. Andrea Azcarate-Peril, Timothy P. Moran, and Mike Kulis
- Subjects
Antigen Sensitization ,Antigen ,Chemistry ,Immunology ,Immunology and Allergy ,Composition (visual arts) ,Absorption (skin) ,Feces ,Gut microbiome ,Microbiology - Published
- 2021
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13. Mast cell desensitization inhibits calcium flux and aberrantly remodels actin
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W.X. Gladys Ang, Alison Church, Hae Woong Choi, Soman N. Abraham, A. Wesley Burks, and Mike Kulis
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0301 basic medicine ,medicine.medical_treatment ,CHO Cells ,Biology ,Immunoglobulin E ,Cell Degranulation ,Mice ,03 medical and health sciences ,Cricetulus ,0302 clinical medicine ,Cricetinae ,Calcium flux ,medicine ,Animals ,Calcium Signaling ,Mast Cells ,Receptor ,Anaphylaxis ,Desensitization (medicine) ,Receptors, IgE ,Degranulation ,Actin remodeling ,General Medicine ,Mast cell ,Actin cytoskeleton ,Actins ,humanities ,Cell biology ,Actin Cytoskeleton ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Immunology ,biology.protein ,Signal Transduction ,Research Article - Abstract
Rush desensitization (DS) is a widely used and effective clinical strategy for the rapid inhibition of IgE-mediated anaphylactic responses. However, the cellular targets and underlying mechanisms behind this process remain unclear. Recent studies have implicated mast cells (MCs) as the primary target cells for DS. Here, we developed a murine model of passive anaphylaxis with demonstrated MC involvement and an in vitro assay to evaluate the effect of DS on MCs. In contrast with previous reports, we determined that functional IgE remains on the cell surface of desensitized MCs following DS. Despite notable reductions in MC degranulation following DS, the high-affinity IgE receptor FcεRI was still capable of transducing signals in desensitized MCs. Additionally, we found that displacement of the actin cytoskeleton and its continued association with FcεRI impede the capacity of desensitized MCs to evoke the calcium response that is essential for MC degranulation. Together, these findings suggest that reduced degranulation responses in desensitized MCs arise from aberrant actin remodeling, providing insights that may lead to improvement of DS treatments for anaphylactic responses.
- Published
- 2016
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14. Component-resolved analysis of IgA, IgE, and IgG4 during egg OIT identifies markers associated with sustained unresponsiveness
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A.W. Burks, Scott H. Sicherer, Brian P. Vickery, D. Stablein, Hugh A. Sampson, Stacie M. Jones, Benjamin L. Wright, Peter Dawson, Kelly Orgel, Robert A. Wood, Donald Y.M. Leung, Robert Lindblad, Mike Kulis, and Alice K. Henning
- Subjects
Male ,0301 basic medicine ,Eggs ,medicine.medical_treatment ,Immunology ,Administration, Oral ,Immunoglobulin E ,Placebo ,Article ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,Food allergy ,medicine ,Humans ,Immunology and Allergy ,Treatment Failure ,Egg Hypersensitivity ,Desensitization (medicine) ,biology ,business.industry ,Allergens ,medicine.disease ,Immunoglobulin A ,Ovalbumin ,Treatment Outcome ,030104 developmental biology ,030228 respiratory system ,Desensitization, Immunologic ,Immunoglobulin G ,Egg allergy ,biology.protein ,Female ,business ,Biomarkers ,Egg white - Abstract
Background In a previously reported CoFAR study, 55 subjects with egg allergy underwent randomized, placebo-controlled egg oral immunotherapy (eOIT). Active treatment induced desensitization in most and sustained unresponsiveness (SU) in a smaller subset. We hypothesized that component-resolved analysis of IgE, IgG4, IgA, IgA1, and IgA2 may identify potential biomarkers of SU in OIT subjects. Methods Longitudinal samples for 51 egg-allergic subjects (37 active and 14 placebo) were available. Egg white (EW)-, ovalbumin (OVA)-, and ovomucoid (OVM)-specific levels of IgA, IgA1, and IgA2 were quantified by ELISA. IgE and IgG4 to these antigens were quantified using ImmunoCAP®. Clinical responders achieved SU to egg; all others were considered nonresponders. Between-group comparisons were made among active and placebo, as well as responders and nonresponders. Results No placebo subjects achieved responder status. Through month 48, among the 37 active subjects, baseline IgE-OVM was lower in responders (median 3.97 kU/l, n = 19) than in nonresponders (10.9 kU/l, n = 18, P = 0.010). Logistic regression analysis revealed that lower baseline IgE-EW (P = 0.038), IgE-OVM (P = 0.032), and a higher IgG4/IgE-OVM ratio (P = 0.013) were associated with clinical response. Relative increases in IgG4-EW, IgA-EW, and IgA2-EW were observed in responders (P = 0.024, 0.024, and 0.029, respectively). IgG4/IgE, IgA/IgE, and IgA2/IgE ratios for EW and IgA/IgE ratio for OVA were found to be significantly elevated among responders (P = 0.004, 0.009, 0.028, and 0.008, respectively). Conclusions Increased IgG4-EW, IgA-EW, and IgA2-EW during eOIT are associated with clinical response to eOIT. Lower pretreatment IgE-EW and IgE-OVM are also associated with SU. Future studies are needed to evaluate and validate these potential biomarkers.
- Published
- 2016
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15. Utility of component analyses in subjects undergoing sublingual immunotherapy for peanut allergy
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Brian P. Vickery, Caitlin M. Burk, Nicole Leung, Edwin H. Kim, A.W. Burks, and Mike Kulis
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Male ,0301 basic medicine ,medicine.medical_treatment ,Immunology ,Peanut allergy ,Immunoglobulin E ,Article ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,medicine ,Humans ,Immunology and Allergy ,Peanut Hypersensitivity ,Sublingual immunotherapy ,Clinical significance ,Child ,Glycoproteins ,Plant Proteins ,Desensitization (medicine) ,Sublingual Immunotherapy ,biology ,Plasma samples ,business.industry ,Infant ,Membrane Proteins ,food and beverages ,Allergens ,Antigens, Plant ,medicine.disease ,Slit ,030104 developmental biology ,030228 respiratory system ,Child, Preschool ,Immunoglobulin G ,Cohort ,biology.protein ,Female ,business ,2S Albumins, Plant - Abstract
Background Sublingual immunotherapy (SLIT) with peanut changes clinical and immune responses in most peanut-allergic individuals, but the response is highly variable. Objective We sought to examine the component-specific effects of peanut SLIT and determine whether peanut component testing could predict the outcome of a double-blind, placebo-controlled food challenge (DBPCFC) after 12 months of peanut SLIT. Methods We included 33 subjects who underwent peanut SLIT with a DBPCFC of 2500 mg of peanut protein performed after 12 months on therapy. Plasma samples from baseline and after 12 months of peanut SLIT were assayed using ImmunoCAP for IgE and IgG4 against whole peanut, Ara h 1, Ara h 2, Ara h 3, Ara h 8, and Ara h 9. Results Following 12 months of SLIT, 10 subjects (30%) passed the DBPCFC without symptoms and were considered desensitized. Subjects that failed the DBPCFC tolerated a median of 460 mg peanut protein (range: 10-1710 mg). The desensitized group had significantly lower baseline levels of IgE against peanut (median 40.8 vs 231 kUA/L, p = 0.0082), Ara h 2 (median 17 vs 113 kUA/L, p=0.0082), and Ara h 3 (median 0.3 vs 8.5 kUA/L, p = 0.0396). ROC curves indicated that baseline IgE against peanut and Ara h 2 were equally effective at discriminating between the two groups (AUC = 0.7957, p = 0.007752 for both). Conclusion and Clinical Relevance In this cohort of subjects undergoing SLIT for peanut allergy, lower baseline levels of IgE against Ara h 2, Ara h 3, and peanut were associated with successful desensitization. This article is protected by copyright. All rights reserved.
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- 2016
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16. Antigenic Liposomes for Generation of Disease-specific Antibodies
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Dharmendra Raghuwanshi, Lakeya C. Hardy, Shiteng Duan, Johanna Smeekens, Mike Kulis, Kyle J. Bednar, and Matthew S. Macauley
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0301 basic medicine ,Immunogen ,Arachis ,T-Lymphocytes ,General Chemical Engineering ,medicine.medical_treatment ,Peanut allergy ,General Biochemistry, Genetics and Molecular Biology ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,Calcium flux ,medicine ,Animals ,Humans ,Peanut Hypersensitivity ,Anaphylaxis ,Immunology and Infection ,General Immunology and Microbiology ,biology ,General Neuroscience ,Reproducibility of Results ,Allergens ,Immunoglobulin E ,medicine.disease ,Vaccination ,030104 developmental biology ,Immunization ,Liposomes ,Immunology ,biology.protein ,Nanoparticles ,Female ,Antibody ,Adjuvant ,Food Hypersensitivity ,030215 immunology - Abstract
Antibody responses provide critical protective immunity to a wide array of pathogens. There remains a high interest in generating robust antibodies for vaccination as well as understand how pathogenic antibody responses develop in allergies and autoimmune disease. Generating robust antigen-specific antibody responses is not always trivial. In mouse models, it often requires multiple rounds of immunizations with adjuvant that leads to a great deal of variability in the levels of induced antibodies. One example is in mouse models of peanut allergies where more robust and reproducible models that minimize mouse numbers and the use of adjuvant would be beneficial. Presented here is a highly reproducible mouse model of peanut allergy anaphylaxis. This new model relies on two key factors: (1) antigen-specific splenocytes are adoptively transferred from a peanut-sensitized mouse into a naïve recipient mouse, normalizing the number of antigen-specific memory B- and T-cells across a large number of mice; and (2) recipient mice are subsequently boosted with a strong multivalent immunogen in the form of liposomal nanoparticles displaying the major peanut allergen (Ara h 2). The major advantage of this model is its reproducibility, which ultimately lowers the number of animals used in each study, while minimizing the number of animals receiving multiple injections of adjuvant. The modular assembly of these immunogenic liposomes provides relatively facile adaptability to other allergic or autoimmune models that involve pathogenic antibodies.
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- 2018
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17. Tree nut allergies: Allergen homology, cross-reactivity, and implications for therapy
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K. Bagley, Johanna Smeekens, and Mike Kulis
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0301 basic medicine ,Nut ,Allergy ,medicine.medical_treatment ,T-Lymphocytes ,Immunology ,Population ,Disease ,Cross Reactions ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Allergen ,medicine ,Immunology and Allergy ,Animals ,Humans ,Nuts ,education ,Phylogeny ,education.field_of_study ,business.industry ,digestive, oral, and skin physiology ,food and beverages ,Immunotherapy ,Allergens ,Antigens, Plant ,Immunoglobulin E ,medicine.disease ,Clinical trial ,030104 developmental biology ,030228 respiratory system ,Tree nut allergy ,Nut Hypersensitivity ,business - Abstract
Tree nut allergy is a potentially life-threatening disease that is increasing in prevalence, now affecting 1% of the general population in the United States. While other food allergies often resolve spontaneously, tree nut allergies are outgrown in less than 10% of cases. Due to the likelihood of cross-sensitization to multiple tree nut allergens, the current treatment guideline is strict avoidance of all nuts once one tree nut allergy has been diagnosed. For example, walnut and pecan are highly cross-reactive, along with cashew and pistachio, but the extent of clinical, IgE-mediated cross-reactivity among other tree nuts remains unclear, therefore making avoidance of all tree nuts a safe approach. There have been recent advances in immunotherapy for food allergies. For instance, there are investigational immunotherapies for milk, egg and peanut allergies, specifically oral immunotherapy, sublingual immunotherapy and epicutaneous immunotherapy. However, there are no large randomized controlled clinical trials for tree nut allergies. Even though there has been less research into tree nut allergy immunotherapies, the evidence of T-cell cross-reactivity among tree nuts exists in animal models and in T cells from allergic patients indicates that immunotherapeutic interventions may be possible. Here, we review the literature regarding epidemiology, allergen homology and cross-reactivity among tree nuts, and explore how current findings can be employed for effective therapy.
- Published
- 2018
18. Diagnosis, Management, and Investigational Therapies for Food Allergies
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A. Wesley Burks, Benjamin L. Wright, Stacie M. Jones, and Mike Kulis
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Allergy ,medicine.medical_specialty ,Oral immunotherapy ,Article ,Predictive Value of Tests ,Risk Factors ,Food allergy ,medicine ,Animals ,Humans ,Sublingual immunotherapy ,Intensive care medicine ,Sublingual Immunotherapy ,Hepatology ,Oral food challenge ,business.industry ,Therapies, Investigational ,Public health ,Gastroenterology ,Allergens ,Immunoglobulin E ,medicine.disease ,Diet ,Clinical trial ,Treatment Outcome ,Immunology ,Diagnosis management ,business ,Biomarkers ,Food Hypersensitivity - Abstract
Food allergies have increased in prevalence over the past 20 years, now becoming an important public health concern. Although there are no therapies currently available for routine clinical care, recent reports have indicated that immunotherapies targeting the mucosal immune system may be effective. Oral immunotherapy is conducted by administering small, increasing amounts of food allergen; it has shown promise for desensitizing individuals with peanut, egg, or milk allergies. Sublingual immunotherapy also desensitizes allergic patients to foods—2 major studies have examined the effects of sublingual immunotherapy in subjects with peanut allergies. We review the complex nature of IgE-mediated food allergies and the therapies being evaluated in clinical trials. We focus on the diagnosis and management of food allergies and investigational therapies.
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- 2015
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19. Peanut Allergy: New Developments and Clinical Implications
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Edwin H. Kim, Scott P. Commins, Kelly Orgel, and Mike Kulis
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0301 basic medicine ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Allergy ,Arachis ,medicine.medical_treatment ,Immunology ,Peanut allergy ,03 medical and health sciences ,0302 clinical medicine ,Food allergy ,medicine ,Immunology and Allergy ,Animals ,Humans ,Sublingual immunotherapy ,Peanut Hypersensitivity ,Intensive care medicine ,Anaphylaxis ,business.industry ,Public health ,Immunotherapy ,Allergens ,Immunoglobulin E ,medicine.disease ,Clinical trial ,030104 developmental biology ,030228 respiratory system ,business - Abstract
Food allergies have increased in prevalence over the past 20 years, now becoming an important public health concern. Although there are no therapies currently available for routine clinical care, recent reports have indicated that immunotherapies targeting the mucosal immune system may be effective. Oral immunotherapy is conducted by administering small, increasing amounts of food allergen; it has shown promise for desensitizing individuals with peanut, egg, or milk allergies. Sublingual immunotherapy also desensitizes allergic patients to foods—two major studies have examined the effects of sublingual immunotherapy in subjects with peanut allergies. We review the complex nature of IgE-mediated food allergies and the therapies being evaluated in clinical trials. We focus on the diagnosis and management of food allergies and investigational therapies.
- Published
- 2016
20. Peanut allergen Ara h 2-specific T cells are activated via Ras-Erk MAP kinase pathway signalling and identified by CD154 expression
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Yingxian Li, Mike Kulis, Xiao-Ping Zhong, A. Wesley Burks, and Laurent Pons
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MAPK/ERK pathway ,T cell ,Immunology ,food and beverages ,Biology ,Molecular biology ,medicine.anatomical_structure ,Biochemistry ,medicine ,Splenocyte ,Secretion ,Cytokine secretion ,IL-2 receptor ,CD154 ,Protein kinase A ,Agronomy and Crop Science ,Food Science - Abstract
Background. Peanut allergy is driven by peanut-specific Th2 cells. Ara h 2, a peanut 2S albumin, is one of the major peanut allergens. Methods. An Ara h 2-specific T cell line was generated from peanut sensitised C3H/HeJ mice and used to analyse allergen-induced cytokine secretion and activation of signalling molecules. Results. Peanut stimulated splenocytes from peanut sensitised mice had strong proliferation responses and highly elevated IL-4 secretion. The Ara h 2-specific T cells generated from sensitised mice were mainly CD4+ T helper cells with a Th2 cytokine profile. The expression of CD154 on the surface of these T cell clones was detected following Ara h 2 stimulation. Ara h 2 stimulation induced phosphorylation of ZAP-70 and Erk1/2 in the T cells. Conclusions. CD154 is a useful marker for identifying activated, allergen-specific T cells. The Ras-Erk mitogen-activated protein kinase pathway is involved in the activation of Ara h 2-specific Th2 cells.
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- 2011
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21. Single–tree nut immunotherapy attenuates allergic reactions in mice with hypersensitivity to multiple tree nuts
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Laurent Pons, Wesley Burks, Yifan Li, Mike Kulis, and Hannah G. Lane
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Nut ,Allergy ,Arachis ,medicine.medical_treatment ,Blotting, Western ,Immunology ,Enzyme-Linked Immunosorbent Assay ,Juglans ,Cross Reactions ,medicine.disease_cause ,Cross-reactivity ,Mice ,Food allergy ,medicine ,Animals ,Immunology and Allergy ,Anacardium ,Sensitization ,Desensitization (medicine) ,business.industry ,food and beverages ,Immunotherapy ,Immunoglobulin E ,medicine.disease ,medicine.anatomical_structure ,Desensitization, Immunologic ,Immunoglobulin G ,Pistacia ,Tree nut allergy ,Female ,Nut Hypersensitivity ,business - Abstract
Background Allergic reactions to tree nuts are often severe and are outgrown in less than 10% of diagnosed patients. Objectives To determine whether treatment of underlying tree nut sensitization will prevent allergic reactions to cross-reacting tree nuts and to determine the effects of single–tree nut immunotherapy on true multi–tree nut sensitization. Methods Cross-reactivity model: Cashew-sensitized mice underwent immunotherapy with cashew and were subsequently challenged with cashew and pistachio. Multisensitization model: Cashew plus walnut-sensitized mice were treated with cashew alone, walnut alone, or both cashew and walnut and then underwent challenges to cashew and walnut. Challenges were assessed on the basis of symptoms, changes in body temperature, and mouse mast cell protease-1 release. Results In the cross-reactivity model, cashew immunotherapy completely prevented allergic reactions on challenges with cashew or the cross-reactive pistachio. In the multisensitization model, mice with cashew plus walnut allergy were significantly protected from anaphylactic reactions on cashew challenge in both the cashew-alone and walnut-alone immunotherapy groups. Results from the walnut challenge demonstrated significantly decreased allergic responses in the walnut immunotherapy group, whereas mice in the cashew immunotherapy group experienced significantly lower symptoms. In the cross-reactivity model, immunotherapy effectively decreased IL-4 and IL-5 production and increased IL-12 relative to placebo while also inducing a 5-fold increase in specific IgG 1 . Conclusion Single–tree nut immunotherapy can effectively decrease allergic responses in both the cross-reactivity and multisensitization mouse models. Further studies are needed to determine which single–tree nut immunotherapies will be most effective for specific multi–tree nut allergy profiles.
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- 2011
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22. Pioneering immunotherapy for food allergy: clinical outcomes and modulation of the immune response
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A. Wesley Burks, Mike Kulis, and Brian P. Vickery
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Allergy ,medicine.medical_treatment ,Immunology ,Peanut allergy ,Administration, Oral ,Basophil ,T-Lymphocytes, Regulatory ,Immune system ,Food allergy ,Immune Tolerance ,medicine ,Humans ,Mast Cells ,Desensitization (medicine) ,Clinical Trials as Topic ,business.industry ,Immunotherapy ,Allergens ,Immunoglobulin E ,medicine.disease ,Basophils ,Clinical trial ,Treatment Outcome ,medicine.anatomical_structure ,Desensitization, Immunologic ,Immunoglobulin G ,Langerhans Cells ,business ,Food Hypersensitivity - Abstract
There is no approved therapy for food allergies, which affect 12 million people in the United States and millions more worldwide. In the last few years, our research team at Duke has begun to develop protocols to treat peanut and other food allergies. Two distinct therapies are being developed. Oral immunotherapy (OIT), which relies on ingestion of increasing amounts of the allergenic food, has been used to successfully desensitize more than 50 peanut allergic subjects. Sublingual immunotherapy (SLIT) involves placing small quantities of peanut allergens under the tongue and has shown promise in our initial placebo-controlled clinical trial. Immunologic changes associated with OIT and SLIT include reduction in mast cell reactivity as determined by skin prick test size, decreased basophil responses, decreased specific-IgE, increased IgG4, and induction of regulatory T cells. Development of these immunotherapy strategies has generated much excitement in the food allergy community; however, further studies are needed before these approaches are ready for clinical use.
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- 2010
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23. Impact of Irradiation on the Protein Content and Microbial Levels of Sesame Seed Flour for use in Oral Immunotherapy
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Edwin H. Kim, A. Wesley Burks, Anusha Penumarti, Elizabeth Gabel, Jelena Petrovic Berglund, Mike Kulis, Janelle Kesselring, and Nicole Szczepanski
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Protein content ,Oral immunotherapy ,Chemistry ,Immunology ,Immunology and Allergy ,Irradiation ,Food science ,Sesame seed - Published
- 2018
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24. Intragastric sensitization to peanut in the absence of a Th2-skewing adjuvant in mice genetically predisposed to food allergy
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A. Wesley Burks, Kelly Orgel, Darla R. Miller, Fernando Pardo-Manuel de Villena, Martin T. Ferris, Johanna Smeekens, and Mike Kulis
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medicine.anatomical_structure ,Food allergy ,business.industry ,medicine.medical_treatment ,Immunology ,medicine ,Immunology and Allergy ,medicine.disease ,business ,Adjuvant ,Sensitization - Published
- 2018
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25. Exploiting CD22 on antigen-specific B cells to prevent allergy to the major peanut allergen Ara h 2
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Matthew S. Macauley, Brian P. Vickery, Soheila J. Maleki, A. Wesley Burks, Kelly Orgel, Shiteng Duan, John C. Wolf, Benjamin L. Wright, Mike Kulis, and James C. Paulson
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0301 basic medicine ,Allergy ,Sialic Acid Binding Ig-like Lectin 2 ,medicine.medical_treatment ,Immunology ,Biology ,medicine.disease_cause ,Article ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Allergen ,Antigen ,Antigen specific ,medicine ,Animals ,Immunology and Allergy ,Peanut Hypersensitivity ,Glycoproteins ,Desensitization (medicine) ,Sialic Acid Binding Immunoglobulin-like Lectins ,chemistry.chemical_classification ,B-Lymphocytes ,Mice, Inbred BALB C ,CD22 ,Antigens, Plant ,medicine.disease ,Treatment Outcome ,030104 developmental biology ,chemistry ,Desensitization, Immunologic ,Liposomes ,Female ,Glycoprotein ,2S Albumins, Plant ,030215 immunology - Published
- 2017
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26. Diacylglycerol kinase ζ deficiency in a non-CD4+ T-cell compartment leads to increased peanut hypersensitivity
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Chi Keung Wan, A. Wesley Burks, Balachandra K. Gorentla, Xiao-Ping Zhong, and Mike Kulis
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Diacylglycerol Kinase ,T-Lymphocytes ,Diacylglycerol kinase zeta ,Immunology ,Biology ,Article ,Mice ,Immune system ,Immunopathology ,medicine ,Animals ,Immunology and Allergy ,Peanut Hypersensitivity ,Sensitization ,Diacylglycerol kinase ,chemistry.chemical_classification ,food and beverages ,medicine.disease ,Phenotype ,Molecular biology ,Mice, Mutant Strains ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Enzyme ,chemistry ,Female ,Anaphylaxis - Abstract
Peanut sensitization in diacylglycerol kinase zeta (DGKζ) deficient mice led to elevated peanut-IgE levels and severe anaphylaxis. DGKζ deficient CD4+T cells did not account for the phenotype. Future studies will determine which immune lineage caused increased food hypersensitivity.
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- 2011
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27. Novel strategy to create hypoallergenic peanut protein-polyphenol edible matrices for oral immunotherapy
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A. Wesley Burks, Rishu Guo, Nathalie J. Plundrich, Mary Ann Lila, Brittany L. White, Jack P. Davis, Mike Kulis, and Mary H. Grace
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Arachis ,Peanut allergy ,Administration, Oral ,Basophil ,Immunoglobulin E ,Basophil degranulation ,Spectroscopy, Fourier Transform Infrared ,medicine ,Humans ,Peanut Hypersensitivity ,Chromatography, High Pressure Liquid ,Plant Proteins ,biology ,Chemistry ,food and beverages ,Polyphenols ,Hypoallergenic ,General Chemistry ,medicine.disease ,Mast cell ,medicine.anatomical_structure ,Biochemistry ,Polyphenol ,Immunology ,biology.protein ,Electrophoresis, Polyacrylamide Gel ,Immunotherapy ,General Agricultural and Biological Sciences ,Ex vivo - Abstract
Peanut allergy is an IgE-mediated hypersensitivity. Upon peanut consumption by an allergic individual, epitopes on peanut proteins bind and cross-link peanut-specific IgE on mast cell and basophil surfaces triggering the cells to release inflammatory mediators responsible for allergic reactions. Polyphenolic phytochemicals have high affinity to bind proteins and form soluble and insoluble complexes with unique functionality. This study investigated the allergenicity of polyphenol-fortified peanut matrices prepared by complexing various polyphenol-rich plant juices and extracts with peanut flour. Polyphenol-fortified peanut matrices reduced IgE binding to one or more peanut allergens (Ara h 1, Ara h 2, Ara h 3, and Ara h 6). Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) suggested changes in secondary protein structure. Peanut protein-cranberry polyphenol fortified matrices triggered significantly less basophil degranulation than unmodified flour in an ex vivo assay using human blood and less mast cell degranulation when used to orally challenge peanut-allergic mice. Polyphenol fortification of peanut flour resulted in a hypoallergenic matrix with reduced IgE binding and degranulation capacity, likely due to changes in protein secondary structure or masking of epitopes, suggesting potential applications for oral immunotherapy.
- Published
- 2014
28. Food Allergens
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Mike Kulis and A. Wesley Burks
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- 2014
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29. Carrying peptides towards the ideal allergen-specific immunotherapy
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Mike Kulis
- Subjects
Vaccines ,Ideal (set theory) ,allergy vaccination ,Immunology ,Vaccination ,Specific immunotherapy ,Epitopes, T-Lymphocyte ,Rhinitis, Allergic, Seasonal ,hemic and immune systems ,chemical and pharmacologic phenomena ,Original Articles ,Biology ,respiratory system ,Antigens, Plant ,Antibodies, Neutralizing ,respiratory tract diseases ,peptides ,Immunology and Allergy ,Animals ,Female ,allergens ,Betula ,specific immunotherapy - Abstract
Background Vaccines consisting of allergen-derived peptides lacking IgE reactivity and allergen-specific T cell epitopes bound to allergen-unrelated carrier molecules have been suggested as candidates for allergen-specific immunotherapy. Objective To study whether prophylactic and therapeutic vaccination with carrier-bound peptides from the major birch pollen allergen Bet v 1 lacking allergen-specific T cell epitopes has influence on Bet v 1-specific T cell responses. Methods Three Bet v 1-derived peptides, devoid of Bet v 1-specific T cell epitopes, were coupled to KLH and adsorbed to aluminium hydroxide to obtain a Bet v 1-specific allergy vaccine. Groups of BALB/c mice were immunized with the peptide vaccine before or after sensitization to Bet v 1. Bet v 1- and peptide-specific antibody responses were analysed by ELISA. T cell and cytokine responses to Bet v 1, KLH, and the peptides were studied in proliferation assays. The effects of peptide-specific and allergen-specific antibodies on T cell responses and allergic lung inflammation were studied using specific antibodies. Results Prophylactic and therapeutic vaccination with carrier-bound Bet v 1 peptides induced a Bet v 1-specific IgG antibody response without priming/boosting of Bet v 1-specific T cells. Prophylactic and therapeutic vaccination of mice with the peptide vaccine induced Bet v 1-specific antibodies which suppressed Bet v 1-specific T cell responses and allergic lung inflammation. Conclusion and Clinical Relevance Vaccination with carrier-bound allergen-derived peptides lacking allergen-specific T cell epitopes induces allergen-specific IgG antibodies which suppress allergen-specific T cell responses and allergic lung inflammation.
- Published
- 2014
30. Pepsinized cashew proteins are hypoallergenic and immunogenic and provide effective immunotherapy in mice with cashew allergy
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Rishu Guo, Yifan Li, Ian MacQueen, A. Wesley Burks, Xiao-Ping Zhong, and Mike Kulis
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Allergy ,medicine.medical_treatment ,Immunology ,Biology ,Article ,Mice ,Th2 Cells ,Food allergy ,medicine ,Immunology and Allergy ,Animals ,Anacardium ,Plant Proteins ,Mice, Inbred C3H ,Immunogenicity ,Hypoallergenic ,Immunotherapy ,medicine.disease ,Pepsin A ,Peptide Fragments ,Disease Models, Animal ,Desensitization, Immunologic ,Immunoglobulin G ,Tree nut allergy ,Cytokine secretion ,Female ,Nut Hypersensitivity ,Anaphylaxis - Abstract
Background IgE-mediated allergic reactions to cashews and other nuts can trigger life-threatening anaphylaxis. Proactive therapies to decrease reaction severity do not exist. Objectives We aimed to determine the efficacy of pepsin-digested cashew proteins used as immunotherapy in a murine model of cashew allergy. Methods Mice were sensitized to cashew and then underwent challenges with digested or native cashew allergens to assess the allergenicity of the protein preparations. Using native or pepsinized cashew proteins, mice underwent oral or intraperitoneal sensitization protocols to determine the immunogenic properties of the protein preparations. Finally, cashew-sensitized mice underwent an immunotherapy protocol with native or pepsinized cashew proteins and subsequent provocation challenges. Results Pepsinized cashew proteins elicited weaker allergic reactions than native cashew proteins but importantly retained the ability to stimulate cellular proliferation and cytokine production. Mice sensitized with pepsinized proteins reacted on challenge with native allergens, demonstrating that pepsinized allergens retain immunogenicity in vivo . Immunotherapy with pepsinized cashew allergens significantly decreased allergic symptoms and body temperature decrease relative to placebo after challenge with native and pepsinized proteins. Immunologic changes were comparable after immunotherapy with native or pepsinized allergens: T H 2-type cytokine secretion from splenocytes was decreased, whereas specific IgG 1 and IgG 2a levels were increased. Conclusions Pepsinized cashew proteins are effective in treating cashew allergy in mice and appear to work through the same mechanisms as native protein immunotherapy.
- Published
- 2012
31. Type B CpG oligodeoxynucleotides induce Th1 responses to peanut antigens: modulation of sensitization and utility in a truncated immunotherapy regimen in mice
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A. Wesley Burks, Xiao-Ping Zhong, Balachandra K. Gorentla, and Mike Kulis
- Subjects
Arachis ,CpG Oligodeoxynucleotide ,medicine.medical_treatment ,Peanut allergy ,Immunoglobulin E ,Article ,Interferon-gamma ,Mice ,Immune system ,Antigen ,Adjuvants, Immunologic ,medicine ,Animals ,Peanut Hypersensitivity ,Anaphylaxis ,Sensitization ,Mice, Inbred C3H ,biology ,Tumor Necrosis Factor-alpha ,food and beverages ,TLR9 ,Immunotherapy ,Dendritic Cells ,Antigens, Plant ,Th1 Cells ,medicine.disease ,Interleukin-12 ,medicine.anatomical_structure ,Oligodeoxyribonucleotides ,Immunoglobulin G ,Immunology ,biology.protein ,Female ,Food Science ,Biotechnology - Abstract
Peanut allergy stems from a Th2-biased immune response to peanut allergens leading to IgE production and allergic reactions upon ingestion.A model of peanut allergy in C3H/HeJ mice was used to assess whether type A, B, or C CpG oligodeoxynucleotide (ODN) molecules would be effective in: (i) a prophylactic approach to prevent peanut allergy when administered simultaneously with a Th2-skewing adjuvant, and (ii) a therapeutic model to allow for shortened immunotherapy. Type B ODNs were extremely effective in inhibiting anaphylaxis in the sensitization protocol as evidenced by differences in symptom scores, body temperature, and mouse mast cell protease 1 release compared to sham treatment. In the therapeutic model, co-administration of type B ODN plus peanut proteins was highly effective in reducing anaphylactic reactions in mice with established peanut allergy. The therapeutic effect was accompanied by an increase in IFN-γ and peanut-IgG2a, without a significant decrease in peanut IgE or IL-4 responses.CpG ODNs, especially type B, were highly effective in inducing Th1 responses in mice undergoing induction of peanut allergy, as well as in mice undergoing therapy for established peanut allergy. Interestingly, the IgE response was not significantly altered, suggesting that IgG antibodies may be enough to prevent peanut-induced anaphylaxis.
- Published
- 2012
32. Oral immunotherapy for food allergy: clinical and preclinical studies
- Author
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A. Wesley Burks and Mike Kulis
- Subjects
Drug ,Allergy ,media_common.quotation_subject ,medicine.medical_treatment ,T-Lymphocytes ,Population ,Drug Evaluation, Preclinical ,Pharmaceutical Science ,Administration, Oral ,Immunoglobulins ,medicine.disease_cause ,Pediatrics ,Allergen ,Food allergy ,medicine ,Immune Tolerance ,Humans ,Peanut Hypersensitivity ,Dosing ,education ,Egg Hypersensitivity ,media_common ,Desensitization (medicine) ,Adjuvants, Pharmaceutic ,education.field_of_study ,Clinical Trials as Topic ,Drug Carriers ,Dose-Response Relationship, Drug ,business.industry ,medicine.disease ,Clinical trial ,Desensitization, Immunologic ,Toll-Like Receptor 9 ,Immunology ,Immunotherapy ,Milk Hypersensitivity ,business ,Food Hypersensitivity - Abstract
Food allergies affect approximately 5% of the U.S. population and have increased in the last decade. In recent years, oral immunotherapy (OIT) has been tested in clinical trials for peanut, milk, and egg allergies in young children. OIT appears to be fairly well tolerated by most subjects and leads to desensitization with a greatly increased threshold of allergen required to induce reactions. Further approaches being investigated in preclinical studies in mouse models indicate the potential for using adjuvants, such as TLR9 agonists in combination with OIT; peptide OIT; and non-allergen specific applications such as herbal formulations. Further questions about OIT remain, including the optimal dosing and length of treatment; whether tolerance can be developed; and the exact cellular mechanisms resulting in protection following OIT. With many clinical trials underway across the United States and other countries, and a growing pipeline of preclinical research with translational potential, there is great hope for a widely applicable food allergy treatment.
- Published
- 2012
33. A randomized controlled study of peanut oral immunotherapy (OIT): clinical desensitization and modulation of the allergic response
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Tamara T. Perry, Alex R. Kemper, Stacie M. Jones, A. Wesley Burks, J. Kamilaris, Laurent Pons, S.K. Carlisle, Amy M. Scurlock, Pooja Varshney, Anne Hiegel, Brian P. Vickery, Mike Kulis, Xiaohong Yue, and Pamela H. Steele
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Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Immunology ,Peanut allergy ,Administration, Oral ,medicine.disease_cause ,Placebo ,Gastroenterology ,Article ,law.invention ,Randomized controlled trial ,law ,Food allergy ,Internal medicine ,medicine ,Hypersensitivity ,Immunology and Allergy ,Humans ,Peanut Hypersensitivity ,Child ,Desensitization (medicine) ,Cumulative dose ,Oral food challenge ,business.industry ,food and beverages ,Infant ,medicine.disease ,Desensitization, Immunologic ,Child, Preschool ,Allergic response ,Female ,Immunotherapy ,business - Abstract
Open-label oral immunotherapy (OIT) protocols have been used to treat small numbers of patients with peanut allergy. Peanut OIT has not been evaluated in double-blind, placebo-controlled trials.To investigate the safety and effectiveness of OIT for peanut allergy in a double-blind, placebo-controlled study.In this multicenter study, children ages 1 to 16 years with peanut allergy received OIT with peanut flour or placebo. Initial escalation, build-up, and maintenance phases were followed by an oral food challenge (OFC) at approximately 1 year. Titrated skin prick tests (SPTs) and laboratory studies were performed at regular intervals.Twenty-eight subjects were enrolled in the study. Three peanut OIT subjects withdrew early in the study because of allergic side effects. During the double-blind, placebo-controlled food challenge, all remaining peanut OIT subjects (n = 16) ingested the maximum cumulative dose of 5000 mg (approximately 20 peanuts), whereas placebo subjects (n = 9) ingested a median cumulative dose of 280 mg (range, 0-1900 mg; P.001). In contrast with the placebo group, the peanut OIT group showed reductions in SPT size (P.001), IL-5 (P = .01), and IL-13 (P = .02) and increases in peanut-specific IgG(4) (P.001). Peanut OIT subjects had initial increases in peanut-specific IgE (P.01) but did not show significant change from baseline by the time of OFC. The ratio of forkhead box protein 3 (FoxP3)(hi): FoxP3(intermediate) CD4+ CD25+ T cells increased at the time of OFC (P = .04) in peanut OIT subjects.These results conclusively demonstrate that peanut OIT induces desensitization and concurrent immune modulation. The current study continues and is evaluating the hypothesis that peanut OIT causes long-term immune tolerance.
- Published
- 2011
34. Food allergies and hypersensitivity: a review of pharmacotherapy and therapeutic strategies
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Laurent Pons, Mike Kulis, and Wesley Burks
- Subjects
medicine.medical_specialty ,Allergy ,medicine.medical_treatment ,Peanut allergy ,Traditional Chinese medicine ,Pharmacotherapy ,Food allergy ,medicine ,Vaccines, DNA ,Humans ,Pharmacology (medical) ,Medicine, Chinese Traditional ,Intensive care medicine ,Pharmacology ,Mechanism (biology) ,business.industry ,Proteins ,General Medicine ,Immunotherapy ,Immunoglobulin E ,medicine.disease ,Immunology ,Mutation ,business ,Peptides ,Anaphylaxis ,Food Hypersensitivity ,Drugs, Chinese Herbal - Abstract
Food allergy is a major cause of life-threatening hypersensitivity reactions. Food-induced anaphylaxis is the most common reason for someone to present to the emergency department for an anaphylactic reaction. At present, the avoidance of the allergenic food is the only method of preventing further reactions for allergic patients.With better characterization of allergens and an understanding of the immunologic mechanism involved in this reaction, investigators have developed several therapeutic modalities potentially applicable to the treatment and eventual prevention of food allergy. This review identifies and discusses the potential treatment options for food allergy that are under development.Relevant articles are reviewed pertaining to the treatment of food allergy.Among the therapeutic options currently under investigation are anti-IgE therapy, peptide immunotherapy, traditional Chinese medicine, mutated protein immunotherapy, DNA immunization and immunization with immunostimulatory sequences linked to allergens. These novel forms of treatment for allergic disease hold promise for the safe and effective treatment of food-allergic individuals and the prevention of food allergy in the future.
- Published
- 2008
35. Peanut Oral Immunotherapy and Omalizumab Treatment for Peanut Allergy
- Author
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J. Kamilaris, Michele R. Henson, A. Thyagarajan, A.H. Edie, Brian P. Vickery, Pamela H. Steele, Mike Kulis, and A.W. Burks
- Subjects
medicine.medical_specialty ,Oral immunotherapy ,business.industry ,Immunology ,Peanut allergy ,medicine ,Immunology and Allergy ,Omalizumab ,business ,medicine.disease ,Dermatology ,medicine.drug - Published
- 2012
- Full Text
- View/download PDF
36. Peanut Challenge Outcomes Following Sublingual Immunotherapy (SLIT) Correlate With Increased Peanut-Specific Salivary IgA
- Author
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J.A. Bird, N. Kamilaris, A.W. Burks, Edwin H. Kim, Katie Saba, Brian P. Vickery, Mike Kulis, and Herman F. Staats
- Subjects
business.industry ,Immunology ,Immunology and Allergy ,Medicine ,Sublingual immunotherapy ,business ,Slit ,Salivary iga - Published
- 2012
- Full Text
- View/download PDF
37. Nasal Immunization with Peanut Antigen and The Cationic Peptide Adjuvant Mastoparan 7 Induces Serum Humoral Immunity That Protects Peanut Allergic Mice Against Systemic Anaphylaxis
- Author
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A.W. Burks, Mike Kulis, Brandi T. Johnson, Soman N. Abraham, and Herman F. Staats
- Subjects
chemistry.chemical_classification ,business.industry ,medicine.medical_treatment ,Immunology ,Peptide ,Immunization ,chemistry ,Antigen ,Systemic anaphylaxis ,Mastoparan ,Humoral immunity ,Immunology and Allergy ,Medicine ,business ,Adjuvant - Published
- 2012
- Full Text
- View/download PDF
38. Allergenicity of Peanut Proteins is Retained Following Enzymatic Hydrolysis
- Author
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Rishu Guo, A.W. Burks, Brittany L. White, Xiaolei Shi, Timothy H. Sanders, Jack P. Davis, and Mike Kulis
- Subjects
Biochemistry ,Chemistry ,Enzymatic hydrolysis ,Immunology ,Immunology and Allergy - Published
- 2012
- Full Text
- View/download PDF
39. Participation in Peanut Oral Immunotherapy Improves Quality of Life
- Author
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Pamela H. Steele, A.W. Burks, Brian P. Vickery, A.H. Edie, J. Kamilaris, and Mike Kulis
- Subjects
medicine.medical_specialty ,Quality of life (healthcare) ,Oral immunotherapy ,business.industry ,Immunology ,medicine ,Immunology and Allergy ,Intensive care medicine ,business - Published
- 2012
- Full Text
- View/download PDF
40. Plasma from Subjects on Peanut Oral Immunotherapy (OIT) Suppresses ex vivo Basophil Activation in Peanut-Allergic Subjects
- Author
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Caitlin M. Burk, A.W. Burks, Mike Kulis, Stacy Chin, and N. Kamilaris
- Subjects
Basophil activation ,Oral immunotherapy ,business.industry ,Immunology ,Immunology and Allergy ,Medicine ,business ,Ex vivo - Published
- 2012
- Full Text
- View/download PDF
41. Comparison of Sublingual Immunotherapy (SLIT) versus Oral Immunotherapy (OIT) in the Treatment of Peanut Allergy
- Author
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J. Kamilaris, Pooja Varshney, Stacie M. Jones, Pamela H. Steele, A.W. Burks, Stacy Chin, Brian P. Vickery, Amy M. Scurlock, Mike Kulis, P.B. Smith, Anne Hiegel, Edwin H. Kim, and S.K. Carlisle
- Subjects
medicine.medical_specialty ,Oral immunotherapy ,business.industry ,Immunology ,Peanut allergy ,Immunology and Allergy ,Medicine ,Sublingual immunotherapy ,business ,medicine.disease ,Dermatology ,Slit - Published
- 2012
- Full Text
- View/download PDF
42. Early Intervention with Oral Immunotherapy is a Promising Strategy for the Treatment of Peanut Allergy
- Author
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A.W. Burks, Brian P. Vickery, J. Kamilaris, Pamela H. Steele, Mike Kulis, and A.H. Edie
- Subjects
medicine.medical_specialty ,Oral immunotherapy ,business.industry ,Internal medicine ,Intervention (counseling) ,Immunology ,Peanut allergy ,medicine ,Immunology and Allergy ,medicine.disease ,business - Published
- 2012
- Full Text
- View/download PDF
43. Effect of Peanut Oral Immunotherapy (OIT) on Other Food Allergen-Specific IgE Levels
- Author
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A.W. Burks, J.A. Bird, N. Kamilaris, Pooja Varshney, Brian P. Vickery, Laurent Pons, and Mike Kulis
- Subjects
Oral immunotherapy ,biology ,business.industry ,Immunology ,biology.protein ,Immunology and Allergy ,Medicine ,Food allergens ,Immunoglobulin E ,business - Published
- 2011
- Full Text
- View/download PDF
44. Peanut Oral Immunotherapy (OIT) Induces a Transient Increase in CD4+CD25+FoxP3+ Tregs and a Sustained Decrease of Th2-type Cytokines
- Author
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Mike Kulis, Stacie M. Jones, Brian P. Vickery, A.W. Burks, Pooja Varshney, Tamara T. Perry, and Amy M. Scurlock
- Subjects
Cd4 cd25 ,Oral immunotherapy ,business.industry ,Immunology ,Immunology and Allergy ,Medicine ,FOXP3 ,Transient (computer programming) ,business - Published
- 2011
- Full Text
- View/download PDF
45. Evidence of Desensitization by Sublingual Immunotherapy in Peanut-Allergic Children
- Author
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Laurent Pons, Wayne G. Shreffler, Edwin H. Kim, Mike Kulis, Pamela H. Steele, Susan Laubach, Brian P. Vickery, A.W. Burks, J.A. Bird, and J. Kamilaris
- Subjects
business.industry ,medicine.medical_treatment ,Immunology ,Immunology and Allergy ,Medicine ,Sublingual immunotherapy ,business ,Desensitization (medicine) - Published
- 2011
- Full Text
- View/download PDF
46. Peanut Oral Immunotherapy (OIT) Induces Immunologic Changes Supporting the Development of Tolerance
- Author
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Mike Kulis, Tamara T. Perry, Pamela H. Steele, Laurent Pons, Pooja Varshney, Stacie M. Jones, Alex R. Kemper, Amy M. Scurlock, and A.W. Burks
- Subjects
Oral immunotherapy ,business.industry ,Immunology ,Immunology and Allergy ,Medicine ,business - Published
- 2010
- Full Text
- View/download PDF
47. Peanut Oral Immunotherapy (OIT) Confers Long-Term Tolerance Mediated by Decreased T-helper Type 2 (TH2) Cytokines and Cytokines Generated by Regulatory T cells (Tregs)
- Author
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Laurent Pons, Moira E. Breslin, A.W. Burks, Xiaohong Yue, Stacie M. Jones, Brian P. Vickery, and Mike Kulis
- Subjects
Oral immunotherapy ,business.industry ,Immunology ,Immunology and Allergy ,Medicine ,Th2 cytokines ,business - Published
- 2010
- Full Text
- View/download PDF
48. Removal of Peanut 2S Albumins, Ara h 2 and Ara h 6, from a Soluble Peanut Protein Extract Significantly Reduces Allergic Reactions in Peanut-Sensitized Mice
- Author
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Xueni Chen, H. S. Porterfield, Laurent Pons, A.W. Burks, J. Lew, Stephen C. Dreskin, and Mike Kulis
- Subjects
Immunology ,Immunology and Allergy - Published
- 2010
- Full Text
- View/download PDF
49. Double-Blinded Placebo Controlled Sublingual Immunotherapy (SLIT) Trial for Peanut Allergy
- Author
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Pamela H. Steele, A.H. Edie, Alex R. Kemper, Susan Laubach, Mike Kulis, J.A. Bird, J. Kamilaris, A. Thyagarajan, Pooja Varshney, A.W. Burks, Laurent Pons, Edwin H. Kim, and Brian P. Vickery
- Subjects
medicine.medical_specialty ,business.industry ,Double blinded ,Immunology ,Peanut allergy ,Immunology and Allergy ,Medicine ,Sublingual immunotherapy ,business ,Placebo ,medicine.disease ,Dermatology ,Slit - Published
- 2010
- Full Text
- View/download PDF
50. Peanut Oral Immunotherapy (OIT) Induces Epitope-Specific Isotype Shift From IgE to IgG4
- Author
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Pamela H. Steele, Mike Kulis, A.W. Burks, Hugh A. Sampson, Stacie M. Jones, Ludmilla Bardina, Brian P. Vickery, and Jing Lin
- Subjects
biology ,Oral immunotherapy ,business.industry ,Immunology ,biology.protein ,Immunology and Allergy ,Medicine ,Immunoglobulin E ,business ,Isotype ,Epitope - Published
- 2010
- Full Text
- View/download PDF
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