H. A. Sampson

Icahn School of Medicine at Mount Sinai, Manhattan, New York, United States

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Publications (350)3213 Total impact

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    ABSTRACT: Background Heating destroys many conformational epitopes and reduces allergenicity of some foods. IgE-epitope binding has been shown to be different amongst patients who outgrew their cow milk or hen's egg allergy and those who did not. A significant proportion of milk or egg allergic children are tolerant to these foods in their baked forms. We sought to explore the effects of heating on milk and egg proteins and to evaluate for differences in immunolabeling amongst children with regards to reactivity to heated milk or egg.Methods Sera from participants in clinical dietary intervention trials were utilized. Milk and egg samples were variably heated and prepared (at times within a wheat matrix). Sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE), protein transfer, and Western blot were completed.ResultsSera from 20 milk- and 24 egg-allergic children were utilized. Gel electrophoresis showed strongly staining casein bands that persisted for up to 60 minutes of heating. In contrast, β-lactoglobulin and α-lactalbumin bands became progressively weaker with increasing heating times, with no detectable β-lactoglobulin after 15-20 minutes of heating. The ovalbumin band became progressively weaker, whereas ovomucoid remained stable after 25 minutes of heating. Immunolabeling revealed that all heated milk-reactive children possessed IgE antibodies that bound the casein fraction regardless of heating time. Presence of wheat during heating resulted in decreased IgE antibody binding to milk and egg white proteins.Conclusion Heating has a different effect on whey and caseins in cow's milk and ovalbumin and ovomucoid in hen's egg white. The effect of heat on protein allergenicity is affected by the temperature and duration, along with the presence of wheat.This article is protected by copyright. All rights reserved.
    Pediatric Allergy and Immunology 09/2014; DOI:10.1111/pai.12283 · 3.86 Impact Factor
  • Hugh A Sampson
    Pediatric Allergy and Immunology 02/2014; 25(1):25-6. DOI:10.1111/pai.12202 · 3.86 Impact Factor
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    ABSTRACT: In Press
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    ABSTRACT: Molecular-based allergy (MA) diagnostics is an approach used to map the allergen sensitization of a patient at a molecular level, using purified natural or recombinant allergenic molecules (allergen components) instead of allergen extracts. Since its introduction, MA diagnostics has increasingly entered routine care, with currently more than 130 allergenic molecules commercially available for in vitro specific IgE (sIgE) testing.MA diagnostics allows for an increased accuracy in allergy diagnosis and prognosis and plays an important role in three key aspects of allergy diagnosis: (1) resolving genuine versus cross-reactive sensitization in poly-sensitized patients, thereby improving the understanding of triggering allergens; (2) assessing, in selected cases, the risk of severe, systemic versus mild, local reactions in food allergy, thereby reducing unnecessary anxiety for the patient and the need for food challenge testing; and (3) identifying patients and triggering allergens for specific immunotherapy (SIT).Singleplex and multiplex measurement platforms are available for MA diagnostics. The Immuno-Solid phase Allergen Chip (ISAC) is the most comprehensive platform currently available, which involves a biochip technology to measure sIgE antibodies against more than one hundred allergenic molecules in a single assay. As the field of MA diagnostics advances, future work needs to focus on large-scale, population-based studies involving practical applications, elucidation and expansion of additional allergenic molecules, and support for appropriate test interpretation. With the rapidly expanding evidence-base for MA diagnosis, there is a need for allergists to keep abreast of the latest information. The aim of this consensus document is to provide a practical guide for the indications, determination, and interpretation of MA diagnostics for clinicians trained in allergology.
    World Allergy Organization Journal 10/2013; 6(1):17. DOI:10.1186/1939-4551-6-17
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    ABSTRACT: BACKGROUND: Immunotherapy for peanut allergy may be limited by the risk of adverse reactions. OBJECTIVE: To investigate the safety and immunologic effects of a vaccine containing modified peanut proteins. METHODS: This was a phase 1 trial of EMP-123, a rectally administered suspension of recombinant Ara h 1, Ara h 2, and Ara h 3, modified by amino acid substitutions at major IgE-binding epitopes, encapsulated in heat/phenol-killed E. coli. Five healthy adults were treated with 4 weekly escalating doses after which 10 peanut-allergic adults received weekly dose escalations over 10 weeks from 10 mcg to 3063 mcg, followed by three biweekly doses of 3063 mcg. RESULTS: There were no significant adverse effects in the healthy volunteers. Of the 10 peanut-allergic subjects [4 with intermittent asthma, median peanut IgE 33.3 kUA /l (7.2-120.2), and median peanut skin prick test wheal 11.3 mm (6.5-18)]; four experienced no symptoms; one had mild rectal symptoms; and the remaining five experienced adverse reactions preventing completion of dosing. Two were categorized as mild, but the remaining three were more severe, including one moderate reaction and two anaphylactic reactions. Baseline peanut IgE was significantly higher in the five reactive subjects (median 82.4 vs 17.2 kUA /l, P = 0.032), as was baseline anti-Ara h 2 IgE (43.3 versus 8.3, P = 0.036). Peanut skin test titration and basophil activation (at a single dilution) were significantly reduced after treatment, but no significant changes were detected for total IgE, peanut IgE, or peanut IgG4. CONCLUSIONS: Rectal administration of EMP-123 resulted in frequent adverse reactions, including severe allergic reactions in 20%.
    Allergy 04/2013; DOI:10.1111/all.12158 · 6.00 Impact Factor
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    ABSTRACT: Despite the frequency and severity of peanut allergy, the only approved treatment is strict avoidance. Different types of immunotherapy with crude peanut extract are not universally effective and have been associated with relatively high adverse reaction rates. We sought to determine whether in silico predictive algorithms were useful in identifying candidate peptides for an Ara h 2 peptide-based vaccine using peanut-allergic patients' peripheral blood mononuclear cells (PBMCs) in vitro. A human leucocyte antigen (HLA) distribution analysis was also performed. Major histocompatibility complex (MHC)-class II-binding peptides were predicted using NetMHCIIpan-2.0 and NetMHCII-2.2 algorithms. PBMCs from 80 peanut-allergic patients were stimulated with overlapping 20-mer Ara h 2 peptides. Cell supernatant cytokine profiles were evaluated by multiplex assays. HLA-DRB1* and HLA-DQB1* typing were performed. Four regions of overlapping sequences induced PBMC proliferation and predominant Th2 cytokine production. HLA genotyping showed 30 different DRB1* allele specificities and eight DQ serological specificities. The in silico analysis revealed similar relevant regions and predicted identical or similar core 9-mer epitopes to those identified in vitro. If relevant peptides, as determined by either in vitro or in silico analysis (15 peptides and 9 core epitopes respectively), were used in a peptide-based vaccine, they would cover virtually all subjects in the cohort studied. Four dominant regions in Ara h 2 have been identified, containing sequences that could serve as potential candidates for peptide-based immunotherapy. MHC-class II-based T cell epitope prediction algorithms for HLA-DR and -DQ loci accurately predicted Ara h 2 T cell epitopes in peanut-allergic subjects, suggesting their potential utility in a peptide-based vaccine design for food allergy.
    Clinical & Experimental Allergy 01/2013; 43(1):116-27. DOI:10.1111/cea.12014 · 4.32 Impact Factor
  • Journal of Allergy and Clinical Immunology 02/2012; 129(2):AB174. DOI:10.1016/j.jaci.2011.12.214 · 11.25 Impact Factor
  • Journal of Allergy and Clinical Immunology 02/2012; 129(2):AB22. DOI:10.1016/j.jaci.2011.12.943 · 11.25 Impact Factor
  • Jean-Christoph Caubet, Hugh A Sampson
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    ABSTRACT: Food allergy affects approximately 1% to 10.8% of the general population, and its prevalence seems to be increasing. An accurate diagnosis is particularly important because a misdiagnosis could lead to life-threatening reactions or to unnecessary restrictive diets. However, allergy tests currently used in clinical practice have limited accuracy, and an oral food challenge, considered as the gold standard, is often required to confirm or exclude a food allergy. This article reviews several promising novel approaches for the diagnosis of food allergy, such as new molecular diagnostic technologies and functional assays, along with their potential clinical applications.
    Immunology and allergy clinics of North America 02/2012; 32(1):97-109. DOI:10.1016/j.iac.2011.11.002 · 2.22 Impact Factor
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    Journal of Allergy and Clinical Immunology 02/2012; 129(2):AB21. DOI:10.1016/j.jaci.2011.12.942 · 11.25 Impact Factor
  • Journal of Allergy and Clinical Immunology 02/2012; 129(2):AB21. DOI:10.1016/j.jaci.2011.12.939 · 11.25 Impact Factor
  • Journal of Allergy and Clinical Immunology 02/2012; 129(2):AB13. DOI:10.1016/j.jaci.2011.12.911 · 11.25 Impact Factor
  • Journal of Allergy and Clinical Immunology 02/2012; 129(2):AB184. DOI:10.1016/j.jaci.2011.12.253 · 11.25 Impact Factor
  • Journal of Allergy and Clinical Immunology 02/2012; 129(2):AB20. DOI:10.1016/j.jaci.2011.12.938 · 11.25 Impact Factor
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    ABSTRACT: Shrimp is a frequent cause of severe allergic reactions world-wide. Due to issues such as cross-reactivity, diagnosis of shrimp allergy is still inaccurate, requiring the need for double-blind, placebo-controlled food challenges (DBPCFC). A better understanding of the relationship between laboratory findings and clinical reactivity is needed. To determine whether sensitization to certain shrimp allergens or recognition of particular IgE epitopes of those allergens are good biomarkers of clinical reactivity to shrimp. Thirty-seven consecutive patients were selected with clinical histories of shrimp allergy. Skin prick test, specific IgE determinations, DBPCFC and immunoblot assays to shrimp extract were performed. IgE binding to synthetic overlapping peptides representing the sequence of the four allergens from the Pacific white shrimp (Litopenaeus vannamei) identified to date (Lit v1, Lit v2, Lit v3 and Lit v4) was analysed. Of 37 (46%) patients, 17 had a positive challenge to shrimp (11 children and 6 adults). By microarray, patients with positive challenges showed more intense binding to shrimp peptides than those with negative challenges. Statistically significant differences in terms of the frequency and intensity of IgE binding to some epitopes were observed between the two groups. Diagnostic efficiency was higher for individual epitopes than for proteins. Particularly, efficiency was highest for certain Lit v 1 and Lit v 2 epitopes, followed by Lit v 3 and Lit v 4 epitopes. Patients with positive shrimp challenges present in general more intense and diverse epitope recognition to all four shrimp allergens. IgE antibodies to these shrimp epitopes could be used as biomarkers for prediction of clinical reactivity in subjects with sensitization to shrimp. Patients with positive shrimp challenges show more intense sensitization and more diverse epitope recognition. Several IgE-binding shrimp epitopes could be used as biomarkers for predicting clinical reactivity in subjects with sensitization to shrimp.
    Clinical & Experimental Allergy 12/2011; 42(2):293-304. DOI:10.1111/j.1365-2222.2011.03920.x · 4.32 Impact Factor
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    ABSTRACT: Previous studies have indicated that specific molecular properties of proteins may determine their allergenicity. Allergen interaction with epithelia as the first contact site could be decisive for a resulting immune response. We investigate here for the major peanut allergen Ara h 2 whether thermal processing results in structural changes which may impact the protein's molecular interactions with enterocytes, subsequent cellular signalling response, and immunogenicity.Ara h 2 was heat processed and analyzed in terms of patient IgE binding, structural alterations, interaction with human enterocytes and associated signalling as well as immunogenicity in a food allergy mouse model.Heating of Ara h 2 led to significantly enhanced binding to Caco-2/TC7 human intestinal epithelial cells. Structural analyses indicated that heating caused persistent structural changes and led to the formation of Ara h 2 oligomers in solution. Heated protein exhibited a significantly higher immunogenic potential in vivo as determined by IgG and IgE serum antibody levels as well as IL-2 and IL-6 release by splenocytes. In human Caco-2/TC7 cells, Ara h 2 incubation led to a response in immune- and stress signalling related pathway components at the RNA level, whereas heated allergen induced a stress-response only.We suggest from this peanut allergen example that food processing may change the molecular immunogenicity and modulate the interaction capacity of food allergens with the intestinal epithelium. Increased binding behaviour to enterocytes and initiation of signalling pathways could trigger the epimmunome and influence the sensitization capacity of food proteins.
    The Open Allergy Journal 12/2011; 4:24-34. DOI:10.2174/1874838401104010024
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    ABSTRACT: Occasionally, exclusively breastfed infants with cow's milk allergy (CMA) remain symptomatic despite strict maternal milk avoidance. To determine whether or not persistence of symptoms could be due to sensitization against endogenous human milk proteins with a high degree of similarity to bovine allergens. Ten peptides representing known bovine milk IgE-binding epitopes [α-lactalbumin (ALA), β- and κ-casein] and the corresponding, highly homologous human milk peptides were labelled with sera from 15 breastfed infants with CMA, aged 3 weeks to 12 months, and peptide (epitope)-specific IgE antibodies were assessed. Nine of the 15 breastfed infants became asymptomatic during strict maternal avoidance of milk and other major food allergens; six infants remained symptomatic until weaned. Ten older children, aged 5-15 years, with CMA were also assessed. The functional capacity of specific IgE antibodies was assessed by measuring β-hexosaminidase release from rat basophilic leukaemia cells passively sensitized and stimulated with human and bovine ALA. A minimum of one human milk peptide was recognized by IgE antibodies from 9 of 15 (60%) milk-allergic infants, and the majority of older children with CMA. Genuine sensitization to human milk peptides in the absence of IgE to bovine milk was occasionally seen. There was a trend towards specific IgE being detected to more human milk peptides in those infants who did not respond to the maternal milk elimination diet than in those who did (P = 0.099). Functional IgE antibody to human ALA was only detected in infants not responding to the maternal diet. Endogenous human milk epitopes are recognized by specific IgE from the majority of infants and children with CMA. Such autoreactive, human milk-specific IgE antibodies appear to have functional properties in vitro. Their role in provoking allergic symptoms in infants exclusively breastfed by mothers strictly avoiding dietary milk remains unclear.
    Clinical & Experimental Allergy 09/2011; 42(2):238-47. DOI:10.1111/j.1365-2222.2011.03864.x · 4.32 Impact Factor
  • Brian P Vickery, A Wesley Burks, Hugh A Sampson
    New England Journal of Medicine 09/2011; 365(9):867-8; author reply 868. DOI:10.1056/NEJMc1106934#SA1 · 54.42 Impact Factor
  • Journal of Allergy and Clinical Immunology 02/2011; 127(2). DOI:10.1016/j.jaci.2010.12.112 · 11.25 Impact Factor
  • M. Masilamani, J. Wei, H. A. Sampson
    Journal of Allergy and Clinical Immunology 02/2011; 127(2). DOI:10.1016/j.jaci.2010.12.373 · 11.25 Impact Factor

Publication Stats

17k Citations
3,213.00 Total Impact Points

Institutions

  • 1998–2014
    • Icahn School of Medicine at Mount Sinai
      • • Department of Pediatrics
      • • Division of Allergy and Immunology
      Manhattan, New York, United States
    • University of Geneva
      • Division of Paediatrics
      Genève, GE, Switzerland
  • 2013
    • Università degli Studi di Genova
      Genova, Liguria, Italy
  • 2011
    • Ain Shams University
      Al Qāhirah, Muḩāfaz̧at al Qāhirah, Egypt
  • 1998–2011
    • Mount Sinai Medical Center
      New York, New York, United States
  • 1988–2010
    • Johns Hopkins University
      • Department of Pediatrics
      Baltimore, Maryland, United States
    • University of Arkansas
      Fayetteville, Arkansas, United States
  • 2009
    • University of Portsmouth
      Portsmouth, England, United Kingdom
  • 2003–2009
    • Gracie Square Hospital, New York, NY
      New York, New York, United States
    • University of Cincinnati
      Cincinnati, Ohio, United States
  • 1998–2009
    • Mount Sinai Hospital
      New York City, New York, United States
  • 1991–2008
    • University of Arkansas at Little Rock
      Little Rock, Arkansas, United States
  • 2007
    • University of Texas Medical Branch at Galveston
      • Department of Pediatrics
      Galveston, Texas, United States
    • Sinai Hospital
      New York, New York, United States
    • Finnish Institute of Occupational Health
      Helsinki, Southern Finland Province, Finland
  • 2006
    • University of Alberta
      Edmonton, Alberta, Canada
    • Harvard University
      Cambridge, Massachusetts, United States
    • Instituto de Salud Carlos III
      Madrid, Madrid, Spain
    • Duke University
      Durham, North Carolina, United States
  • 2005
    • University of Manitoba
      Winnipeg, Manitoba, Canada
    • University of Southampton
      Southampton, England, United Kingdom
  • 1998–2000
    • University of Arkansas for Medical Sciences
      • • Department of Pediatrics
      • • Department of Biochemistry and Molecular Biology
      Little Rock, AR, United States
  • 1988–1999
    • Arkansas Children's Hospital
      Little Rock, Arkansas, United States
  • 1988–1996
    • Johns Hopkins Medicine
      • • Department of Medicine
      • • Department of Pediatrics
      Baltimore, Maryland, United States
  • 1982–1985
    • Duke University Medical Center
      • Department of Pediatrics
      Durham, North Carolina, United States