Anna Nowak-Węgrzyn

Albany Medical College, Albany, NY, United States

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Publications (32)217.62 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: Decreased serum food-specific IgA antibodies have been associated with allergic disease in cross-sectional, case-control studies. The purpose of this study was to prospectively compare egg-white-(EW)-specific IgA and IgA2 levels between egg-allergic children and children tolerating egg. Seventeen egg-allergic children were followed prospectively. Total IgA, EW-specific IgA, and EW-specific IgA2 levels were measured in their sera with a sensitive ELISA. As negative controls were used children with no previous history of egg allergy. Egg-allergic children with or without concomitant milk allergy were evaluated as additional controls with measurement of casein-specific IgA. After 2.5 ± 0.9 yrs, nine out of the 17 allergic children became tolerant and eight remained allergic to baked egg. Baseline EW-specific IgA2 levels were significantly lower in the egg-allergic subjects (median 23.9 ng/ml) compared with the negative control subjects (99.4 ng/ml) and increased significantly by 28% over the study time period in eight out of the nine allergic children that became tolerant to baked egg. There was no significant change over time in EW-specific IgA in any of the study groups. Non-milk-allergic subjects with concomitant egg allergy had almost threefold higher casein-specific IgA levels than the milk- and egg-allergic subjects (p = 0.025). These results suggest a potential role for allergen-specific IgA2 antibodies in the induction of food tolerance. Furthermore, they support the hypothesis that immature or impaired production of allergen-specific IgA2 may be associated with the pathophysiology of food allergy, a defect that seems to be selective for the culprit allergen.
    Pediatric Allergy and Immunology 10/2013; · 3.38 Impact Factor
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    ABSTRACT: Children with food allergy have been shown to have increased small intestinal permeability (IP) following ingestion of the offending food as well as during elimination diets. We investigated IP in asymptomatic food allergic children during an elimination diet to identify clinical characteristics associated with altered IP. Urinary recovery ratios of lactulose and mannitol (L/M) were determined 5 h following ingestion of 7.5 g of lactulose and 2 g of mannitol in 131 cow's milk and egg allergic children. An L/M ratio of ≥0.025 was considered abnormal based upon previously established laboratory internal references. A chart review was conducted to assess the clinical characteristics of these patients. A total of 50 (38%) of the 131 children (median 6.7, range 4.8-8.9 yr; 66.2% male) with food allergy had elevated IP while asymptomatic on strict elimination diets. Age and height negatively correlated with IP. However, in the regression model analysis, abnormal IP was associated with shorter stature independently of age. Otherwise, food allergic patients with increased IP were comparable in gender, nutritional status, age of onset of food allergy, history of reactions, atopic diseases, and family history of food allergies to those with normal IP. Elevated IP was found in about one-third of asymptomatic food allergic children on elimination diets and was associated with shorter stature. Our results suggest that increased IP may be an intrinsic trait in a subset of food allergic children. However, large, prospective studies are necessary to determine the role of impaired intestinal barrier in food allergy.
    Pediatric Allergy and Immunology 08/2013; · 3.38 Impact Factor
  • Kirsi M. Järvinen, Anna Nowak-Węgrzyn
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    ABSTRACT: Food protein-induced enterocolitis syndrome (FPIES) is a non–IgE-mediated gastrointestinal food hypersensitivity that manifests as profuse, repetitive vomiting, often with diarrhea, leading to acute dehydration and lethargy or weight loss and failure to thrive if chronic. FPIES is elicited most commonly by milk and soy proteins; however, rice, oat, and other solid foods may also elicit FPIES. Certain FPIES features overlap with food protein-induced enteropathy and proctocolitis, whereas others overlap with anaphylaxis. FPIES is not well recognized among pediatricians and emergency department physicians; the affected children are often mismanaged as having acute viral gastrointestinal illness, sepsis, or surgical disease, delaying diagnosis of FPIES for many months. The aim of this review is to provide case-driven presentation of the features of FPIES. Although randomized clinical trials on management options are missing, the relevant current literature and authors' experience are reviewed in detail.
    The Journal of Allergy and Clinical Immunology: In Practice. 01/2013; 1(4):317–322.e4.
  • Stephanie A Leonard, Anna Nowak-Węgrzyn
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    ABSTRACT: PURPOSE OF REVIEW: To provide an overview of clinical manifestations, diagnosis and pathophysiology of food protein-induced enterocolitis syndrome (FPIES), an under-recognized and often misdiagnosed nonimmunoglobulin E-mediated food hypersensitivity. This review will highlight updates on natural history and clinical management. RECENT FINDINGS: The main developments in FPIES involve epidemiology, common presentation and variants thereof, and natural history. Improved understanding and recognition of FPIES have influenced changes in clinical management. SUMMARY: A large prospective population-based study reported cow's milk-FPIES cumulative incidence to be 0.34% by 1 year of age; immunoglobulin E-mediated cow's milk allergy was 0.5%. A case report has suggested that FPIES pathophysiology involves Th2 activation, and a shift away from Th2 signalling may be associated with resolution. Appreciation of the frequent incidence of multiple food-FPIES has influenced anticipatory guidance. Two case reports have described FPIES to food proteins in maternal breast milk. The threshold dose for FPIES reactivity may decrease with successive episodes. Reports from different populations indicate that children may outgrow FPIES sooner than previously thought.
    Current opinion in pediatrics 10/2012; · 2.01 Impact Factor
  • Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 09/2012; 109(3):221-2. · 3.45 Impact Factor
  • The Journal of allergy and clinical immunology 08/2012; · 12.05 Impact Factor
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    ABSTRACT: Baked egg is tolerated by a majority of egg-allergic children. To characterize immunologic changes associated with ingestion of baked egg and evaluate the role that baked egg diets play in the development of tolerance to regular egg. Egg-allergic subjects who tolerated baked egg challenge incorporated baked egg into their diet. Immunologic parameters were measured at follow-up visits. A comparison group strictly avoiding egg was used to evaluate the natural history of the development of tolerance. Of the 79 subjects in the intent-to-treat group followed for a median of 37.8 months, 89% now tolerate baked egg and 53% now tolerate regular egg. Of 23 initially baked egg-reactive subjects, 14 (61%) subsequently tolerated baked egg and 6 (26%) now tolerate regular egg. Within the initially baked egg-reactive group, subjects with persistent reactivity to baked egg had higher median baseline egg white (EW)-specific IgE levels (13.5 kU(A)/L) than those who subsequently tolerated baked egg (4.4 kU(A)/L; P= .04) and regular egg (3.1 kU(A)/L; P= .05). In subjects ingesting baked egg, EW-induced skin prick test wheal diameter and EW-, ovalbumin-, and ovomucoid-specific IgE levels decreased significantly, while ovalbumin- and ovomucoid-specific IgG(4) levels increased significantly. Subjects in the per-protocol group were 14.6 times more likely than subjects in the comparison group (P< .0001) to develop regular egg tolerance, and they developed tolerance earlier (median 50.0 vs 78.7 months; P< .0001). Initiation of a baked egg diet accelerates the development of regular egg tolerance compared with strict avoidance. Higher serum EW-specific IgE level is associated with persistent baked and regular egg reactivity, while initial baked egg reactivity is not.
    The Journal of allergy and clinical immunology 08/2012; 130(2):473-80.e1. · 12.05 Impact Factor
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    ABSTRACT: BACKGROUND: In our previous study about 75% of children with cow's milk allergy tolerated baked milk products, which improved their prognosis and quality of life. OBJECTIVE: We sought to identify biomarkers of varying degrees of clinical tolerance among a cohort of children with cow's milk allergy. METHODS: One hundred thirty-two subjects were initially classified as baked milk-reactive, baked milk-tolerant, or having "outgrown milk allergy" based on the results of oral food challenges. The baked milk-tolerant group was then divided into 3 groups based on the amount and degree of heat-denatured milk protein that they could tolerate. Serum was analyzed for allergen-specific IgE and IgG(4) levels, basophil reactivity was assessed in whole blood stimulated with serial 10-fold dilutions of milk protein, and skin prick tests (SPTs) were performed to commercial milk extract. Activated basophils were defined by using flow cytometry as CD63(bright)CD203c(+)CD123(+)HLA-DR(dim/-)CD41a(-)lineage(-). Data were analyzed by using the Jonckheere-Terpstra test. RESULTS: Significant differences across the 5 clinical groups were seen for median casein- and milk-specific IgE levels, casein-specific IgG(4) levels, and casein IgE/IgG(4) ratios; milk-specific to nonspecific basophil activation ratio, median basophil reactivity, and spontaneous basophil activation (CD203c expression after stimulation with RPMI); and milk SPT wheal diameters. Casein- and milk-specific IgE level, milk-specific basophil reactivity, and milk SPT wheal diameter are all significantly greater among patients with milk allergy who react to baked milk than among those who tolerate it. CONCLUSIONS: The majority of patients with milk allergy are able to tolerate some forms of baked milk in their diets. Different phenotypes of children with cow's milk allergy can be distinguished by casein- and milk-specific IgE levels, milk-specific basophil reactivity, and milk SPT mean wheal diameters. Spontaneous basophil activation is greater among patients with more severe clinical milk reactivity.
    The Journal of allergy and clinical immunology 07/2012; · 12.05 Impact Factor
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    ABSTRACT: A licensed inactivated MF59-adjuvanted seasonal influenza vaccine (Optaflu) produced in canine kidney cells (MDCK 33016-PF) contained no egg proteins and did not trigger degranulation in rat basophilic leukemia (RBL) cells passively sensitized with human anti-dog IgE, supporting its safe use in dog-allergic individuals. The cell-derived pandemic H1N1 influenza vaccine was also adjuvanted with the emulsion adjuvant MF59, and support for its similar safe use was sought. We sought to evaluate in vitro allergenicity of the MF59-adjuvanted cell-derived pandemic H1N1 influenza vaccine in subjects with dog allergy, with a mediator release assay. RBL-2H3 cells transfected with human Fcε receptor type 1 were sensitized with sera from adult dog-allergic subjects and stimulated with serial dilutions of pandemic H1N1 influenza vaccine and dog dander extract. β-N-hexosaminidase release (NHR) was used as a marker of RBL degranulation.. Median dog dander-specific IgE in 30 dog-allergic subjects was 27.7 kUA/L (range 10.1; > 100); and in 5 dog non-allergic subjects was < 0.35 kUA/L (UniCAP system). Median (range) maximum NHR in dog-allergic subjects was: pandemic H1N1 influenza vaccine 1.1% (0; 4.4) and dog dander 6.9% (0.7; 37.3), P < 0.001. In conclusion, MF59-adjuvanted pandemic H1N1 influenza vaccine produced in continuous canine kidney cells did not trigger degranulation in RBL cells passively sensitized with human anti-dog IgE, supporting its safe use in dog-allergic individuals.
    Human vaccines & immunotherapeutics. 07/2012; 8(7):863-5.
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    ABSTRACT: Children have increased prevalence of food allergy (FA) and eosinophilic gastrointestinal disease (EGID) following liver transplantation. The aim of this study was to identify related risk factors. Chart review of pediatric liver transplant (LT) recipients with de novo FA and/or EGID post-LT and non-allergic controls. We identified 30 (8.5%) children with FA and/or EGID among 352 pediatric LT recipients. Median age at transplant was 0.9 inter-quartile range (IQR 0.6-2.0) years. FA developed at a median 1.0 (IQR 0.5-8.2) yr post-LT and manifested with gastrointestinal symptoms (53%) or urticaria/angioedema (40%). Commonly avoided foods included milk (60%), egg (57%), and peanut (47%). Of the 15 children with FA who underwent endoscopy, 11 had eosinophilic infiltrates in multiple segments of the esophagus alone or in combination with other bowel segments. FA and EGID were linked to transplantation at a younger age (median, 0.9 vs. 5.5 yr), higher frequency of blood eosinophilia, and prior history of rhinitis and atopic dermatitis. Tacrolimus use and tacrolimus serum levels were similar between allergic subjects and controls. Findings suggest that exposure to tacrolimus alone post-LT is insufficient to initiate de novo allergic disease in LT recipients; rather, younger age and underlying predisposition to atopic disease may play larger roles.
    Clinical Transplantation 06/2012; 26(4):E365-71. · 1.63 Impact Factor
  • The Journal of allergy and clinical immunology 06/2012; 129(6):1682-4.e2. · 12.05 Impact Factor
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    ABSTRACT: Oral immunotherapy (OIT) is a promising treatment for food allergy. Studies are needed to elucidate mechanisms of clinical protection and to identify safer and potentially more efficacious methods for desensitizing patients to food allergens. We established a mouse model of OIT to determine how the dose or form of antigen may affect desensitization and to identify mechanisms of desensitization. Increasing doses of egg white or ovomucoid as OIT were administered orally to sensitized mice. The impact of OIT on anaphylaxis elicited by oral allergen challenge was determined. Allergen-specific antibody and cytokine responses and mast cell and basophil activation in response to OIT were measured. Gene expression in the small intestine was studied by microarray and real-time PCR. OIT resulted in desensitization but not tolerance of mice to the allergen. OIT did not result in desensitization of systemic effector cells, and protection was localized to the gastrointestinal tract. OIT was associated with significant changes in gene expression in the jejunum, including genes expressed by intestinal epithelial cells. Extensively heated ovomucoid that does not trigger anaphylaxis when given orally to sensitized mice was as efficacious as native ovomucoid in desensitizing mice. OIT results in clinical protection against food-induced anaphylaxis through a novel mechanism that is localized to the intestinal mucosa and is associated with significant changes in small intestinal gene expression. Extensively heating egg allergen decreases allergenicity and increases safety while still retaining the ability to induce effective desensitization.
    The Journal of allergy and clinical immunology 05/2012; 129(6):1579-1587.e1. · 12.05 Impact Factor
  • Faith Huang, Anna Nowak-Węgrzyn
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    ABSTRACT: The introduction of extensively heated milk and egg protein into the diet has been explored in recent years. Studies have suggested that a large subset of children who react to unheated milk or egg can tolerate extensively heated forms of these foods. Immunologic changes induced by a diet containing baked milk and egg are similar to changes that have been observed during oral immunotherapy trials. The baked milk and egg diet appears to accelerate the development of regular milk and egg tolerance when compared with strict avoidance. An oral challenge to extensively heated milk and egg into milk and egg allergic children's diets should be considered when appropriate. Oral food challenges are the most reliable means of establishing a diagnosis and should be undertaken under physician supervision.
    Current Opinion in Allergy and Clinical Immunology 04/2012; 12(3):283-92. · 3.40 Impact Factor
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    ABSTRACT: The role of specific IgG(4) antibodies in natural tolerance acquisition remains a matter of debate; the specific IgE/IgG(4) ratio might add value to the measurement of absolute amounts of IgE for assessing the ongoing status of egg reactivity. We sought to determine the significance of IgG(4) antibodies to ovalbumin (OVA) and ovomucoid (OVM) in egg-allergic children. One hundred seven egg-allergic children (mean age 6.9 years; range 1.6-18.6 years) were challenged to baked egg. The outcomes of the challenges were related to the level of specific IgE and IgG(4) to OVM and OVA, component IgE/IgG(4) ratios, and mediator release in a functional assay based on the rat basophil leukemia cell line. Baked egg-reactive children had significantly higher OVA and OVM ratios of IgE/IgG(4) and mediator release in the rat basophil leukemia-based assay than did tolerant children (P < .05 for both). The OVA- and OVM-specific IgE/IgG(4) ratios and mediator release were correlated. In the receiver operating characteristic analysis, the areas under the curve for a logistic regression model including specific IgE and IgG(4) to OVA and OVM were significantly greater compared with the areas under the curve for egg white-specific IgE and OVM-specific IgE. The balance between IgE and IgG(4) to OVA and OVM has functional consequences. A model that includes the interactions between IgE and IgG(4) to OVA and OVM accurately predicts reactivity to baked egg and warrants further investigation.
    The Journal of allergy and clinical immunology 03/2012; 129(3):739-47. · 12.05 Impact Factor
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    ABSTRACT: Anaphylaxis incidence is increasing. We sought to characterize anaphylaxis in children in an urban pediatric emergency department (PED). We performed a review of PED records for anaphylactic reactions over 5 years. We identified 213 anaphylactic reactions in 192 children (97 male patients): 6 were infants, 20 had multiple reactions, and the median age was 8 years (age range, 4 months to 18 years). Sixty-two reactions were coded as anaphylaxis; 151 additional reactions met the second symposium anaphylaxis criteria. There was no increase in incidence over 5 years. The triggers included the following: foods, 71%; unknown, 15%; drugs, 9%; and "other," 5%. Food was more likely to be a trigger in multiple PED visits (P = .03). Epinephrine was administered in 169 (79%) reactions; in 58 (27%) reactions epinephrine was administered before arrival in the PED. Patients with Medicaid were less likely to receive epinephrine before arrival in the PED (P < .001). Twenty-eight (14.6%) patients were hospitalized, 9 in the intensive care unit. For 13 (6%) of the reactions, 2 doses of epinephrine were administered; 69% of the patients treated with 2 doses of epinephrine were hospitalized compared with 12% of the patients treated with a single dose (P < .001). Administration of both epinephrine doses before arrival to the PED was associated with a lower rate of hospitalization compared with epinephrine administration in the PED (P = .05). Food is the main anaphylaxis trigger in the urban PED, although the International Classification of Diseases-ninth revision code for anaphylaxis is underused. Treatment with 2 doses of epinephrine is associated with a higher risk of hospitalization; epinephrine treatment before arrival to the PED is associated with a decreased risk. Children with Medicaid are less likely to receive epinephrine before arrival in the PED.
    The Journal of allergy and clinical immunology 01/2012; 129(1):162-8.e1-3. · 12.05 Impact Factor
  • Jay A Lieberman, Anna Nowak-Węgrzyn
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    ABSTRACT: The apparent increase in food allergy prevalence has led to a surge in the amount of clinical and basic science research dedicated to the field. At the current time, allergen avoidance remains the cornerstone of treatment; however, recent clinical trials investigating various forms of immunotherapy have opened doors to the possible future application of an active treatment strategy in everyday practice. In addition, improvements in molecular biology have allowed researchers to purify, clone, and modify allergens, thus laying the groundwork for research on vaccines using modified proteins of decreased allergenicity. Finally, various allergen-nonspecific immunomodulatory therapies are also being investigated as a means to alter the immune response to food allergens. With these emerging therapeutic strategies, it is hoped that practitioners will have options in caring for their food-allergic patients in the near future.
    Current Allergy and Asthma Reports 11/2011; 12(1):55-63. · 2.75 Impact Factor
  • Jean-Christoph Caubet, Anna Nowak-Węgrzyn
    The Journal of allergy and clinical immunology 08/2011; 128(6):1386-8. · 12.05 Impact Factor
  • Article: Reply.
    The Journal of allergy and clinical immunology 08/2011; 128(2):435. · 12.05 Impact Factor
  • Stephanie A Leonard, Anna Nowak-Węgrzyn
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    ABSTRACT: To review the clinical features, pathophysiology, and management of food protein-induced enterocolitis syndrome (FPIES) and to discuss new observations in epidemiology and natural history. PubMed searches were performed for articles published between 1978 and May 2011 using the keywords food-induced enterocolitis and FPIES. Articles were selected based on their relevance to the topic of this review. The newest developments in FPIES were defined by articles published in the past 3 years. FPIES is a non-IgE-mediated gastrointestinal food hypersensitivity thought to be cell-mediated, although the exact pathophysiologic mechanism requires further study. In a recent birth cohort, the incidence of cow's milk FPIES was 0.34% in the first year of life compared with 0.5% for IgE-mediated cow's milk allergy. FPIES typically presents before 6 months of age in formula-fed infants with repetitive emesis, diarrhea, dehydration, and lethargy 1 to 5 hours after ingesting the offending food. Four cases of FPIES in breastfed infants have recently been reported. The most common offending foods are cow's milk, soy, and rice. Diagnosis is based primarily on clinical history and, when unclear, physician-supervised oral food challenges. FPIES is usually outgrown by school age. Although management remains avoidance of the offending food, observations that natural history varies for different foods has redefined the timing of reintroduction. Early recognition of FPIES and removal of the offending food are imperative to prevent misdiagnosis and mismanagement of symptoms that may mimic other causes. Close follow-up is required to determine when foods may be added back into the diet.
    Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 08/2011; 107(2):95-101; quiz 101, 162. · 3.45 Impact Factor
  • Jennifer S Kim, Anna Nowak-Węgrzyn
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    ABSTRACT: No abstract available.
    International Archives of Allergy and Immunology 06/2011; 156(3):231-3. · 2.25 Impact Factor

Publication Stats

252 Citations
217.62 Total Impact Points

Institutions

  • 2013
    • Albany Medical College
      • Center for Immunology and Microbial Disease
      Albany, NY, United States
    • 424 General Military Hospital, Thessaloniki
      Saloníki, Central Macedonia, Greece
  • 2010–2013
    • Mount Sinai School of Medicine
      • Department of Pediatrics
      Manhattan, New York, United States
  • 2012
    • Rady Children's Hospital
      San Diego, California, United States