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Transient Peanut Allergy Following Solid Organ Transplant
AB256 Abstracts
832
Persisting Food Allergen Sensitization after Allogeneic Hematopoietic Stem Cell Transplantation for DOCK8 Deficiency Corinne Savides Happel, MD1, Kelly D. Stone, MD, PhD, FAAAAI2, Dennis D. Hickstein, MD3, Alexandra F. Freeman, MD4, Helen C. Su, MD, PhD1; 1NIH/NIAID, Laboratory of Host Defenses, Bethesda, MD, 2 NIH/NIAID, Laboratory of Allergic Diseases, Bethesda, MD, 3NIH/ NCI, Department of Experimental Transplantation and Immunology, Bethesda, MD, 4NIH/NIAID, Laboratory of Clinical Infectious Diseases, Bethesda, MD. RATIONALE: DOCK8 deficiency is a combined primary immunodeficiency commonly associated with eczema and clinical food allergy. Previous reports of hematopoietic stem cell transplantation for DOCK8 deficiency have described mixed clinical food allergy outcomes. The leading hypothesis explaining mixed outcomes is that mixed donor chimerism allows for food allergy persistence. METHODS: Among a cohort of 6 patients receiving hematopoietic stem cell transplantation with a reduced intensity myeloablative regimen at the National Institutes of Health, allergy-specific history revealed 2 patients with food allergy-induced anaphylaxis prior to transplantation. Skin prick testing was performed after transplant for relevant food allergens for these 2 patients. Food challenges were not performed. RESULTS: Skin prick testing performed 2 years after transplant for a 27year-old male with history of DOCK8 deficiency and peanut allergy was positive for peanut. Similarly, skin prick testing performed 6 months after transplant for a 10-year-old female with history of DOCK8 deficiency and egg, milk, wheat, and tree nut allergies was positive for milk, egg, wheat, and cashew. Peripheral donor chimerism was 100% in myeloid and lymphoid cells for both patients. CONCLUSIONS: These cases are the first demonstrating food allergen sensitization by skin prick testing in DOCK8 patients after hematopoietic stem cell transplantation, despite 100% donor chimerism in peripheral blood. Food allergy may not be cured by hematopoietic stem cell transplantation, even when full donor chimerism in peripheral blood is achieved.
833
TUESDAY
Transient Peanut Allergy Following Solid Organ Transplant Erin J. Klaffky, MD, PhD1, Carolyn R. Word, MD1, Christina Ortiz, MD2, Walter Oliveira2, Lisa J. Workman, BA3, Julia Wisniewski2; 1 University of Virginia, Charlottesville, VA, 2University of Virginia, 3Division of Asthma, Allergy and Immunology, University of Virginia Health System, Charlottesville, VA. RATIONALE: Food allergy acquisition following solid organ transplant is poorly understood; prior management of post-transplant reactions to foods has focused on avoidance. Here, we present a case report of transient peanut allergy in a patient who experienced anaphylaxis to peanut after liver transplant from a peanut allergic donor. METHODS: IgE directed against peanut and peanut components were quantified in both liver donor and recipient serum prior to transplant, at two weeks post-transplant following anaphylaxis and 3 months after liver transplantation. Skin prick tests were used to monitor sensitivity prior to food challenge. RESULTS: Total IgE and peanut-specific IgE were measured in the donor prior to transplant and in the recipient pre and post-transplant. Donor peanut IgE was 387kUA/L. Recipient pre-transplant IgE was 648 kUA/L with a peanut IgE of <0.35kUA/L. Anaphylaxis occurred at two weeks post- transplant, when total IgE was 146 kUA/L and peanut-specific IgE was 4.39kUA/L. At that time, previously negative (<0.1kUA/L) IgE to Ara h 1, h 2 and h 3 were noted to be positive with the values of 1.20, 1.43 and 0.39kUA/L, respectively. Repeat serum testing for peanut performed prior to food challenge was negative at 3 months with negative SPT within 6 months. CONCLUSIONS: Here we demonstrate the passive transfer of specific peanut component IgE from a deceased donor liver to a previously peanut tolerant recipient who presented with de novo peanut anaphylaxis. We
J ALLERGY CLIN IMMUNOL FEBRUARY 2015
proved the transient nature of this allergy by following serial SPT and IgE over 6 months followed by a successful negative food challenge.
834
Stratification of Health Risk Posed By Allergic Responses at Peanut Threshold Doses: A Pilot Study Stefano Luccioli, MD1, Jianmei Zhu, PhD1, David Mark Fleischer, MD2, Whitney Hiemstra, RN3, Edwin H. Kim, MD, MS4, Susan B. Leung, RN3, Robert W. Lindblad, MD5, Kim E. Mudd, RN, MSN, CCRP6, Rene Reames, RN3, Pamela H. Steele, MSN, CPNP, AE-C4, Hugh A. Sampson, MD7, Scott H. Sicherer, MD8, Brian P. Vickery, MD9, Ernest K. Kwegyir-Afful, PhD1; 1Center for Food Safety and Applied Nutrition, Food and Drug Administration, College Park, MD, 2Childrens Hospital Colorado, Aurora, CO, 3Department of Pediatrics, Division of AllergyImmunology, National Jewish Health, Denver, CO, 4University of North Carolina at Chapel Hill, Chapel Hill, NC, 5The EMMES Corporation, 6 Johns Hopkins University School of Medicine, Baltimore, MD, 7Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA, 8Icahn School of Medicine at Mount Sinai, New York, NY, 9 Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina, USA. RATIONALE: Stratifying the health risk posed by allergic responses at threshold doses has important value in food allergy risk assessment. METHODS: Peanut challenge data with both eliciting dose (ED) and symptom information were collected from published challenge studies and unpublished Consortium of Food Allergy Research (CoFAR) data. Symptoms were independently graded by a panel of 12 health professionals according to risk score [yes (Y) or no (N) to whether symptoms posed risk to human health] and severity score (1 to 5). Threshold distributions of cumulative EDs for health risk consensus groups (defined _ 7/12 reviewers reporting either a Y or N risk score) were modeled by as > interval censored analysis to assess intergroup differences. RESULTS: 302 ED symptom data points from 18 different studies were identified and scored. Although lack of scoring consistency was noted between reviewers, symptoms associated with consensus Y risk (N5104; 34% of total) had mean severity score, 3.37 +/- 0.57, significantly higher than consensus N risk (N5167) score, 1.74 +/- 0.43, p<0.001. 31 data points with no consensus (6 Y/ N) were excluded from analysis. Applying this consensus grading approach to threshold data, ED01/ED05/ED50 values for consensus N risk (.0003/.02/22 mg) were significantly lower than those for consensus Y risk (.01/.4/86 mg; Weibull model; p<.0001). CONCLUSIONS: Based on health professional consensus, Y grading of ED symptoms posing risk to human health had significantly higher mean severity scores and was associated with higher peanut threshold doses. Refinement of this grading mechanism is ongoing as a tool to stratify threshold health risk.
832
Persisting Food Allergen Sensitization after Allogeneic Hematopoietic Stem Cell Transplantation for DOCK8 Deficiency Corinne Savides Happel, MD1, Kelly D. Stone, MD, PhD, FAAAAI2, Dennis D. Hickstein, MD3, Alexandra F. Freeman, MD4, Helen C. Su, MD, PhD1; 1NIH/NIAID, Laboratory of Host Defenses, Bethesda, MD, 2 NIH/NIAID, Laboratory of Allergic Diseases, Bethesda, MD, 3NIH/ NCI, Department of Experimental Transplantation and Immunology, Bethesda, MD, 4NIH/NIAID, Laboratory of Clinical Infectious Diseases, Bethesda, MD. RATIONALE: DOCK8 deficiency is a combined primary immunodeficiency commonly associated with eczema and clinical food allergy. Previous reports of hematopoietic stem cell transplantation for DOCK8 deficiency have described mixed clinical food allergy outcomes. The leading hypothesis explaining mixed outcomes is that mixed donor chimerism allows for food allergy persistence. METHODS: Among a cohort of 6 patients receiving hematopoietic stem cell transplantation with a reduced intensity myeloablative regimen at the National Institutes of Health, allergy-specific history revealed 2 patients with food allergy-induced anaphylaxis prior to transplantation. Skin prick testing was performed after transplant for relevant food allergens for these 2 patients. Food challenges were not performed. RESULTS: Skin prick testing performed 2 years after transplant for a 27year-old male with history of DOCK8 deficiency and peanut allergy was positive for peanut. Similarly, skin prick testing performed 6 months after transplant for a 10-year-old female with history of DOCK8 deficiency and egg, milk, wheat, and tree nut allergies was positive for milk, egg, wheat, and cashew. Peripheral donor chimerism was 100% in myeloid and lymphoid cells for both patients. CONCLUSIONS: These cases are the first demonstrating food allergen sensitization by skin prick testing in DOCK8 patients after hematopoietic stem cell transplantation, despite 100% donor chimerism in peripheral blood. Food allergy may not be cured by hematopoietic stem cell transplantation, even when full donor chimerism in peripheral blood is achieved.
833
TUESDAY
Transient Peanut Allergy Following Solid Organ Transplant Erin J. Klaffky, MD, PhD1, Carolyn R. Word, MD1, Christina Ortiz, MD2, Walter Oliveira2, Lisa J. Workman, BA3, Julia Wisniewski2; 1 University of Virginia, Charlottesville, VA, 2University of Virginia, 3Division of Asthma, Allergy and Immunology, University of Virginia Health System, Charlottesville, VA. RATIONALE: Food allergy acquisition following solid organ transplant is poorly understood; prior management of post-transplant reactions to foods has focused on avoidance. Here, we present a case report of transient peanut allergy in a patient who experienced anaphylaxis to peanut after liver transplant from a peanut allergic donor. METHODS: IgE directed against peanut and peanut components were quantified in both liver donor and recipient serum prior to transplant, at two weeks post-transplant following anaphylaxis and 3 months after liver transplantation. Skin prick tests were used to monitor sensitivity prior to food challenge. RESULTS: Total IgE and peanut-specific IgE were measured in the donor prior to transplant and in the recipient pre and post-transplant. Donor peanut IgE was 387kUA/L. Recipient pre-transplant IgE was 648 kUA/L with a peanut IgE of <0.35kUA/L. Anaphylaxis occurred at two weeks post- transplant, when total IgE was 146 kUA/L and peanut-specific IgE was 4.39kUA/L. At that time, previously negative (<0.1kUA/L) IgE to Ara h 1, h 2 and h 3 were noted to be positive with the values of 1.20, 1.43 and 0.39kUA/L, respectively. Repeat serum testing for peanut performed prior to food challenge was negative at 3 months with negative SPT within 6 months. CONCLUSIONS: Here we demonstrate the passive transfer of specific peanut component IgE from a deceased donor liver to a previously peanut tolerant recipient who presented with de novo peanut anaphylaxis. We
J ALLERGY CLIN IMMUNOL FEBRUARY 2015
proved the transient nature of this allergy by following serial SPT and IgE over 6 months followed by a successful negative food challenge.
834
Stratification of Health Risk Posed By Allergic Responses at Peanut Threshold Doses: A Pilot Study Stefano Luccioli, MD1, Jianmei Zhu, PhD1, David Mark Fleischer, MD2, Whitney Hiemstra, RN3, Edwin H. Kim, MD, MS4, Susan B. Leung, RN3, Robert W. Lindblad, MD5, Kim E. Mudd, RN, MSN, CCRP6, Rene Reames, RN3, Pamela H. Steele, MSN, CPNP, AE-C4, Hugh A. Sampson, MD7, Scott H. Sicherer, MD8, Brian P. Vickery, MD9, Ernest K. Kwegyir-Afful, PhD1; 1Center for Food Safety and Applied Nutrition, Food and Drug Administration, College Park, MD, 2Childrens Hospital Colorado, Aurora, CO, 3Department of Pediatrics, Division of AllergyImmunology, National Jewish Health, Denver, CO, 4University of North Carolina at Chapel Hill, Chapel Hill, NC, 5The EMMES Corporation, 6 Johns Hopkins University School of Medicine, Baltimore, MD, 7Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA, 8Icahn School of Medicine at Mount Sinai, New York, NY, 9 Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina, USA. RATIONALE: Stratifying the health risk posed by allergic responses at threshold doses has important value in food allergy risk assessment. METHODS: Peanut challenge data with both eliciting dose (ED) and symptom information were collected from published challenge studies and unpublished Consortium of Food Allergy Research (CoFAR) data. Symptoms were independently graded by a panel of 12 health professionals according to risk score [yes (Y) or no (N) to whether symptoms posed risk to human health] and severity score (1 to 5). Threshold distributions of cumulative EDs for health risk consensus groups (defined _ 7/12 reviewers reporting either a Y or N risk score) were modeled by as > interval censored analysis to assess intergroup differences. RESULTS: 302 ED symptom data points from 18 different studies were identified and scored. Although lack of scoring consistency was noted between reviewers, symptoms associated with consensus Y risk (N5104; 34% of total) had mean severity score, 3.37 +/- 0.57, significantly higher than consensus N risk (N5167) score, 1.74 +/- 0.43, p<0.001. 31 data points with no consensus (6 Y/ N) were excluded from analysis. Applying this consensus grading approach to threshold data, ED01/ED05/ED50 values for consensus N risk (.0003/.02/22 mg) were significantly lower than those for consensus Y risk (.01/.4/86 mg; Weibull model; p<.0001). CONCLUSIONS: Based on health professional consensus, Y grading of ED symptoms posing risk to human health had significantly higher mean severity scores and was associated with higher peanut threshold doses. Refinement of this grading mechanism is ongoing as a tool to stratify threshold health risk.