B L Wright1,2, M Kulis3, K A Orgel1, A W Burks1, P Dawson4, A K Henning4, S M Jones5, R A Wood6, S H Sicherer7, R W Lindblad4, D Stablein4, D Y M Leung8, B P Vickery1, H A Sampson7. 1. University of North Carolina School of Medicine, Chapel Hill, NC, USA. 2. Duke University Medical Center, Durham, NC, USA. 3. University of North Carolina School of Medicine, Chapel Hill, NC, USA. mike.kulis@unc.edu. 4. The EMMES Corporation, Rockville, MD, USA. 5. University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock, AR, USA. 6. Johns Hopkins University School of Medicine, Baltimore, MD, USA. 7. Icahn School of Medicine at Mt. Sinai, New York, NY, USA. 8. National Jewish Health, Denver, CO, USA.
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 14placebo) 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.
RCT Entities:
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.
Authors: Andrew H Liu; Renee Jaramillo; Scott H Sicherer; Robert A Wood; S Allan Bock; A Wesley Burks; Mark Massing; Richard D Cohn; Darryl C Zeldin Journal: J Allergy Clin Immunol Date: 2010-10 Impact factor: 10.793
Authors: Scott H Sicherer; Robert A Wood; Brian P Vickery; Stacie M Jones; Andrew H Liu; David M Fleischer; Peter Dawson; Lloyd Mayer; A Wesley Burks; Alexander Grishin; Donald Stablein; Hugh A Sampson Journal: J Allergy Clin Immunol Date: 2014-02 Impact factor: 10.793
Authors: A Thyagarajan; S M Jones; A Calatroni; L Pons; M Kulis; C S Woo; M Kamalakannan; B P Vickery; A M Scurlock; A Wesley Burks; W G Shreffler Journal: Clin Exp Allergy Date: 2012-08 Impact factor: 5.018
Authors: Richard T Strait; Ashley Mahler; Simon Hogan; Marat Khodoun; Akira Shibuya; Fred D Finkelman Journal: J Allergy Clin Immunol Date: 2011-02-26 Impact factor: 10.793
Authors: Michael Kulis; Katie Saba; Edwin H Kim; J Andrew Bird; Nikolas Kamilaris; Brian P Vickery; Herman Staats; A Wesley Burks Journal: J Allergy Clin Immunol Date: 2012-01-10 Impact factor: 10.793
Authors: Justin M Skripak; Scott D Nash; Hannah Rowley; Nga H Brereton; Susan Oh; Robert G Hamilton; Elizabeth C Matsui; A Wesley Burks; Robert A Wood Journal: J Allergy Clin Immunol Date: 2008-10-25 Impact factor: 10.793
Authors: Willem van de Veen; Barbara Stanic; Görkem Yaman; Marcin Wawrzyniak; Stefan Söllner; Deniz G Akdis; Beate Rückert; Cezmi A Akdis; Mübeccel Akdis Journal: J Allergy Clin Immunol Date: 2013-02-26 Impact factor: 10.793
Authors: Stacie M Jones; Laurent Pons; Joseph L Roberts; Amy M Scurlock; Tamara T Perry; Mike Kulis; Wayne G Shreffler; Pamela Steele; Karen A Henry; Margaret Adair; James M Francis; Stephen Durham; Brian P Vickery; Xiaoping Zhong; A Wesley Burks Journal: J Allergy Clin Immunol Date: 2009-07-03 Impact factor: 10.793
Authors: P Xepapadaki; A Fiocchi; L Grabenhenrich; G Roberts; K E C Grimshaw; A Fiandor; J I Larco; S Sigurdardottir; M Clausen; N G Papadopoulos; L Dahdah; A Mackie; A B Sprikkelman; A A Schoemaker; R Dubakiene; I Butiene; M L Kowalski; K Zeman; S Gavrili; T Keil; K Beyer Journal: Allergy Date: 2015-12-22 Impact factor: 13.146
Authors: François Graham; Natacha Tardio; Louis Paradis; Anne Des Roches; Philippe Bégin Journal: Hum Vaccin Immunother Date: 2017-10-03 Impact factor: 3.452