PMID- 38469303
OWN - NLM
STAT- MEDLINE
DCOM- 20240313
LR  - 20240412
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 15
DP  - 2024
TI  - Gene-edited pigs: a translational model for human food allergy against alpha-Gal 
      and anaphylaxis.
PG  - 1358178
LID - 10.3389/fimmu.2024.1358178 [doi]
LID - 1358178
AB  - The prevalence of food allergy is rising and is estimated to approach 10%. Red 
      meat allergy is the first known food allergy elicited by immunoglobulin E (IgE) 
      antibodies recognizing a carbohydrate. Due to the loss of function of the 
      alpha-1,3-galactosyltransferase (GGTA1) gene in humans, the disaccharide 
      galactose-alpha-1,3-galactose (alpha-Gal) cannot be synthesized and therefore became 
      immunogenic. IgE sensitization is elicited through the skin by repetitive tick 
      bites transmitting alpha-Gal. The underlying mechanisms regarding innate and adaptive 
      immune cell activation, including the B-cell isotype switch to IgE, are poorly 
      understood, requiring further research and physiologically relevant animal 
      models. Here, we describe a new animal model of red meat allergy using 
      percutaneous alpha-Gal sensitization of gene-edited GGTA1-deficient pigs. Total and 
      alpha-Gal-specific IgG, IgG1, IgG2, IgG4, and IgE levels were tracked. Further key 
      factors associated with allergic skin inflammation, type 2 immunity, and allergy 
      development were measured in PBMCs and skin samples. Significant increases in 
      alpha-Gal-specific IgG1 and IgE levels indicated successful sensitization to the 
      allergen alpha-Gal. Intracutaneous sensitizations with alpha-Gal recruited lymphocytes to 
      the skin, including elevated numbers of T helper 2 (Th2) cells. Finally, 
      alpha-Gal-sensitized pigs not only recognized alpha-Gal as non-self-antigen following 
      alpha-Gal exposure through the skin but also developed anaphylaxis upon antigen 
      challenge. Based on the similarities between the porcine and human skin, this new 
      large animal model for alpha-Gal allergy should help to unveil the consecutive steps 
      of cutaneous sensitization and aid the development of prophylactic and treatment 
      interventions.
CI  - Copyright (c) 2024 Wang, Hils, Fischer, Wolbing, Biedermann, Schnieke and Fischer.
FAU - Wang, Ying
AU  - Wang Y
AD  - Chair of Livestock Biotechnology, School of Life Sciences Weihenstephan, 
      Technical University of Munich, Freising, Germany.
FAU - Hils, Miriam
AU  - Hils M
AD  - Department of Dermatology and Allergy Biederstein, School of Medicine, Technical 
      University of Munich, Munich, Germany.
FAU - Fischer, Andrea
AU  - Fischer A
AD  - Chair of Livestock Biotechnology, School of Life Sciences Weihenstephan, 
      Technical University of Munich, Freising, Germany.
FAU - Wolbing, Florian
AU  - Wolbing F
AD  - Department of Dermatology and Allergy Biederstein, School of Medicine, Technical 
      University of Munich, Munich, Germany.
FAU - Biedermann, Tilo
AU  - Biedermann T
AD  - Department of Dermatology and Allergy Biederstein, School of Medicine, Technical 
      University of Munich, Munich, Germany.
FAU - Schnieke, Angelika
AU  - Schnieke A
AD  - Chair of Livestock Biotechnology, School of Life Sciences Weihenstephan, 
      Technical University of Munich, Freising, Germany.
FAU - Fischer, Konrad
AU  - Fischer K
AD  - Chair of Livestock Biotechnology, School of Life Sciences Weihenstephan, 
      Technical University of Munich, Freising, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20240226
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - X2RN3Q8DNE (Galactose)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 0 (Immunoglobulin G)
RN  - red meat allergy
SB  - IM
MH  - Humans
MH  - Animals
MH  - Swine
MH  - *Anaphylaxis
MH  - Galactose
MH  - Gene Editing
MH  - *Food Hypersensitivity
MH  - Immunoglobulin E
MH  - Immunoglobulin G
PMC - PMC10925645
OTO - NOTNLM
OT  - anaphylaxis to alpha-Gal
OT  - intracutaneous sensitization
OT  - red meat allergy
OT  - translational pig model
OT  - alpha-Gal allergy
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2024/03/12 06:43
MHDA- 2024/03/13 06:46
PMCR- 2024/01/01
CRDT- 2024/03/12 03:54
PHST- 2023/12/19 00:00 [received]
PHST- 2024/02/06 00:00 [accepted]
PHST- 2024/03/13 06:46 [medline]
PHST- 2024/03/12 06:43 [pubmed]
PHST- 2024/03/12 03:54 [entrez]
PHST- 2024/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2024.1358178 [doi]
PST - epublish
SO  - Front Immunol. 2024 Feb 26;15:1358178. doi: 10.3389/fimmu.2024.1358178. 
      eCollection 2024.