T and B Lymphocyte Transcriptional States Differentiate between Sensitized and Unsensitized Individuals in Alpha-Gal Syndrome

Abstract

The mechanisms of pathogenesis driving alpha-gal syndrome (AGS) are not fully understood. Differences in immune gene expression between AGS individuals and non-allergic controls may illuminate molecular pathways and targets critical for AGS development. We performed immune expression profiling with RNA from the peripheral blood mononuclear cells (PBMCs) of seven controls, 15 AGS participants, and two participants sensitized but not allergic to alpha-gal using the NanoString nCounter PanCancer immune profiling panel, which includes 770 genes from 14 different cell types. The top differentially expressed genes (DEG) between AGS subjects and controls included transcription factors regulating immune gene expression, such as the NFκB pathway (NFKBIA, NFKB2, REL), antigen presentation molecules, type 2/allergic immune responses, itch, and allergic dermatitis. The differential expression of genes linked to T and B cell function was also identified, including transcription factor BCL-6, markers of antigen experience (CD44) and memory (CD27), chemokine receptors (CXCR3, CXCR6), and regulators of B-cell proliferation, cell cycle entry and immunoglobulin production (CD70). The PBMCs from AGS subjects also had increased TNF and IFN-gamma mRNA expression compared to controls. AGS is associated with a distinct gene expression profile in circulating PBMCs. DEGs related to antigen presentation, antigen-experienced T-cells, and type 2 immune responses may promote the development of alpha-gal specific IgE and the maintenance of AGS.

Where’s the Beef? Understanding Allergic Responses to Red Meat in Alpha-Gal Syndrome

“…In addition, we recently showed that the transcriptional immune profiles in circulating PBMCs from alpha-galsensitized human subjects were distinct from controls without detectable alpha-galsIgE. There was increased expression of genes associated with Ag presentation, MHC-II surface expression, and cytokines and chemokines associated with itch and allergic dermatitis, including IL-13RA, which encodes the receptor for the Th2 cytokine IL-13 (19). These findings suggest that the generation of alpha-galsIgE may depend in part on MHC-IImediated Ag presentation to CD4 1 Th2 cells, although to date, this has not been formally demonstrated.…”

“…In $20% of AGS cases, the clinical phenotype involves only gastrointestinal symptoms, primarily severe persistent abdominal cramping, diarrhea, and gastroesophageal reflux (20). Like conventional food allergies, AGS can develop during childhood (20,21) but also arises in older adults who have tolerated mammalian meat for decades (19,22).…”

Food Allergy a Constant Concern to the Medical World and Healthcare Providers: Practical Aspects

“…Alpha-gal syndrome (AGS) is an immune-mediated disorder caused by hypersensitivity responses to glycan galactose-alpha-1,3-galactose (alpha-gal). A significant difference between usual food allergies and AGS is the reaction time, with symptom onset occurring two or more hours after alpha-gal consumption [31].…”

“…It works by binding to the Fc region of IgE antibodies, blocking the binding to specific receptors on mast cells and basophils [59,60,68], preventing their degranulation and therefore the appearance of allergic manifestations. Omalizumab should be initiated before the OIT and continued for a few more weeks in parallel [31,69,70]. The recommendation considers both the increase of the safety profile of immunotherapy and its effectiveness.…”

Editorial of Special Issue “Molecular Mechanisms of Allergy and Asthma”

“…Mattison et al [15] performed a microbiological, physicochemical, and immunological analysis of a commercial cashew nut-based yogurt, which indicated that it was not suitable for individuals with a cashew nut allergy. Iweala and coworkers [16] investigated, in turn, a unique type of allergy. They demonstrated that in alpha-gal syndrome, peripheral blood T and B lymphocyte transcriptional states could differentiate between sensitized and sensitized individuals.…”