RNA sequencing uncovers more than 60 monoclonal antibodies linked to alpha-gal syndrome

Key takeaways:

• Alpha-gal syndrome is a “relatively new disease,” with little research before a decade ago.
• The variable domain gene usage was diverse in these monoclonal antibodies.

SAN DIEGO — An antibody discovery platform revealed more than 60 monoclonal antibodies specific to patients with alpha-gal syndrome, according to a poster presented here.

This molecular characterization may inform diagnostics and treatment, researchers said at the 2025 American Academy of Allergy, Asthma & Immunology/World Allergy Organization Joint Congress.

“Alpha-gal syndrome (AGS) is a relatively new disease. There were almost no publications on it even just a decade ago,” Jessica Grossman, MD, CEO of IgGenix, told Healio.

“Thus, the technologies and techniques for diagnosis are still emerging,” Grossman, who was not one of the study authors, continued. “Similarly, there is an unmet medical need for treatment, a need which IgGenix is hoping to address.”

IgE, which is a specific class of monoclonal antibody, triggers reactions after people are exposed to allergens, Grossman said.

“Individuals with AGS have IgE specific to various animal proteins and lipids, which give rise to the symptoms of AGS when someone consumes or is exposed to animal products,” she said. “This is why another name for AGS is ‘red meat’ allergy.”

However, the researchers said, the technical difficulties in isolating rare single B cells that produce monoclonal antibodies specific to AGS have limited the understanding of their properties.

Developed by IgGenix, the SEQ SIFTER discovery platform isolates single B cells that produce IgE antibodies from the blood of patients with immune-mediated conditions including allergy. Single-cell RNA sequencing then identifies the sequences of antibodies that cause these diseases.

“Next, we re-engineer IgE antibodies into IgG antibodies that can protect from, rather than cause, reactions,” Grossman said. “For example, we have used this technology to develop a peanut-specific IgG antibody therapeutic known as IGNX001 that is currently being evaluated in a phase 1 clinical trial.”

Using bioinformatics, the researchers assessed similarities in these monoclonal antibodies within individuals and between individuals, recombinantly expressing and characterizing them for their specificity, activity and functional properties.

These in vitro and biochemical assays yielded more than 60 monoclonal antibodies among patients with AGS, including one patient who was tested at three different time points.

Alpha-gal is a glycan of limited size compared with canonical protein allergens, the researchers said, but the variable domain gene usage of these monoclonal antibodies was diverse. Also, these monoclonal antibodies came from plasmablasts and memory B cells.

However, the researchers continued, these monoclonal antibodies were “strikingly” similar to several antigens that included alpha-gal despite this sequence variability.

The persistence over time that clonal families of similar antibodies exhibited indicated the presence of mechanisms that underpin immunological memory in AGS as well, the researchers said.

“This is the first reported discovery and characterization of alpha-gal specific monoclonal antibodies from several individuals with AGS,” Grossman said.

These insights may inform hypotheses for why the symptoms of AGS can differ from the symptoms of other food allergies, she said.

“These monoclonal antibodies also tell us about the diversity of immune response mounted by different individuals, and even the diversity of the immune response within a single person,” she added.

Although researchers are in the early phases of understanding AGS, Grossman said, these foundational discoveries will form the basis of future approaches in therapy.

“At IgGenix, we’re continuing to discover antibodies and characterize the immune responses of individuals with AGS leveraging our SEQ SIFTER discovery platform,” Grossman said. “In the next phase, we’ll turn those learnings towards developing therapeutics for affected individuals.”

Reference:

• IgGenix to present alpha-gal syndrome monoclonal antibody discovery at 2025 AAAAI/WAO Joint Congress. https://iggenix.com/pressreleases/iggenix-to-present-alpha-gal-syndrome-monoclonal-antibody-discovery-at-2025-aaaai-wao-joint-congress/. Published Feb. 10, 2025. Accessed Feb. 10, 2025.