Researchers clarify diagnostic values for alpha-gal syndrome
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LOUISVILLE, Ky. — Because alpha-gal specific IgE levels differ among sexes, ratios or percentages should be used instead, according to a study presented at the American College of Asthma & Immunology Annual Scientific Meeting.
The use of ratios or percentages would improve diagnosis of alpha-gal syndrome (AGS), according to Ari Heffes-Doon, MD, chief pediatric resident at NYU Long Island School of Medicine, and colleagues.
“Though Long Island is a known Lone Star tick endemic area, there is currently no literature describing the clinical experience of patients with alpha-gal syndrome in our region,” Heffes-Doon told Healio. “We sought to describe the clinical experience of this patient cohort and to evaluate the diagnostic utility of alpha-gal serum IgE to total IgE ratios.”
The researchers conducted a retrospective chart review of 688 patients aged 5 to 95 years with positive alpha-gal sIgE of greater than 0.1 kU/L and tick bite history who were evaluated for suspected AGS on Eastern Long Island between 2011 and 2020.
Analysis revealed 532 patients with AGS, two with idiopathic anaphylaxis and 43 who were sensitized to alpha-gal without clinical reactivity. The patients with AGS had alpha-gal sIgE levels that ranged from 0.21 kU/L to more than 100.99 kU/L, with a mean of 33.43 kU/L, although the researchers found no correlation between level and reaction severity.
There were no statistically significant differences between male patients and female patients among those with AGS in time from exposure to meat to allergic reaction, type of symptoms experienced, rate of any reaction symptoms or reaction severity.
However, the researchers found significant variations between male patients and female patients in alpha-gal sIgE (23.3 kU/L vs. 17.5 kU/L; P = .0066) and total IgE (181 kU/L vs. 133 kU/L; P = .0007), but there was no difference between sexes in the ratio of alpha-gal IgE to total IgE.
Further, the researchers observed a significant correlation between weight and alpha-gal sIgE and total IgE but not with alpha-gal sIgE:total IgE, adding that men and boys were heavier than women and girls (P < .0001).
“When comparing serum levels between male and female patients, we saw that male patients had significantly higher levels of alpha-gal IgE and total IgE levels compared with female patients,” Heffes-Doon said. “However, ratios of alpha-gal to total IgE were nearly identical between males and females.”
Noting that AGS should be on the differential when patients present with idiopathic anaphylaxis, the researchers said that weight may be one of many contributors to these differences in alpha-gal sIgE levels between males and females, which indicate a need to use ratios or percentages instead of these levels in isolation in diagnosis.
Researchers also characterized a subgroup of patients with evidence of sensitization to alpha-gal by serum IgE testing, but without clinical symptoms following mammalian meat exposures. This group had significantly lower alpha-gal sIgE (4.74 kU/L vs. 19.9 kU/L; P = .0001) and alpha-gal IgE:total IgE (0.04 vs. 0.12; P < .0001) than patients with AGS and symptoms.
Previous studies have suggested that the use of an alpha-gal percentage greater than 2% is more likely to be associated with clinically relevant allergy, Heffes-Doon said.
“Our work supports the role for calculating alpha-gal specific IgE level to total IgE level for a particular patient in making the diagnosis of AGS,” he said. “The comparison can be made either by use of the ratio or by calculating alpha-gal specific IgE as a percentage of total IgE.”
In practice, checking both total IgE and serum sIgE for alpha-gal will enable physicians to determine a ratio or percentage that would support an AGS diagnosis and help predict the likelihood of future reactions to mammalian meats, Heffes-Doon said.
“The sensitivity and specificity of these numbers have not been well defined, so it’s important that we continue to use a combination of supporting clinical history with this lab work to guide our discussions with patients,” he said.
Next, Heffes-Doon said that he and his colleagues will work to better determine the alpha-gal IgE ratio or percentage that is most likely to predict clinical reactivity and to separate patients with AGS from those with evidence of sensitization without clinical reactivity.