Tick bites, male sex, polysensitization risk factors for alpha-gal sensitization
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Risk factors for sensitization to alpha-gal include tick bites, male sex and polysensitization to food or airborne allergens, according to a study published in The Journal of Allergy and Clinical Immunology: In Practice.
Alpha-gal syndrome (AGS) is characterized by delayed severe allergic reactions after mammalian meat or mammalian-derived products are consumed, Marit Westman, MD, PhD, of Karolinska Institutet and Karolinska University Hospital in Stockholm, Sweden, and colleagues wrote.
With 5.9% of young adults in the general population sensitized to alpha-gal, the researchers wrote, AGS is most common in middle age. Tick bites appear to present the route to sensitization, the researchers continued.
The researchers examined data of 2,201 individuals from the BAMSE population-based birth cohort (n = 4,089), which followed individuals through early adulthood from urban and semiurban areas of Stockholm where the tick Ixodes ricinus is prevalent.
When the participants were aged 4, 8 and 16 years, researchers analyzed blood samples for IgE to 14 common food and airborne allergens. Participants aged 24 years again had blood samples analyzed for IgE to these allergens as well as for IgE to alpha-gal; they also answered a questionnaire about symptoms and tick bites.
The prevalence of IgE reactivity to alpha-gal at 24 years in the study population was 5.9% (median IgE level to alpha-gal, 0.26 kUA/L; range, 0.1-37 kUA/L), which is similar to the prevalence of sensitivity to soy (5.5%) and wheat (6%).
Participants who were sensitized to alpha-gal were significantly more often sensitized to other food such as peanut, soy, wheat, milk, egg or fish, or to airborne allergens including cat, dog, horse, pollen, mites and mold. Also, 24% of the study population was sensitized to another food item.
Meanwhile, 81.4% of the study population said that they had been bitten by a tick, and this proportion reached 93% among the 129 participants who were sensitized to alpha-gal.
More specifically, 44.2% of the participants who were sensitized to alpha-gal reported tick bites within the previous 2 years, compared with 24.2% of the participants who were not sensitized (P < .001). A multiple regression model showed that increasing number of tick bites correlated with sensitization to alpha-gal ( 10 vs. 0 tick bites, OR = 5.5; 95% CI, 2.7-11.2)
The researchers further found significantly more IgE reactivity to alpha-gal among males than females (8.9% vs. 3.4%; P < .001; OR = 2.8; 95% CI, 1.9-4). But the researchers found no difference in alpha-gal IgE levels between males and females (median IgE, 0.31 vs. 0.2 kUA/L).
Previous studies have attributed the overrepresentation of males among subjects with alpha-gal sensitivity to differences in tick exposure between men and women. Males reported more tick bites than females in this study, the researchers wrote, although this association remained significant after adjustment. Still, the researchers added that residual confounding could not be ruled out.
A longitudinal analysis that included sex and the number of sensitization and tick bites showed the polysensitization at any time point through age 16 years was associated with alpha-gal sensitization at 24 years (OR = 2.4; 95% CI, 1.4-4.3).
“This suggests that no allergen source per se is important for the development of alpha-gal sensitization, and the previously reported risk factor of sensitization to airborne allergens may be extended to food allergens,” the researchers wrote.
Two males and one female (2.3%) who were sensitized to alpha-gal reported symptoms after ingesting mammalian meat, which corresponds with the 0.1% population-based prevalence of mammalian meat allergy among young adults. All three reported tick bites, and none reported specific symptoms to milk.
Noting the rarity of symptoms suggestive of mammalian meat allergy, the researchers concluded that tick bites, male sex and polysensitization were risk factors for alpha-gal sensitization.
Perspective
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Jay Lieberman, MD
The results of this study are not too surprising or new. We have known that sensitization or presence of the allergic antibody to alpha-gal is common in certain geographic areas and that the best-known risk factor is a history of tick bites. In fact, a lot of data suggest that the tick bite is required to develop sensitization to alpha-gal.
Another risk factor that has been shown in other studies is a history of atopy or having other allergic diseases, which bears out in this population as well. This study also suggests that male gender is a risk factor, but this could be secondary to a higher likelihood of outdoor work or activities, which is not accounted for in this study.
Finally, we know that many people are sensitized to alpha-gal but do not have clinical symptoms with mammalian meats, and this study clearly showed that as well.
Although this study was conducted in Sweden, similar results could be expected in the United States, though it would depend on the population studied. If you sampled a young adult population in the Southeast, you would find sensitization rates at least this high. But that could be different if you sampled a cohort in the north, where alpha-gal is likely less prominent.
Where I practice in Tennessee, alpha-gal syndrome is not uncommon. Anecdotally, I do not specifically see more males than females, but most of my patients who have alpha-gal syndrome do spend time outdoors. I have plenty of patients who are children, adolescents and young adults, so it is not surprising to me to see a prevalence of sensitization as high as 6% in this cohort.
If they are not already, doctors should be aware of alpha-gal and understand that most of the data and studies suggest a history of tick bite as paramount to the development of the syndrome. Doctors should also realize that while sensitization to alpha-gal may be common if they live in a tick-endemic area, clinical symptoms are much less common.
In the cohort reported, 6% were sensitized, but only 2.3% of all sensitized patients (three patients out of the 129 who had alpha-gal antibodies) reported symptoms. Thus, do not test unless you have a high suspicion of disease, and realize that sensitization does not equal clinical reactivity.
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