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IgE Ratios May Provide More Accurate Allergy Diagnosis

Researchers have proposed the use of ratios, in addition to in vitro allergy testing, to provide more accurate diagnosis of allergy. The concept is outlined in an article published in Clinical and Translational Allergy.

“Determination of sIgE [serum-specific IgE] to a whole extract or to a single component might not be sufficient to make an accurate diagnosis because many other factors, such as antibody affinity or clonality, play an essential role but are not feasible in routine, clinical practice,” said first author Olga Luengo, MD, PhD, an allergist at the Vall d’Hebron University Hospital, Barcelona, Spain, in an interview with Medscape Medical News.

“Another challenge is the difficulty of differentiating between cross-reactivity and genuine sensitization,” she continued. “In this case, molecular diagnosis, together with the comparative assessment of IgE values, can help determine if sensitization is due to cross-reactivity and its clinical significance.”

Luengo and co-investigators have proposed using two ratios to analyze the relationship between total immunoglobulin E (tIgE) and sIgE against the whole extract or allergen molecules. “The whole idea is that we are using molecular diagnosis more and more,” said Luengo. “It would be very helpful in daily practice if molecular diagnosis could be integrated with diagnostic tests that are available in vitro.”

The first ratio they propose is the ratio of whole extract serum-specific IgE to total IgE. It is intended to help determine sensitization attributable to the whole extract, expressed as a percentage or ratio. The second ratio they propose can determine the extent to which a given allergenic component is responsible for sensitization to a whole extract.

Luengo noted that no defined cutoff points have been established for the proposed ratios, inasmuch as there are no clear numerical values to indicate that a given whole‐allergen extract or its components are the main cause of an allergic reaction. Future studies would establish cutoff values to improve diagnostic accuracy.

“With this work, we would like to provide allergists with a series of validated recommendations to encourage them to use ratios as a complementary diagnostic tool,” said Luengo.

Antonella Muraro, MD, PhD, of Padua University Hospital, Padua, Italy, and past president of the European Academy of Allergy and Clinical Immunology, described the approach as thought provoking but said that it would first have to be proven before being incorporated into clinical practice.

“Molecular allergology has added improvement to allergy diagnosis,” said Muraro in an interview with Medscape Medical News. “It is an interesting idea and would represent an advance when validated.”

Jay M. Portnoy, MD, of Children’s Mercy Hospital, Kansas City, Missouri, described the article as expressing expert opinions about allergy testing but that it fails to offer an evidence-based approach.

“Their concern is that diagnosis of allergy is extremely variable,” said Portnoy in an interview. “Allergists use lots of different methods for making the diagnosis. They [the researchers] agree that the history has to be important. Allergists will then use a series of different kinds of tests, such as skin tests and blood tests. Sometimes the blood tests are augmented by component testing, measuring individual allergens. The interpretation of these tests is extremely variable, and they are trying to come up with a more consistent approach to interpreting the results.”

But the article lacks sensitivity and specificity data to support the approach, said Portnoy. He noted that it would not be feasible to conduct the tests in the United States, where individual components are not listed on allergy extract labels.

“The approach they are proposing is to do in vitro tests with blood tests,” said Portnoy. “There isn’t evidence that this method [using ratios] works. They also don’t provide the performance characteristics of the tests. Also, the extracts are not labeled in the United States, such that you can see the components.”

The study was funded by Thermo Fisher Scientific. Luengo is a speaker and consultant for Thermo Fisher Scientific and is a speaker for Aimmune, DVB Technologies, Nestlè Purina, Nestlè Health Institute, Mylan-Viatris, and AlK and is a member of advisory boards for Novartis, Regeneron-Sanofi, Aimmune, and DVB Technologies. Portnoy has been a speaker for Thermo Fisher Scientific.

Clin Transl Allergy. 2021;e12052. Full text

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