When Are Serum Specific IgE Levels Positive?

We read with interest the article by Stringari et al1Stringari G. Tripodi S. Caffarelli C. Dondi A. Asero R. Di Rienzo Businco A. et al.The effect of component-resolved diagnosis on specific immunotherapy prescription in children with hay fever.J Allergy Clin Immunol. 2014; 134: 75-81Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar on how component-resolved diagnosis (CRD) might play a role in allergen immunotherapy (AIT) prescription in patients with allergic rhinitis. We agree with the authors' conclusion that improving the exactness of the diagnosis improves the prescription specificity, which will likely improve the effectiveness of the immunotherapy, even though this remains to be demonstrated in randomized trials, as the authors themselves say. The authors underline that sometimes skin prick tests (SPTs) or serum specific IgE levels for allergen extracts might not be consistent with the CRD results and that this might reflect a significant change in the AIT prescription. Of course, the relationship between SPTs with extracts and CRD varies according to the respective cutoff levels (millimeters of cutaneous wheal diameter and serum kilounits per liter). We wonder why the authors classify as “negative” those patients with serum specific IgE levels of less than 0.7 kU/L, whereas in a previous article with the same study group, the same authors considered a value of less than 0.35 kU/L to be negative.2Tripodi S. Frediani T. Lucarelli S. Macrì F. Pingitore G. Di Rienzo Businco A. et al.Molecular profiles of IgE to Phleum pratense in children with grass pollen allergy: implications for specific immunotherapy.J Allergy Clin Immunol. 2012; 129: 834-839Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar Furthermore, to our knowledge, the normal value for the used methodology, ImmunoCAP FEIA, is less than 0.1 kU/L, according to the manufacturer's instructions (www.phadia.com). The choice of a particular cutoff should be matched against the diagnostic gold standard. We all agree that SPT responses are considered positive when the elicited wheal diameter is 3 mm or greater. As for concerns about the CRD, if Stringari et al1Stringari G. Tripodi S. Caffarelli C. Dondi A. Asero R. Di Rienzo Businco A. et al.The effect of component-resolved diagnosis on specific immunotherapy prescription in children with hay fever.J Allergy Clin Immunol. 2014; 134: 75-81Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar had considered all values of greater than 0.1 kU/L to be positive or at least had confirmed their previous limit of 0.35 kU/L, we could assume that their results would have likely changed. By moving the cutoff from 0.35 to 0.7 kU/L, the authors increase the test specificity but might have lost something in sensitivity, which means that they risk excluding a number of patients from the benefits of AIT. In our everyday practice, if we had a patient with rhinitis symptoms in the spring, positive SPT responses for grass pollen, and a Phl p 1–specific IgE level of greater than 0.1 kU/L (eg, 0.5 or 0.6 kU/L), we would consider those results consistent with the diagnosis of allergic rhinitis caused by grass pollen and determine the patient to be eligible for immunotherapy. However, in their study, such a patient would be considered to have negative results. Could the authors clarify how they reached the decision to move the normal serum specific IgE value from 0.35 to 0.7 kU/L and how their results would change if they had set the cutoff at 0.35 kU/L (or 0.1 kU/L) instead of 0.7 kU/l? We would also be interested in reading the different likelihood ratios relative to the different cutoff values. We understand and agree that the more specific the therapy, the better the clinical results, but we also have to speak the same language: When is a specific IgE level considered positive, and when is it considered negative? The effect of component-resolved diagnosis on specific immunotherapy prescription in children with hay feverJournal of Allergy and Clinical ImmunologyVol. 134Issue 1PreviewSensitization to profilins and other cross-reacting molecules might hinder proper specific immunotherapy (SIT) prescription in polysensitized patients with pollen-related allergic rhinitis (AR). In these patients, component-resolved diagnosis (CRD) might modify SIT prescription by improving the identification of the disease-eliciting pollen sources. Full-Text PDF ReplyJournal of Allergy and Clinical ImmunologyVol. 135Issue 1PreviewIn a survey of 651 Italian children with moderate-to-severe seasonal allergic rhinoconjunctivitis, we found that a significant proportion of positive skin reactions to pollen extracts were not confirmed by the detection of serum IgE specific for major genuine allergen molecules. This inconsistency was partially explained in many cases by IgE sensitization to profilin, polcalcin, or both (ie, highly cross-reacting molecules that are shared by many different pollen sources).1 The study also demonstrated that the use of molecular diagnosis profoundly affected the decision about allergen immunotherapy prescription based on international guidelines or a doctor's opinion. Full-Text PDF