IgE to cyclophilins in pollen allergic children: epidemiological, clinical and diagnostic relevance of a neglected panallergen

Matricardi PM, Potapova E, Panetta V et al. J Allergy Clin Immunol. 2024 Mar 19:S0091-6749(24)00235-5. doi: 10.1016/j.jaci.2024.01.030.

Abstract

Background: - Cyclophilins are ubiquitous panallergens whose epidemiological, diagnostic, and clinical relevance is largely unknown and whose sensitization is rarely examined in routine allergy practice. The aim of this study was to investigate the epidemiological, diagnostic, and clinical relevance of cyclophilin in seasonal allergic rhinitis and its comorbidities.

Methods: - We examined a random sample (25%, n 253) of 1263 Italian children affected by seasonal allergic rhinitis from the "Panallergen in Pediatrics" (PAN-PED) cohort. Patients' disease phenotype had been already fully characterized through questionnaires (ARIA), skin prick tests (ALK), IgE tests to extracts, major and cross-reactive allergenic molecules of a comprehensive variety of allergenic pollen (immunoCAP), and carbohydrate cross-reacting determinants (CCD) (NOVEOS).

Graphical Abstract

We also performed nested studies of sensitization prevalence, correlation and allergen extract inhibition in patients (A) sensitized to birch pollen extract but lacking IgE to Bet v 1, Bet v 2, and Bet v 4, (74/1263) or with the highest serum level of IgE to Bet v 1 (26 within 1263), and (B) in patients with sensitization to extracts of ragweed (18), mugwort (18), pellitory (20), Plantago (19), and plane tree (20), but not to their respective major allergenic molecule, profilins and polcalcins. IgE to cyclophilin was detected with recombinant Bet v 7 (ImmunoCAP) and extract inhibition tests were performed with the same rBet v 7.

Results: In the randomized population, IgE to rBet v 7 was detected in 43/253 (17%) patients. It was associated with asthma (p<0.028) and oral allergy syndrome (p<0.017) in univariate, but not in a multivariate analysis adjusted for IgE to profilins (Phl p 12), PR.10s (Bet v 1), and LTPs (Pru p 3). IgE to r Bet v 7 was also highly prevalent (47/74; 63%) among patients with unexplained sensitization to birch pollen extract. In patients with unexplained sensitization to ragweed, mugwort, pellitory, Plantago and plane tree pollen, the levels of IgE to those extracts correlated with the levels of IgE to rBet v 7, and they were also significantly inhibited by rBet v 7 (inhibition range 45%-74%).

Conclusions: - IgE sensitization to cyclophilin is very frequent in pollen-allergic patients living in temperate areas and can produce "false" positive outcomes in SPT and IgE tests to many different pollen extracts. The spectrum of pollen species containing allergenic cyclophilins is probably broader than previously known. Our results suggest that guidelines of molecular diagnostics should include this allergen family and that new tests based on plant cyclophilins should be produced and used with sera of pollen-allergic patients for a more precise identification of the culprit pollen extract and a tailored prescription of allergen immunotherapy.

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