IgE to cyclophilins in pollen-allergic children: Epidemiologic, clinical, and diagnostic relevance of a neglected panallergen - 05/06/24

Doi : 10.1016/j.jaci.2024.01.030

Paolo Maria Matricardi, MD ^a,^b,^c,^⁎ , Ekaterina Potapova, MD ^a, Valentina Panetta, PhD ^d, Jonas Lidholm, PhD ^e, Lars Mattsson, PhD ^e, Enrico Scala, MD ^f, Roberto Bernardini, MD ^g, Carlo Caffarelli, MD ^h, Antonella Casani, MD ⁱ, Rosa Cervone, MD ^g, Loredana Chini, MD ^j, Pasquale Comberiati, MD ^k, Giovanna De Castro, MD ^l, Michele Miraglia del Giudice, MD ^m, Iride Dello Iacono, MD ⁿ, Andrea Di Rienzo Businco, MD ^o, Marcella Gallucci, MD ^p, Arianna Giannetti, MD ^q, Viviana Moschese, MD ^j, Elena Varin, MD ^r, Annamaria Bianchi, MD ^s, Mauro Calvani, MD ^s, Tullio Frediani, MD ^l, Francesco Macrì, MD ^l, Nunzia Maiello, MD ^m, Francesco Paravati, MD ^t, Umberto Pelosi, MD ^u, Diego Peroni, MD ^v, Giuseppe Pingitore, MD ^w, Mariangela Tosca, MD ^x, Anna Maria Zicari, MD ^l, Giampaolo Ricci, MD ^p, Riccardo Asero, MD ^y, Salvatore Tripodi, MD ^o
for the
Italian Pediatric Allergy Network
^a Charité–Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin and Humboldt–Universität zu Berlin, the Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Berlin, Germany
^b Institute of Allergology, Charité-Universitätsmedizin Berlin, Berlin, Germany
^c Department of Allergology and Immunology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany
^d Consultancy & Training, Biostatistics, L’altrastatistica, Rome, Italy
^e Thermo Fisher Scientific, Uppsala, Sweden
^f Clinical and Laboratory Molecular Allergy Unit, IDI-IRCCS, Rome, Italy
^g Pediatric Unit, San Giuseppe Hospital, Empoli, Italy
^h Department of Medicine and Surgery, Clinica Pediatrica, University of Parma, Parma, Italy
ⁱ Pediatra di Libera Scelta, Benevento, Italy
^j UOSD di Immunopatologia ed Allergologia Pediatrica, Policlinico Tor Vergata, Università di Roma Tor Vergata, Rome, Italy
^k Department of Clinical and Experimental Medicine, Section of Paediatrics, University of Pisa, Pisa, Italy
^l Pediatric Department, La Sapienza University, Rome, Italy
^m Dipartimento della Donna, del Bambino e di Chirurgia Generale e Specialistica, Università della Campania Luigi Vanvitelli, Naples, Italy
ⁿ Pediatric Unit, Fatebenefratelli Hospital, Benevento, Italy
^o Pediatric Department and Pediatric Allergology Unit, Sandro Pertini Hospital, Rome, Italy
^p Pediatric Unit, IRCCS Azienda Ospedaliero, Universitaria di Bologna, Bologna, Italy
^q Pediatric Intermediate Care Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
^r Allergology Service, San Carlo Clinic, Paderno Dugnano, Milan, Italy
^s Pediatric Unit, San Camillo Forlanini Hospital, Rome, Italy
^t Pediatric Unit, ASL Crotone, Crotone, Italy
^u Pediatric Unit, Santa Barbara Hospital, Iglesias, Italy
^v Pediatric Section, Department of Life and Reproduction Sciences, University of Verona, Verona, Italy
^w Pediatric Unit, Grassi Hospital, Rome, Italy
^x Pulmonary Disease and Allergy Unit, G. Gaslini Hospital, Genoa, Italy
^y Ambulatorio di Allergologia, Clinica San Carlo, Paderno Dugnano, Italy

^∗Corresponding author: Paolo M. Matricardi, MD, Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité–Universitätsmedizin Berlin, Augustenburgerplatz, 1, 13353 Berlin, Germany.Department of Pediatric Respiratory MedicineImmunology and Critical Care MedicineCharité–Universitätsmedizin BerlinAugustenburgerplatz1Berlin13353Germany

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Abstract

Background

Cyclophilins are ubiquitous panallergens whose epidemiologic, diagnostic, and clinical relevance is largely unknown and whose sensitization is rarely examined in routine allergy practice.

Objective

We investigated the epidemiologic, diagnostic, and clinical relevance of cyclophilins in seasonal allergic rhinitis and its comorbidities.

Methods

We examined a random sample of 253 (25%) of 1263 Italian children with seasonal allergic rhinitis from the Panallergens in Pediatrics (PAN-PED) cohort with characterized disease phenotypes. Nested studies of sensitization prevalence, correlation, and allergen extract inhibition were performed in patients sensitized to birch pollen extract but lacking IgE to Bet v 1/2/4 (74/1263) or with highest serum level of IgE to Bet v 1 (26/1263); and in patients with sensitization to various extracts (ragweed, mugwort, pellitory, Plantago, and plane tree), but not to their respective major allergenic molecule, profilins, and polcalcins. IgE to cyclophilin was detected with recombinant Bet v 7, and extract inhibition tests were performed with the same rBet v 7.

Results

IgE to rBet v 7 was detected in 43 (17%) of 253 patients. It was associated with asthma (P < .028) and oral allergy syndrome (P < .017) in univariate but not multivariate analysis adjusted for IgE to profilins (Phl p 12), PR-10s (Bet v 1), and lipid transfer proteins (Pru p 3). IgE to rBet 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 frequent in pollen-allergic patients living in temperate areas and can produce “false” positive outcomes in skin prick and IgE tests to pollen extracts. Molecular diagnostic guidelines should include this panallergen family.

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Key words : Allergic rhinitis, allergy, asthma, component resolved diagnostics, cross-reactivity, cyclophilins, diagnosis, immunoglobulin E, oral allergy syndrome, panallergens, pollen, precision medicine

Abbreviations used : AIT, CCD, Cyp, nsLTP, OAS, PAN-PED, PR-10, rBet v 7, SAR, sIgE, SPT

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Vol 153 - N° 6

P. 1586 - juin 2024 Regresar al número

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IgE to cyclophilins in pollen-allergic children: Epidemiologic, clinical, and diagnostic relevance of a neglected panallergen - 05/06/24

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Abstract

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Conclusions

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