Clinical and immunological biomarkers in hypereosinophilic syndrome: the second step after diagnostic algorithms

David Longhino¹Ilaria Baglivo¹Maria Antonietta Zavarella²Stefania Colantuono³Chiara Laface¹Gabriele Lucca¹Laura Bruno¹Fabio Romano Selvi¹Vincenzo Patella⁴Aikaterini Detoraki⁵Rosa Buonagura⁵Caterina Tatarelli⁶Barbara Moscatelli⁷Serena D'Avelli⁸Elisabetta Abruzzese⁹Elisabetta Greco¹⁰Antonio Gasbarrini²Livio Pagano¹¹Marianna Criscuolo¹¹Sabrina Giammarco¹¹Cristiano Caruso^1*

• ¹UOSD Allergology and Clinical Immunology Unit, Fondazione Policlinico Universitario 'A. Gemelli' IRCCS, Università Cattolica del Sacro Cuore,, Rome, Sicily, Italy
• ²Centre for Digestive Disease (CEMAD) and Gastroenterology Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
• ³UOSD DH Internal Medicine and Digestive Diseases, Fondazione Policlinico A. Gemelli, IRCCS, Rome, Sicily, Italy
• ⁴Division of Allergy and Clinical Immunology, Department of Medicine, 'Santa Maria della Speranza' Hospital, Battipaglia, Salerno, Italy
• ⁵Division of Internal medicine and Clinical Immunology, Department of Internal Medicine and Clinical Complexity University of Naples Federico II, Naples, Campania, Italy
• ⁶Hematology S. Andrea Hospital, Rome, Sicily, Italy
• ⁷Department of Internal Medicine, Gemelli Isola, Rome, Italy
• ⁸ASL Frosinone, Pneumology Unit, Frosinone, Italy
• ⁹Hematology, Sant'Eugenio Hospital, Tor Vergata University, Rome, Italy
• ¹⁰U.O.C. Reumatologia, Dipartimento di Medicina dei Sistemi, Università di Roma "Tor Vergata", Rome, Italy
• ¹¹Department of Hematology, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy

Background: Idiopathic hypereosinophilic syndrome currently represents a major unmet need for all medical specialties dealing with this disease. Markers capable of characterising the wide variability of its clinical presentation are currently lacking. Objective: This study aims to evaluate a panel of possible markers in idiopathic hypereosinophilic syndrome.Methods: In this pilot prospective single-centre cohort study, we analysed clinical (age, years of disease, steroid therapy) and laboratory (absolute eosinophil count, total IgE antibodies, IgE antibodies against Staphylococcus aureus enterotoxins, serum eosinophil cationic protein, serum immunoglobulin free light chains k and λ and their ratio) data obtained from 21 patients suffering from idiopathic hypereosinophilic syndrome from June 2023 to December 2024.Results: Mean absolute eosinophilic count was 3758.57 cells/µL. 17 patients were receiving treatment with > 7.5 mg of prednisone or equivalent at the time of the diagnosis. 13 patients had positive Staphylococcus aureus enterotoxins IgE, while the mean total serum IgE was 241.64 kU/L. We observed a high serum eosinophil cationic protein value as well as a high serum κ free light chain, while serum λ and κ/λ were normal. Patients with higher absolute eosinophilic count had higher eosinophil cationic protein levels (p < 0.05), such as higher steroid consumption (p < 0.05). In addition, we found a strong association between high κ free light chain levels and high previous steroid use and with Staphylococcus aureus enterotoxins IgE positivity.Conclusions: Our results could increase the number of possible biomarkers for risk stratification in idiopathic hypereosinophilic syndrome.