Involvement of the IgE-basophil system and mild complement activation in haemophilia B with anti-factor IX neutralizing antibodies and anaphylaxis

Autor:	Flora Peyvandi, P. M. Mannucci, Maria Elisa Mancuso, Alberto Tedeschi, V. Carbonelli, Maurizio Lorini, Massimo Cugno, Elena Santagostino
Rok vydání:	2017
Předmět:	Male 030204 cardiovascular system & hematology Basophil Haemophilia Immunoglobulin E Hemophilia B Factor IX 03 medical and health sciences 0302 clinical medicine medicine Humans Haemophilia B Anaphylaxis Complement Activation Genetics (clinical) biology business.industry Hematology General Medicine medicine.disease Antibodies Neutralizing Basophils Complement system medicine.anatomical_structure Child Preschool Immunology biology.protein Antibody business 030215 immunology medicine.drug
Zdroj:	Haemophilia. 23:e348-e353
ISSN:	1351-8216
Popis:	Introduction Patients with haemophilia B who develop factor IX (FIX) neutralizing antibodies (inhibitors) after FIX infusion are at high risk of hypersensitivity reactions upon FIX re-exposure, but the underlying mechanisms are incompletely understood. Aim To investigate biomechanisms of FIX hypersensitivity. Methods A cellular antigen stimulation test (CAST) was employed to evaluate leukotriene C4 (LTC4) release from basophils stimulated by FIX in three treated children with haemophilia B, one of whom developed FIX inhibitor and experienced anaphylaxis following FIX re-exposure. Anti-FIX IgE and IgG antibodies and markers of complement activation (C5b9, C3d and iC3b) were measured in plasma, the last also after FIX infusion. Ten healthy children served as controls. Results The patient who developed anti-FIX inhibitors and anaphylaxis had a nonsense mutation in FIX gene (p.Arg298Stop) and, compared to controls, had higher plasma levels of specific anti-FIX IgE (2.285 vs 0.084 OD492 nm), with marked LTC4 release from his FIX-stimulated basophils (519.8 vs 39.9 pg/mL). Further, he had higher plasma levels of anti-FIX IgG of all the four subclasses (total IgG 1.180 vs 0.120 OD492 nm) with FIX neutralizing activity (1.5 BU); mild complement activation occurred during FIX-induced anaphylaxis (C5b9 increased from 258.5 to 351.1 ng/mL). The same parameters were normal in the two patients who tolerated FIX infusion. Conclusion In the patient with haemophilia B who experienced anaphylaxis after FIX, but not in the patients with haemophilia B who tolerated FIX, the CAST assay showed FIX-induced LTC4 release, which was associated with high plasma levels of specific anti-FIX IgE and IgG antibodies.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::db50e32c2b1e0f9f390c76405e093e65 https://doi.org/10.1111/hae.13282 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.