Pedro Giavina-Bianchi1, Violeta Régnier Galvão2, Matthieu Picard3, Joana Caiado4, Mariana C Castells5. 1. Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass; Clinical Immunology and Allergy Division, University of São Paulo, São Paulo, Brazil. Electronic address: pbianchi@usp.br. 2. Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass; Clinical Immunology and Allergy Division, University of São Paulo, São Paulo, Brazil. 3. Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass; Division of Allergy and Immunology, Department of Medicine, Hôpital Maisonneuve-Rosemont, Université de Montreal, Montreal, Canada. 4. Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass; Immunoallergology Department, Hospital de Santa Maria/Centro Hospitalar Lisboa Norte, Lisbon, Portugal. 5. Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.
Abstract
BACKGROUND: Rapid drug desensitization (RDD) has become a cornerstone in the management of immediate drug hypersensitivity reactions (DHRs) to chemotherapeutic agents. Because of the inherent risk of anaphylaxis during RDD, biomarkers to predict patients at risk of developing such severe reactions are needed. The basophil activation test (BAT) has been used in DHRs as a diagnostic tool. OBJECTIVE: We evaluated basophil CD63 and CD203c expression (BAT) as a biomarker to assess the safety and effectiveness of RDD in platinum compounds-allergic patients. METHODS: Patients allergic to platinum compounds (n = 15) undergoing RDD were assessed through clinical history, skin testing, serum tryptase levels, and BAT. BAT was performed immediately before RDD, assessing CD203c and CD63 expression on basophils. BAT was also performed in 6 patients tolerant to platinum compounds and in 6 healthy volunteers. RESULTS: BAT was positive to CD203c or CD63 in 11 out of 15 patients allergic to platinum compounds (73%), with increased expression of CD203c and CD63 in 11 (73%) and 6 (40%) patients, respectively. Increased CD63 expression tended to be associated with more severe initial reactions. All controls had negative test results. Reactions during RDD were associated with BAT positivity and increased tryptase levels. Only 1 of 4 patients with negative BAT had a mild reaction during RDD. BAT remained positive in multiple sequential RDD. CONCLUSIONS: BAT identified patients allergic to platinum compounds with an increased risk of reactions during desensitization and higher CD63 expression was observed in severe reactions. Multiple RDDs to platinum compounds did not induce persistent hyporesponsiveness on basophils. BAT is a potential biomarker for RDD.
BACKGROUND: Rapid drug desensitization (RDD) has become a cornerstone in the management of immediate drug hypersensitivity reactions (DHRs) to chemotherapeutic agents. Because of the inherent risk of anaphylaxis during RDD, biomarkers to predict patients at risk of developing such severe reactions are needed. The basophil activation test (BAT) has been used in DHRs as a diagnostic tool. OBJECTIVE: We evaluated basophil CD63 and CD203c expression (BAT) as a biomarker to assess the safety and effectiveness of RDD in platinum compounds-allergicpatients. METHODS:Patientsallergic to platinum compounds (n = 15) undergoing RDD were assessed through clinical history, skin testing, serum tryptase levels, and BAT. BAT was performed immediately before RDD, assessing CD203c and CD63 expression on basophils. BAT was also performed in 6 patients tolerant to platinum compounds and in 6 healthy volunteers. RESULTS: BAT was positive to CD203c or CD63 in 11 out of 15 patientsallergic to platinum compounds (73%), with increased expression of CD203c and CD63 in 11 (73%) and 6 (40%) patients, respectively. Increased CD63 expression tended to be associated with more severe initial reactions. All controls had negative test results. Reactions during RDD were associated with BAT positivity and increased tryptase levels. Only 1 of 4 patients with negative BAT had a mild reaction during RDD. BAT remained positive in multiple sequential RDD. CONCLUSIONS: BAT identified patientsallergic to platinum compounds with an increased risk of reactions during desensitization and higher CD63 expression was observed in severe reactions. Multiple RDDs to platinum compounds did not induce persistent hyporesponsiveness on basophils. BAT is a potential biomarker for RDD.
Authors: Leticia de Las Vecillas Sánchez; Leila A Alenazy; Marlene Garcia-Neuer; Mariana C Castells Journal: Int J Mol Sci Date: 2017-06-20 Impact factor: 5.923
Authors: Heather J Bax; Jitesh Chauhan; Chara Stavraka; Atousa Khiabany; Mano Nakamura; Giulia Pellizzari; Kristina M Ilieva; Sara Lombardi; Hannah J Gould; Christopher J Corrigan; Stephen J Till; Sidath Katugampola; Paul S Jones; Claire Barton; Anna Winship; Sharmistha Ghosh; Ana Montes; Debra H Josephs; James F Spicer; Sophia N Karagiannis Journal: Cells Date: 2020-07-07 Impact factor: 6.600