Natalizumab-related anaphylactoid reactions in MS patients are associated with HLA class II alleles
Belén de la Hera1, Elena Urcelay1, David Brassat1
1Department of Immunology (B.d.l.H., E.U., A.G.V.) and Department of Neurology, Multiple Sclerosis Unit (R.A.), Hospital Clínico San Carlos (IdISSC), Madrid, Spain; Pole des neurosciences et INSERM U1043 (D.B.), Université de Toulouse III, Hopital Purpan, Toulouse, France; Department of Neurology (A.C., A. Salmen), St. Josef-Hospital, Ruhr University, Bochum, Germany; Servei de Neurologia-Neuroimmunologia (A.V.-J., S.M., N.F., A.H., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; Departments of Neurology and Immunology (L.M.V., J.C.A.-C.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria, Madrid, Spain; Hospital Universitario Virgen Macarena (G.I.), Seville, Spain; Unidad de Gestión Clínica de Neurociencias (O.F., B.O.), Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Regional de Málaga, Universidad de Málaga, Spain; Service of Neurology (A. Saiz), Hospital Clínic, Universitat de Barcelona and Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Biochemistry, Molecular and Cellular Biology (J.R.A.), Science Faculty, University of Zaragoza, Spain; and Fundación de Investigación Biomédica (V.M.), Hospital Universitario de la Princesa, Madrid, Spain.
Objectives:
We aimed to investigate potential associations between human leukocyte antigen (HLA) class I and class II alleles and the development of anaphylactic/anaphylactoid reactions in patients with multiple sclerosis (MS) treated with natalizumab.
Methods:
HLA class I and II genotyping was performed in patients with MS who experienced anaphylactic/anaphylactoid reactions and in patients who did not develop infusion-related allergic reactions following natalizumab administration.
Results:
A total of 119 patients with MS from 3 different cohorts were included in the study: 54 with natalizumab-related anaphylactic/anaphylactoid reactions and 65 without allergic reactions. HLA-DRB1*13 and HLA-DRB1*14 alleles were significantly increased in patients who developed anaphylactic/anaphylactoid reactions (p M-H = 3 × 10(-7); odds ratio [OR]M-H = 8.96, 95% confidence interval [CI] = 3.40-23.64), with a positive predictive value (PPV) of 82%. In contrast, the HLA-DRB1*15 allele was significantly more represented in patients who did not develop anaphylactic/anaphylactoid reactions to natalizumab (p M-H = 6 × 10(-4); ORM-H = 0.2, 95% CI = 0.08-0.50), with a PPV of 81%.
Conclusions:
HLA-DRB1 genotyping before natalizumab treatment may help neurologists to identify patients with MS at risk for developing serious systemic hypersensitivity reactions associated with natalizumab administration.
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