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Natalizumab-related anaphylactoid reactions in MS patients are associated with HLA class II alleles.

ABSTRACT: 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.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.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%.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.

SUBMITTER: de la Hera B

PROVIDER: S-EPMC4268037 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Natalizumab-related anaphylactoid reactions in MS patients are associated with HLA class II alleles.

de la Hera Belén B Urcelay Elena E Brassat David D Chan Andrew A Vidal-Jordana Angela A Salmen Anke A Villar Luisa Maria LM Alvarez-Cermeño José Carlos JC Izquierdo Guillermo G Fernández Oscar O Oliver Begoña B Saiz Albert A Ara Jose Ramón JR Vigo Ana G AG Arroyo Rafael R Meca Virginia V Malhotra Sunny S Fissolo Nicolás N Horga Alejandro A Montalban Xavier X Comabella Manuel M

Neurology(R) neuroimmunology & neuroinflammation 20141211 4

<h4>Objectives</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 25520955

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Project description:Human leukocyte antigen (HLA) class I and II are known to have association with severe cutaneous adverse reactions (SCARs) when exposing to certain drug treatment. Due to genetic differences at population level, drug hypersensitivity reactions are varied, and thus common pharmacogenetics markers for one country might be different from another country, for instance, HLA-A*31:01 is associated with carbamazepine (CBZ)-induced SCARs in European and Japanese while HLA-B*15:02 is associated with CBZ-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) among Taiwanese and Southeast Asian. Such differences pose a major challenge to prevent drug hypersensitivity when pharmacogenetics cannot be ubiquitously and efficiently translated into clinic. Therefore, a population-wide study of the distribution of HLA-pharmacogenetics markers is needed. This work presents a study of Thai HLA alleles on both HLA class I and II genes from 470 unrelated Thai individuals by means of polymerase chain reaction sequence-specific oligonucleotide (PCR-SSO) in which oligonucleotide probes along the stretches of HLA-A, -B, -C, -DRB1, -DQA1, and -DQB1 genes were genotyped. These 470 individuals were selected according to their regional locations, which were from North, Northeast, South, Central, and a capital city, Bangkok. Top ranked HLA alleles in Thai population include HLA-A*11:01 (26.06%), -B*46:01 (14.04%), -C* 01:02 (17.13%), -DRB1*12:02 (15.32%), -DQA1*01:01 (24.89%), and -DQB1*05:02 (21.28%). The results revealed that the distribution of HLA-pharmacogenetics alleles from the South had more HLA-B75 family that a typical HLA-B*15:02 pharmacogenetics test for SJS/TEN screening would not cover. Besides the view across the nation, when compared HLA alleles from Thai population with HLA alleles from both European and Asian countries, the distribution landscape of HLA-associated drug hypersensitivity across many countries could be observed. Consequently, this pharmacogenetics database offers a comprehensive view of pharmacogenetics marker distribution in Thailand that could be used as a reference for other Southeast Asian countries to validate the feasibility of their future pharmacogenetics deployment.

Dataset Information

Natalizumab-related anaphylactoid reactions in MS patients are associated with HLA class II alleles.

Publications

Natalizumab-related anaphylactoid reactions in MS patients are associated with HLA class II alleles.

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