Incidência aumentada de haplótipo de HLA de classe II na anafilaxia grave secundária à carboplatina
Increased incidence of a class II HLA haplotype in severe anaphylaxis secondary to carboplatin
Violeta Régnier Galvão; Elizabeth Phillips; Mariana Castells; Pedro Giavina-Bianchi
Resumo
Objetivo: O papel de biomarcadores nas reações de hipersensibilidade a platinas tem sido estudado, e é conhecido que a presença da mutação do gene BRCA1/2 é fator de risco para reações de hipersensibilidade à carboplatina. A genotipagem de HLA de classes I e II auxilia na identificação de pacientes de risco para reações IgE-mediadas e mediadas por linfócitos T associadas a beta-lactâmicos e abacavir, respectivamente. Não são conhecidos alelos ou haplótipos de HLA mais prevalentes em pacientes alérgicos à carboplatina. O objetivo principal do estudo foi avaliar se alelos específicos de HLA de classe II são mais prevalentes em pacientes alérgicos à carboplatina submetidos à dessensibilização (DS). Método: Genotipagem de HLA de classe II realizada em 11 pacientes portadoras de neoplasias malignas tubo-ovarianas, alérgicas à carboplatina, e submetidas à DS, e em 12 pacientes tolerantes à carboplatina, por no mínimo oito ciclos. Analisou-se também a prevalência da mutação BRCA1/2 nos dois grupos estudados. Resultados: O alelo HLA-DRB1*15:01 foi mais prevalente entre as pacientes alérgicas (5/11; 45%) do que nos controles (1/12; 8,3%) (p = 0,06). O haplótipo de classe II DQA1*01:02-DQB1*06:02-DRB1*15:01 foi mais expresso no grupo de pacientes alérgicas. A mutação do BRCA1/2 mostrou-se mais prevalente no grupo alérgico. Conclusões: A identificação de pacientes de risco para reações alérgicas à carboplatina é de extrema importância com o uso crescente da medicação. A genotipagem de HLA e a pesquisa da mutação BRCA1/2 mostramse ferramentas promissoras que podem aumentar a segurança durante infusão regular de carboplatina e DS.
Palavras-chave
Abstract
Objective: The role of biomarkers in hypersensitivity reactions (HSR) to platinum compounds has been studied, and the presence of BRCA1/2 gene mutation is known to be a risk factor for carboplatin HSR. Class I and II HLA genotyping helps identify patients at risk for IgE-mediated and T lymphocyte-mediated reactions associated with beta-lactams and abacavir, respectively. Associations between HLA alleles or haplotypes and carboplatin HSR are not known. The main objective of the present study was to evaluate whether specific class II HLA alleles are more prevalent in patients allergic to carboplatin who underwent rapid drug desensitization (RDD). Methods: Class II HLA genotyping was performed in 11 carboplatin-allergic patients with tubo-ovarian malignancies who were submitted to RDD, and in 12 patients who tolerated carboplatin, for at least eight cycles. The prevalence of the BRCA1/2 mutation was also analyzed in both groups. Results: The HLA-DRB1*15:01 allele was more prevalent among allergic patients (5/11; 45%) than in controls (1/12; 8.3%) (p = 0.06). Class II haplotype DQA1*01:02-DQB1*06:02-DRB1*15:01 and the BRCA1/2 mutation were also more prevalent in the allergic group. Conclusions: The identification of patients at risk for carboplatin HSR is of utmost importance, as the use of this medication is increasing. HLA genotyping and screening for the BRCA1/2 mutation are promising tools that may increase safety during regular carboplatin infusion and RDD.
Keywords
Referências
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Submetido em:
03/11/2017
Aceito em:
20/11/2017
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