Erros inatos de imunidade em humanos: um quarto de século de mudanças de paradigma na classificação, fenotipagem clínica e diagnóstico molecular
DOI:
https://doi.org/10.5281/zenodo.22271455Palavras-chave:
erros inatos da imunidade; doenças da imunodeficiência primária; doenças do sistema imunológico; transtornos da imunidade; doenças genéticas inatas; doenças autoimunesResumo
Introdução: os erros inatos da imunidade (EII) são trastornos predominantemente monogênicos que cursam com um espectro clínico que inclui infecções, autoimunidade, autoinflamação, alergia e neoplasias. Ao longo de 25 anos, a União Internacional de Sociedades de Imunologia (IUIS) publicou 14 relatórios de classificação que orientaram o campo.
Objetivo: sintetizar de forma abrangente a evolução conceitual e quantitativa dos EII documentada nos relatórios publicados pela IUIS desde 1999 até 2024.
Método: revisão de escopo da literatura (Arksey&O'Malley) com uma busca sistemática na base de dados PubMed dos relatórios oficiais (1999-2024). Foram extraídos os dados referentes ao número de transtornos, defeitos genéticos, classificação e fenótipos clínicos, categorizados em infecciosos, autoimunes, autoinflamatórios, alérgicos, malignos ou não imunológicos.
Resultados: os EII reconhecidos aumentaram em oito vezes, passando de 59 em 1999 para 559 em 2024, derivados de 508 genes e 17 fenocópias somáticas. Identificaram-se três fases de crescimento: linear (1999-2005), acelerada (2005-2015) e exponencial com consolidação estrutural (2015-2024). As principais mudanças de paradigma incluíram tabelas específicas de desregulação e autoinflamação (2005), a mudança de nomenclatura para "erros inatos da imunidade" (2017) e a introdução de fenocópias (2014). Em 2024, 43% dos novos EII são de autoinflamação ou desregulação. As manifestações não imunológicas afetam 100% dos EII sindrômicos e das síndromes de insuficiência da medula óssea.
Conclusões: a evolução da classificação reflete uma reconceituação fundamental, de deficiências infecciosas para transtornos multissistêmicos por desregulação. Este arcabouço apoia o diagnóstico por vias moleculares e a terapia de precisão, com implicações na reumatologia, hematologia, alergologia e neurologia.
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Copyright (c) 2026 Carlos Alfredo Miló Valdés, Adrián Alejandro Vitón-Castillo, Lidia Cecilia Pérez Acevedo, Marla González Martínez
Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License.
