Distinct TNF-alpha and HLA polymorphisms associate with fibrotic and non-fibrotic subtypes of hypersensitivity pneumonitis

Autores da FMUP

• Cláudia Susana Soares De Freitas

  Autor

• Hélder Novais E Bastos

  Autor

• Hélio José Da Costa Alves

  Autor

• Oksana Sokhatska

  Autor

• José Luís Dias Delgado

  Autor

• Antonio Manuel Martins De Morais

  Autor

Participantes de fora da FMUP

• Lima, B
• Melo, N
• Mota, P

Unidades de investigação

• Biomedicina

• Ciências da Saúde Pública e Forenses, e Educação Médica

• Laboratório Associado RISE- Rede de Investigação em Saúde

  

  Investigador

  Fernando Carlos De Landér Schmitt

• Medicina

• Patologia

• RISE-Health

  

  Investigador

  Fernando Carlos De Landér Schmitt

Abstract

Introduction: Since Hypersensitivity Pneumonitis (HP) categorization in fibrotic and nonfibrotic/inflammatory types seems to be more consistent with the distinctive clinical course and outcomes, recent international guidelines recommended the use of this classification. Moreover, fibrotic subtype may share immunogenetic and pathophysiological mechanisms with other fibrotic lung diseases. Aim: To investigate HLA -A, -B, -DRB1 and TNF-alpha -308 gene polymorphisms among fibrotic and nonfibrotic HP patients due to avian exposure, also in comparison with asymptomatic exposed controls. Methods: We prospectively enrolled 40 HP patients, classified as fibrotic or nonfibrotic/inflammatory, and 70 exposed controls. HLA and TNF-alpha polymorphisms were determined by polymerase chain reaction-sequence specific primer amplification. Results: While HLA alleles were not associated to HP susceptibility, fibrotic HP patients showed increased frequencies of HLA A*02 (46.7% vs 25.7%; OR=2.53, p = 0.02) and HLA DRB1*14 (10.0% vs 0.7%; OR=15.44, p=0.02) alleles when compared with exposed controls, although not statistically significant after correction for multiple comparisons. TNF-alpha G/G genotype (associated with low TNF-alpha production) frequencies were significantly increased among the non-fibrotic/inflammatory HP patients comparatively to fibrotic presentations (88% vs 60%; RR=0.44; p=0.04) and controls (88% vs 63%, OR 4.33, p=0.037). Also, these patients had a significantly increased frequency of the G allele (94.0% vs 73.3%, RR=0.44, p=0.01), while fibrotic HP patients predominantly presented the A allele (26.7% vs 6.0%, RR=2.28, p=0.01). Conclusions: Our results support the hypothesis that fibrotic and non-fibrotic HP subtypes exhibit a distinct profile of TNF-alpha and HLA polymorphisms, which may be relevant to predict disease course and better define treatment strategies. (c) 2021 Sociedade Portuguesa de Pneumologia. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/).

Keywords

• HP; Fibrotic HP; Progressive fibrosing lung diseases; HLA polymorphisms; TNF-alpha polymorphisms