RESUMO
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be curative, but is associated with significant morbidity and mortality. Chronic graft-versus-host disease (cGvHD), characterized by inflammation and fibrosis of multiple target organs, considerably contributes to the morbidity and mortality even years after allo-HSCT. Diagnosis of cGvHD is based on clinical features and histology of biopsies. Here, we report the generation of a urinary cGvHD-specific proteome-pattern (cGvHD_MS14) established by capillary electrophoresis-mass spectrometry to predict onset and severity of cGvHD as an unbiased laboratory test. cGvHD_MS14 was evaluated on samples from 412 patients collected prospectively in four transplant centers. Sensitivity and specificity was 84 and 76% by cGvHD_MS14 classification. Sensitivity further increased to 93% by combination of cGvHD_MS14 with relevant clinical variables to a logistic regression model. cGvHD was predicted up to 55 days prior to clinical diagnosis. Acute GvHD is not recognized by cGvHD_MS14. cGvHD_MS14 consists of 14 differentially excreted peptides, six of those have been sequenced to date and are fragments from thymosin ß-4, eukaryotic translation initiation factor 4γ2, fibrinogen ß-chain or collagens. In conclusion, the cGvHD_MS14-pattern allows early, highly sensitive and specific prediction of cGvHD as an independent diagnostic criterion of clinical diagnosis potentially allowing early therapeutic intervention.
Assuntos
Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/metabolismo , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Proteoma , Proteômica , Adolescente , Adulto , Idoso , Doença Crônica , Análise por Conglomerados , Estudos de Coortes , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Razão de Chances , Peptídeos/metabolismo , Proteômica/métodos , Curva ROC , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Transplante Homólogo , Adulto JovemRESUMO
The gut microbiota presents a symbiotic relationship with the human host playing a beneficial role in human health. Since its establishment, the bacterial community is subjected to the influence of many different factors that shape its composition within each individual. However, an important convergence is observed at functional level in the gut microbiota. A metatranscriptomic study of healthy individuals showed homogeneity in the composition of the active microbiota that increased further at functional level.
