RESUMEN
Despite improvement in clinical management, allogeneic hematopoietic stem cell transplantation (HSCT) is still hampered by high morbidity and mortality rates, mainly due to graft versus host disease (GvHD). Recently, it has been demonstrated that the allogeneic immune response might be influenced by external factors such as tissues microenvironment or host microbiota. Here we used high throughput metabolomics to analyze two cohorts of genotypically HLA-identical related recipient and donor pairs. Metabolomic profiles markedly differ between recipients and donors. At the onset of acute GvHD, in addition to host-derived metabolites, we identify significant variation in microbiota-derived metabolites, especially in aryl hydrocarbon receptor (AhR) ligands, bile acids and plasmalogens. Altogether, our findings support that the allogeneic immune response during acute GvHD might be influenced by bile acids and by the decreased production of AhR ligands by microbiota that could limit indoleamine 2,3-dioxygenase induction and influence allogeneic T cell reactivity.
Asunto(s)
Microbioma Gastrointestinal/fisiología , Enfermedad Injerto contra Huésped/metabolismo , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Metaboloma/inmunología , Enfermedad Aguda , Adulto , Anciano , Ácidos y Sales Biliares/análisis , Ácidos y Sales Biliares/inmunología , Ácidos y Sales Biliares/metabolismo , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Enfermedad Injerto contra Huésped/sangre , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Ligandos , Donadores Vivos , Masculino , Metabolómica/métodos , Persona de Mediana Edad , Plasmalógenos/análisis , Plasmalógenos/inmunología , Plasmalógenos/metabolismo , Receptores de Hidrocarburo de Aril/inmunología , Receptores de Hidrocarburo de Aril/metabolismo , Hermanos , Linfocitos T/inmunología , Trasplante Homólogo/efectos adversos , Trasplante Homólogo/métodos , Triptófano/inmunología , Triptófano/metabolismo , Adulto JovenRESUMEN
A novel phospholipid has been purified from strain Dm 28c of Trypanosoma cruzi, and characterized by fast atom bombardment mass spectrometry and nuclear magnetic resonance spectroscopy as a plasmenylethanolamine with a hexadec-l-enyl group in the sn-1 position and an approximately equimolar mixture of octadecenoate and octadecadienoate esterified to the sn-2 hydroxyl. The purified plasmenylethanolamine reacted positively when probed with sera from patients with chronic Chagas' disease. Since plasmenylethanolamines of similar structure are abundant in mammalian cardiac and neuronal tissues, cross reactions between these epitopes may be a factor in the mechanism of autoimmune pathology in the chronic phase of Chagas' disease.
Asunto(s)
Fosfolípidos/química , Plasmalógenos/análisis , Trypanosoma cruzi/química , Animales , Anticuerpos Antiprotozoarios/sangre , Enfermedad de Chagas/sangre , Cromatografía Líquida de Alta Presión , Cromatografía en Capa Delgada , Células Clonales , Ácidos Grasos Insaturados/análisis , Cromatografía de Gases y Espectrometría de Masas , Humanos , Resonancia Magnética Nuclear Biomolecular , Fosfolípidos/inmunología , Plasmalógenos/inmunología , Espectrometría de Masa Bombardeada por Átomos Veloces , Ácidos Esteáricos/análisisRESUMEN
Ethanol-soluble mycardial material which reacts with anti-streptococcal sera in a number of immunological tests has been isolated and identified as ethanolamine plasmalogen. The reactions of cardiac plasmalogen with antistreptococcal sera was specific and could be inhibited by streptococcus-derived materials. Guinea-pigs sensitized to streptococci gave positive skin reactions when challenged with myocardial plasmalogen. The pattern of the immunofluorescent staining given by antiplasmalogen sera was very much like that given by antistreptococcal sera. Nevertheless, the plasmalogen failed to compete for tissue-bound myocardial antigens when tried as an inhibitor of the immunofluorescent staining of myocardium either by antistreptococcal sera or by antiplasmalogen sera. A hypothesis of the role of the plasmalogen in the formation of complexes between streptococci and myocardium-derived material in the initiation of autoimmune processes is presented.