ABSTRACT
Favism is an acute hemolytic syndrome caused by the ingestion of fava bean (FB) in glucose 6-phosphate dehydrogenase (G6PD) deficient individuals. However, little is known about the global transcripts alteration in liver tissue after FB ingestion in G6PD-normal and -deficient states. In this study, deep sequencing was used to analyze liver genes expression alterations underlying the effects of FB in C3H (Wild Type, WT) and G6PD-deficient (G6PDx) mice and to evaluate and visualize the collective annotation of a list of genes to Gene Ontology (GO) terms associated with favism. Our results showed that FB resulted in a decrease of glutathione (GSH)-to-oxidized glutathione (GSSG) ratio and an increase of malondialdehyde (MDA) both in the G6PDx and WT-control check (CK) mice plasma. Significantly, liver transcript differences were observed between the control and FB-treated groups of both WT and G6PDx mice. A total of 320 differentially expressed transcripts were identified by comparison of G6PDx-CK with WT-CK and were associated with immune response and oxidation-reduction function. A total of 149 differentially expressed genes were identified by comparison of WT-FB with WT-CK. These genes were associated with immune response, steroid metabolic process, creatine kinase activity, and fatty acid metabolic process. A total of 438 differential genes were identified by comparing G6PDx-FB with G6PD-CK, associated with the negative regulation of fatty acid metabolic process, endoplasmic reticulum, iron binding, and glutathione transferase activity. These findings indicate that G6PD mutations may affect the functional categories such as immune response and oxidation-reduction.
Subject(s)
Favism/genetics , Glucosephosphate Dehydrogenase Deficiency/genetics , Liver/drug effects , Transcriptome , Vicia faba/toxicity , Animals , Favism/complications , Favism/immunology , Favism/pathology , Gene Expression Profiling , Gene Expression Regulation , Gene Ontology , Glucosephosphate Dehydrogenase Deficiency/complications , Glucosephosphate Dehydrogenase Deficiency/immunology , Glucosephosphate Dehydrogenase Deficiency/pathology , Glutathione/blood , High-Throughput Nucleotide Sequencing , Immunity, Innate , Liver/metabolism , Male , Malondialdehyde/blood , Mice , Mice, Inbred C3H , Mice, Knockout , Molecular Sequence Annotation , Oxidation-Reduction , Oxidative Stress/drug effects , Plant Extracts/toxicity , Vicia faba/chemistryABSTRACT
Lymphocyte subpopulations were studied by means of sheep red blood cell (SRC)-rosetting technique and OKT11, OKT3, OKT4, and OKT8 monoclonal antibodies in ten Sicilian glucose-6-phosphate dehydrogenase-deficient children during the hemolytic crisis due to fava bean ingestion. The number of SRC-rosetting lymphocytes was significantly reduced, while the number of OKT3-positive cells was normal. An inversion of the OKT4/OKT8 ratio was observed, due to a decrease of OKT4-positive cells and an increase of OKT8-positive cells. All these abnormalities reverted to normal in the four children studied after recovery.
Subject(s)
Favism/blood , Glucosephosphate Dehydrogenase Deficiency/blood , T-Lymphocytes/classification , Antibodies, Monoclonal , Antigens, Differentiation, T-Lymphocyte , Antigens, Surface/analysis , Child, Preschool , Favism/immunology , Glucosephosphate Dehydrogenase Deficiency/immunology , Hemolysis , Humans , Infant , Male , Rosette FormationABSTRACT
Lymphocyte subpopulations were studied in 13 Sicilian glucose-6-phosphate dehydrogenase (G6PD)-deficient children during and after the hemolytic crisis due to fava bean ingestion. A statistically significant reduction of sheep-red-cell (SRC)-rosetting lymphocytes occurred in all patients during the hemolytic crisis, whereas B lymphocytes were not affected. In order to establish the possible relationship between serum changes occurring during hemolysis and reduction of SRC-rosetting lymphocytes, the effect in vitro of varying concentrations of bilirubin and hemoglobin on the rosette formation capacity of lymphocytes was studied. Both substances produced a statistically significant reduction of SRC-rosetting lymphocytes both in normal and deficient subjects. This effect showed a direct relationship with the concentrations of bilirubin and hemoglobin used and was more pronounced on lymphocytes from G6PD-deficient children. These data suggested that the reduction of SRC-rosetting lymphocytes observed during acute hemolysis of favism can be related to a modifying effect of bilirubin and hemoglobin.
Subject(s)
Bilirubin/physiology , Favism/blood , Hemoglobins/physiology , Lymphocytes/immunology , Receptors, Immunologic/immunology , Child , Child, Preschool , Favism/complications , Favism/immunology , Glucosephosphate Dehydrogenase Deficiency/etiology , Hemolysis , Humans , Immunity, Cellular , Lymphocytes/classification , Male , Rosette Formation , T-Lymphocytes/enzymologySubject(s)
Favism/immunology , Leukocytes/immunology , Humans , Immunity , Leukocyte Count , PhagocytosisABSTRACT
On the basis of in vivo data Jayne-Williams (1) has proposed that the toxicity of dietary legumes is due to their content of lectins which are immunosuppressive. On the basis of in vitro data with cultured lymphocytes (2), it is now proposed that ingested lectins bind to cell surfaces and cause autologous complement components to bind to and destroy immunologically competent cells. The hypothesis throws a possible light on the aetiology of favism and Whipple's disease.
