ABSTRACT
Liver biopsy is the gold-standard method to stage fibrosis; however, it is an invasive procedure and is potentially dangerous. The main objective of this study was to evaluate biological markers, such as cytokines IL-13, IFN-gamma, TNF-alpha and TGF-beta, platelets, bilirubins (Bil), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), total proteins, gamma-glutamil transferase (gamma-GT) and alkaline phosphatase (AP), that could be used to predict the severity of hepatic fibrosis in schistosomiasis and hepatitis C (HC) as isolated diseases or co-infections. The following patient groups were selected: HC (n = 39), HC/hepatosplenic schistosomiasis (HSS) (n = 19), HSS (n = 22) and a control group (n = 13). ANOVA and ROC curves were used for statistical analysis. P < 0.05 was considered significant. With HC patients we showed that TNF-alpha (p = 0.020) and AP (p = 0.005) could differentiate mild and severe fibrosis. With regard to necroinflammatory activity, AST (p = 0.002), gamma-GT (p = 0.034) and AP (p = 0.001) were the best markers to differentiate mild and severe activity. In HC + HSS patients, total Bil (p = 0.008) was capable of differentiating between mild and severe fibrosis. In conclusion, our study was able to suggest biological markers that are non-invasive candidates to evaluate fibrosis and necroinflammatory activity in HC and HC + HSS.
Subject(s)
Biomarkers/blood , Hepatitis C/blood , Liver Cirrhosis/blood , Liver Diseases, Parasitic/blood , Schistosomiasis/blood , Splenic Diseases/blood , Adolescent , Adult , Aged , Analysis of Variance , Case-Control Studies , Hepatitis C/complications , Hepatitis C/pathology , Humans , Liver Cirrhosis/complications , Liver Cirrhosis/pathology , Liver Diseases, Parasitic/complications , Liver Diseases, Parasitic/pathology , Middle Aged , Necrosis/pathology , ROC Curve , Schistosomiasis/complications , Schistosomiasis/pathology , Severity of Illness Index , Splenic Diseases/complications , Splenic Diseases/pathology , Young AdultABSTRACT
Liver biopsy is the gold-standard method to stage fibrosis; however, it is an invasive procedure and is potentially dangerous. The main objective of this study was to evaluate biological markers, such as cytokines IL-13, IFN-ã, TNF-á and TGF-â, platelets, bilirubins (Bil), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), total proteins, ã-glutamil transferase (ã-GT) and alkaline phosphatase (AP), that could be used to predict the severity of hepatic fibrosis in schistosomiasis and hepatitis C (HC) as isolated diseases or co-infections. The following patient groups were selected: HC (n = 39), HC/hepatosplenic schistosomiasis (HSS) (n = 19), HSS (n = 22) and a control group (n = 13). ANOVA and ROC curves were used for statistical analysis. P < 0.05 was considered significant. With HC patients we showed that TNF-á (p = 0.020) and AP (p = 0.005) could differentiate mild and severe fibrosis. With regard to necroinflammatory activity, AST (p = 0.002), ã-GT (p = 0.034) and AP (p = 0.001) were the best markers to differentiate mild and severe activity. In HC + HSS patients, total Bil (p = 0.008) was capable of differentiating between mild and severe fibrosis. In conclusion, our study was able to suggest biological markers that are non-invasive candidates to evaluate fibrosis and necroinflammatory activity in HC and HC + HSS.
Subject(s)
Adolescent , Adult , Aged , Humans , Middle Aged , Young Adult , Biomarkers/blood , Hepatitis C/blood , Liver Cirrhosis/blood , Liver Diseases, Parasitic/blood , Schistosomiasis/blood , Splenic Diseases/blood , Analysis of Variance , Case-Control Studies , Hepatitis C , Hepatitis C/pathology , Liver Cirrhosis , Liver Cirrhosis/pathology , Liver Diseases, Parasitic , Liver Diseases, Parasitic/pathology , Necrosis/pathology , ROC Curve , Severity of Illness Index , Schistosomiasis , Schistosomiasis/pathology , Splenic Diseases , Splenic Diseases/pathologyABSTRACT
The production and regulation of interleukin (IL) IL-13, IL-4 and interferon-gamma (IFN-gamma) was evaluated in 43 schistosomiasis patients with different clinical forms. Whole-blood cultures cytokine production in response to soluble egg antigen (SEA), soluble worm adult preparation (SWAP), mitogens, neutralizing antibodies or recombinant IL-13 were measured by ELISA. After SWAP stimulation, chronic patients, particularly hepatointestinals, produced higher levels of IL-4 in comparison with acute patients, suggesting the presence of a type 2 cytokine profile in these patients. Following SEA and SWAP stimulation, hepatosplenic (HS) patients showed increased levels of IFN-gamma when compared with acute patients, indicating that HS disease in humans is associated with a type 1 cytokine response. The mechanisms of immune regulation are apparently different between the clinical stages of the disease, some of which are antigen-specific.
Subject(s)
Interferon-gamma/biosynthesis , Interleukin-3/biosynthesis , Interleukin-4/biosynthesis , Schistosomiasis mansoni/immunology , Acute Disease , Adolescent , Adult , Case-Control Studies , Child , Chronic Disease , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged , Schistosomiasis mansoni/metabolism , Young AdultABSTRACT
The production and regulation of interleukin (IL) IL-13, IL-4 and interferon-gamma (IFN-³) was evaluated in 43 schistosomiasis patients with different clinical forms. Whole-blood cultures cytokine production in response to soluble egg antigen (SEA), soluble worm adult preparation (SWAP), mitogens, neutralizing antibodies or recombinant IL-13 were measured by ELISA. After SWAP stimulation, chronic patients, particularly hepatointestinals, produced higher levels of IL-4 in comparison with acute patients, suggesting the presence of a type 2 cytokine profile in these patients. Following SEA and SWAP stimulation, hepatosplenic (HS) patients showed increased levels of IFN-³ when compared with acute patients, indicating that HS disease in humans is associated with a type 1 cytokine response. The mechanisms of immune regulation are apparently different between the clinical stages of the disease, some of which are antigen-specific.
Subject(s)
Adolescent , Adult , Child , Female , Humans , Male , Middle Aged , Young Adult , Interferon-gamma/biosynthesis , /biosynthesis , /biosynthesis , Schistosomiasis mansoni/immunology , Acute Disease , Case-Control Studies , Chronic Disease , Enzyme-Linked Immunosorbent Assay , Schistosomiasis mansoni/metabolism , Young AdultABSTRACT
The aim of this work was to study the difference in interferon gamma (IFN-gamma) production by T lymphocytes after early secretory antigen target 6 (ESAT-6) or purified protein derivate (PPD) stimulation in whole blood culture supernatants from children with suspected tuberculosis (TB) disease (n = 21), latent TB infection (n = 16) and negative controls (NC) (n = 22) from an endemic area in Brazil. The concentration of IFN-gamma (pg/ml) was measured by enzyme linked immunosorbent assay and the differences in the IFN-gamma levels for each group were compared and evaluated using an unpaired Student's t-test; p values < 0.05 were considered significant. Measurement of IFN-gamma levels after ESAT-6 stimulation raised the possibility of early diagnosis in the latent TB group (p = 0.0030). Nevertheless, the same group showed similar responses to the NC group (p > 0.05) after PPD stimulation. The IFN-gamma assay using ESAT-6 as an antigenic stimulus has the potential to be used as a tool for the immunodiagnosis of early TB in children.
Subject(s)
Antigens, Bacterial , Bacterial Proteins , Interferon-gamma/biosynthesis , Mycobacterium tuberculosis/immunology , Tuberculosis, Pulmonary/diagnosis , Adolescent , Antigens, Bacterial/immunology , Bacterial Proteins/immunology , Case-Control Studies , Child , Child, Preschool , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Sensitivity and Specificity , Tuberculosis, Pulmonary/immunologyABSTRACT
The aim of this work was to study the difference in interferon gamma (IFN-gamma) production by T lymphocytes after early secretory antigen target 6 (ESAT-6) or purified protein derivate (PPD) stimulation in whole blood culture supernatants from children with suspected tuberculosis (TB) disease (n = 21), latent TB infection (n = 16) and negative controls (NC) (n = 22) from an endemic area in Brazil. The concentration of IFN-gamma (pg/ml) was measured by enzyme linked immunosorbent assay and the differences in the IFN-gamma levels for each group were compared and evaluated using an unpaired Student's t-test; p values < 0.05 were considered significant. Measurement of IFN-gamma levels after ESAT-6 stimulation raised the possibility of early diagnosis in the latent TB group (p = 0.0030). Nevertheless, the same group showed similar responses to the NC group (p > 0.05) after PPD stimulation. The IFN-gamma assay using ESAT-6 as an antigenic stimulus has the potential to be used as a tool for the immunodiagnosis of early TB in children.
Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Male , Antigens, Bacterial , Bacterial Proteins , Interferon-gamma/biosynthesis , Mycobacterium tuberculosis/immunology , Tuberculosis, Pulmonary/diagnosis , Antigens, Bacterial/immunology , Bacterial Proteins/immunology , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Sensitivity and Specificity , Tuberculosis, Pulmonary/immunologyABSTRACT
Evaluation of hepatic fibrosis is usually performed by histopathological examination of biopsies. However, this is an invasive and potentially dangerous procedure. Several studies have proposed serum biological markers of hepatic fibrosis. This communication evaluates the use of serum cytokines as markers of hepatic fibrosis in hepatitis C, schistosomiasis, and co-infection.
Subject(s)
Adult , Humans , Cytokines/blood , Hepatitis C/immunology , Liver Cirrhosis/parasitology , Schistosomiasis/immunology , Biomarkers/blood , Cytokines/immunology , Enzyme-Linked Immunosorbent Assay , Hepatitis C/complications , /blood , Liver Cirrhosis/immunology , Predictive Value of Tests , Reproducibility of Results , Schistosomiasis/complications , Transforming Growth Factor beta/blood , Tumor Necrosis Factor-alpha/bloodABSTRACT
Evaluation of hepatic fibrosis is usually performed by histopathological examination of biopsies. However, this is an invasive and potentially dangerous procedure. Several studies have proposed serum biological markers of hepatic fibrosis. This communication evaluates the use of serum cytokines as markers of hepatic fibrosis in hepatitis C, schistosomiasis, and co-infection.
Subject(s)
Cytokines/blood , Hepatitis C/immunology , Liver Cirrhosis/parasitology , Schistosomiasis/immunology , Adult , Biomarkers/blood , Cytokines/immunology , Enzyme-Linked Immunosorbent Assay , Hepatitis C/complications , Humans , Interleukin-13/blood , Liver Cirrhosis/immunology , Predictive Value of Tests , Reproducibility of Results , Schistosomiasis/complications , Transforming Growth Factor beta/blood , Tumor Necrosis Factor-alpha/bloodABSTRACT
Specific IgG and IgM responses to soluble egg antigen (SEA) and keyhole limpet haemocyanin (KLH) were measured by ELISA in patients with acute and chronic schistosomiasis. The tests based upon IgM and IgG antibodies responses to KLH presented the best diagnostic discrimination, and can be used in conjunction with clinical and epidemiological data to the differential diagnosis of acute schistosomiasis.
Subject(s)
Antigens, Helminth/blood , Helminth Proteins/blood , Hemocyanins/immunology , Schistosoma mansoni/immunology , Schistosomiasis mansoni/diagnosis , Acute Disease , Animals , Antibodies, Helminth/immunology , Biomarkers/blood , Chronic Disease , Enzyme-Linked Immunosorbent Assay , Hemocyanins/analysis , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Schistosomiasis mansoni/blood , Sensitivity and SpecificityABSTRACT
Specific IgG and IgM responses to soluble egg antigen (SEA) and keyhole limpet haemocyanin (KLH) were measured by ELISA in patients with acute and chronic schistosomiasis. The tests based upon IgM and IgG antibodies responses to KLH presented the best diagnostic discrimination, and can be used in conjunction with clinical and epidemiological data to the differential diagnosis of acute schistosomiasis.
Subject(s)
Humans , Animals , Antigens, Helminth , Schistosoma mansoni , Schistosomiasis mansoni , Acute Disease , Antibodies, Helminth , Biomarkers , Chronic Disease , Enzyme-Linked Immunosorbent Assay , Immunoglobulin G , Immunoglobulin M , Sensitivity and SpecificityABSTRACT
The production and regulation of interleukin (IL) IL-13, IL-4 and interferon-gamma was evaluated in different clinical forms of human schistosomiasis. The mechanisms of immune regulation are apparently different in the various clinical stages of the disease, some of them being antigen specific.
Subject(s)
Interferon-gamma/biosynthesis , Interleukin-13/biosynthesis , Interleukin-4/biosynthesis , Schistosomiasis mansoni/immunology , Acute Disease , Animals , Antigens, Helminth , Chronic Disease , Histocompatibility Antigens Class II , HumansABSTRACT
Whole-blood-cell cultures from schistosomiasis patients were stimulated with a variety of T-cell-dependent and T-cell-independent stimuli to determine whether the defect in type 1 cytokine expression observed following helminth infection is associated with alterations in interleukin-12 (IL-12) or CD40 ligand (CD40L) responsiveness. Cultures from uninfected individuals produced abundant gamma interferon in response to Staphylococcus aureus Cowan 1 (SAC), while patients with intestinal and hepatosplenic disease displayed intermediate and weak responses, respectively. Importantly, the decrease in type 1 cytokine expression was not attributed to defects in IL-12- or CD40L-induced activity. Indeed, schistosomiasis patients displayed heightened responses and even produced more biologically active IL-12 when stimulated with SAC and CD40L than did uninfected controls. Finally, additional studies suggested only a partial role for IL-10, since intestinal patients were the only group that overproduced this downregulatory cytokine. Together, these studies demonstrate that the type 1 deficiency in chronic hepatosplenic schistosomiasis is not related to specific defects in IL-12, IL-10, or CD40L activity, although changes in the functional status of antigen-presenting cells appear to be involved.
Subject(s)
CD40 Ligand/pharmacology , Interleukin-12/pharmacology , Schistosomiasis mansoni/immunology , Staphylococcus aureus/immunology , Th1 Cells/immunology , Adolescent , Adult , Aged , Cells, Cultured , Female , Humans , Interferon-gamma/biosynthesis , Interleukin-10/biosynthesis , Lipopolysaccharides/pharmacology , Male , Middle Aged , Tumor Necrosis Factor-alpha/biosynthesisABSTRACT
The production and regulation of interleukin (IL) IL-13, IL-4 and interferon-gamma was evaluated in different clinical forms of human schistosomiasis. The mechanisms of immune regulation are apparently different in the various clinical stages of the disease, some of them being antigen specific
Subject(s)
Animals , Humans , Interferon-gamma , Interleukin-13 , Interleukin-4 , Schistosomiasis mansoni , Acute Disease , Antigens, Helminth , Chronic Disease , Histocompatibility Antigens Class IIABSTRACT
In this communication the authors analyzed the pattern of expression of IFN-gamma as a surrogate type 1 response in different clinical forms of schistosomiasis in response to stimulation involving T-cell dependent and T-cell independent pathways, to investigate which pathways were functional in human schistosomiasis, and to further characterize the nature of Th1 response impairment in this parasitic disease