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2.
Int Immunopharmacol ; 93: 107405, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33529909

ABSTRACT

Few studies on the immunoglobulin E (IgE) immune response in chronic hepatitis C have been reported. In this study, we tested the antigenicity of commercial recombinant hepatitis C virus (HCV) core and nonstructural protein NS3, NS4, and NS5 antigens and the IgE immune response to these antigens in chronic hepatitis C patients before and after antiviral treatment with pegylated interferon (IFN)-α plus ribavirin for 12 weeks. The effects of antiviral treatment were investigated in 20 out of 35 participants. We developed amplified immunoassays using these antigens and IgG-depleted patient sera. Seropositivity for IgE antibodies was determined, and serum IgE and cytokine levels were measured. Anti-core, anti-NS3, and anti-NS4 IgE antibodies were observed in most patients, whereas anti-NS5 antibodies were less prevalent. Antiviral treatment decreased the production of anti-core, anti-NS3, and anti-NS4 IgE antibodies, but not anti-NS5 IgE antibodies. A significant decrease in the anti-NS3 and anti-NS4 IgE antibody levels was observed in patients who presented with an early sustained virological response, but no effects on anti-core and anti-NS5 IgE antibodies was observed. The serum levels of IFN-γ, interleukin (IL)-2, IL-6, tumor necrosis factor-α, and IL-10, but not IL-4, were similar between patients before and after antiviral therapy. Thus, the immune response of IgE antibodies to HCV antigens was comparable to that of anti-HCV IgG antibodies. The usefulness of anti-NS3 IgE antibodies in diagnosing occult hepatitis C and monitoring antiviral treatment with directly acting antiviral medication must be investigated in future studies.


Subject(s)
Antiviral Agents/therapeutic use , Hepacivirus/physiology , Hepatitis C, Chronic/drug therapy , Interferon-alpha/therapeutic use , Polyethylene Glycols/therapeutic use , Ribavirin/therapeutic use , Viral Core Proteins/immunology , Viral Nonstructural Proteins/immunology , Adult , Aged , Antibodies, Viral/blood , Female , Hepatitis C, Chronic/immunology , Humans , Immunoglobulin E/blood , Male , Middle Aged , Recombinant Proteins/therapeutic use
3.
Cytokine ; 115: 24-31, 2019 03.
Article in English | MEDLINE | ID: mdl-30771700

ABSTRACT

There appears to be an associative link between chronic hepatitis C (CHC) and cardiovascular diseases (CVDs). However, the exact nature of the relationship between CHC and CVDs has not been elucidated. We investigated the presence of CVDs and the clinical and laboratory alterations associated with these diseases in CHC patients. Twenty-six CHC patients, 35 individuals with atherosclerosis (Athero) and 27 healthy individuals were examined for risk factors for CVD, lipid profile, atherogenic risk indexes, and insulin resistance (IR). Cardiac biomarkers and the chemokines and cytokines involved in atherosclerosis were also evaluated. A higher prevalence of prior acute myocardial infarction was found in the Athero group. Most CHC patients were infected with the hepatitis C virus genotype 1 and exhibited either no hepatic fibrosis or a mild to moderate liver fibrosis. The apolipoprotein B/apolipoprotein A-I and triglyceride/high-density lipoprotein cholesterol ratios and C-reactive protein levels were lower in CHC patients than in the Athero group. Further, IR was elevated in the CHC group and associated with the waist circumference. High GDF-15 levels were observed in the CHC group, which were inversely correlated with APOB levels. Peripheral blood mononuclear cells from CHC patients produced more IFN-γ, TNF-α and IL-6 than CAD PBMC but the production of IL-10 and IL-1ß was similar. CHC and CAD groups presented similar levels of IL-8, MCP-1 and LAP-TGF-ß1. Increased IR, elevated levels of GDF-15, and high production of atherogenic cytokines can be observed in Brazilian CHC patients without association with diabetes and clinical manifestation of cardiovascular diseases.


Subject(s)
Cardiovascular Diseases/metabolism , Chemokines/metabolism , Cytokines/metabolism , Hepatitis C, Chronic/metabolism , Adult , Aged , Female , Genotype , Humans , Insulin Resistance/physiology , Leukocytes, Mononuclear/metabolism , Liver Cirrhosis/metabolism , Male , Middle Aged , Waist Circumference/physiology
4.
Clin Rheumatol ; 37(6): 1539-1546, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29516281

ABSTRACT

Systemic lupus erythematosus (SLE) is associated with dyslipidemia, atherosclerosis, and cardiovascular disease. In this study, we investigated the presence of dyslipidemia in Brazilian SLE patients by evaluating their lipid profile and immune status, including the production of autoantibodies and cytokines involved in atherogenesis. Ninety-four female SLE patients participated in this study and, based on their lipid profile, were classified as dyslipidemic or not. All were tested for antinuclear antibodies (ANAs), antiphospholipid antibodies, and autoantibodies to extractable nuclear antigens and double-stranded DNA. Serum levels of apolipoproteins A and B, C3, C4, and C-reactive protein were measured, as well as serum levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-10. Lupus activity was scored according to the Systemic Lupus Erythematosus Disease Activity Index 2000. Sixty-nine patients (73.4%) had dyslipidemia, and the remaining 25 patients (26.6%) were non-dyslipidemic. Lupus activity was correlated with non-high-density lipoprotein cholesterol and triglyceride (TG) levels (non-HDL-C, r = 0.34 and p = 0.0043 and r = 0.46 and p < 0.0001, respectively). Atherogenic indexes apolipoprotein B/apolipoprotein A and TG:HDL-C ratios were higher in dyslipidemic women, and TG:HDL was correlated with disease activity (r = 0.40, p = 0.0007). IL-6, TNF-α, and IL-10 levels were similar between groups; however, a positive correlation between IL-6 and CRP levels was only observed in the group with dyslipidemia (r = 0.55, p < 0.0001). Female Brazilian SLE patients present a high prevalence of dyslipidemia and exhibit a higher risk of cardiovascular diseases as compared with female SLE patients without dyslipidemia and healthy individuals.


Subject(s)
Atherosclerosis/etiology , Dyslipidemias/etiology , Lupus Erythematosus, Systemic/complications , Adult , Brazil/epidemiology , Cytokines/blood , Dyslipidemias/blood , Dyslipidemias/epidemiology , Dyslipidemias/immunology , Female , Humans , Lipids/blood , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/epidemiology , Lupus Erythematosus, Systemic/immunology , Middle Aged , Risk Assessment
6.
Cytokine ; 102: 200-205, 2018 02.
Article in English | MEDLINE | ID: mdl-28969940

ABSTRACT

Hepatitis C virus (HCV) chronic infection causes severe cellular immune dysfunction. Here, we investigated the production of Th17-associated cytokines by peripheral blood mononuclear cells (PBMCs) of untreated patients with HCV, patients presenting an early virologic response (EVR) after 12weeks of treatment with interferon-α plus ribavirin with or without HCV protease inhibitors, and patients who were nonresponders to HCV therapy. PBMCs were stimulated with HCV core and nonstructural antigens, and the production of Th17-associated cytokines was measured with a Milliplex MAP immunoassay. Core-stimulated PBMCs from both untreated and nonresponder patients produced interleukin (IL)-17A, and vigorous production of IL-17A in response to NS3 antigen was only verified in the untreated group. Nonresponder patients also produced IL-17F after core antigen stimulation. IL-21 production was unaltered in the three groups of patients, whereas IL-17E and IL-22 were not detected. The production of Th17 cytokines by cells from patients showing an EVR was insignificant. IL-17A and IL-17F levels were not correlated with alanine aminotransferase levels or viremia. However, advanced fibrosis was associated with higher IL-17A production in T0 cells stimulated with core antigen. Untreated patients with HCV and patients who were nonresponders to antiviral treatment differed in their PBMC immune responses of Th17-associated cytokines. The early virological response to antiviral treatment dramatically decreased Th17 immune responses to HCV antigens.


Subject(s)
Cytokines/blood , Hepatitis C, Chronic/immunology , Leukocytes, Mononuclear/immunology , Th17 Cells/immunology , Adult , Aged , Antiviral Agents/therapeutic use , Female , Hepacivirus/immunology , Hepatitis C Antigens/immunology , Hepatitis C, Chronic/blood , Hepatitis C, Chronic/drug therapy , Humans , Immunity, Cellular , Interferon-alpha/therapeutic use , Interleukin-17/blood , Interleukins/blood , Male , Middle Aged , Protease Inhibitors/therapeutic use , Ribavirin/therapeutic use , Sustained Virologic Response , Interleukin-22
7.
PLoS One ; 11(5): e0156733, 2016.
Article in English | MEDLINE | ID: mdl-27243459

ABSTRACT

Visceral leishmaniasis (VL) is a disease caused by Leishmania infantum, which is transmitted by phlebotomine sandflies. Dogs are the main urban reservoir of this parasite and the disease presents similar characteristics in both humans and dogs. In this paper, we investigated the potential pathways involved in plasma cell replacement of normal cell populations in the spleen, with respect to disease severity in dogs from an endemic area for visceral leishmaniasis. To this end, canine spleen samples were grouped into three categories: TYPE1SC- (non-infected dogs or without active infection with organized white pulp), TYPE1SC+ (infected dogs with organized white pulp) or TYPE3SC+ (infected animals with disorganized white pulp). We analyzed the distribution of different plasma cell isotypes (IgA, IgG and IgM) in the spleen. The expression of cytokines and chemokines involved in plasma cell homing and survival were assessed by real time RT-PCR. Polyclonal B cell activation and hypergammaglobulinemia were also evaluated. The proportion of animals with moderate or intense plasmacytosis was higher in the TYPE3SC+ group than in the other groups (Fisher test, P<0.05). This was mainly due to a higher density of IgG+ plasma cells in the red pulp of this group. The albumin/globulin ratio was lower in the TYPE3SC+ animals than in the TYPE1SC- or TYPE1SC+ animals, which evidences VL-associated dysproteinemia. Interestingly, TYPE3SC+ animals showed increased expression of the BAFF and APRIL cytokines, as well as chemokine CXCL12. Aberrant expression of BAFF, APRIL and CXCL12, together with amplified extrafollicular B cell activation, lead to plasma cell homing and the extended survival of these cells in the splenic red pulp compartment. These changes in the distribution of immunocompetent cells in the spleen may contribute to the progression of VL, and impair the spleen's ability to protect against blood borne pathogens.


Subject(s)
Dog Diseases/parasitology , Leishmania infantum/immunology , Leishmaniasis, Visceral/pathology , Leishmaniasis, Visceral/parasitology , Lymphoid Tissue/immunology , Plasma Cells/immunology , Spleen/immunology , Animals , Antibodies, Protozoan/blood , Antibodies, Protozoan/immunology , B-Cell Activating Factor/biosynthesis , Chemokine CXCL12/biosynthesis , Dogs , Hypergammaglobulinemia/immunology , Immunoglobulin A/blood , Immunoglobulin A/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Leishmania infantum/genetics , Lymphocyte Activation/immunology , Lymphoid Tissue/cytology , Lymphoid Tissue/parasitology , Serum Albumin/analysis , Spleen/cytology , Spleen/parasitology , Tumor Necrosis Factor Ligand Superfamily Member 13/biosynthesis
8.
Microb Pathog ; 91: 155-60, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26718098

ABSTRACT

Chronic infection with hepatitis C virus (HCV) causes a quantitative and functional alteration in innate and adaptative immunity. In the present work, we determined by flow-cytometry the profile of blood lymphocyte of untreated HCV patients and in subjects of this group that achieved or not an early virologic response at 12-weeks of treatment with interferon-α plus ribavirin. Twenty-six untreated HCV patients and 20 control healthy individuals were enrolled in the study. Untreated HCV patients had a higher proportion of B cell and a lower proportion of CD8(+) T cell and NK cells than healthy individuals did, but the proportions of CD4(+) T cells and Treg cells (CD4(+)CD25(+)Foxp3(+)) were similar in these patients and controls. Untreated HCV patients presenting cryoglobulinemia had a lower proportion of Treg cells and a lower Treg/NK cell ratio when compared with those without cryoglobulins. Nineteen out of 26 untreated HCV patients remained in the study and were treated with Interferon-α plus ribavirin. At 12-weeks of treatment, 10 of them achieved early virologic response (EVR), whereas 9 were non-responders (NR). EVR patients differed from NR patients in the increase of their proportion of NK cells at 12 weeks of treatment. In conclusion, untreated HCV patients exhibit an altered profile of blood lymphocyte subsets, including a reduction in the proportion of CD4(+)CD25(+)FoxP3(+)T regulatory cells in patients that present cryoglobulinemia. An early virological response at 12-weeks of treatment with IFN-α plus ribavirin seems to be associated a significant improvement in the proportion of NK cells of HCV treated patients.


Subject(s)
Antiviral Agents/administration & dosage , Hepacivirus/drug effects , Hepatitis C, Chronic/drug therapy , Interferon-alpha/administration & dosage , Ribavirin/administration & dosage , Adult , Aged , Drug Therapy, Combination , Female , Hepacivirus/physiology , Hepatitis C, Chronic/immunology , Hepatitis C, Chronic/virology , Humans , Male , Middle Aged , T-Lymphocyte Subsets/drug effects , T-Lymphocyte Subsets/immunology , Treatment Outcome
9.
J Immunol Res ; 2015: 814748, 2015.
Article in English | MEDLINE | ID: mdl-26583157

ABSTRACT

We investigated in Brazilian women with SLE the prevalence and levels of high avidity (HA) dsDNA antibodies and tested their correlation with lupus activity and biomarkers of renal disease. We also compared these correlations to those observed with total dsDNA antibodies and antibodies against nucleosome (ANuA). Autoantibodies were detected by ELISA, while C3 and C4 levels were determined by nephelometry. Urine protein/creatinine ratio was determined, and lupus activity was measured by SLEDAI-2K. The prevalence of total and HA dsDNA antibodies was similar to but lower than that verified for ANuA. The levels of the three types of antibodies were correlated, but the correlation was more significant between HA dsDNA antibodies and ANuA. High avidity dsDNA antibodies correlated positively with ESR and SLEDAI and inversely with C3 and C4. Similar correlations were observed for ANuA levels, whereas total dsDNA antibodies only correlated with SLEDAI and C3. The levels of HA dsDNA antibodies were higher in patients with proteinuria, but their levels of total dsDNA antibodies and ANuA were unaltered. High avidity dsDNA antibodies can be found in high prevalence in Brazilian women with SLE and are important biomarkers of active disease and kidney dysfunction.


Subject(s)
Antibodies, Antinuclear/immunology , Antibody Affinity/immunology , Lupus Erythematosus, Systemic/immunology , Adolescent , Adult , Aged , Antibodies, Antinuclear/blood , Biomarkers , Brazil , Complement C3/immunology , Complement C4/immunology , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Lupus Erythematosus, Systemic/pathology , Lupus Erythematosus, Systemic/physiopathology , Middle Aged , Proteinuria/etiology , Proteinuria/metabolism , Young Adult
10.
Rheumatol Int ; 35(10): 1773-7, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26310503

ABSTRACT

Jaccoud's arthropathy (JA) is a clinical situation nowadays present mostly in systemic lupus erythematosus (SLE). It is characterized by the presence of joint deformities such as "swan neck," ulnar deviation and "Z-thumb" resembling rheumatoid arthritis (RA) but that are passively correctable and without bone erosion on plain radiographs. From our cohort of SLE patients with JA, we selected a subgroup with a more severe form of this arthropathy and looked at their clinical and laboratory profile as well as studied the magnetic resonance imaging (MRI) findings or ultrasound (US) obtained from the hand with most evident deformities. Seven SLE patients with a severe form of JA were identified. All seven patients have "swan neck," ulnar deviation and "Z-thumb" deformities. Two out of seven had "mutilans-type JA" and four had fixed deformities in the metacarpophalangeal (MCP) joints. The MRI of the hand with more evident deformity clinically performed in six cases and US performed in one case showed mild synovitis in five and moderate synovitis in two patients, mild flexor tenosynovitis in six and severe tenosynovitis in one. Only two small bone erosions were observed in the second and third MCP joints of one patient with moderate synovitis. Severe JA compromises the functional capacity of the joints and imposes the risk of misdiagnosis of RA. With the improvement of the survival rate of SLE and the lack of specific prophylactic or therapeutical measures for JA, it is reasonable to assume that more and more cases of severe JA are going to be identified.


Subject(s)
Fingers , Hand Deformities, Acquired/etiology , Joint Diseases/etiology , Lupus Erythematosus, Systemic/complications , Adult , Aged , Female , Humans , Male , Middle Aged
11.
Braz. j. infect. dis ; 18(6): 638-642, Nov-Dec/2014. tab, graf
Article in English | LILACS | ID: lil-730423

ABSTRACT

Hepatitis C virus (HCV) infects B-lymphocytes, provokes cellular dysfunction and causes lymphoproliferative diseases such as cryoglobulinemia and non-Hodgkin's B-cell lymphoma. In the present study, we investigated the serum levels of kappa and lambda free light chains (FLC) of immunoglobulins and the kappa/lambda FLC ratio in Brazilian patients with chronic HCV infection and cryoglobulinemia. We also analyzed the immunochemical composition of the cryoglobulins in these patients. Twenty-eight cryoglobulinemic HCV patients composed the target group, while 37 HCV patients without cryoglobulinemia were included as controls. The median levels of kappa and lambda FLC were higher in patients with cryoglobulinemia compared to controls (p = 0.001 and p = 0.003, respectively), but the kappa/lambda FLC ratio was similar in patients with and without cryoglobulinemia (p > 0.05). The median FLC ratio was higher in HCV patients presenting with advanced fibrosis of the liver compared to HCV patients without fibrosis (p = 0.004). Kappa and lambda FLC levels were strongly correlated with the IgA, IgG and IgM levels in the patients with cryoglobulinemia. In patients without cryoglobulinemia, the kappa FLC level was only correlated with the IgG level, whereas the lambda FLC were weakly correlated with the IgA, IgG and IgM levels. An immunochemical pattern of mixed cryoglobulins (MC), predominantly IgM, IgG, IgA and kappa light chain, was verified in these immune complexes. We concluded that HCV-infected patients presenting cryoglobulinemia have vigorous polyclonal B-lymphocyte activation due to chronic HCV infection and persistent immune stimulation.


Subject(s)
Female , Humans , Male , Middle Aged , Cryoglobulinemia/etiology , Cryoglobulins/analysis , Hepatitis C, Chronic/complications , Immunoglobulin kappa-Chains/blood , Immunoglobulin lambda-Chains/blood , Case-Control Studies , Hepatitis C, Chronic/blood , Immunohistochemistry , Immunoglobulin G/blood , Immunoglobulin M/blood
12.
Braz J Infect Dis ; 18(6): 638-42, 2014.
Article in English | MEDLINE | ID: mdl-25193081

ABSTRACT

Hepatitis C virus (HCV) infects B-lymphocytes, provokes cellular dysfunction and causes lymphoproliferative diseases such as cryoglobulinemia and non-Hodgkin's B-cell lymphoma. In the present study, we investigated the serum levels of kappa and lambda free light chains (FLC) of immunoglobulins and the kappa/lambda FLC ratio in Brazilian patients with chronic HCV infection and cryoglobulinemia. We also analyzed the immunochemical composition of the cryoglobulins in these patients. Twenty-eight cryoglobulinemic HCV patients composed the target group, while 37 HCV patients without cryoglobulinemia were included as controls. The median levels of kappa and lambda FLC were higher in patients with cryoglobulinemia compared to controls (p=0.001 and p=0.003, respectively), but the kappa/lambda FLC ratio was similar in patients with and without cryoglobulinemia (p>0.05). The median FLC ratio was higher in HCV patients presenting with advanced fibrosis of the liver compared to HCV patients without fibrosis (p=0.004). Kappa and lambda FLC levels were strongly correlated with the IgA, IgG and IgM levels in the patients with cryoglobulinemia. In patients without cryoglobulinemia, the kappa FLC level was only correlated with the IgG level, whereas the lambda FLC were weakly correlated with the IgA, IgG and IgM levels. An immunochemical pattern of mixed cryoglobulins (MC), predominantly IgM, IgG, IgA and kappa light chain, was verified in these immune complexes. We concluded that HCV-infected patients presenting cryoglobulinemia have vigorous polyclonal B-lymphocyte activation due to chronic HCV infection and persistent immune stimulation.


Subject(s)
Cryoglobulinemia/etiology , Cryoglobulins/analysis , Hepatitis C, Chronic/complications , Immunoglobulin kappa-Chains/blood , Immunoglobulin lambda-Chains/blood , Case-Control Studies , Female , Hepatitis C, Chronic/blood , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Immunohistochemistry , Male , Middle Aged
13.
Int Immunopharmacol ; 18(1): 66-70, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24252254

ABSTRACT

The anti-inflammatory effect of 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (statins) has been investigated in dyslipidemic patients treated with these pharmacologic agents. The aim of this study was to investigate the serum levels of cytokines and chemokines that have been associated with atherosclerosis and cardiovascular disease in Brazilian patients treated for hypercholesterolemia with statin. The serum levels of the cytokines IL-1ß, IL-6, IL-10, TNF-α and TGF-ß, and the levels of the chemokines IL-8 (CXCL8) and MCP-1 were determined by enzyme-linked immunosorbent assay and tested for their association with cardiovascular disease. The suppression of circulating levels of TNF-α, MCP-1 and IL-8 and their enhancing effect on IL-10 and TGF-ß production were more pronounced in male patients. Female patients treated with statins who had a previous myocardial infarction presented higher median levels of both TNF-α and IL-8 (P<0.05) and a lower median level of IL-10 than female patients without MI (P<0.05). Except in women with a previous myocardial infarction, the treatment of dyslipidemic Brazilian patients with statins down-modulates the production of atherogenic cytokines and chemokines and increases the circulating levels of anti-atherogenic cytokines.


Subject(s)
Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/immunology , Dyslipidemias/drug therapy , Dyslipidemias/immunology , Simvastatin/administration & dosage , Adult , Aged , Atherosclerosis/immunology , Brazil , Chemokine CCL2/blood , Chemokine CXCL9/blood , Chemokines/blood , Cytokines/blood , Female , Gene Expression Regulation/drug effects , Humans , Male , Middle Aged , Simvastatin/adverse effects , Treatment Outcome , Young Adult
14.
Cytokine ; 60(1): 138-42, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22748467

ABSTRACT

The Th17-mediated immune response was investigated in patients chronically infected with hepatitis C virus (HCV) by determining the serum levels of the cytokines involved in the induction of the Th17 response (TGF-ß and IL-6), the cytokines produced by Th17 cells (IL-17A, IL-17F and IL-22) and the cytokines whose production is stimulated by Th17 lymphocytes (IL-8 and GM-CSF). We investigated the relationships among the levels of these cytokines by assessing clinical findings, liver histology and viremia. Sixty untreated patients and 28 healthy individuals were included in the study. Cytokine levels were determined using ELISA. Differences between HCV and control groups were identified in the median levels of IL-17F (controls=172.4 pg/mL; HCV=96.8 pg/mL, p<0.001) and IL-8 (controls=30.1 pg/mL; HCV=18.1 pg/mL, p<0.05). IL-6 levels were higher in patients presenting moderate liver necroinflammation than in patients with mild or no liver necroinflammation (p<0.05). IL-17F levels were increased in patients that had increased ALT levels. Additionally, a strong positive correlation was observed between IL-17F and IL-22 levels in the two groups investigated, and the IL-17F/IL-22 ratio was lower in the patients infected with HCV (p<0.0001). Patients with low HCV viral loads had higher median levels of IL-8 (32.5 pg/mL) than did patients with high HCV loads (16.7 pg/mL, p<0.05). These results suggest that in chronic hepatitis C infection, IL-17F and IL-8 could be associated with the control of liver injury and infection, respectively.


Subject(s)
Cytokines/immunology , Hepacivirus/immunology , Hepatitis C, Chronic/immunology , Th17 Cells/immunology , Adult , Aged , Alanine Transaminase/blood , Alanine Transaminase/immunology , Cytokines/blood , Enzyme-Linked Immunosorbent Assay , Female , Granulocyte-Macrophage Colony-Stimulating Factor/blood , Granulocyte-Macrophage Colony-Stimulating Factor/immunology , Hepacivirus/physiology , Hepatitis C, Chronic/blood , Hepatitis C, Chronic/virology , Host-Pathogen Interactions/immunology , Humans , Interleukin-17/blood , Interleukin-17/immunology , Interleukin-6/blood , Interleukin-6/immunology , Interleukin-8/blood , Interleukin-8/immunology , Interleukins/blood , Interleukins/immunology , Liver/immunology , Liver/pathology , Liver/virology , Male , Middle Aged , Th17 Cells/metabolism , Transforming Growth Factor beta/blood , Transforming Growth Factor beta/immunology , Viral Load , Interleukin-22
15.
Autoimmun Rev ; 10(4): 210-3, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20951240

ABSTRACT

BACKGROUND: Ferritin and prolactin have been associated with active autoimmune diseases as systemic lupus erythematosus and autoantibody production, but have been little studied in viral infections that present autoimmunity. OBJECTIVE: To investigate the association of these two autoimmune mediators with the presence of cryoglobulinaemia and non-organ-specific autoantibodies (RF, SMA, ß2GPI IgA antibody and ANA) in Brazilian individuals chronically infected with hepatitis C virus (HCV). METHODS: Ninety-nine patients were evaluated. Ferritin and prolactin levels were determined by chemiluminescent immunoassays. RESULTS: Hyperprolactinemia was found in 10 (six men and four women) out of 99 (10.1%) hepatitis C patients. Thirty-eight out of 99 (38.4%) HCV carriers had hyperferritinemia (median level 385ng/mL). Neither hyperprolactinemia nor hyperferritinemia was associated with cryoglobulinaemia or non-organ-specific autoantibodies (p>.05). There was an association between hyperprolactinemia and the infection with HCV genotype 3 (p<.01). Ferritin and ALT levels were correlated (p<.05). CONCLUSION: Our results suggest that neither prolactin nor ferritin is involved with the extra-hepatic manifestation of autoimmunity observed in HCV carriers.


Subject(s)
Autoimmunity , Carrier State , Ferritins/immunology , Hepatitis C, Chronic/immunology , Prolactin/immunology , Adult , Autoantibodies/blood , Carrier State/blood , Carrier State/immunology , Cryoglobulinemia/complications , Female , Ferritins/blood , Hepacivirus/immunology , Hepatitis C, Chronic/complications , Humans , Hyperprolactinemia/complications , Iron Metabolism Disorders/complications , Male , Middle Aged , Prolactin/blood
16.
Lipids Health Dis ; 9: 91, 2010 Aug 27.
Article in English | MEDLINE | ID: mdl-20799970

ABSTRACT

BACKGROUND: The search for sickle cell disease (SCD) prognosis biomarkers is a challenge. These markers identification can help to establish further therapy, later severe clinical complications and with patients follow-up. We attempted to study a possible involvement of levels of high-density lipoprotein cholesterol (HDL-C) in steady-state children with SCD, once that this lipid marker has been correlated with anti-inflammatory, anti-oxidative, anti-aggregation, anti-coagulant and pro-fibrinolytic activities, important aspects to be considered in sickle cell disease pathogenesis. METHODS: We prospectively analyzed biochemical, inflammatory and hematological biomarkers of 152 steady-state infants with SCD and 132 healthy subjects using immunochemistry, immunoassay and electronic cell counter respectively. Clinical data were collected from patient medical records. RESULTS: Of the 152 infants investigated had a significant positive association of high-density lipoprotein cholesterol with hemoglobin (P < 0.001), hematocrit (P < 0.001) and total cholesterol (P < 0.001) and a negative significant association with reticulocytes (P = 0.046), leukocytes (P = 0.015), monocytes (P = 0.004) and platelets (P = 0.005), bilirubins [total bilirubin (P < 0.001), direct bilirubin (P < 0.001) and indirect bilirubin (P < 0.001], iron (P < 0.001), aminotransferases [aspartate aminotransferase (P = 0.004), alanine aminotransferase (P = 0.035)], lactate dehydrogenase (P < 0.001), urea (P = 0.030), alpha 1-antitrypsin (P < 0.001), very low-density lipoprotein cholesterol (P = 0.003), triglycerides (P = 0.005) and hemoglobin S (P = 0.002). Low high-density lipoprotein cholesterol concentration was associated with the history of cardiac abnormalities (P = 0.025), pneumonia (P = 0.033) and blood transfusion use (P = 0.025). Lipids and inflammatory markers were associated with the presence of cholelithiasis. CONCLUSIONS: We hypothesize that some SCD patients can have a specific dyslipidemic subphenotype characterized by low HDL-C with hypertriglyceridemia and high VLDL-C in association with other biomarkers, including those related to inflammation. This represents an important step toward a more reliable clinical prognosis. Additional studies are warranted to test this hypothesis and the probably mechanisms involved in this complex network of markers and their role in SCD pathogenesis.


Subject(s)
Anemia, Sickle Cell/blood , Anemia, Sickle Cell/physiopathology , Cholesterol, HDL/blood , Dyslipidemias/blood , Dyslipidemias/complications , Adolescent , Anemia, Sickle Cell/complications , Anemia, Sickle Cell/diagnosis , Biomarkers/blood , Brazil/epidemiology , Child , Cholelithiasis/complications , Cholelithiasis/epidemiology , Dyslipidemias/epidemiology , Female , Heart Defects, Congenital/complications , Heart Defects, Congenital/epidemiology , Hemolysis , Humans , Inflammation Mediators/blood , Lipids/blood , Male , Medical Records , Pneumonia/complications , Pneumonia/epidemiology , Prevalence , Prognosis
17.
Microb Pathog ; 48(2): 53-6, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20005287

ABSTRACT

This work investigated the serum cytokine profile (IL-2, IL-4, IL-5, IL-10, IFN-gamma and BAFF) of hepatitis C virus (HCV) carriers with autoimmunity. Forty-seven HCV carriers and 28 healthy controls were evaluated. Cytokine levels were measured by ELISA. Patients and controls presented similar levels of IL-2, IL-4, IL-5, IL-10, IFN-gamma and BAFF (p>0.05). Cryoglobulinaemic HCV carriers had increased IL-2 (p=0.013), IL-5 (p=0.018) and BAFF (p=0.050). IFN-gamma level was decreased in HCV carriers with rheumatoid factor in comparison with those that were RF-seronegative (p=0.035). Patients with beta2GPI IgA antibodies when were compared with those without this autoantibody, had more serum IL-2 (p=0.009), IL-5 (p=0.018) and BAFF (p=0.039). Interleukin-2 was increased in HCV carriers with positive ANA when they were compared with ANA-seronegative carriers (p=0.044). Interleukins IL-4 and IL-10 were not associated with autoimmunity (P>0.05). In HCV carriers, IL-2 was correlated with IL-5 (p<0.0001) and IFN-gamma (p=0.015), and IL-5 with IFN-gamma (p=0.015). We concluded that the serum profile of cytokines in HCV carriers presenting autoimmune markers may be mainly represented by increased IL-2, IL-5 and BAFF.


Subject(s)
Autoantibodies/blood , Carrier State/immunology , Cryoglobulinemia/immunology , Cytokines/blood , Hepatitis C, Chronic/immunology , Autoimmunity , B-Cell Activating Factor/blood , Cryoglobulinemia/complications , Enzyme-Linked Immunosorbent Assay , Female , Hepacivirus/classification , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/virology , Humans , Interleukin-2/blood , Interleukin-5/blood , Male , Middle Aged , Rheumatoid Factor/blood
18.
Pediatr Allergy Immunol ; 15(2): 142-7, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15059190

ABSTRACT

Helminthic infections and allergic diseases are highly prevalent in many parts of the world. Although skin reactivity to indoor allergens is decreased in subjects from helminthic endemic areas, the degree of exposure to mite allergens has not yet been investigated in these areas. This study evaluated the association between exposure to dust mites and skin reactivity to mite allergens in subjects with a history of wheezing in the last 12 months selected from a rural endemic area for schistosomiasis (group I, n = 21), and two non-Schistosoma mansoni endemic locale, a rural area (group II, n = 21) and a urban slum area (group III, n = 21). All subjects were evaluated by skin prick tests with mite allergens, and for total and specific immunoglobulin E (IgE) against dust mites, antibodies for S. mansoni, and for intestinal parasites. Dust samples from each subjects' home were quantified for mite allergen and species of the mite identification. Except for S. mansoni infection which was more prevalent in group I than in groups II and III (p < 0.0001), the prevalence of intestinal parasites, and total and specific IgE levels were similar for all groups. Despite the levels of mite allergens and specifically to Der p 1 detected in dust samples of subjects home from all three areas, the frequency of positive skin reactivity to mite antigens was significantly lower (19.0%) in subjects from group I relative to group II (76.2%) and group III (57.1%; p < 0.001). This result suggests that S. mansoni infection could modulate the immediate hypersensitivity skin response to mite allergens in highly exposed subjects.


Subject(s)
Asthma/immunology , Hypersensitivity, Immediate/complications , Hypersensitivity, Immediate/immunology , Schistosomiasis mansoni/immunology , Adolescent , Adult , Asthma/complications , Child , Dust/analysis , Dust/immunology , Environmental Exposure , Environmental Monitoring/methods , Female , Humans , Immunoglobulin E/immunology , Male , Schistosomiasis mansoni/complications , Skin Tests/methods
19.
J Allergy Clin Immunol ; 111(5): 947-51, 2003 May.
Article in English | MEDLINE | ID: mdl-12743556

ABSTRACT

BACKGROUND: Helminthic infections decrease skin reactivity to indoor allergens, but data on whether they influence asthma severity are lacking. OBJECTIVE: This study evaluated the course of asthma in patients with and without Schistosoma mansoni infection. METHODS: Asthmatic subjects were enrolled from 3 low-socioeconomic areas: a rural area endemic for schistosomiasis (group 1) in addition to a rural area (group 2) and a slum area (group 3), both of which were not endemic for schistosomiasis. A questionnaire on the basis of the International Study of Asthma and Allergies in Childhood study was applied in these 3 areas, and from each area, 21 age- and sex-matched asthmatic subjects were selected for a prospective 1-year study. Pulmonary function tests, skin prick tests with indoor allergens, stool examinations, and serum evaluations were performed in these subjects. Every 3 months, the subjects were evaluated for asthma exacerbation through physical examination, and a questionnaire regarding asthma symptoms and use of antiasthma medicine was administered. RESULTS: The prevalence of S mansoni infection was greater in group 1 compared with in groups 2 and 3 (P <.0001), whereas the frequency of other helminth and protozoa infections was similar among the 3 groups. The frequency of positive skin test responses to indoor allergens was less (19.0%) in group 1 subjects relative to those in group 2 (76.2%) and group 3 (57.1%; P <.001). The frequencies of symptoms, use of antiasthma drugs, and pulmonary abnormal findings at physical examination were less in group 1 subjects than in group 2 and 3 subjects (P =.0001). CONCLUSION: Our results suggest that S mansoni infection is associated with a milder course of asthma.


Subject(s)
Asthma/prevention & control , Schistosomiasis mansoni/immunology , Adolescent , Antibodies, Helminth/blood , Female , Histamine Release , Humans , Immunoglobulin E/blood , Interleukin-10/biosynthesis , Male , Skin Tests
20.
Int Arch Allergy Immunol ; 129(3): 237-41, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12444321

ABSTRACT

BACKGROUND: Mite allergens have been involved in airway sensitization and allergic diseases. Immunoassays for the identification and quantifiction of house dust mite (HDM) allergens are useful to improve the knowledge of regional mite fauna and the remediation of mite allergens in allergic diseases. The present study analyzed the association between levels of HDM allergen and results of mite identification or skin prick test (SPT) in two different areas of Bahia, Brazil. METHODS: Forty-two asthmatic subjects from a rural area (group I; n = 21) and a slum (group II; n = 21) were evaluated through SPT with HDM allergens and had dust samples collected at their homes for mite identification and allergen measurements. RESULTS: Positive SPT to Dermatophagoides pteronyssinus, Dermatophagoides farinae and Blomia tropicalis allergens were observed in 42.9, 38.0 and 42.9% subjects from group I and in 47.6, 19.0 and 33.3% subjects from group II, respectively. D. pteronyssinus and B. tropicalis were identified in approximately 76 and 50% of samples from both groups, respectively. D. farinae was identified in 38.0 and 9.5% of samples from groups I and II, respectively (p < 0.005). Der p 1, Der f 1 and Blo t 5 detection were associated with mite identification (p < 0.05). Association between HDM allergen levels over 2 microg/g of dust and positive SPT occurred only with D. pteronyssinus (p < 0.0001). CONCLUSIONS: D. pteronyssinus was the most prevalent mite species in this study followed by B. tropicalis and D. farinae. Immunoassays done to measure mite allergens were associated with mite-species identification. We conclude that these three mite species must be included on panels for the diagnosis of allergic airway diseases in subjects living in such regions.


Subject(s)
Air Pollution, Indoor/analysis , Allergens/classification , Allergens/immunology , Antigens, Dermatophagoides/classification , Antigens, Dermatophagoides/immunology , Asthma/immunology , Microscopy , Pyroglyphidae/classification , Pyroglyphidae/immunology , Skin Tests , Adolescent , Adult , Air Pollution, Indoor/adverse effects , Antigens, Plant , Arthropod Proteins , Brazil , Child , Cysteine Endopeptidases , Female , Humans , Male , Rural Health , Statistics as Topic
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