IgE antibodies to hepatitis C virus core and nonstructural antigens in chronic hepatitis C patients before and after antiviral treatment.

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.

Clinical and laboratory aspects of dyslipidemia in Brazilian women with systemic lupus erythematosus.

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.

Higher level of IL-6 in Jaccoud's arthropathy secondary to systemic lupus erythematosus: a perspective for its treatment?

Jaccoud's arthropathy (JA) is a condition characterized clinically by 'reversible' joint deformities along with an absence of articular erosions on a plain radiograph. The main clinical entity associated with JA is systemic lupus erythematosus (SLE) with a prevalence of around 5 %. The aim of the present study was to compare the inflammatory markers including cytokine levels in blood of SLE patients with and without JA. Patients with diagnosis of SLE as defined by ACR criteria were screened and divided in two groups, one with JA and one control group without JA. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complement C3 and C4 levels antinuclear antibodies (ANA), anti-dsDNA antibodies and serum levels of IL-2, IL-6, IL-10, IL-21, IL-22 and TNF-α were determined in all patients. Eighty female patients with SLE, 18 (22.5 %) with JA and 62 (77.5 %) without JA, were included in this study. JA patients had higher disease duration (p = 0.008), ESR (p < 0.001), CRP level (p = 0.002), ANA titer (p < 0.001) and dsDNA antibody level (p = 0.009). The serum levels of IL-2, IL-10, IL-21, IL-22 and TNF-α were not significantly different between the two groups (p > 0.05), but the level of IL-6 was higher in JA group (p < 0.001). The serum level of IL-6 might have a correlation with JA secondary to SLE.

Serum levels of immunoglobulin free light chains in patients with chronic hepatitis C presenting cryoglobulinemia

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.

Jaccoud's Arthropathy in Gout: An Unusual Association.

Jaccoud's arthropathy (JA) is a deforming arthropathy observed mainly in patients with systemic lupus erythematosus. We report the case of a 41-year-old Brazilian man with a 10-year history of intermittent monoarthritis followed by bouts of polyarthritis affecting large and small joints. He presented deformities typical of JA and subcutaneous nodules. Histopathological findings of a nodule biopsy were consistent with gouty tophi. To our knowledge, this is the first report of JA secondary to chronic gout.

Serum levels of immunoglobulin free light chains in patients with chronic hepatitis C presenting cryoglobulinemia.

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.

Serum levels of Th17 associated cytokines in chronic hepatitis C virus infection.

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.

Serum cytokine profile in hepatitis C virus carriers presenting cryoglobulinaemia and non-organ-specific autoantibodies.

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.