IgG1 and IgG4 antibodies against core and NS3 antigens of hepatitis C virus

Abstract INTRODUCTION: IgG subclasses involved in the immune response to hepatitis C virus (HCV) antigens have been rarely studied. We investigated the immune response mediated by IgG1 and IgG4 antibodies against the recombinant core and NS3 antigens in patients with chronic hepatitis C. METHODS: Sixty patients infected with HCV genotype 1 without antiviral treatment and 60 healthy subjects participated in the study. Serum levels of alanine aminotransferase, HCV viremia, and the presence of cryoglobulinemia and liver fibrosis were determined. We investigated the serum IgG1 and IgG4 antibodies against recombinant HCV core and NS3 non-structural protein antigens using amplified indirect ELISA. RESULTS: Anti-core and anti-NS3 IgG1 antibodies were detected in 33/60 (55%) and 46/60 (77%) patients, respectively, whereas only two healthy control samples reacted with an antigen (NS3). Anti-core IgG4 antibodies were not detected in either group, while 30/60 (50%) patients had anti-NS3 IgG4 antibodies. Even though there were higher levels of anti-NS3 IgG4 antibodies in patients with low viremia (< 8 × 105 IU/mL), IgG1 and IgG4 antibody levels did not correlate with ALT levels, the presence of cryoglobulinemia, or degree of hepatic fibrosis. High production of anti-core and anti-NS3 IgG1 antibodies was observed in chronic hepatitis C patients. In contrast, IgG4 antibodies seemed to only be produced against the NS3 non-structural antigen and appeared to be involved in viremia control. CONCLUSIONS: IgG1 antibodies against structural and non-structural antigens can be detected in chronic hepatitis C, while IgG4 antibodies seem to be selectively stimulated by non-structural HCV proteins, such as the NS3 antigen.

Thyroid disorders in patients with chronic hepatitis C using interferon-alpha and ribavirin therapy

OBJECTIVE: To investigate the frequency of thyroid disorders (TD) in patients with chronic hepatitis C before and during interferon-alpha (IFN-α) and ribavirin (RIB) treatment. STUDY DESIGN: Prospective study. PATIENTS AND METHODS: We prospectively studied 65 anti-HCV and viral RNA positive patients. Free thyroxine, thyroid-stimulating hormone, and thyroid peroxidase antibodies (TPO-Ab) were systematically tested at entry (m0), week 12 (m3) and week 24 (m6) of treatment. RESULTS: Mean age of the 65 patients (38 females and 27 males) was 49.61 ± 11.83 years. Seven (10.76 percent) patients presented baseline thyroid disorders (m0), three had thyroid dysfunction, and four were TPO-Ab positive. Thyroid disorders occurred in the first 12 weeks of treatment in 11 (16.92 percent) patients, four with thyroid dysfunction, and seven with TPO-Ab positive (m3). A total of 18 patients (27.69 percent) developed TD after 24 weeks of treatment, 7 with thyroid dysfunction, and 11 with TPO-Ab positive (m6). The relative risk of developing hypothyroidism found in this study was 1.3 (95 percent CI: 1.1 to 1.6), hyperthyroidism 1.2 (95 percent CI: 1.1 to 1.4), and TPO-Ab positivity 7.6 (95 percent CI: 3.9 to 14.5). The study showed a significant association between female sex and thyroid disease (p = 0.009). CONCLUSION: Thyroid dysfunction and autoimmune TD were observed during IFN-α and RIB therapy.

Smooth muscle antibodies and cryoglobulinemia are associated with advanced liver fibrosis in Brazilian hepatitis C virus carriers

Cryoglobulinemia and non-organ-specific-autoantibody are biomarkers of autoimmunity of the chronic infection caused by hepatitis C virus (HCV). In this work, we report the association between the presence of smooth muscle antibodies (SMA) and cryoglobulinemia and chronic liver disease in HCV carriers. Sixty-five untreated HCV patients, 38 women and 27 men were included in this study. Cryoglobulinemia was tested by cryoprecipitation, SMA by indirect fluorescent antibody test, and liver fibrosis and hepatocellular inflammation activity was investigated by histology of liver biopsy using the METAVIR score. The prevalence of SMA in the patients was 33.8 percent and cryoglobulinemia was demonstrated in 36.9 percent patients. Cryoglobulinemia and SMA seropositivity was associated with advanced fibrosis (p < 0.05). The presence of SMA and cryoglobulinemia was not associated with hepatocellular inflammation activity, age, carrier gender or HCV genotype. We concluded that liver biopsy should be recommended for HCV carriers that are seropositive for SMA or cryoglobulinemia.

Thyroid dysfunction in hepatitis C individuals treated with interferon-alpha and ribavirin: a review

Hepatitis C (HCV) is now the main cause of chronic hepatic disease, cirrhosis and hepatocellular carcinoma. Several extrahepatic diseases have been associated with chronic HCV infection, and in most cases appear to be directly related to the viral infection. Thyroid disorders are common in patients with chronic HCV. Some patients with chronic hepatitis C experience thyroid problems, and thyroid dysfunction may also be a side effect of interferon-based treatment. The principal risk factor for developing thyroid disease in the course of antiviral therapy is the previous positivity for anti-thyroid antibodies (anti-thyroid peroxidase) especially in older women. Screening for autoantibodies and serum thyroid-stimulating hormone is recommended before, during and after interferon-alpha treatment, and patients should be informed of the risk of thyroid dysfunction. This review includes a summary of thyroid disease associated with chronic HCV infection, interferon-alpha and ribavirin for treatment of HCV and potential to induce thyroid dysfunction.

Ação dos inibidores plasmáticos humanos sobre a atividade da proteinase do Trypanosma cruzi (Chagas, 1909) / Action plasma inhibitors of human activity on the proteinase of Trypanosma cruzi (Chagas, 1909)

No presente trabalho procuramos obter informações sobre as proteínas responsáveis pela atividade inibitória dos soros humanos normais sobre a atividade, proteolítica da proteinase do Trypanosoma cruzi. Na investigação destas proteínas foram realizados testes de inibição da atividade proteinásica com amostras de soros fracionados por eletroforese em gel de agarose e por cromatografia em coluna de Sephadex G-200. Através destes testes foi demonstrado que a atividade inibitória dos soros era mediada por proteínas como mobilidade eletroforética nas regiões das alfa-globulinas, que por sua vez foram eluidas em diferentes volumes da gel-filtração do soro, indicando que possuiam diferentes pesos moleculares. Utilizando-se preparações purificadas de antitrombina III e de alfal-antitripsina foi demonstrada a atividade inibitória destas proteínas sobre a ação proteinásica da enzima do Trypanosoma cruzi. A avaliação da atividade inibitória dos soros procedentes de pacientes com a Doença de Chagas crônica, sobre a proteinase do T. cruzi, indicou uma diminuição desta atividade nas formas clínicas assintomática e cardíaca da doença, enquanto que a mesma se apresentou aumentada nos soros dos pacientes chagásicos com manifestações clínicas digestivas. Foram dosados os níveis de alfa2-macroglobulina, de antitrombina III e de alfal-antitripsina nos soros destes pacientes com a Doença de Chagas crônica, tendo sido verificado que, com exceção da diminuição dos níveis séricos de alfa2-macroglobulina nos indivíduos chagásicos com a forma clínica digestiva, estas proteínas apresentaram-se quantitativamente inalteradas durante esta fase da infecção pelo Trypanosoma cruzi, independentemente da forma clínica testada. Estes resultados sobre a atividade inibitória e níveis de inibidores nos soros dos pacientes chagásicos na fase crônica sugerem uma inativação de parte destas proteínas durante esta fase da doença, assim como a presença de anticorpos com especificidade para a proteinase do Trypanosoma cruzi, produzidos durante a infecção, que poderiam ser capazes de bloquear a atividade proteolítica desta enzima.