Analysis of Successful Immune Responses in Persons Infected with Hepatitis C Virus

Although hepatitis C virus (HCV) infection is very common, identification of patients during acute infection is rare. Consequently, little is known about the immune response during this critical stage of the disease. We analyzed the T lymphocyte response during and after acute resolving HCV infection in three persons, using interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) and human histocompatibility leukocyte antigen (HLA) peptide tetramer assays. Acute infection was associated with a broadly directed T helper and cytotoxic T lymphocyte (CTL) response, which persisted after resolution of clinical hepatitis and clearance of viremia. At the earliest time point studied, highly activated CTL populations were observed that temporarily failed to secrete IFN-γ, a “stunned” phenotype, from which they recovered as viremia declined. In long-term HCV-seropositive persons, CTL responses were more common in persons who had cleared viremia compared with those with persistent viremia, although the frequencies of HCV-specific CTLs were lower than those found in persons during and after resolution of acute HCV infection. These studies demonstrate a strong and persistent CTL response in resolving acute HCV infection, and provide rationale to explore immune augmentation as a therapeutic intervention in chronic HCV infection

The association between negative symptoms, psychotic experiences and later schizophrenia: a population-based longitudinal study.

Psychotic experiences are common in the general population, and predict later psychotic illness. Much less is known about negative symptoms in the general population.This study utilized a sample of 4,914 Israel-born individuals aged 25-34 years who were screened for psychopathology in the 1980's. Though not designed to specifically assess negative symptoms, data were available on 9 self-report items representing avolition and social withdrawal, and on 5 interviewer-rated items assessing speech deficits, flat affect and poor hygiene. Psychotic experiences were assessed using the False Beliefs and Perceptions subscale of the Psychiatric Epidemiology Research Interview. Psychiatric hospitalization was ascertained 24 years later using a nation-wide psychiatric hospitalization registry.After removing subjects with diagnosable psychotic disorders at baseline, 20.2% had at least one negative symptom. Negative symptoms were associated with increased risk of later schizophrenia only in the presence of strong (frequent) psychotic experiences (OR = 13.0, 9% CI: 2.1-79.4).Negative symptoms are common in the general population, though the majority of people with negative symptoms do not manifest a clinically diagnosed psychiatric disorder. Negative symptoms and psychotic experiences critically depend on each other's co-occurrence in increasing risk for later schizophrenia