Clonality and specificity of cryoglobulins associated with HCV: pathophysiological implications

Background/Aims: Hepatitis C virus (HCV) infection plays a central role in the pathogenesis of mixed cryoglobulinemia through molecular mechanisms which remain to be elucidated. The aim of this study was to investigate the role of antibody responses to HCV in the pathogenesis of cryoglobulinemia through characterization of the anti-HCV specificity and immunochemical characteristics of the immunoglobulins involved in cryoprecipitation.Methods: Sera from 50 consecutive patients with chronic HCV infection (RNA positive) were screened for the presence of cryoglobulins. The two major components of cryoprecipitates, IgM rheumatoid factors and IgG, were separated by high performance liquid chromatography and analyzed for immunochemical composition by immunoblotting and antibody specificity by ELISA and immunoblotting using recombinant HCV proteins and synthetic peptides as antigens.Results: Cryoprecipitates were observed in 27 patients and characterized by immunofixation: 13 (48%) were classified as type II and 14 (52%) as type III. Monoclonal immunoglobulins were detected by immunoblotting in 20 cryoprecipitates: IgM in 14 samples and IgG in 14, which a clear preponderance of IgG3 (). Specificity studies on sera and purified IgM and IgG fractions from cryoprecipitates revealed enrichment in cryoglobulins, predominantly polyclonal IgG1, reactive with the HCV structural proteins, whereas specificities for nonstructural viral proteins were relatively less represented compared to whole serum. No restricted pattern of fine specificity was observed. IgG3 subclass was apparently not involved in HCV nucleoprotein binding.Conclusions: Our findings do not support a direct link between monoclonal cryoglobulins and immune response to HCV. According to the proposed pathogenetic model, HCV infection can induce the formation of cryoprecipitable rheumatoid factors, sustain their production, and eventually lead to monoclonal B-cell expansion through several cooperative mechanisms.     

Survey of US Correctional Institutions for Routine HCV Testing

To ascertain HCV testing practices among US prisons and jails, we conducted a survey study in 2012, consisting of medical directors of all US state prisons and 40 of the largest US jails, that demonstrated a minority of US prisons and jails conduct routine HCV testing. Routine voluntary HCV testing in correctional facilities is urgently needed to increase diagnosis, enable risk-reduction counseling and preventive health care, and facilitate evaluation for antiviral treatment.There are an estimated 4 to 7 million persons in the United States infected with HCV.1,2 Morbidity and mortality from HCV are increasing and in 2007, death from HCV exceeded that from HIV infection for the first time.3,4 Persons who inject drugs are at increased risk for HCV infection and for being incarcerated. Multiple studies have demonstrated high HCV prevalence rates among persons behind bars.5–7 In 2010, the Institute of Medicine (IOM) called for the development of comprehensive viral hepatitis services for incarcerated populations including offering testing, hepatitis B virus vaccination, education, and medical management in partnership with community providers.8Despite the Centers for Disease Control and Prevention (CDC) releasing HCV testing recommendations in 1998 and subsequent recommendations for prevention and control of viral hepatitis within correctional facilities in 2003,9-10 recent studies estimate that 50% of persons infected with HCV are unaware of their infection,11–14 thus reducing opportunities for risk-reduction counseling and treatment. In response to this, the CDC updated HCV testing recommendations for the US general population in 2012, which added at least 1-time testing among persons born between 1945 and 1965, now commonly referred to as the “birth cohort” screening recommendations.15 However, the 2012 recommendations did not provide a specific testing recommendation for incarcerated individuals. Given the increased prevalence of HCV among criminal justice populations, we conducted a survey among US prisons and jails to gain a better understanding of current HCV testing practices within correctional facilities.     

Trends and Differences Among Three New Indicators of HIV Infection Progression

Objective

This study proposes three indicators of, and assesses the disparities and trends in, the risk of HIV infection progression among people living with diagnosed HIV infection in the United States.

Methods

Using data reported to national HIV surveillance through June 2012, we calculated the AIDS diagnosis hazard, HIV (including AIDS) death hazard, and AIDS death hazard for people living with diagnosed HIV infection for each calendar year from 1997 to 2010. We also calculated a stratified hazard in 2010 by age, race/ethnicity, mode of transmission, region of residence at diagnosis, and year of diagnosis.

Results

The risk of HIV infection progression among people living with diagnosed HIV infection decreased significantly from 1997 to 2010. The risks of progression to AIDS and death in 2010 were higher among African Americans and people of multiple races, males exposed through injection drug use (IDU) or heterosexual contact, females exposed through IDU, people residing in the South at diagnosis, and people diagnosed in 2009 compared with white individuals, men who have sex with men, females with infection attributed to heterosexual contact, those residing in the Northeast, and those diagnosed in previous years, respectively. People aged 15–29 years had the highest AIDS diagnosis hazard in 2010.

Conclusion

Continued efforts are needed to ensure early HIV diagnosis as well as initial linkage to and continued engagement in HIV medical care among all people living with HIV. Targeted interventions are needed to improve health-care and supportive services for those with worse health outcomes.In the United States, the number of people aged 13 years and older living with human immunodeficiency virus (HIV) infection was estimated to be more than 1.1 million as of December 2010, a 9% increase from 2006.¹ For people living with HIV, increasing their access to care and eliminating disparities are primary goals of the National HIV/AIDS Strategy (NHAS) and the Healthy People 2020 objectives.^2,3 Assuring that all people with HIV are diagnosed early, promptly linked to care, retained in care, and offered antiretroviral treatment is essential to achieve the ultimate goal of the continuum of care,⁴ leading to viral suppression, improved health, survival, and prevention of HIV transmission.Several studies have used national HIV surveillance data to examine the disparities and determinants of progression to acquired immunodeficiency syndrome (AIDS; i.e., stage 3 HIV infection⁵) and death after HIV diagnosis. These studies have focused on individuals diagnosed in a certain time period and have examined the differences in time from HIV diagnoses to AIDS and death (i.e., the number of months/years from HIV diagnosis to AIDS or death) using survival analyses, including Kaplan-Meier survival curves, the Cox proportional hazard model, or the standardized relative risk.^6–8 However, previous studies have not assessed the risks of progression to AIDS and death among all people living with HIV, and have not reported the trends in these outcomes.To fill this gap, we propose in this study three cross-sectional indicators to estimate the risks of progression to AIDS and death in a calendar year after HIV diagnoses among people living with diagnosed HIV infection, regardless of their time of diagnosis (i.e., the year when an HIV infection was first diagnosed). The results allow for an annual assessment of the risks of HIV infection progression and can be used to monitor the trends in these outcomes among people living with HIV.Specifically, this study (1) examined the disparities in the risk of progression to AIDS in 2010 among people living with diagnosed HIV (not AIDS) infection at year-end 2009 (AIDS diagnosis hazard), the risk of death in 2010 among those living with diagnosed HIV (including AIDS) infection at year-end 2009 (HIV death hazard), and the risk of death in 2010 among individuals living with AIDS at year-end 2009 (AIDS death hazard); and (2) assessed the trends in the risks of HIV infection progression among people living with diagnosed HIV infection from 1997 to 2010 using the three indicators.     

Feasibility and Preliminary Validation of an Online Version of the Ohio State University Traumatic Brain Injury Identification Method

Objective

To test the feasibility and validity of an online version of an established interview designed to determine a lifetime history of traumatic brain injury (TBI).

Prediction of Falls in Subjects Suffering From Parkinson Disease,Multiple Sclerosis,and Stroke

Objective

To compare the risk of falls and fall predictors in patients with Parkinson disease (PD), multiple sclerosis (MS), and stroke using the same study design.