Systemic translocation of Staphylococcus drives autoantibody production in HIV disease.

BACKGROUND: Increased autoreactive antibodies have been reported in HIV disease; however, the mechanism accounting for autoantibody induction in HIV remains unknown. RESULTS: Herein, we show that seasonal influenza vaccination induces autoantibody production (e.g., IgG anti-nuclear antibody (ANA) and anti-double-stranded DNA antibody (anti-dsDNA)) in some viral-suppressed antiretroviral therapy (ART)-treated HIV+ subjects, but not in healthy controls. These autoantibodies were not derived from antigen-specific B cells but from activated "bystander" B cells analyzed by single-cell assay and by study of purified polyclonal ANAs from plasma. To explore the mechanism of autoantibody generation in HIV+ subjects, plasma level of microbial products, gene expression profile of B cells, and B cell receptor (BCR) repertoires were analyzed. We found that autoantibody production was associated with increased plasma level of microbial translocation; the patients with high autoantibodies had skewed B cell repertoires and upregulation of genes related to innate immune activation in response to microbial translocation. By analyzing circulating microbial 16S rDNA in plasma, the relative abundance of Staphylococcus was found to be associated with autoantibody production in HIV+ subjects. Finally, we found that injection of heat-killed Staphylococcus aureus promoted germinal center B cell responses and autoantibody production in mice, consistent with the notion that autoantibody production in HIV+ patients is triggered by microbial products. CONCLUSIONS: Our results showed that translocation of Staphylococcus can promote B cell activation through enhancing germinal center response and induces autoantibody production. It uncovers a potential mechanism linking microbial translocation and autoimmunity in HIV+ disease and provides a strong rationale for targeting Staphylococcus to prevent autoantibody production.

The Use of Qualitative Methods in Developing Implementation Strategies in Prevention Research for Stroke Survivors in Nigeria.

Implementing complex clinical interventions is a key challenge in many global regions. Local communities play a necessary role in enhancing feasibility and strengthening adaptive issues in the design and implementation of stroke interventions in developing countries. Drawing on the knowledge of physicians, patients, and caregivers, the authors employed qualitative methods as a phase 1 strategy to explore the challenges of stroke management and improve the adaptability and efficient delivery of a multimodal preventive intervention for secondary stroke disease in Nigeria. A total of 22 individual interviews were conducted with healthcare professionals, as well as 12 focus groups with patients and caregivers. Findings revealed four operational domains to improve strategies for phase 2 implementation and intervention: (1) barriers influencing optimal adherence in stroke survivors, (2) patient health beliefs and perceptions of patient health beliefs by others, (3) adoption of the "patient report card," and (4) "medical action plan" and family management strategies.

Key differences in B cell activation patterns and immune correlates among treated HIV-infected patients versus healthy controls following influenza vaccination.

BACKGROUND: There is increasing recognition of the role of B cell dysfunction in HIV pathogenesis, but little is known about how these perturbations may influence responses to vaccinations. METHODS: Healthy controls (n=16) and antiretroviral therapy (ART)-treated aviremic HIV-infected subjects (n=26) receiving standard-of-care annual influenza vaccinations were enrolled in the present study. Total bacterial 16S rDNA levels were assessed by quantitative polymerase chain reactions in plasma. Serologic responses were characterized by ELISA, hemagglutination inhibition assay (HI), and microneutralization, and cell-mediated responses were assessed by ELISPOT (antigen-specific IgG+ antibody-secreting cells (ASCs)) and flow cytometry at pre-vaccination (D0), day 7-10 (D7) and day 14-21 (D14) post-vaccination. RESULTS: Decreased peripheral CD4+ T cell absolute counts and increased frequencies of cycling and apoptotic B cells were found at baseline in HIV-infected subjects relative to healthy controls. In healthy controls, post-vaccination neutralizing activities were related to the frequencies of vaccine-mediated apoptosis and cycling of B cells, but not to CD4+ T cell counts. In patients, both baseline and post-vaccination neutralizing activities were directly correlated with plasma level of bacterial 16S rDNA. However, overall vaccine responses including antibody titers and fold changes were comparable or greater in HIV-infected subjects relative to healthy controls. CONCLUSION: B cell function correlates with measures of recall humoral immunity in response to seasonal influenza vaccination in healthy controls but not in ART-treated patients.

Pretesting Qualitative Data Collection Procedures to Facilitate Methodological Adherence and Team Building in Nigeria.

Qualitative methods are becoming widely used and increasingly accepted in biomedical research involving teams formed by experts from developing and developed practice environments. Resources are rare in offering guidance on how to surmount challenges of team integration and resolution of complicated logistical issues in a global setting. In this article we present a critical reflection of lessons learned and necessary steps taken to achieve methodological coherence and international team synergy. A series of 10 pretest interviews were conducted to assess instrumentation rigor and formulate measures to address any limitations or threats to bias and management procedures before carrying out the formal phase of qualitative research, contributing to an evidence-based stroke-preventive care clinical trial study. The experience of pretesting notably helped to identify obstacles and thus increase the methodological and social reliability central to conducting credible qualitative research, while also ensuring both personal and professional fulfillment of our team members.