THE VALUE OF DIFFERENTIATION OF WEAK FORMS OF D ANTIGEN OF THE ERYTHROCYTE SYSTEM RHESUS IN CLINICAL TRANSFUSIOLOGY AND OBSTETRICS

Summary. The characteristics of variants of antigen D are important because their immunogenicity and, consequently, clinical value depend on them. Objective. To identify weak forms of D antigen of the Rhesus erythrocyte system using available methods, to investigate their frequency and to determine a strategy for interpreting the rhesus status of the individual. Materials and methods. Rhesus affiliation of 3501 blood donors was determined, RhD affiliation of 44 people was specified. The studies were performed in hemagglutination reactions on a plane, test tubes, indirect Coombs’ test, micromethod in gel with MCA anti-D IgM, anti-D IgG, anti-D/DVI IgM/IgG, standard universal reagent antirhesus and standard serum antirhesus. Results and discussion. Dweak was defined 1 % among donors, which is no different from its frequency among Europeans. 40 of the 44 subjects had Dweak and were classified as RhD +, 2 – DVI + — as RhD–, taking into account the world practice of referring an individual with serologically weak D depending on the category of the subject. Conclusions. Due to significant differences in the immune response of individuals with Dweak and Dpartial to D + antigenic stimulus, in-depth examination of their RhD status is appropriate to determine transfusion and obstetric tactics.

Implantable vaccines: a solution for immune system manipulation to any antigenic stimulus

Effective and side-effect-free vaccines are still difficult tasks to achieve for a great majority of antigenic stimuli. Pathogen manipulation to abort infectivity and antigen delivery to ensure immune responsiveness are the major components vaccine technology tries to resolve. However, the development of an immune response is still a complicated matter, lies on hundreds of parameters and any effort towards activation can easily lead to adverse effects, making immunotherapy very difficult to control. The present review attempts to highlight the major parameters affecting immune responsiveness and show that vaccine technology, except from pathogen manipulation and the development of antigen delivery systems, requires attention to additional check-points. Analyzing the recently described personalized implantable vaccine technology, it becomes obvious that the nature of each antigenic stimulus dictates different responsiveness to the organism, which discourages the use of universal adjuvant and antigen-delivery systems. On the contrary, the ex vivo tuning of the immune response proposed by the implantable vaccine technology, allows controllable amendment of the response. The development of personalized technologies is expected to provide valuable tools for the management of human pathology.

Sarcoidosis and other granulomatous lung disease

Sarcoidosis is a multisystem disorder characterized by the formation of non-caseating granulomas in many tissues. A granuloma is an organized aggregate of immune cells; it forms in response to an antigenic stimulus. It contains abnormal macrophages (epithelioid histiocytes, which often fuse to form multinucleated giant cells), lymphocytes, neutrophils, eosinophils, fibroblasts, and collagen.

Anti-HIV-1 ADCC Antibodies following Latency Reversal and Treatment Interruption

ABSTRACT There is growing interest in utilizing antibody-dependent cellular cytotoxicity (ADCC) to eliminate infected cells following reactivation from HIV-1 latency. A potential barrier is that HIV-1-specific ADCC antibodies decline in patients on long-term antiretroviral therapy (ART) and may not be sufficient to eliminate reactivated latently infected cells. It is not known whether reactivation from latency with latency-reversing agents (LRAs) could provide sufficient antigenic stimulus to boost HIV-1-specific ADCC. We found that treatment with the LRA panobinostat or a short analytical treatment interruption (ATI), 21 to 59 days, was not sufficient to stimulate an increase in ADCC-competent antibodies, despite viral rebound in all subjects who underwent the short ATI. In contrast, a longer ATI, 2 to 12 months, among subjects enrolled in the Strategies for Management of Antiretroviral Therapy (SMART) trial robustly boosted HIV-1 gp120-specific Fc receptor-binding antibodies and ADCC against HIV-1-infected cells in vitro. These results show that there is a lag between viral recrudescence and the boosting of ADCC antibodies, which has implications for strategies toward eliminating latently infected cells. IMPORTANCE The “shock and kill” HIV-1 cure strategy aims to reactivate HIV-1 expression in latently infected cells and subsequently eliminate the reactivated cells through immune-mediated killing. Several latency reversing agents (LRAs) have been examined in vivo, but LRAs alone have not been able to achieve HIV-1 remission and prevent viral rebound following analytical treatment interruption (ATI). In this study, we examined whether LRA treatment or ATI can provide sufficient antigenic stimulus to boost HIV-1-specific functional antibodies that can eliminate HIV-1-infected cells. Our study has implications for the antigenic stimulus required for antilatency strategies and/or therapeutic vaccines to boost functional antibodies and assist in eliminating the latent reservoir.

Statistical Inference of a Convergent Antibody Repertoire Response to Influenza Vaccine

BackgroundVaccines dramatically affect an individual’s adaptive immune system, and thus provide an excellent means to study human immunity. Upon vaccination, the B cells that express antibodies (Abs) that happen to bind the vaccine are stimulated to proliferate and undergo mutagenesis at their Ab locus. This process may alter the composition of B cell lineages within an individual, which are known collectively as the antibody repertoire (AbR). Antibodies are also highly expressed in whole blood, potentially enabling unbiased RNA sequencing technologies to query this diversity. Less is known about the diversity of AbR responses across individuals to a given vaccine and if individuals tend to yield a similar response to the same antigenic stimulus.MethodsHere we implement a bioinformatic pipeline that extracts the AbR information from a time-series RNA-seq dataset of 5 patients who were administered a seasonal trivalent influenza vaccine (TIV). We harness the detailed time-series nature of this dataset and use methods based in functional data analysis (FDA) to identify the B cell lineages that respond to the vaccine. We then design and implement rigorous statistical tests in order to ask whether or not these patients exhibit a convergent AbR response to the same TIV.ResultsWe find that high-resolution time-series data can be used to help identify the Ab lineages that respond to an antigenic stimulus, and that this response can exhibit a convergent nature across patients inoculated with the same vaccine. However, correlations in AbR diversity among individuals prior to inoculation can confound inference of a convergent signal unless it is taken into account.ConclusionsWe developed a framework to identify the elements of an AbR that respond to an antigen. This information could be used to understand the diversity of different immune responses in different individuals, as well as to gauge the effectiveness of the immune response to a given stimulus within an individual. We also present a framework for testing a convergent hypothesis between AbRs; a hypothesis that is more difficult to test than previously appreciated. Our discovery of a convergent signal suggests that similar epitopes do select for antibodies with similar sequence characteristics.