Human immunodeficiency virus type 1 (HIV-1) vaccine immunogens capable of inducing broadly neutralizing antibodies (bNAbs) remain obscure. HIV-1 evades immune responses through enormous diversity and hides its conserved vulnerable epitopes on the envelope glycoprotein (Env) by displaying an extensive immunodominant glycan shield. In elite HIV-1 viremic controllers, glycan-dependent bNAbs targeting conserved Env epitopes have been isolated and are utilized as vaccine design templates. However, immunological tolerance mechanisms limit the development of these antibodies in the general population. The well characterized bNAbs monoclonal variants frequently exhibit extensive levels of somatic hypermutation, a long third heavy chain complementary determining region, or a short third light chain complementarity determining region, and some exhibit poly-reactivity to autoantigens. This review elaborates on the obstacles to engaging and manipulating the Env glycoprotein as an effective immunogen and describes an alternative reverse vaccinology approach to develop a novel category of bNAb-epitope-derived non-cognate immunogens for HIV-1 vaccine design.
- MeSH
- Epitopes immunology MeSH
- env Gene Products, Human Immunodeficiency Virus immunology MeSH
- HIV Infections immunology MeSH
- HIV Antibodies * immunology MeSH
- HIV-1 * immunology MeSH
- Humans MeSH
- Ligands MeSH
- Molecular Mimicry immunology MeSH
- Antibodies, Neutralizing * immunology MeSH
- Polysaccharides immunology MeSH
- AIDS Vaccines * immunology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- MeSH
- Lymphoma, Large B-Cell, Diffuse * drug therapy MeSH
- Fluorodeoxyglucose F18 therapeutic use MeSH
- Lymphoma, Follicular * drug therapy MeSH
- Humans MeSH
- Positron-Emission Tomography MeSH
- Prognosis MeSH
- Antineoplastic Combined Chemotherapy Protocols MeSH
- Radiopharmaceuticals therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Letter MeSH
Although complex approaches in haematopoietic stem cell transplantation (aHSCT) improved substantially in the last decades, considerable proportion of patients still suffer from life-threatening complications including graft versus host disease (GvHD). Great effort has therefore been dedicated to identification of biomarkers of the aHSCT outcome. Recently, prognostic scores for the prediction of GvHD and non-relapse mortality based on circulating molecules, such as tumour necrosis factor receptor-1, IL-33receptor (ST2) and regenerating islet-derived 3-alpha were proposed and evaluated in multicentre studies. Furthermore, several biomarkers, for example, ST2, represent promising targets for therapeutic intervention in severe GvHD. These results bring us closer to the clinical strategies to effectively control complications following aHSCT, and therefore to the tailored stem cell therapy with higher benefits for the patients.
- MeSH
- Biomarkers blood MeSH
- Hematologic Neoplasms blood diagnosis therapy MeSH
- Transplantation, Homologous adverse effects MeSH
- Humans MeSH
- Graft vs Host Disease blood diagnosis MeSH
- Predictive Value of Tests MeSH
- Prognosis MeSH
- Hematopoietic Stem Cell Transplantation * adverse effects MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
A Euro-Lupus regimen of low-dose intravenous cyclophosphamide (CFA) is commonly used to treat severe organ manifestations of systemic lupus erythematosus (SLE), particularly lupus nephritis (LN). There are no data on the distributions and dynamics of immune cell populations in patients with various treatment outcomes. The circulating immune cells of 11 female SLE patients were assessed before and after Euro-Lupus regimen (cumulative dose of 3000 mg CFA) by flow cytometry together with those of 16 healthy women. A subanalysis was performed in LN patients who achieved complete remission (CR; n = 3), partial remission (PR; n = 4), and no response (NR; n = 2). In SLE, the Euro-Lupus regimen decreased the percentage and absolute count of B cells; increased the percentage of CD8+ T cells, T regulatory cells, neutrophils, and monocyte subsets; and activated T and NK cells compared to healthy controls (P < 0.050). Patients with LN achieving CR had significantly lower proportions of CD27+ B memory cells compared to poor responders (PR/NR, P = 0.035). The post-treatment percentages and absolute numbers of B cells, T cells, NK cells, monocytes, and neutrophils showed high inter-individual variability with no association with treatment outcome. Our pilot study revealed the dynamics of changes in immune cell populations in SLE patients during a Euro-Lupus regimen, mainly the lowering of B cells. In LN patients who achieved CR, a lower proportion of CD27+ B memory cells was evident compared to poor responders (PR/NR). Further studies on usefulness of monitoring immune cells for treatment response prediction on larger cohorts are needed.
- MeSH
- Cyclophosphamide therapeutic use MeSH
- Adult MeSH
- Immunologic Memory MeSH
- Immunomodulation MeSH
- Immunosuppressive Agents therapeutic use MeSH
- Remission Induction MeSH
- Administration, Intravenous MeSH
- Clinical Protocols MeSH
- Cohort Studies MeSH
- Blood Circulation MeSH
- Middle Aged MeSH
- Humans MeSH
- Lymphocytes drug effects immunology MeSH
- Young Adult MeSH
- Lupus Nephritis drug therapy MeSH
- Flow Cytometry MeSH
- Lupus Erythematosus, Systemic drug therapy MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Na počátku byla nespokojenost přednostů, primářů a vrchních sester se systémem hodnocení zaměstnanců, na konci pak začátek koncepce řízení pracovního výkonu ve fakultní nemocnici. Mezi prvním a druhým počátkem byla čtyřměsíční individuální i skupinová práce zástupců vedoucích pracovníků z řad přednostů, primářů, vrchních sester i TO P managementu. Závěry těchto pracovních skupin daly nezávisle na sobě jasný impuls k přechodu od pouhého hodnocení zaměstnanců k plánovaní a posuzování pracovního výkonu, založeného na dohodě o pracovním výkonu, vzdělávání a rozvoji. Pro fakultní nemocnici to znamená propojení cílů organizace s cíly jednotlivých klinik, zlepšení pracovního výkonu jednotlivců i týmů, zvýšení odpovědnosti a motivace zaměstnanců. Výsledkem je spokojený a kvalitně léčený pacient.
The basis of this project was dissatisfaction of the health care management with the used personal evaluation methodology. The result is the beginning of the new concept of the leading in our hospital. In between these two points was four months long individual and team work of health care managers, like heads of departments, heads nurses and also TO P management of the hospital. The outputs of these working groups gave independently clear impulse to the movement from simple evaluation to precise planning of the individual performance. This planned individual performance is based on the settlement of working results, education and individual development. For our institution this clear matching of the individual and institutional goals improves motivation and performance of individuals and also working teams. Our staff gains greater motivation and responsibility. The final result is satisfied and properly treated patient.
