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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
- epitopy imunologie MeSH
- genové produkty env - virus lidské imunodeficience imunologie MeSH
- HIV infekce imunologie MeSH
- HIV protilátky * imunologie MeSH
- HIV-1 * imunologie MeSH
- lidé MeSH
- ligandy MeSH
- molekulární mimikry imunologie MeSH
- neutralizující protilátky * imunologie MeSH
- polysacharidy imunologie MeSH
- vakcíny proti AIDS * imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- MeSH
- difúzní velkobuněčný B-lymfom * farmakoterapie MeSH
- fluorodeoxyglukosa F18 terapeutické užití MeSH
- folikulární lymfom * farmakoterapie MeSH
- lidé MeSH
- pozitronová emisní tomografie MeSH
- prognóza MeSH
- protokoly protinádorové kombinované chemoterapie MeSH
- radiofarmaka terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy 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
- biologické markery krev MeSH
- hematologické nádory krev diagnóza terapie MeSH
- homologní transplantace škodlivé účinky MeSH
- lidé MeSH
- nemoc štěpu proti hostiteli krev diagnóza MeSH
- prediktivní hodnota testů MeSH
- prognóza MeSH
- transplantace hematopoetických kmenových buněk * škodlivé účinky MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy 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
- cyklofosfamid terapeutické užití MeSH
- dospělí MeSH
- imunologická paměť MeSH
- imunomodulace MeSH
- imunosupresiva terapeutické užití MeSH
- indukce remise MeSH
- intravenózní podání MeSH
- klinické protokoly MeSH
- kohortové studie MeSH
- krevní oběh MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfocyty účinky léků imunologie MeSH
- mladý dospělý MeSH
- nefritida při lupus erythematodes farmakoterapie MeSH
- průtoková cytometrie MeSH
- systémový lupus erythematodes farmakoterapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- dospělí MeSH
- hlášení nemocí metody normy MeSH
- infekce spojené se zdravotní péčí prevence a kontrola přenos MeSH
- kontrola infekčních nemocí metody MeSH
- lidé MeSH
- molekulární biologie metody MeSH
- pooperační komplikace diagnóza etiologie MeSH
- Pseudomonas aeruginosa imunologie patogenita MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
