Termínem gibberellin-regulated proteins je označována skupina alergenů zkoumaná v posledních letech v souvislosti se zkříženými pylově potravinovými alergiemi (pollen/food allergy syndrome). Gibereliny jsou skupinou fytohormonů figurující v ochraně rostlin, mají baktericidní, virucidní a fungicidní účinky. Fungují jako růstové hormony a vylučují se při zrání, ale i při stresu rostlin. Jedná se o antimikrobiální peptidy o molekulové hmotnosti 7–8 kDa bohaté na cystein, jejichž struktura je obdobná v celé řadě vyšších rostlin. Díky vysokému obsahu cysteinu jsou termostabilní a acidorezistentní, proto jsou považovány za rizikové potravinové alergeny, schopné vyvolat závažné alergické reakce. Klinické projevy potravinové alergie na gibberellin-regulated proteiny jsou poměrně charakteristické, jsou jimi otok obličeje (zvláště očních víček) a laryngeální otok. Alergické reakce bývají se závažnějším průběhem zvláště tehdy, pokud jsou přítomny další faktory (tělesná náma- ha, léčba nesteroidními antiflogistiky, inhibitory proteinové pumpy, vliv alkoholu, infekce, menstruace apod.). Dosud bylo identifikováno 9 těchto alergenních proteinů různých rostlinných zdrojů pylových Cry j 7, Cup s 7, Jun a 7, potravinových Pru p 7, Pru m 7, Pun g 7, Cit s 7, Pru av 7, Cap a 7. Byly popsány i dvě nealergenní molekuly – applemaclein, snakin-1. K primární senzibilizaci dochází nejspíše prostřednictvím inhalační alergie na pyl cypřišovitých.
Gibberellin-regulated proteins are a group of allergens investigated in recent years in relation with pollen/food allergy syndrome. Gibberellins are a group of phytohormones, which play role in plant protection, have bactericidal, virucidal and fungicidal effects, function as growth hormones and are secreted during ripening process, but also during plant stress. These proteins are antimicrobial peptides with a molecular weight of 7–8 kDa, rich in cysteine, which stucture is very conserved across a wide number of higher plants. Due to their high cysteine content, they are thermostable and acidoresistant, which is why they are considered as a risky food allergens capable of causing serious allergic reactions. Clinical symptoms of gibberellin-regulated proteins allergy are quite characteristic, including facial swelling (especially eyelid oedema) a laryngeal tightness. Allergic reactions to GRPs tend to be more severe, especially if co-factors are present (exercise, nonsteroid – antiinflammatory drugs or proton pump inhibitors therapy, alcohol, infection, menstruation and others). So far 9 allergenic gibberellin-regulated proteins have been identified from different plant sources pollen Cry j 7, Cup s 7, Jun a 7 and food Pru p 7, Pru m 7, Pun g 7, Cit s 7, Pru av 7, Cap a 7 and 2 non-allergenic applemaclein, snakin-1. Most probably primary sensitization occurs through inha- lation allergy to cypress pollen.
Multiple myeloma (MM) is a disease which remains incurable. One of the main reasons is a weakened immune system that allows MM cells to survive. Therefore, the current research is focused on the study of immune system imbalance in MM to find the most effective immunotherapy strategies. Aiming to identify the key points of immune failure in MM patients, we analysed peripheral lymphocytes subsets from MM patients (n = 57) at various stages of the disease course and healthy individuals (HI, n = 15) focusing on T, NK, iNKT, B cells and NK-cell cytokines. Our analysis revealed that MM patients exhibited immune alterations in all studied immune subsets. Compared to HI, MM patients had a significantly lower proportion of CD4 + T cells (19.55% vs. 40.85%; p < 0.001) and CD4 + iNKT cells (18.8% vs. 40%; p < 0.001), within B cells an increased proportion of CD21LCD38L subset (4.5% vs. 0.4%; p < 0.01) and decreased level of memory cells (unswitched 6.1% vs. 14.7%; p < 0.001 and switched 7.8% vs. 11.2%; NS), NK cells displaying signs of activation and exhaustion characterised by a more than 2-fold increase in SLAMF7 MFI (p < 0.001), decreased expression of NKG2D (MFI) and NKp46 (%) on CD16 + 56 + and CD16 + 56- subset respectively (p < 0.05), Effective immunotherapy needs to consider these immune defects and monitoring of the immune status of MM patients is essential to define better interventions in the future.
- MeSH
- B-lymfocyty imunologie MeSH
- buňky NK imunologie MeSH
- cytokiny krev MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mnohočetný myelom * krev imunologie terapie MeSH
- NKT buňky imunologie MeSH
- podskupiny lymfocytů imunologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Kidney transplant recipients are at risk for a severe course of COVID-19 with a high mortality rate. A considerable number of patients remains without a satisfactory serological response after the baseline and adjuvant SARS-CoV-2 vaccination schedule. METHODS: In this prospective, randomized study, we evaluated the efficacy and safety of one and two booster doses of mRNA vaccines (either mRNA-1273 or BNT162b2) in 125 COVID-19 naive, adult kidney transplant recipients who showed an insufficient humoral response (SARS-CoV-2 IgG <10 AU/ml) to the previous 2-dose vaccination schedule. The primary outcome was the difference in the rate of a positive antibody response (SARS-CoV-2 IgG ≥10 AU/ml) between one and two booster doses at 1 month after the final booster dose. RESULTS: A positive humoral response was observed in 36 (62%) patients receiving two booster doses and in 28 (44%) patients receiving one booster dose (odds ratio [OR], 2.10, 95% confidence interval [CI], 1.02-4.34, p = .043). Moreover, median SARS-CoV-2 IgG levels were higher with two booster doses (p = .009). The number of patients with positive virus neutralizing antibody (VNA) levels was numerically higher with two booster doses compared to one booster dose, but without statistical significance (66% vs. 50%, p = .084). There was no significant difference in positive seroconversions rate and antibody levels between mRNA-1273 and BNT162b2. CONCLUSION: A higher number of kidney transplant recipients achieved a positive antibody response after two booster doses compared to one booster dose.
- MeSH
- COVID-19 * prevence a kontrola MeSH
- dospělí MeSH
- imunoglobulin G MeSH
- lidé MeSH
- mRNA vakcíny MeSH
- příjemce transplantátu MeSH
- protilátky virové MeSH
- SARS-CoV-2 MeSH
- transplantace ledvin * škodlivé účinky MeSH
- vakcína BNT162 MeSH
- vakcína firmy Moderna proti COVID-19 MeSH
- vakcíny proti COVID-19 škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
SIGNIFICANCE STATEMENT: Although cytomegalovirus (CMV) infection is an important factor in the pathogenesis of kidney allograft rejection, previous studies have not determined the optimal CMV prevention strategy to avoid indirect effects of the virus. In this randomized trial involving 140 kidney transplant recipients, incidence of acute rejection at 12 months was not lower with valganciclovir prophylaxis (for at least 3 months) compared with preemptive therapy initiated after detection of CMV DNA in whole blood. However, prophylaxis was associated with a lower risk of subclinical rejection at 3 months. Although both regimens were effective in preventing CMV disease, the incidence of CMV DNAemia (including episodes with higher viral loads) was significantly higher with preemptive therapy. Further research with long-term follow-up is warranted to better compare the two approaches. BACKGROUND: The optimal regimen for preventing cytomegalovirus (CMV) infection in kidney transplant recipients, primarily in reducing indirect CMV effects, has not been defined. METHODS: This open-label, single-center, randomized clinical trial of valganciclovir prophylaxis versus preemptive therapy included kidney transplant recipients recruited between June 2013 and May 2018. After excluding CMV-seronegative recipients with transplants from seronegative donors, we randomized 140 participants 1:1 to receive valganciclovir prophylaxis (900 mg, daily for 3 or 6 months for CMV-seronegative recipients who received a kidney from a CMV-seropositive donor) or preemptive therapy (valganciclovir, 900 mg, twice daily) that was initiated after detection of CMV DNA in whole blood (≥1000 IU/ml) and stopped after two consecutive negative tests (preemptive therapy patients received weekly CMV PCR tests for 4 months). The primary outcome was the incidence of biopsy-confirmed acute rejection at 12 months. Key secondary outcomes included subclinical rejection, CMV disease and DNAemia, and neutropenia. RESULTS: The incidence of acute rejection was lower with valganciclovir prophylaxis than with preemptive therapy (13%, 9/70 versus 23%, 16/70), but the difference was not statistically significant. Subclinical rejection at 3 months was lower in the prophylaxis group (13% versus 29%, P = 0.027). Both regimens prevented CMV disease (in 4% of patients in both groups). Compared with prophylaxis, preemptive therapy resulted in significantly higher rates of CMV DNAemia (44% versus 75%, P < 0.001) and a higher proportion of patients experiencing episodes with higher viral load (≥2000 IU/ml), but significantly lower valganciclovir exposure and neutropenia. CONCLUSION: Among kidney transplant recipients, the use of valganciclovir prophylaxis did not result in a significantly lower incidence of acute rejection compared with the use of preemptive therapy. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Optimizing Valganciclovir Efficacy in Renal Transplantation (OVERT Study), ACTRN12613000554763 .
- MeSH
- antivirové látky škodlivé účinky MeSH
- cytomegalovirové infekce * epidemiologie MeSH
- Cytomegalovirus genetika MeSH
- lidé MeSH
- neutropenie * chemicky indukované komplikace MeSH
- příjemce transplantátu MeSH
- transplantace ledvin * škodlivé účinky MeSH
- valganciklovir škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination may fail to sufficiently protect transplant recipients against coronavirus disease 2019 (COVID-19). We retrospectively evaluated COVID-19 in kidney transplant recipients (n = 226) after BNT162b2 mRNA vaccine administration. The control group consisted of unvaccinated patients (n = 194) during the previous pandemic wave. We measured anti-spike protein immunoglobulin G (IgG) levels and cellular responses, using enzyme-linked immunosorbent spot assay, in a prospective cohort after vaccination (n = 31) and recovery from COVID-19 (n = 19). COVID-19 was diagnosed in 37 (16%) vaccinated and 43 (22%) unvaccinated patients. COVID-19 severity was similar in both groups, with patients exhibiting a comparable need for hospitalization (41% vs. 40%, p = 1.000) and mortality (14% vs. 9%, p = .726). Short posttransplant periods were associated with COVID-19 after vaccination (p < .001). Only 5 (16%) patients achieved positive SARS-CoV-2 IgG after vaccination, and 17 (89%, p < .001) recovered from COVID-19 (median IgG levels, 0.6 vs. 52.5 AU/ml, p < .001). A cellular response following vaccination was present in the majority (n = 22, 71%), with an increase in interleukin 2 secreting T cells (p < .001). Despite detectable T cell immunity after mRNA vaccination, kidney transplant recipients remained at a high risk of severe COVID-19. Humoral responses induced by vaccination were significantly lower than that after COVID-19.
- MeSH
- COVID-19 * epidemiologie prevence a kontrola MeSH
- incidence MeSH
- lidé MeSH
- messenger RNA MeSH
- mRNA vakcíny MeSH
- pandemie MeSH
- příjemce transplantátu MeSH
- prospektivní studie MeSH
- protilátky virové MeSH
- retrospektivní studie MeSH
- SARS-CoV-2 MeSH
- syntetické vakcíny MeSH
- transplantace ledvin * škodlivé účinky MeSH
- vakcína BNT162 MeSH
- vakcíny proti COVID-19 MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Cryopreserved haematopoietic progenitor cells are used to restore autologous haematopoiesis after high dose chemotherapy. Although the cells are routinely stored for a long period, concerns remain about the maximum storage time and the possible negative effect of storage on their potency. We evaluated the effect of cryopreservation on the quality of peripheral stem cell grafts stored for a short (3 months) and a long (10 years) period and we compared it to native products.The viability of CD34+ cells remained unaffected during storage, the apoptotic cells were represented up to 10% and did not differ between groups. The clonogenic activity measured by ATP production has decreased with the length of storage (ATP/cell 1.28 nM in native vs. 0.63 in long term stored products, P < 0.05). Only borderline changes without statistical significance were detected when examining mitochondrial and aldehyde dehydrogenase metabolic activity and intracellular pH, showing their good preservation during cell storage. Our experience demonstrates that cryostorage has no major negative effect on stem cell quality and potency, and therefore autologous stem cells can be stored safely for an extended period of at least 10 years. On the other hand, long term storage for 10 years and longer may lead to mild reduction of clonogenic capacity. When a sufficient dose of stem cells is infused, these changes will not have a clinical impact. However, in products stored beyond 10 years, especially when a low number of CD34+ cells is available, the quality of stem cell graft should be verified before infusion using the appropriate potency assays.
Diagnostika alergie I. typu je založena na anamnéze, provokačních testech a in vitro diagnostice. V současné době je v klinické praxi používá-na v diagnostice alergií molekulární biologie. Více jak 100 alergenních komponent či extraktů je dostupných pro testování specifického IgE, a to buď singleplexovými, či multiplexovými metodami. Naším cílem bylo porovnat dva multiplexy, a to ImmunoCAP ISAC (Thermo Fisher Scientific, Švédsko) a ALEX (Macro Array Diagnostics, Rakousko). Byla pozorována velmi dobrá korelace mezi oběma metodami. Testování specifického IgE pomocí multiplexových metod je jednou z možností pro diagnostiku pacientů s alergií I. typu. Pomáhá lékařům v diagnostice a indikaci léčby těchto pacientů.
Diagnosis of type I allergy is based on the patient history, provocation testing, and in vitro diagnostic tests. Currently, molecular allergy dia-gnostics are using in clinical routine, and more than 100 allergenic molecules and extracts are available for in vitro specific immunoglobulin E testing, which can be performed on singleplex or multiplex measurement platforms. Our claim was to compare the multiplex ImmunoCAP ISAC (Thermo Fisher Scientific, Sweden) and the multiplex ALEX (Macro Array Diagnostics, Austria) platform.A good correlation of presently used methods to detect serum sIgE was observed. Multiplex testing of allergen-specific IgE is one of the methods for detection allergy type I in patients. It helps clinicians with diagnosing and establishing treatment for these patients.
INTRODUCTION: Frequently observed multiple sensitizations to several animals highlights the importance of a molecular diagnosis, distinguishing between sensitizations specific to single species and sensitizations due to cross-reactivity. OBJECTIVE: The aim of our study was to assess the usefulness of a molecular diagnosis in the description of sensitization profiles in allergy patients living in Central Europe, with a particular focus on animal-derived molecules. METHODS: The molecular diagnosis was performed using the ImmunoCAP ISAC microarray. Results of 1,255 allergy patients were subjected to statistical analysis. RESULTS: The highest sensitization rates were observed for uteroglobin Fel d 1 (31.8%) and kallikrein Can f 5 (16.4%), followed by animal lipocalins Can f 1 (13.9%), Equ c 1 (6.2%), Fel d 4 (5.3%), Can f 2 (4.2%), and Mus m 1 (4.1%). Sensitization rates to serum albumins Fel d 2, Can f 3, Equ c 3, and Bos d 6 were very low, with the highest being 3.2% to Fel d 2. Detailed subanalysis confirmed the dominant role of Fel d 1 or Can f 5 and/or Can f 1 in cat- or dog-sensitized patients, respectively. Further analysis focused on lipocalins and albumins confirmed a high rate of cosensitizations within both groups. CONCLUSION: The sensitization to animal allergen molecules is very frequent in Central Europe. The most common is sensitization to species-specific cat uteroglobin Fel d 1 and dog kallikrein Can f 5, followed by sensitizations to animal lipocalins. Our data suggest that commonly observed multiple sensitizations detected by extract approach can be explained not only by true cosensitization, but also by cross-reactivity, mainly in the frame of lipocalins. Cross-reactive serum albumins are minor sensitizers and are probably not important from this point of view.
- MeSH
- alergeny imunologie MeSH
- alergie imunologie MeSH
- dítě MeSH
- dospělí MeSH
- druhová specificita MeSH
- kočky MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipokaliny imunologie MeSH
- mladiství MeSH
- mladý dospělý MeSH
- myši MeSH
- předškolní dítě MeSH
- psi MeSH
- senioři MeSH
- sérový albumin imunologie MeSH
- zkřížené reakce imunologie MeSH
- zvířata MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kočky MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- myši MeSH
- předškolní dítě MeSH
- psi MeSH
- senioři MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH