The association of graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effects after allogeneic stem-cell transplantation (SCT) is well-established but was not confirmed in the modern era and following post-transplant cyclophosphamide (PTCy). We assessed GVHD/ GVL association in AML patients following HLA-matched SCT with standard calcineurin-based (n = 12,653, 57% with additional in-vivo T-cell depletion) or PTCy-based (n = 508) GVHD prophylaxis. Following standard prophylaxis, acute GVHD grade II-IV and III-IV, chronic GVHD, and extensive chronic GVHD rates were 23.8%, 7.5%, 37.0%, and 16.3%, respectively. Acute GVHD grade II and III-IV were associated with lower relapse [hazard-ratio (HR) 0.85, P = 0.002; HR 0.76, P = 0.003, respectively)], higher non-relapse mortality (NRM) (HR 1.5, P < 0.001; HR 6.21, P < 0.001) and lower overall survival (OS) (HR 1.49, P < 0.001; HR 6.1, P < 0.001). Extensive chronic GVHD predicted lower relapse (HR 0.69, P < 0.001), higher NRM (HR 2.83, P < 0.001), and lower OS (HR 2.74, P < 0.001). Following PTCy, GVHD rates were 22.8%, 6.2%, 35.5%, and 17.7%, respectively. Acute GVHD was not associated with relapse (HR 1.37, P = 0.15) but predicted higher NRM (HR 3.34, P < 0.001) and lower OS (HR 1.92, P = 0.001). Chronic GVHD was not prognostic for these outcomes. In conclusion, GVHD and GVL are strongly associated with contemporary SCT. However, following PTCy, GVHD is not associated with reduced relapse.
- MeSH
- akutní myeloidní leukemie * terapie MeSH
- cyklofosfamid * terapeutické užití MeSH
- dospělí MeSH
- HLA antigeny imunologie MeSH
- homologní transplantace MeSH
- imunosupresiva terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nemoc štěpu proti hostiteli * etiologie prevence a kontrola MeSH
- reakce štěpu proti leukémii * MeSH
- senioři MeSH
- testování histokompatibility MeSH
- transplantace hematopoetických kmenových buněk * škodlivé účinky metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Pacienti se syndromem suchého oka tvoří významnou část každodenní oftalmologické péče. Mezi rizikové faktory rozvoje syndromu suchého oka patří i diabetes mellitus. Významnou roli zde hrají změny homeostázy slzného filmu, chronický zánět povrchu oka a doprovázející patologie povrchových nervových vláken rohovky. Cílem této práce bylo popsat stav moderních biomarkerů poškození povrchu oka u pacientů s diabetem 1. typu a posoudit jejich využitelnost pro časný záchyt rozvoje syndromu suchého oka. Materiál a metodika: Do studie bylo zahrnuto celkem 19 pacientů s diabetem 1. typu a 15 pacientů v kontrolní skupině. Pacienti podstoupili detailní vyšetření povrchu oka, odběr biomateriálu k laboratorní analýze hladin matrixové metaloproteinázy 9 (MMP-9), exprese HLA-DR epiteliemi a snímání rohovky pomocí rohovkového konfokálního mikroskopu. Výsledky: Ve skupině pacientů s diabetem 1. typu byla statisticky významně nižší celková délka nervových vláken (p = 0,0482). Osmolarita, citlivost rohovky, vitální barvení povrchu oka, tear break-up time (TBUT) ani MMP-9 v slzném filmu se mezi skupinami statisticky významně nelišily (p = 0,8272, p = 0,6029, p = 0,3507, p = 0,7561 a p = 0,0826 respektive). HLA-DR exprese byla testována na skupině 10 pacientů s diabetem 1. typu a 8 pacientech kontrolní skupiny a u obou skupin byla mírná nebo žádná (p > 0,9999). Závěr: V souladu s dříve publikovanou literaturou jsme v naší studii potvrdili snížení celkové délky nervových vláken subbazálního plexu rohovky u pacientů s diabetem 1. typu oproti subjektům v kontrolní skupině. Neprokázali jsme však změny povrchu oka pomocí standardních ani nových markerů (hladina MMP-9, exprese HLA-DR antigenu na povrchu oka) u pacientů s DM1 oproti kontrolní skupině.
Patients with dry eye syndrome form a significant proportion of those treated in everyday ophthalmology practice. Diabetes mellitus is a major risk factor for the development of dry eye syndrome. Changes in tear film homeostasis, chronic inflammation and subsequent corneal nerve fiber pathology play a key role in its progression. The aim of this study was to describe the status of modern biomarkers of ocular surface damage in patients with type 1 diabetes and asses their utility in early diagnosis of dry eye syndrome. Material and methods: In total the pilot study included 19 patients with type 1 diabetes (T1D) and 15 patients in the control group. All patients underwent a detailed ocular surface examination, sample collection for matrix metalloproteinase-9 (MMP-9) laboratory analysis and epithelial HLA-DR expression evaluation, and in-vivo corneal confocal microscopy. Results: T1D patients showed statistically significantly reduced corneal nerve fiber length (p = 0.0482). The differences between the groups in terms of osmolarity, corneal sensitivity, Oxford score, tear break-up time and MMP-9 level were not statistically significant (p = 0.8272, p = 0.6029, p = 0.3507, p = 0.7561 and p = 0.0826 respectively). HLA-DR expression was examined in 10 T1D patients and 8 patients in the control group. Both groups showed minimal or no expression (p > 0.9999). Conclusion: The previously published literature supports our finding of corneal nerve fiber length reduction in T1D patients compared to controls. However, we did not find any significant changes in standard or modern ocular surface markers (MMP-9 levels, HLA-DR expression) measured in patients with dry eye syndrome.
BACKGROUND AND OBJECTIVES: HLA-B27 is a genetic marker associated with spondyloarthropathies, particularly ankylosing spondylitis and axial spondyloarthritis. While its prevalence varies across populations, no data exist for Slovak patients. This study aimed to determine HLA-B27 prevalence in Slovak patients with suspected spondyloarthropathies and assess differences by sex and age. METHODS: A retrospective cohort of 1,614 patients (888 females and 726 males) was analyzed for HLA-B27 status (positive/negative) using reverse hybridisation (HLA-B27 StripAssay). Statistical analyses included Pearson's Chi-square test and non-parametric Mann-Whitney U and Kruskal-Wallis tests for sex- and age-related differences. RESULTS: HLA-B27 positivity was 20.57%, with a higher proportion in males (23.28%) than females (18.36%, p = 0.0177). The less than 20 age group had the highest absolute number of positive cases (126 cases; 17.80%), while the 21-40 group had the highest relative positivity (119 cases; 29.38%). The lowest positivity was in the more than 61 age group (17 cases; 13.08%), though age distribution differences were not statistically significant (p = 0.7765). Positivity varies across diagnoses, peaking in musculoskeletal (M) and eye disorders (H), where it exceeds 29%. CONCLUSION: HLA-B27 positivity is strongly associated with rheumatologic and ophthalmologic conditions and exhibits age- and sex-related variability. These findings emphasize the diagnostic significance of HLA-B27 testing in Slovak patients, especially for early detection and management of spondyloarthropathies. Further research on HLA-B27 variability and its clinical implications is needed to optimize diagnostic strategies and patient care.
- MeSH
- dítě MeSH
- dospělí MeSH
- HLA-B27 antigen * genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- retrospektivní studie MeSH
- senioři MeSH
- spondylartropatie genetika epidemiologie imunologie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Slovenská republika MeSH
Highly sensitized (HS) patients in need of kidney transplantation (KTx) typically spend a longer time waiting for compatible kidneys, are unlikely to receive an organ offer, and are at increased risk of antibody-mediated rejection (AMR). Desensitization using imlifidase, which is more rapid and removes total body immunoglobulin G (IgG) to a greater extent than other methods, enables transplantation to occur between HLA-incompatible (HLAi) donor-recipient pairs and allows patients to have greater access to KTx. However, when the project was launched there was limited data and clinical experience with desensitization in general and with imlifidase specifically. Hence, this Delphi methodology was used to reach a consensus from a multi-disciplinary team (MDT) of experts from 15 countries on the management of HS patients undergoing imlifidase HLAi from a deceased donor (DD) KTx. This Delphi consensus provides clinical practice guidance on the use of imlifidase in the end-to-end management of HS patients undergoing an HLAi DD KTx and supports centers in the development of guidelines for the utilization and integration of imlifidase into clinical practice.
- MeSH
- dárci tkání * MeSH
- delfská metoda * MeSH
- desenzibilizace imunologická * metody MeSH
- HLA antigeny * imunologie MeSH
- imunoglobulin G MeSH
- konsensus * MeSH
- lidé MeSH
- rejekce štěpu prevence a kontrola imunologie MeSH
- transplantace ledvin * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Spondyloarthritis (SpA) constitute a group of chronic inflammatory immune-mediated rheumatic diseases characterized by genetic, clinical, and radiological features. Recent efforts have concentrated on identifying biomarkers linked to axial SpA associated with inflammatory bowel disease (IBD), offering predictive insights into disease onset, activity, and progression. Genetically, the significance of the HLA-B27 antigen is notably diminished in ankylosing spondylitis (AS) associated with IBD, but is heightened in concurrent sacroiliitis. Similarly, certain polymorphisms of endoplasmic reticulum aminopeptidase (ERAP-1) appear to be involved. Carriage of variant NOD2/CARD15 polymorphisms has been demonstrated to correlate with the risk of subclinical intestinal inflammation in AS. Biomarkers indicative of pro-inflammatory activity, including C-reactive protein (CRP) along with erythrocyte sedimentation rate (ESR), are among the consistent predictive biomarkers of disease progression. Nevertheless, these markers are not without limitations and exhibit relatively low sensitivity. Other promising markers encompass IL-6, serum calprotectin (s-CLP), serum amyloid (SAA), as well as biomarkers regulating bone formation such as metalloproteinase-3 (MMP-3) and Dickkopf-related protein 1 (DKK-1). Additional candidate indicators of structural changes in SpA patients include matrix metalloproteinase-3 (MMP-3), vascular endothelial growth factor (VEGF), tenascin C (TNC), and CD74 IgG. Fecal caprotein (f-CLP) levels over long-term follow-up of AS patients have demonstrated predictive value in anticipating the development of IBD. Serologic antibodies characteristic of IBD (ASCA, ANCA) have also been compared; however, results exhibit variability. In this review, we will focus on biomarkers associated with both axial SpA and idiopathic intestinal inflammation, notably enteropathic spondyloarthritis.
- MeSH
- ankylózující spondylitida krev diagnóza imunologie MeSH
- axiální spondyloartritida krev diagnóza MeSH
- biologické markery * krev MeSH
- C-reaktivní protein analýza metabolismus MeSH
- HLA-B27 antigen genetika imunologie MeSH
- idiopatické střevní záněty * krev imunologie diagnóza komplikace MeSH
- leukocytární L1-antigenní komplex krev MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Live donor kidney transplantation is considered the optimal choice for renal replacement therapy, providing established benefits, such as superior patient survival and improved quality of life. However, immunological challenges, including ABO blood group incompatibility and, particularly, donor-specific HLA antibodies, may impact long-term outcomes considerably or even prevent safe direct transplantation with the intended donor. METHODS: In this review, the authors discuss kidney paired donation (KPD) as a viable strategy to overcome immunological barriers to living donation through organ exchanges. We thereby lay special focus on the Czech-Austrian transnational KPD program. RESULTS: While the benefits of KPD programs are well established for adult recipients, recent data suggest that this may hold true also for pediatric patients. Complex algorithms, considering factors like the intricate patterns of HLA sensitization, play a pivotal role in predicting suitable matches, but for pediatric patients also non-immunological factors including age and weight match may play a role. As pool size proves crucial for program efficacy, several countries in Europe have now initiated transnational collaborations to maximize match rates. Among those, the Czech-Austrian transnational joint program, established in 2015 and now expanded to a cooperation with the Israel transplant program to further increase transplant rates, represents a successful example. CONCLUSION: KPD programs, with their innovative approaches and international partnerships, hold promise for enhancing outcomes and addressing the increasing demand for kidney transplantation.
- MeSH
- dítě MeSH
- dospělí MeSH
- HLA antigeny imunologie MeSH
- lidé MeSH
- transplantace ledvin * MeSH
- žijící dárci * MeSH
- získávání tkání a orgánů * MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Geografické názvy
- Česká republika MeSH
- Evropa MeSH
A comprehensive knowledge of human leukocyte antigen (HLA) molecular variation worldwide is essential in human population genetics research and disease association studies and is also indispensable for clinical applications such as allogeneic hematopoietic cell transplantation, where ensuring HLA compatibility between donors and recipients is paramount. Enormous progress has been made in this field thanks to several decades of HLA population studies allowing the development of helpful databases and bioinformatics tools. However, it is still difficult to appraise the global HLA population diversity in a synthetic way. We thus introduce here a novel approach, based on approximately 2000 data sets, to assess this complexity by providing a fundamental synopsis of the most frequent HLA alleles observed in different regions of the world. This new knowledge will be useful not only as a fundamental reference for basic research, but also as an efficient guide for clinicians working in the field of transplantation.
- MeSH
- alely * MeSH
- frekvence genu MeSH
- HLA antigeny * genetika imunologie MeSH
- lidé MeSH
- transplantace hematopoetických kmenových buněk * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- MeSH
- dospělí MeSH
- fenotyp * MeSH
- frekvence genu MeSH
- genetická predispozice k nemoci MeSH
- genetické asociační studie MeSH
- HLA antigeny genetika MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé středního věku MeSH
- lidé MeSH
- sarkoidóza * genetika MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- dopisy MeSH
- Geografické názvy
- Řecko MeSH
There is a paucity of information on how to select the most appropriate unrelated donor (UD) in hematopoietic stem cell transplantation (HSCT) using posttransplant cyclophosphamide (PTCy). We retrospectively analyzed the characteristics of 10/10 matched UDs (MUDs) and 9/10 mismatched UDs (MMUDs) that may affect transplant outcomes in patients with acute myeloid leukemia (AML) in first or second complete remission (CR1 or CR2). The primary end point was leukemia-free survival (LFS). Overall, 1011 patients were included with a median age of 54 years (range, 18-77). Donors had a median age of 29 years (range, 18-64); 304 (30%) were females, of which 150 (15% of the whole group) were donors to male recipients, and 621 (61%) were MUDs; 522 (52%) had negative cytomegalovirus (CMV-neg) serostatus, of which 189 (19%) were used for CMV-neg recipients. Donor age older than 30 years had a negative impact on relapse (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.06-1.8), LFS (HR, 1.4; 95% CI, 1.12-1.74), overall survival (HR 1.45; 95% CI, 1.14-1.85) and graft-versus-host disease (GVHD) free, relapse-free survival (HR, 1.29; 95% CI, 1.07-1.56). In addition, CMV-neg donors for CMV-neg recipients were associated with improved LFS (HR, 0.74; 95% CI, 0.55-0.99). The use of MMUD and female donors for male recipients did not significantly impact any transplant outcomes. For patients undergoing HSCT from a UD with PTCy for AML, donor age <30 years significantly improves survival. In this context, donor age might be prioritized over HLA match considerations. In addition, CMV-neg donors are preferable for CMV-neg recipients. However, further research is needed to validate and refine these recommendations.
- MeSH
- akutní myeloidní leukemie * terapie mortalita MeSH
- cyklofosfamid terapeutické užití MeSH
- dospělí MeSH
- HLA antigeny imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nemoc štěpu proti hostiteli etiologie MeSH
- nepříbuzný dárce * MeSH
- přežití bez známek nemoci MeSH
- retrospektivní studie MeSH
- senioři MeSH
- testování histokompatibility MeSH
- transplantace hematopoetických kmenových buněk * MeSH
- věkové faktory MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
