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1.
Thorax ; 79(6): 524-537, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38286613

RESUMEN

INTRODUCTION: Environmental pollutants injure the mucociliary elevator, thereby provoking disease progression in chronic obstructive pulmonary disease (COPD). Epithelial resilience mechanisms to environmental nanoparticles in health and disease are poorly characterised. METHODS: We delineated the impact of prevalent pollutants such as carbon and zinc oxide nanoparticles, on cellular function and progeny in primary human bronchial epithelial cells (pHBECs) from end-stage COPD (COPD-IV, n=4), early disease (COPD-II, n=3) and pulmonary healthy individuals (n=4). After nanoparticle exposure of pHBECs at air-liquid interface, cell cultures were characterised by functional assays, transcriptome and protein analysis, complemented by single-cell analysis in serial samples of pHBEC cultures focusing on basal cell differentiation. RESULTS: COPD-IV was characterised by a prosecretory phenotype (twofold increase in MUC5AC+) at the expense of the multiciliated epithelium (threefold reduction in Ac-Tub+), resulting in an increased resilience towards particle-induced cell damage (fivefold reduction in transepithelial electrical resistance), as exemplified by environmentally abundant doses of zinc oxide nanoparticles. Exposure of COPD-II cultures to cigarette smoke extract provoked the COPD-IV characteristic, prosecretory phenotype. Time-resolved single-cell transcriptomics revealed an underlying COPD-IV unique basal cell state characterised by a twofold increase in KRT5+ (P=0.018) and LAMB3+ (P=0.050) expression, as well as a significant activation of Wnt-specific (P=0.014) and Notch-specific (P=0.021) genes, especially in precursors of suprabasal and secretory cells. CONCLUSION: We identified COPD stage-specific gene alterations in basal cells that affect the cellular composition of the bronchial elevator and may control disease-specific epithelial resilience mechanisms in response to environmental nanoparticles. The identified phenomena likely inform treatment and prevention strategies.


Asunto(s)
Células Epiteliales , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/etiología , Células Epiteliales/metabolismo , Masculino , Persona de Mediana Edad , Células Cultivadas , Bronquios/patología , Femenino , Anciano , Óxido de Zinc , Mucosa Respiratoria/metabolismo , Mucosa Respiratoria/patología , Cilios , Nanopartículas , Diferenciación Celular
2.
Transpl Int ; 37: 13010, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39381015

RESUMEN

Human leukocyte antigen (HLA) mismatches (MM) between donor and recipient lead to eplet MM (epMM) in lung transplantation (LTX), which can induce the development of de-novo donor-specific HLA-antibodies (dnDSA), particularly HLA-DQ-dnDSA. Aim of our study was to identify risk factors for HLA-DQ-dnDSA development. We included all patients undergoing LTX between 2012 and 2020. All recipients/donors were typed for HLA 11-loci. Development of dnDSA was monitored 1-year post-LTX. EpMM were calculated using HLAMatchmaker. Differences in proportions and means were compared using Chi2-test and Students' t-test. We used Kaplan-Meier curves with LogRank test and multivariate Cox regression to compare acute cellular rejection (ACR), chronic lung allograft dysfunction (CLAD) and survival. Out of 183 patients, 22.9% patients developed HLA-DQ-dnDSA. HLA-DQ-homozygous patients were more likely to develop HLA-DQ-dnDSA than HLA-DQ-heterozygous patients (p = 0.03). Patients homozygous for HLA-DQ1 appeared to have a higher risk of developing HLA-DQ-dnDSA if they received a donor with HLA-DQB1*03:01. Several DQ-eplets were significantly associated with HLA-DQ-dnDSA development. In the multivariate analysis HLA-DQ-dnDSA was significantly associated with ACR (p = 0.03) and CLAD (p = 0.01). HLA-DQ-homozygosity, several high-risk DQ combinations and high-risk epMM result in a higher risk for HLA-DQ-dnDSA development which negatively impact clinical outcomes. Implementation in clinical practice could improve immunological compatibility and graft outcomes.


Asunto(s)
Rechazo de Injerto , Antígenos HLA-DQ , Trasplante de Pulmón , Humanos , Trasplante de Pulmón/efectos adversos , Femenino , Masculino , Antígenos HLA-DQ/inmunología , Antígenos HLA-DQ/genética , Persona de Mediana Edad , Adulto , Rechazo de Injerto/inmunología , Factores de Riesgo , Prueba de Histocompatibilidad , Estudios Retrospectivos , Donantes de Tejidos , Isoanticuerpos/inmunología , Supervivencia de Injerto/inmunología
3.
Clin Transplant ; 37(1): e14850, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36398875

RESUMEN

INTRODUCTION: Posterior reversible encephalopathy syndrome is a rare neurologic complication that can occur under immunosuppressive therapy with CNI after organ transplantation. METHODS: We retrospectively reviewed medical records of 545 patients who underwent lung transplantation between 2012 and 2019. Within this group, we identified 30 patients with neurological symptoms typical of PRES and compared the characteristics of patients who were diagnosed with PRES (n = 11) to those who were not (n = 19). RESULTS: The incidence of PRES after lung transplantation was 2%. Notably, 73% of the patients with PRES were female and the mean age was 39.2. Seizure (82% vs. 21%, p = .002) was the most common neurological presentation. The risk of developing PRES was significantly associated with age (OR = .92, p < .0001) and having cystic fibrosis (CF) (OP = 10.1, p < .0001). Creatinine level (1.9 vs. 1.1 mg/dl, p = .047) and tacrolimus trough level (19.4 vs. 16.5 ng/ml, p = .048) within 1 week prior to neurological symptoms were significantly higher in patients with PRES. CONCLUSION: Renal insufficiency and high tacrolimus levels are associated with PRES. A change of immunosuppressive drug should be done after confirmed PRES diagnosis or immediately in case of severe neurological dysfunction to improve neurological outcomes and minimize the risk of early allograft rejection.


Asunto(s)
Trasplante de Pulmón , Síndrome de Leucoencefalopatía Posterior , Humanos , Femenino , Adulto , Masculino , Tacrolimus/efectos adversos , Síndrome de Leucoencefalopatía Posterior/diagnóstico , Síndrome de Leucoencefalopatía Posterior/etiología , Estudios Retrospectivos , Trasplante de Pulmón/efectos adversos , Factores de Riesgo
4.
Infection ; 2023 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-37922037

RESUMEN

PURPOSE: Lung transplant recipients are at increased risk of severe disease following infection with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) due to high-dose immunosuppressive drugs and the lung is the main organ affected by Coronavirus disease 2019 (COVID-19). Several studies have confirmed increased SARS-CoV-2-related mortality and morbidity in patients living with lung allografts; however, detailed immunological studies of patients with SARS-CoV-2 infection in the early phase following transplantation remain scarce. METHODS: We investigated patients who were infected with SARS-CoV-2 in the early phase (18-103 days) after receiving double-lung allografts (n = 4, LuTx) in comparison to immunocompetent patients who had not received solid organ transplants (n = 88, noTx). We analyzed SARS-CoV-2-specific antibody responses against the SARS-CoV-2 spike and nucleocapsid proteins using enzyme-linked immunosorbent assays (ELISA), chemiluminescence immunoassays (CLIA), and immunoblot assays. T cell responses were investigated using Elispot assays. RESULTS: One LuTx patient suffered from persistent infection with fatal outcome 122 days post-infection despite multiple interventions including remdesivir, convalescent plasma, and the monoclonal antibody bamlanivimab. Two patients experienced clinically mild disease with prolonged viral shedding (47 and 79 days), and one patient remained asymptomatic. Antibody and T cell responses were significantly reduced or undetectable in all LuTx patients compared to noTx patients. CONCLUSION: Patients in the early phase following lung allograft transplantation are vulnerable to infection with SARS-CoV-2 due to impaired immune responses. This patient population should be vaccinated before LuTx, protected from infection post-LuTx, and in case of infection treated generously with currently available interventions.

5.
Oral Dis ; 2023 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-36939725

RESUMEN

INTRODUCTION: Poor oral hygiene can cause infections and inflammatory diseases. Data on its impact on outcome after lung transplantation (LuTX) is scarce. Most transplant centers have individual standards regarding dental care as there is no clinical guideline. This study's objective was to assess LuTX-listed patient's dental status and determine its effect on postoperative outcome. METHODS: Two hundred patients having undergone LuTX from 2014 to 2019 were selected. Collected data comprised LuTX-indication, periodontal status, and number of carious teeth/fillings. A preoperative panoramic dental X-ray and a dentist's consultative clarification were mandatory. RESULTS: 63.5% had carious dental status, differing significantly regarding TX-indication (p < 0.001; ILD: 41.7% vs. CF: 3.1% of all patients with carious teeth). Mean age at the time of LuTX differed significantly within these groups. Neither preoperative carious dental status nor periodontitis or bone loss deteriorated post-LuTX survival significantly. No evidence was found that either resulted in a greater number of deaths related to an infectious etiology. CONCLUSION: This study shows that carious dental status, periodontitis, and bone loss do not affect post-TX survival. However, literature indicates that they can cause systemic/pulmonary infections that deteriorate post-LuTX survival. Regarding the absence of standardized guidelines regarding dental care and LuTX, we strongly recommend emphasizing research in this field.

6.
BMC Surg ; 23(1): 44, 2023 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-36849951

RESUMEN

BACKGROUND: Our study aimed to identify preoperative predictors for perioperative allogenic blood transfusion (ABT) in patients undergoing major lung cancer resections in order to improve the perioperative management of patients at risk for ABT. METHODS: Patients admitted between 2014 and 2016 in a high-volume thoracic surgery clinic were retrospectively evaluated in a cohort study based on a control group without ABT and the ABT group requiring packed red blood cell units within 15 days postoperatively until discharge. The association of ABT with clinically established parameters (sex, preoperative anemia, liver and coagulation function, blood groups, multilobar resections) was analyzed by contingency tables, receiver operating characteristics (ROC) and logistic regression analysis, taking into account potential covariates. RESULTS: 60 out of 529 patients (11.3%) required ABT. N1 and non-T1 tumors, thoracotomy approach, multilobar resections, thoracic wall resections and Rhesus negativity were more frequent in the ABT group. In multivariable analyses, female sex, preoperative anemia, multilobar resections, as well as serum alanine-aminotransferase levels, thrombocyte counts and Rhesus negativity were identified as independent predictors of ABT, being associated with OR (95% Confidence interval, p-value) of 2.44 (1.23-4.88, p = 0.0112), 18.16 (8.73-37.78, p < 0.0001), 5.79 (2.50-13.38, p < 0.0001), 3.98 (1.73-9.16, p = 0.0012), 2.04 (1.04-4.02, p = 0.0390) and 2.84 (1.23-6.59, p = 0.0150), respectively. CONCLUSIONS: In patients undergoing major lung cancer resections, multiple independent risk factors for perioperative ABT apart from preoperative anemia and multilobar resections were identified. Assessment of these predictors might help to identify high risk patients preoperatively and to improve the strategies that reduce perioperative ABT.


Asunto(s)
Neoplasias Pulmonares , Cirugía Torácica , Femenino , Humanos , Estudios Retrospectivos , Estudios de Cohortes , Transfusión Sanguínea , Neoplasias Pulmonares/cirugía
7.
Pneumologie ; 77(5): 303-307, 2023 May.
Artículo en Alemán | MEDLINE | ID: mdl-37160111

RESUMEN

Case discussion of a 40-year-old male patient with a history of recurrent pneumothoraces due to Birt-Hogg-Dubé syndrome. In addition to conservative treatment of a pneumothorax on the left side, a subtotal parietal pleurectomy on the right side was performed after recurrence of a pneumothorax 6 years later. CT of the thorax showed high-grade structural remodelling of the lung parenchyma with cystic lung lesions on both sides with a diameter of up to 7.5 cm. After exclusion of alpha-1 antitrypsin deficiency, underlying immunological disease, unremarkable family and occupational history, Birt-Hogg-Dubé syndrome was suspected based on the morphological distribution pattern of the cystic lung lesions. Genetic examination helped detect a heterozygous pathogenic variant in the FLCN gene, namely c.1294_1298del;p.(Ser432Argfs*22). Birt-Hogg-Dubé syndrome is a rare genetic disorder clinically characterized by pulmonary cysts, fibrofolliculomas of the skin and occurrence of clustered renal tumors. In particular, the increased risk of renal malignancies and the risk of spontaneous pneumothoraces underlines the importance of early diagnosis and screening of affected patients and their families.


Asunto(s)
Síndrome de Birt-Hogg-Dubé , Neumotórax , Deficiencia de alfa 1-Antitripsina , Masculino , Humanos , Adulto , Síndrome de Birt-Hogg-Dubé/complicaciones , Síndrome de Birt-Hogg-Dubé/diagnóstico , Síndrome de Birt-Hogg-Dubé/genética , Neumotórax/diagnóstico , Neumotórax/etiología , Neumotórax/cirugía , Enfermedades Raras
8.
Pancreatology ; 22(4): 466-471, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35379557

RESUMEN

BACKGROUND/OBJECTIVES: Autoimmune diseases are often associated with human leukocyte antigen (HLA) haplotypes, indicating that changes in major histocompatibility complex (MHC)-dependent self-peptide or antigen presentation contribute to autoimmunity. In our study, we aimed to investigate HLA alleles in a large European cohort of autoimmune pancreatitis (AIP) patients. METHODS: Hundred patients with AIP, diagnosed and classified according to the International Consensus Diagnostic Criteria (ICDC), were prospectively enrolled in the study. Forty-four patients with chronic pancreatitis (CP) and 254 healthy subjects served as control groups. DNA was isolated from blood samples and two-digit HLA typing was performed with sequence-specific primer (SSP-) PCR. HLA allele association strength to AIP was calculated as odds ratio. RESULTS: We uncovered a strong enrichment of HLA-DQB1 homozygosity in type 1 and type 2 AIP patients. Moreover, a significantly increased incidence of the HLA-DRB1∗16 and HLA-DQB1∗05 alleles and a concomitant lack of the HLA-DRB1∗13 allele was detected in AIP type 1 and type 2 patients. In contrast, the HLA-DQB1∗02 allele was underrepresented in the 'not otherwise specified' (NOS) AIP subtype. We detected no significant difference in the HLA-DRB3, HLA-DRB4 and HLA-DRB5 allele frequency in our cohort. CONCLUSIONS: Although AIP type 1 and type 2 are characterized by distinct histopathological characteristics, both subtypes are associated with the same HLA alleles, indicating that the disease might rely on similar immunogenic mechanisms. However, AIP NOS represented another subclass of AIP.


Asunto(s)
Pancreatitis Autoinmune , Alelos , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Cadenas HLA-DRB1/genética , Cadenas HLA-DRB4/genética , Haplotipos , Humanos
9.
Am J Transplant ; 21(10): 3449-3455, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34118118

RESUMEN

Letermovir is a new antiviral drug approved for the prophylaxis of CMV infection in allogeneic stem cell transplants. The aim of the study was to assess the therapeutic efficacy of letermovir in difficult to treat CMV infections in lung transplant recipients. All lung transplant recipients between March 2018 and August 2020, who have been treated with letermovir for ganciclovir-resistant or refractory CMV infection were included in the study and analysed retrospectively. In total, 28 patients were identified. CMV disease was present in 15 patients (53.6%). In 23 patients (82.1%), rapid response was noticed, and CMV-viral load could be significantly decreased (>1 log10 ) after a median of 17 [14-27] days and cleared subsequently in all of these patients. Five patients (17.9%) were classified as non-responder. Thereof, development of a mutation of the CMV UL56 terminase (UL-56-Gen: C325Y) conferring letermovir resistance could be observed in three patients (60%). Common side effects were mild and mostly of gastrointestinal nature. Mild adjustments of the immunosuppressive drugs were mandatory upon treatment initiation with letermovir. In addition to other interventions, letermovir was effective in difficult to treat CMV infections in lung transplant recipients. However, in patients with treatment failure mutation conferring letermovir, resistance should be taken into account.


Asunto(s)
Infecciones por Citomegalovirus , Trasplante de Células Madre Hematopoyéticas , Acetatos , Antivirales/uso terapéutico , Citomegalovirus , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/prevención & control , Farmacorresistencia Viral , Humanos , Pulmón , Quinazolinas , Estudios Retrospectivos , Receptores de Trasplantes
10.
Clin Transplant ; 35(6): e14294, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33749938

RESUMEN

BACKGROUND: Protecting against CMV infection and maintaining CMV in latent state are largely provided by CMV-specific T-cells in lung transplant recipients. The aim of the study was to assess whether a specific T-cell response is associated with the risk for CMV infection in seronegative patients who are at high risk for delayed CMV infection. METHODS: All CMV-seronegative recipients (R-) from CMV-seropositive donors (D+) between January 2018 and April 2019 were included and retrospectively screened for CMV infection before and after assessment of CMV-specific cell-mediated immunity. RESULTS: Thirty-one of the 50 patients (62%) developed early-onset CMV infection. Lower absolute neutrophil counts were significantly associated with early-onset CMV infection. Antiviral prophylaxis was ceased after 137.2 ± 42.8 days. CMV-CMI were measured at a median of 5.5 months after LTx. 19 patients experienced early and late-onset CMV infection after prophylaxis withdrawal within 15 months post transplantation. Positive CMV-CMI was significantly associated with lower risk of late-onset CMV infection after transplantation in logistic and cox-regression analysis (OR=0.05, p = .01; OR=2,369, p = .026). CONCLUSION: D+/R- lung transplant recipients are at high risk of developing early and late-onset CMV infection. Measurement of CMV-CMI soon after transplantation might further define the CMV infection prediction risk in LTx recipients being at high risk for CMV viremia.


Asunto(s)
Infecciones por Citomegalovirus , Receptores de Trasplantes , Antivirales/uso terapéutico , Citomegalovirus , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/epidemiología , Infecciones por Citomegalovirus/etiología , Humanos , Pulmón , Estudios Retrospectivos , Linfocitos T
11.
Transfus Med Hemother ; 46(5): 337-347, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31832059

RESUMEN

Since almost 30 years, lung transplantation is a considerable therapeutic option in patients suffering from end-stage lung disease. Up to now, the impact of donor-specific antibodies directed against donor HLA (human leukocyte antigen) before and after transplantation is still a matter of debate. As histocompatibility testing is not required for each patient according to the current national guidelines and Eurotransplant recommendations for lung transplantation, each transplantation unit has to establish a local protocol together with the tissue typing laboratory how to implement an immunological risk assessment strategy for their patients while enabling access to transplantation. Desensitization regimens might help in case of highly alloimmunized patients waiting for urgent transplantation.

12.
Transpl Int ; 30(4): 360-370, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27862352

RESUMEN

Many aspects of post-transplant monitoring of donor-specific (DSA) and non-donor-specific (nDSA) anti-HLA antibodies on renal allograft survival are still unclear. Differentiating them by their ability to bind C1q may offer a better risk assessment. We retrospectively investigated the clinical relevance of de novo C1q-binding anti-HLA antibodies on graft outcome in 611 renal transplant recipients. Acute rejection (AR), renal function, and graft survival were assessed within a mean follow-up of 6.66 years. Post-transplant 6.5% patients developed de novo DSA and 11.5% de novo nDSA. DSA (60.0%; P < 0.0001) but not nDSA (34.1%, P = 0.4788) increased rate of AR as compared with controls (27.4%). C1q-binding anti-HLA antibodies did not alter rate of AR in both groups. Renal function was only significantly diminished in patients with DSAC1q+ . However, DSA significantly impaired 5-year graft survival (65.2%; P < 0.0001) in comparison with nDSA (86.7%; P = 0.0054) and controls (90.7%). While graft survival did not differ between DSAC1q- and DSAC1q+ recipients, 5-year allograft survival was reduced in nDSAC1q+ (80.9%) versus nDSAC1q- (90.7%, P = 0.0251). De novo DSA independently of their ability to bind C1q are associated with diminished graft survival.


Asunto(s)
Anticuerpos/inmunología , Complemento C1q/inmunología , Antígenos HLA/inmunología , Trasplante de Riñón/efectos adversos , Insuficiencia Renal/cirugía , Adulto , Anciano , Biopsia , Femenino , Rechazo de Injerto , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , Factores de Tiempo , Resultado del Tratamiento
13.
Transplantation ; 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39250332

RESUMEN

BACKGROUND: Baseline lung allograft dysfunction (BLAD) is characterized by the failure to achieve normal baseline lung function after double lung transplantation (DLTX) and is associated with a high risk of mortality. In single lung transplant (SLTX) recipients, however, cutoff values and associated factors have not been explored. Here, we aimed to define BLAD in SLTX recipients, investigate its impact on allograft survival, and identify potential risk factors for BLAD in SLTX recipients. METHODS: We performed a retrospective, single-center analysis of the LTX cohort of LMU Munich between 2010 and 2018. In accordance with DLTX cutoffs, BLAD in SLTX recipients was defined as failure to achieve percentage of forced expiratory volume in 1 s and percentage of forced vital capacity of >60% on 2 consecutive tests >3 wk apart. Survival analysis and regression analysis for potential predictors of BLAD were performed. RESULTS: In a cohort of 141 SLTX recipients, 43% of patients met BLAD criteria. SLTX recipients with BLAD demonstrated impaired survival. Native lung hyperinflation was associated with BLAD in obstructive disease, whereas donor/recipient lung size mismatch was associated with BLAD in both obstructive and restrictive underlying diseases. Pulmonary function testing at 3 mo after lung transplantation predicted normal baseline lung function in SLTX recipients with obstructive lung disease. CONCLUSIONS: BLAD in SLTX recipients is as relevant as in DLTX recipients and should generally be considered in the follow-up of LTX recipients. Risk factors for BLAD differed between underlying obstructive and restrictive lung disease. A better understanding of associated factors may help in the development of preventive strategies.

14.
Transplant Direct ; 10(9): e1680, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39131238

RESUMEN

Background: Preformed donor-specific HLA antibodies (DSA) are a well-known risk factor in kidney transplantation. There is still considerable debate, however, about the optimal risk stratification among patients with preformed DSA. Additionally, data on the prognostic value of different crossmatch assays in DSA-positive patients are scarce. Methods: DSA-positive living kidney transplant recipients were selected from a multicenter study examining 4233 consecutive renal transplants. An additional 7 patients from 2 further centers were included. Flow cytometric crossmatches (FXM), Luminex-based crossmatches, and virtual crossmatches based on C1q- and C3d-binding antibodies (C1qXM and C3dXM) were performed retrospectively using pretransplant sera and lymphocytes isolated from fresh samples. These samples were obtained from 44 donor and recipient pairs from 12 centers. Clinical outcome data and the control group without DSA were compiled from the previous study and were supplemented by data on 10-y death-censored graft survival (10yGS). Results: Between 19% (C3dXM) and 46% (FXM) of crossmatches were positive. Crossmatch-positive patients showed high incidences of antibody-mediated rejection (AMR) within 6 mo (up to 60% in B-cell FXM+ patients). The incidence of AMR in crossmatch-negative patients ranged between 5% (FXM-) and 13% (C1qXM-). 10yGS was significantly impaired in patients with positive T-cell FXM and total FXM compared with both patients without DSA and those with DSA with negative FXM. Conclusions: Especially FXM are useful for risk stratification, as the outcome of DSA-positive, FXM-negative patients is similar to that of DSA-negative patients, whereas FXM-positive patients have both more AMR and decreased 10yGS. Because of their lower sensitivity, the significance of Luminex-based crossmatches, C1qXM, and C3dXM would have to be examined in patients with stronger DSA.

15.
Eur J Clin Invest ; 43(8): 816-20, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23710757

RESUMEN

INTRODUCTION: Neutrophil gelatinase-associated lipocalin (NGAL) is a powerful biomarker for the early detection of acute kidney injury. However, recent data suggest that NGAL also plays an important role in chronic kidney disease (CKD), reflecting the level of acute kidney damage within the CKD condition. To study whether elevated NGAL levels in CKD are a consequence of damaged tubular cells or rather due to extrarenal production, we investigated NGAL levels in anephric patients on dialysis. METHODS: Plasma NGAL levels were investigated in 14 dialysis patients who underwent bilateral nephrectomy (anephric group), 18 anuric dialysis patients with remaining kidneys (dialysis group) and 12 healthy patients (healthy group). RESULTS: Plasma NGAL levels were significantly lower in the healthy group compared with the anephric group (143 vs. 981 ng/mL; P < 0·001) or the dialysis group (143 vs. 838 ng/mL; P < 0·001), respectively. However, NGAL levels did not differ between the anephric group and the dialysis group (981 vs. 838 ng/mL; P = 0·19). DISCUSSION: Assuming that NGAL is highly expressed in chronically damaged kidneys due to tubular stress, there should be significantly less NGAL in anephric patients compared with anuric dialysis patients with remaining kidneys. In contrast to this hypothesis, we found no difference in NGAL expression between these two groups, proving the entire extrarenal NGAL production in anephric patients and suggesting that the tubular NGAL expression seems to be negligible in anuric dialysis patients.


Asunto(s)
Fallo Renal Crónico/diagnóstico , Lipocalinas/sangre , Proteínas Proto-Oncogénicas/sangre , Diálisis Renal , Proteínas de Fase Aguda , Biomarcadores/sangre , Estudios de Casos y Controles , Creatinina/metabolismo , Tasa de Filtración Glomerular/fisiología , Humanos , Fallo Renal Crónico/fisiopatología , Fallo Renal Crónico/cirugía , Lipocalina 2 , Nefrectomía/métodos , Nefritis/metabolismo , Estudios Retrospectivos
16.
J Clin Med ; 12(15)2023 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-37568398

RESUMEN

Immunosuppressants and antifibrotics are currently used to treat patients with various interstitial lung diseases, which may undergo lung transplantation (LTx). The retrospective study aimed to evaluate the potential effects of therapeutic regimen on the perioperative course in patients with idiopathic pulmonary fibrosis (IPF) or progressive pulmonary fibrosis (PPF) undergoing LTx. All patients with IPF and PPF undergoing LTx between January 2014 and December 2021 were included. We retrospectively screened for previous use of immunosuppressants and antifibrotic therapy. We analyzed perioperative courses, short-term outcomes, and safety retrospectively. In total, 286 patients with diagnosis of IPF or PPF were analyzed. According to the treatment regimen before LTx, the study cohort was divided into four groups and compared. No differences between antifibrotic monotherapy, combined antifibrotic and immunosuppressive therapy with regard to postoperative complications were observed. Length of mechanical ventilation was shorter in patients with antifibrotics prior to LTx. Pretreatment with antifibrotic monotherapy and a combination of antifibrotic drugs with immunosuppressive therapy, lower body mass index (BMI) and lower blood loss, were independently associated with primary graft dysfunction grades 0-3 72 hours after LTx (p < 0.001). Finally, patients with antifibrotic monotherapy developed significantly less de novo donor-specific antibodies (DSA) (p = 0.009). Higher intraoperative blood loss, etiology of interstitial lung disease (ILD) and older age were independently associated with shorter survival after LTx. Use of antifibrotic monotherapy and a combination of antifibrotic drugs with immunosuppressive therapy in IPF/PPF patients undergoing LTx, proved to be safe and might lead to beneficial effects after LTx.

17.
HLA ; 102(3): 331-342, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37068792

RESUMEN

Molecular matching is a new approach for virtual histocompatibility testing in organ transplantation. The aim of our study was to analyze whether the risk for de novo donor-specific HLA antibodies (dnDSA) after lung transplantation (LTX) can be predicted by molecular matching algorithms (MMA) and their combination. In this retrospective study we included 183 patients undergoing LTX at our center from 2012-2020. We monitored dnDSA development for 1 year. Eplet mismatches (epMM) using HLAMatchmaker were calculated and highly immunogenic eplets based on their ElliPro scores were identified. PIRCHE-II scores were calculated using PIRCHE-II algorithm (5- and 11-loci). We compared epMM and PIRCHE-II scores between patients with and without dnDSA using t-test and used ROC-curves to determine optimal cut-off values to categorize patients into four groups. We used logistic regression with AIC to compare the predictive value of PIRCHE-II, epMM, and their combination. In total 28.4% of patients developed dnDSA (n = 52), 12.5% class I dnDSA (n = 23), 24.6% class II dnDSA (n = 45), and 8.7% both class II and II dnDSA (n = 16). Mean epMMs (p-value = 0.005), mean highly immunogenic epMMs (p-value = 0.003), and PIRCHE-II (11-loci) (p = 0.01) were higher in patients with compared to without class II dnDSA. Patients with highly immunogenic epMMs above 30.5 and PIRCHE-II 11-loci above 560.0 were more likely to develop dnDSA (31.1% vs. 14.8%, p-value = 0.03). The logistic regression model including the grouping variable showed the best predictive value. MMA can support clinicians to identify patients at higher or lower risk for developing class II dnDSA and might be helpful tools for immunological risk assessment in LTX patients.


Asunto(s)
Trasplante de Riñón , Trasplante de Pulmón , Humanos , Estudios Retrospectivos , Rechazo de Injerto , Alelos , Anticuerpos , Prueba de Histocompatibilidad , Antígenos HLA , Donantes de Tejidos , Isoanticuerpos
18.
HLA ; 100(1): 3-17, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-34951119

RESUMEN

With the introduction of the virtual allocation crossmatch in the Eurotransplant (ET) region in 2023, the determination of unacceptable antigen mismatches (UAM) in kidney transplant recipients is of utmost importance for histocompatibility laboratories and transplant centers. Therefore, a joined working group of members from the German Society for Immunogenetics (Deutsche Gesellschaft für Immungenetik, DGI) and the German Transplantation Society (Deutsche Transplantationsgesellschaft, DTG) revised and updated the previous recommendations from 2015 in light of recently published evidence. Like in the previous version, a wide range of topics is covered from technical issues to clinical risk factors. This review summarizes the evidence about the prognostic value of contemporary methods for HLA antibody detection and identification, as well as the impact of UAM on waiting time, on which these recommendations are based. As no clear criteria could be determined to differentiate potentially harmful from harmless HLA antibodies, the general recommendation is to assign all HLA against which plausible antibodies are found as UAM. There is, however, a need for individualized solutions for highly immunized patients. These revised recommendations provide a list of aspects that need to be considered when assigning UAM to enable a fair and comprehensible procedure and to harmonize risk stratification prior to kidney transplantation between transplant centers.


Asunto(s)
Trasplante de Riñón , Alelos , Rechazo de Injerto , Antígenos HLA/genética , Histocompatibilidad , Prueba de Histocompatibilidad/métodos , Humanos , Isoanticuerpos , Trasplante de Riñón/métodos
19.
Transplant Proc ; 54(6): 1504-1516, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35120764

RESUMEN

BACKGROUND: COVID-19 causes a wide range of symptoms, with particularly high risk of severe respiratory failure and death in patients with predisposing risk factors such as advanced age or obesity. Recipients of solid organ transplants, and in particular lung transplantation, are more susceptible to viral infection owing to immune suppressive medication. As little is known about the SARS-CoV-2 infection in these patients, this study was undertaken to describe outcomes and potential management strategies in early COVID-19 infection early after lung transplantation. METHODS: We describe the incidence and outcome of COVID-19 in a cohort of recent lung transplant recipients in Munich. Six of 186 patients who underwent lung transplantation in the period between March 2019 and March 2021 developed COVID-19 within the first year after transplantation. We documented the clinical course and laboratory changes for all patients showing differences in the severity of the infection with COVID-19 and their outcomes. RESULTS: Three of 6 SARS-CoV-2 infections were hospital-acquired and the patients were still in inpatient treatment after lung transplantation. All patients suffered from symptoms. One patient did not receive antiviral therapy. Remdesivir was prescribed in 4 patients and the remaining patient received remdesivir, bamlanivimab and convalescent plasma. CONCLUSIONS: COVID-19 does not appear to cause milder disease in lung transplant recipients compared with the general population. Immunosuppression is potentially responsible for the delayed formation of antibodies and their premature loss. Several comorbidities and a general poor preoperative condition showed an extended hospital stay.


Asunto(s)
COVID-19 , Anticuerpos Monoclonales Humanizados , Anticuerpos Neutralizantes , Antivirales/uso terapéutico , COVID-19/terapia , Humanos , Inmunización Pasiva , Pulmón , SARS-CoV-2 , Receptores de Trasplantes , Sueroterapia para COVID-19
20.
J Clin Virol ; 145: 105029, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34798365

RESUMEN

INTRODUCTION: Chronic kidney disease (CKD) is associated with significant morbidity and mortality after lung transplantation (LTX). Calcineurin inhibitor (CNI) nephrotoxicity is the leading cause of CKD. After kidney transplantation, polyomavirus-associated nephropathy (PyVAN) is a well-recognized problem. This study aims to evaluate the role of polyomavirus in patients after LTX. METHODS: From January 2017 to January 2020, all lung transplant recipients who performed follow-up visits in our center were included in the study and retrospectively assessed. We measured renal function (creatinine levels before and after transplantation), JCPyV, and BKPyV load by polymerase chain reaction (PCR) in serum and urine samples after transplantation. RESULTS: In total, 104 consecutive patients (59 males, 56.7%) with a mean age of 49.6 ± 11.1 years were identified. JCPyV was found in urine of 36 patients (34.6%) and serum of 3 patients (2.9%). BKPyV was found in urine of 40 patients (38.5%) and serum of 4 patients (3.8%), respectively. Urine evidence for JCPyV (p < 0.001, coefficient: +21.44) and BKPyV (p < 0.001, coefficient: +29.65) correlated highly with further kidney function decline. CONCLUSION: Kidney function deterioration is associated with JCPyV and BKPyV viruria in patients after LTX. This might indicate a role of PyVAN in lung transplant recipients.


Asunto(s)
Riñón/fisiopatología , Trasplante de Pulmón , Infecciones por Polyomavirus , Infecciones Tumorales por Virus , Adulto , Virus BK , Femenino , Humanos , Trasplante de Pulmón/efectos adversos , Masculino , Persona de Mediana Edad , Poliomavirus , Infecciones por Polyomavirus/complicaciones , Estudios Retrospectivos , Infecciones Tumorales por Virus/complicaciones
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