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Although prediagnostic circulating concentrations of the immune activation markers soluble CD27 (sCD27), sCD30 and chemokine ligand-13 (CXCL13) have been associated with non-Hodgkin lymphoma (NHL) risk, studies have been limited by sample size in associations with NHL subtypes. We pooled data from eight nested case-control studies to investigate subtype-specific relationships for these analytes. Using polytomous regression, we calculated odds ratios (ORs) with 95% confidence intervals (CIs) relating study-specific analyte tertiles to selected subtypes vs controls (n = 3310): chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; n = 623), diffuse large B cell lymphoma (DLBCL; n = 621), follicular lymphoma (FL; n = 398), marginal zone lymphoma (MZL; n = 138), mantle cell lymphoma (MCL; n = 82) and T cell lymphoma (TCL; n = 92). We observed associations with DLBCL for elevated sCD27 [OR for third vs first tertile (ORT3 ) = 2.2, 95% CI = 1.6-3.1], sCD30 (ORT3 = 2.0, 95% CI = 1.6-2.5) and CXCL13 (ORT3 = 2.3, 95% CI = 1.8-3.0). We also observed associations with sCD27 for CLL/SLL (ORT3 = 3.3, 95% CI = 2.4-4.6), MZL (ORT3 = 7.7, 95% CI = 3.0-20.1) and TCL (ORT3 = 3.4, 95% CI = 1.5-7.7), and between sCD30 and FL (ORT3 = 2.7, 95% CI = 2.0-3.5). In analyses stratified by time from phlebotomy to case diagnosis, the sCD27-TCL and all three DLBCL associations were equivalent across both follow-up periods (<7.5, ≥7.5 years). For other analyte-subtype comparisons, associations were stronger for the follow-up period closer to phlebotomy, particularly for indolent subtypes. In conclusion, we found robust evidence of an association between these immune markers and DLBCL, consistent with hypotheses that mechanisms related to immune activation are important in its pathogenesis. Our other findings, particularly for the rarer subtypes MZL and TCL, require further investigation.
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Leucemia Linfocítica Crónica de Células B , Linfoma Folicular , Linfoma de Células B Grandes Difuso , Linfoma de Células del Manto , Linfoma no Hodgkin , Adulto , Humanos , Leucemia Linfocítica Crónica de Células B/complicaciones , Linfoma no Hodgkin/etiología , Biomarcadores , Estudios de Casos y ControlesRESUMEN
Elevated prediagnostic serum levels of the immune activation markers sCD27 and sCD30 have been associated with non-Hodgkin lymphoma (NHL). However, the use of a single sample per participant in these studies has limited etiologic inferences. We report findings, overall and by NHL subtype, from a case-control analysis (422 cases, 434 controls) within the Janus Serum Bank with two samples per subject collected on average 5 years apart. Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) was associated with elevated sCD27 in the later, but not earlier, prediagnostic sample (odds ratio [OR] 4.2, 95% confidence interval [CI] 1.5-11.6 and 1.7, 0.7-4.7 per log increase, respectively) in analyses adjusting for both analytes, while follicular lymphoma (FL) was associated with elevated sCD30 in both the later and earlier samples (OR 2.9, 95% CI 1.4-4.4 and 2.3, 1.2-4.4, respectively). CLL/SLL cases were significantly more likely than controls to have higher sCD27 in the later vs. earlier sample (OR 1.4, 95% CI 1.1-1.9 per standard deviation increase); no such difference in sCD30 was apparent for FL. In a joint analysis, NHL cases were more likely than controls to have below-median sCD27 in the earlier sample and above-median sCD27 in the later sample (OR 1.5, 95% CI 1.0-2.3). For sCD30, the association between sCD30 and FL was confined to subjects with above-median analyte levels in both samples (OR 2.5, 95% CI 1.1-5.9). Our findings are compatible with elevated sCD27 representing a disease-induced effect and sCD30 representing a marker of increased FL susceptibility.
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Biomarcadores de Tumor/sangre , Antígeno Ki-1/sangre , Leucemia Linfocítica Crónica de Células B/epidemiología , Linfoma Folicular/epidemiología , Mieloma Múltiple/epidemiología , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/sangre , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/diagnóstico , Estudios Longitudinales , Linfoma Folicular/diagnóstico , Masculino , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Noruega/epidemiología , Oportunidad Relativa , Medición de Riesgo/métodos , Factores de RiesgoRESUMEN
In this review, we discuss a possible central role of T-cell help in severe forms of graft damage mediated by donor-specific HLA antibodies (DSA). Some kidney transplant recipients with pretransplant DSA show a high graft failure rate, whereas in other patients DSA do not harm the transplanted kidney and in most cases, disappear shortly after transplantation. Analyzing 80 desensitized highly immunized kidney transplant recipients and another multicenter cohort of 385 patients with pretransplant HLA antibodies, we reported recently that an ongoing T-cell help from an activated immune system, as measured by an increased level of soluble CD30 in serum, might be necessary for the DSA to exert a deleterious effect. Patients positive for both pretransplant DSA and sCD30 appear to require special measures, such as the elimination of DSA from the circulation, potent immunosuppression, good HLA-matching, and intense post-transplant monitoring, whereas exclusion of DSA-positive patients from transplantation in the absence of high sCD30 may not be justified in all cases, even if the pretransplant DSA are strong and complement-activating.
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Anticuerpos/inmunología , Rechazo de Injerto/inmunología , Antígenos HLA/inmunología , Linfocitos T/inmunología , Animales , Estudios de Cohortes , Proteínas del Sistema Complemento , Supervivencia de Injerto/inmunología , Humanos , Inmunosupresores , Isoanticuerpos/sangre , Antígeno Ki-1/inmunología , Trasplante de Riñón , Ratones , Insuficiencia Renal/sangre , Insuficiencia Renal/inmunología , Donantes de TejidosRESUMEN
Prediagnostic serum/plasma concentrations of B-cell activation markers have been associated with future risk of B-cell lymphomas (BCL) in HIV-infected patients and in the general population. Current evidence for the general population is however limited and relies on relatively small numbers of observations, especially for specific histologies. We carried out a nested case-control study, including 218 BCL and 218 matched controls, within two prospective cohorts, to investigate the association between plasma levels of soluble (s)CD27 and sCD30 and future risk of BCL, and main histologic subtypes separately. To expand the evidence further, we performed meta-analyses of the published data on these associations from prospective studies among the general population. Our study revealed a significant relationship between sCD30 concentration and BCL risk (OR = 0.86, 1.53, 1.76, for the 2nd-4th quartiles respectively, p trend = 0.01). Similar increased risks were observed for diffuse large B-cell lymphoma and follicular lymphoma. Analyses of sCD27 blood concentrations did not show significant associations with BCL, (OR = 0.90, 1.26, 1.65 for the 2nd-4th quartiles, respectively, p trend = 0.17), but significant associations were observed for chronic lymphocytic leukaemia and for the group of "other BCL" subtypes. Our findings involving sCD30 were confirmed within our meta-analyses of five prospective cohorts, while results were more heterogeneous for sCD27 with the exception of CLL which was found consistently in all studies. Data to date suggest that chronic B-cell stimulation might be an important mechanism involved in B-cell lymphomagenesis both in HIV-infected and in the general population.
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Antígeno Ki-1/sangre , Activación de Linfocitos , Linfoma de Células B/sangre , Linfoma de Células B/epidemiología , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/sangre , Biomarcadores , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Estudios Prospectivos , RiesgoRESUMEN
INTRODUCTION: It has been suggested that soluble immune receptors (SIRs) such as sCD25 and sCD30 may serve as potential biomarkers in evaluation of atopic dermatitis (AD). Previous studies clearly indicated that serum levels of interleukin (IL)-13 and total IgE (tIgE) might be potentially useful in the evaluation of patents with AD. AIM: To evaluate whether serum levels of sCD25 and sCD30 are suitable biomarkers of AD. Moreover, we have decided to estimate the usefulness of tIgE and IL-13 serum level determination in the evaluated population. MATERIAL AND METHODS: A group of 102 AD patients was investigated. Serum concentrations of sCD30, sCD25, IL-13 and tIgE were measured. The clinical phenotype of AD was classified as extrinsic (ADe) or intrinsic (ADi) based on the presence of IgE. Statistical analysis was performed to estimate correlations between obtained results and clinical features of the population such as AD phenotype, age, disease extent and severity. RESULTS: Extrinsic AD was diagnosed in 71% of patients, while ADi phenotype was observed in 29% of the investigated population. A negative correlation between serum levels of sCD25 and sCD30 and disease severity as well patients' age was established. Serum levels of IL-13 did not reach the cut-off point set by the manufacturer. A positive correlation between serum levels of total IgE and disease severity and patients' age was observed. CONCLUSIONS: This paper shows that serum levels of sCD25 and sCD30 as well as tIgE are age dependent. Determination of serum levels of sCD25, sCD30 and IL-13 is not useful in everyday practice.
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Acute rejection (AR) remains a major cause for long-term kidney allograft failure. Reliable immunological parameters suitable to define the pre-transplant immune state and hence the individual risk of graft rejection are highly desired to preferably adapt the immunosuppressive regimen in advance. Donor and third party alloreactivities were determined by mixed lymphocyte cultures. Soluble forms of CD25, CD30, and CD44 were detected in patients' serum by ELISA. Various lymphocyte subpopulations were measured using flow cytometry. All patients received triple immunosuppression (tacrolimus/mycophenolate mofetil/steroids) and were grouped according to biopsy results within the first year: rejection-free (RF, n = 13), borderline (BL, n = 5), or acute rejection (AR, n = 7). Patients with AR showed the highest pre-transplant alloreactivities and serum levels (sCD25/sCD30/sCD44) according to the pattern RF < BL < AR. Relying on serum analysis only, multivariate logistic regression (logit link function) yielded a prognostic score for prediction of rejection with 75.0% sensitivity and 69.2% specificity. Patients with rejection showed markedly higher pre-transplant frequencies of CD4(+) /CD8(+) T cells lacking CD28, but lower numbers of CD8(+) CD161(bright) T cells and NK cells than RF individuals. Pre-transplant immune state defined by alloreactivity, serum markers, and particular lymphocyte subsets seems to correlate with occurrence of graft rejection after kidney transplantation. A prognostic score based on pre-transplant serum levels has shown great potential for prediction of rejection episodes and should be further evaluated.
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Biomarcadores/sangre , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Rechazo de Injerto/diagnóstico , Fallo Renal Crónico/inmunología , Trasplante de Riñón , Donadores Vivos , Adulto , Ensayo de Inmunoadsorción Enzimática , Femenino , Citometría de Flujo , Estudios de Seguimiento , Rechazo de Injerto/sangre , Humanos , Receptores de Hialuranos/sangre , Subunidad alfa del Receptor de Interleucina-2/sangre , Antígeno Ki-1/sangre , Fallo Renal Crónico/cirugía , Activación de Linfocitos , Prueba de Cultivo Mixto de Linfocitos , Masculino , Persona de Mediana Edad , Cuidados Posoperatorios , Valor Predictivo de las Pruebas , Factores de RiesgoRESUMEN
INTRODUCTION: Multiple sclerosis (MS) is a chronic, inflammatory demyelinating disease of the central nervous system. Primary progressive MS (PPMS) is diagnosed in approximately 10-15 % of MS patients. Disease-modifying therapies (DMT) are less effective in modifying the course of progressive types of MS. It seems that inflammatory processes differ in the MS subtypes. OBJECTIVES: The objective of this study was to assess differences in the inflammatory parameters between PPMS and other courses of MS. MATERIALS AND METHODS: A total of 84 subjects were included in the study. The study group was divided according to the course of MS into the following categories: PPMS (n = 24); SPMS-secondary progressive multiple sclerosis (n = 14); RRMS-relapsing-remitting multiple sclerosis (n = 46). PPMS patients were further divided into treated with ocrelizumab and treatment-naive groups. The concentrations of serum inflammatory parameters were evaluated. RESULTS: PPMS and SPMS significantly differed in the serum levels of sCD30, gp130, sIL-6R alpha, osteopontin, pentraxin-3 and sTNF-R1. The serum concentrations of IFN-alpha2, IL-10, IL-20, IL-29 and osteopontin significantly differed between PPMS and RRMS. The serum levels of BAFF, IL-19, IL-20, pentraxin-3, s-TNF-R1 and s-TNF-R2 significantly differed between PPMS treated with ocrelizumab and treatment-naive. CONCLUSION: Although inflammatory processes take part in the pathogenesis of all types of MS, they differ between MS courses. Serum inflammatory parameters seem to be promising biomarkers in helping to differentiate courses of MS, and in assessing reactions to DMT treatment. Further investigations on their usage are required.
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Esclerosis Múltiple Crónica Progresiva , Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Humanos , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/patología , Osteopontina , Esclerosis Múltiple Crónica Progresiva/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , CitocinasRESUMEN
Background: It is still incompletely understood why some patients with preformed donor-specific anti-HLA antibodies (DSA) have reduced kidney allograft survival secondary to antibody-mediated rejection (ABMR), whereas many DSA-positive patients have favorable long-term outcomes. Elevated levels of soluble CD30 (sCD30) have emerged as a promising biomarker indicating deleterious T-cell help in conjunction with DSA in immunologically high-risk patients. We hypothesized that this would also be true in intermediate-risk patients. Methods: We retrospectively analyzed pre-transplant sera from 287 CDC-crossmatch negative patients treated with basiliximab induction and tacrolimus-based maintenance therapy for the presence of DSA and sCD30. The incidence of ABMR according to the Banff 2019 classification and death-censored allograft survival were determined. Results: During a median follow-up of 7.4 years, allograft survival was significantly lower in DSA-positive as compared to DSA-negative patients (p < 0.001). In DSA-positive patients, most pronounced in those with strong DSA (MFI > 5,000), increased levels of sCD30 were associated with accelerated graft loss compared to patients with low sCD30 (3-year allograft survival 75 vs. 95%). Long-term survival, however, was comparable in DSA-positive patients irrespective of sCD30 status. Likewise, the incidence of early ABMR and lesion score characteristics were comparable between sCD30-positive and sCD30-negative patients with DSA. Finally, increased sCD30 levels were not predictive for early persistence of DSA. Conclusion: Preformed DSA are associated with an increased risk for ABMR and long-term graft loss independent of sCD30 levels in intermediate-risk kidney transplant patients.
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The COVID-19 pandemic has pointed to the need to increase our knowledge in fields related to human breathing. In the present study, temperature, relative humidity, carbon dioxide (CO2) concentration, and median particle size diameter measurements were taken into account. These parameters were analyzed in a computer classroom with 15 subjects during a normal 90-minute class; all the subjects wore surgical masks. For measurements, Arduino YUN, Arduino UNO, and APS-3321 devices were used. Natural ventilation efficiency was checked in two different ventilation scenarios: only windows open and windows and doors open. The results show how ventilation affects the temperature, CO2 concentration, and median particle diameter size parameters. By contrast, the relative humidity depends more on the outdoor meteorological conditions. Both ventilation scenarios tend to create the same room conditions in terms of temperature, humidity, CO2 concentration, and particle size. Additionally, the evolution of CO2 concentration as well as the particle size distribution along the time was studied. Finally, the particulate matter (PM2.5) was investigated together with particle concentration. Both parameters showed a similar trend during the time of the experiments.
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Contaminantes Atmosféricos , Contaminación del Aire Interior , COVID-19 , Contaminantes Atmosféricos/análisis , Contaminación del Aire Interior/análisis , Dióxido de Carbono/análisis , Monitoreo del Ambiente , Humanos , Pandemias , Tamaño de la Partícula , Material Particulado/análisis , SARS-CoV-2 , Instituciones Académicas , VentilaciónRESUMEN
Among multiple parameters, applied in the immunologic monitoring of transplantation, the levels of serum soluble CD30 (sCD30) and peripheral regulatory T cells (Tregs) are very promising. These are relatively new biomarkers, considered to reflect immune activation and tolerance in solid organ transplantation. Results are shown here from a preliminary study on the relevance of sCD30 and Tregs in the monitoring of the early post-transplantation period. Sixteen patients with chronic liver or kidney disease were examined. Nine of them were further selected for transplantation. Follow-up of sCD30 and Tregs was carried out during the first month after transplantation. Until day 30 (D30) after transplantation, a progressive decrease in sCD30 levels was observed in all patients. Conversely, the dynamic of Tregs was dependent on the transplanted organ: in liver recipients, an increase of Tregs was detected at day 7 (D7) followed by a gradual decrease until D30, whereas in kidney recipients, a sustained downward trend starting on D7 was observed. In liver recipients, the increase in Tregs preceded albumin normalization, whereas in kidney recipients, sCD30 was found to have predictive significance for the creatinine levels. Our results demonstrated that peripheral blood sCD30 and Tregs are valuable parameters in the immunologic monitoring of transplanted patients.
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Supervivencia de Injerto/inmunología , Antígeno Ki-1/metabolismo , Enfermedades Renales/inmunología , Trasplante de Riñón/métodos , Hepatopatías/inmunología , Trasplante de Hígado/métodos , Linfocitos T Reguladores/inmunología , Adolescente , Adulto , Biomarcadores/análisis , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Humanos , Enfermedades Renales/metabolismo , Enfermedades Renales/cirugía , Hepatopatías/metabolismo , Hepatopatías/cirugía , Masculino , Persona de Mediana Edad , Proyectos Piloto , Complicaciones Posoperatorias , Pronóstico , Adulto JovenRESUMEN
Monitoring of donor-specific HLA antibodies (DSA) has become part of the clinical routine in kidney transplantation. This paper gives a brief overview on data from the Collaborative Transplant Study (CTS) and the Heidelberg Transplant Center on the clinical relevance of post-transplant DSA monitoring in patients undergoing renal transplantation. The obtained findings underline the importance of DSA monitoring in the post-operative course in immunologically high-risk patients and patients with deterioration of graft function. Especially in patients with a pre-activated immune system, a gap in the immunosuppressive therapy appear to lead to persistence, reappearance or de novo occurrence of strong, complement-activating DSA, resulting in severe antibody-mediated rejection (AMR) and, without timely intervention, in AMR-related graft loss.
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Rechazo de Injerto/diagnóstico , Antígenos HLA/inmunología , Isoanticuerpos/sangre , Trasplante de Riñón , Monitoreo Fisiológico/métodos , Donantes de Tejidos , Estudios de Casos y Controles , Complemento C1q/metabolismo , Rechazo de Injerto/sangre , Rechazo de Injerto/inmunología , Humanos , Isoanticuerpos/análisis , Trasplante de Riñón/efectos adversos , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Inmunología del TrasplanteRESUMEN
BACKGROUND: The immaturity of immune system characterizes newborn infants. Possible serological markers of Th1 and Th2 immune response are the lymphocyte activation gene-3 (CD223) and soluble CD30, respectively (sCD30). AIMS: The aim of our study was to evaluate the relationship between Th1 and Th2 immune response and gestational age (GA), comparing data in preterm and term neonates. STUDY DESIGN: Cord blood from 20 preterm (GA: 33±2weeks, BW 1950±490g) and 20 term infants (GA: 38±1weeks, BW: 3177±330g) were tested for sCD30 and CD223 levels by ELISA. IFNγ levels produced by cord blood lymphocytes were also analyzed, both before and after stimulation with phytohaemagglutinin (PHA). RESULTS: sCD30 resulted significantly higher in preterm neonates when compared with term neonates (60±7.6 vs 42.6±3.9U/ml p<0.05). CD223 was undetectable in preterm neonates while resulting at a level of 176.1±112.6ng/ml in term neonates. After stimulation with PHA, a significant increase in IFNγ levels was only observed in term neonates (326.6±72.7pg/ml p<0.05). CONCLUSIONS: Our findings show that sCD30 is present and measurable in term and preterm infants, while CD223 is detectable only in term infants and that Th-cell polarization could also depend on gestational age. Our data suggest that a Th2 immune response seems predominant in preterm neonates.
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Recien Nacido Prematuro/sangre , Células TH1/inmunología , Células Th2/inmunología , Proteína 1 de Intercambio de Anión de Eritrocito/genética , Proteína 1 de Intercambio de Anión de Eritrocito/metabolismo , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Humanos , Recién Nacido , Recien Nacido Prematuro/inmunología , Interferón gamma/genética , Interferón gamma/metabolismo , Antígeno Ki-1/genética , Antígeno Ki-1/metabolismo , Masculino , Células TH1/citología , Células Th2/citologíaRESUMEN
BACKGROUND: It is an unresolved issue why some kidney transplant recipients with pretransplant donor-specific HLA antibodies (DSA) show a high transplant failure rate, whereas in other patients DSA do not harm the graft. We investigated whether help from preactivated T-cells might be necessary for DSA to exert a deleterious effect. METHODS: The impact of pretransplant DSA and immune activation marker soluble CD30 (sCD30) on 3-year graft survival was analyzed in 385 presensitized kidney transplant recipients. FINDINGS: A deleterious influence of pretransplant DSA on graft survival was evident only in patients who were positive for the immune activation marker sCD30. In the absence of sCD30 positivity, 3-year graft survival was virtually identical in patients with or without DSA (83.1±3.9% and 84.3±2.8%, P=0.81). A strikingly lower 3-year graft survival rate of 62.1±6.4% was observed in patients who were both sCD30 and DSA positive (HR 2.92, P<0.001). Even in the presence of strong DSA with ≥5000 MFI, the 3-year graft survival rate was high if the recipients were sCD30 negative. INTERPRETATION: Pretransplant DSA have a significantly deleterious impact on graft survival only in the presence of high pretransplant levels of the activation marker sCD30.
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Antígenos HLA/inmunología , Sistema Inmunológico/metabolismo , Trasplante de Riñón , Adulto , Anciano , Ensayo de Inmunoadsorción Enzimática , Femenino , Supervivencia de Injerto , Antígenos HLA/sangre , Humanos , Antígeno Ki-1/sangre , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Linfocitos T/citología , Linfocitos T/metabolismo , Donantes de TejidosRESUMEN
High serum sCD30 levels are associated with inflammatory disorders and poor outcome in renal transplantation. The contribution to these phenomena of transcripts and proteins related to CD30-activation and -cleavage is unknown. We assessed in peripheral blood of end-stage renal disease patients (ESRDP) transcripts of CD30-activation proteins CD30 and CD30L, CD30-cleavage proteins ADAM10 and ADAM17, and Th1- and Th2-type immunity-related factors t-bet and GATA3. Additionally, we evaluated the same transcripts and release of sCD30 and 32 cytokines after allogeneic and polyclonal T-cell activation. In peripheral blood, ESRDP showed increased levels of t-bet and GATA3 transcripts compared to healthy controls (HC) (both P<0.01) whereas levels of CD30, CD30L, ADAM10 and ADAM17 transcripts were similar. Polyclonal and allogeneic stimulation induced higher levels of CD30 transcripts in ESRDP than in HC (both P<0.001). Principal component analysis (PCA) in allogeneic cultures of ESRDP identified two correlation clusters, one consisting of sCD30, the Th-1 cytokine IFN-γ, MIP-1α, RANTES, sIL-2Rα, MIP-1ß, TNF-ß, MDC, GM-CSF and IL-5, and another one consisting of CD30 and t-bet transcripts, IL-13 and proinflammatory proteins IP-10, IL-8, IL-1Rα and MCP-1. Reflecting an activated immune state, ESRDP exhibited after allostimulation upregulation of CD30 transcripts in T cells, which was associated with Th1 and proinflammatory responses.
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Ligando CD30/sangre , Factor de Transcripción GATA3/metabolismo , Antígeno Ki-1/sangre , Fallo Renal Crónico/inmunología , Proteínas de Dominio T Box/metabolismo , Células TH1/inmunología , Células Th2/inmunología , Proteína ADAM10/sangre , Proteína ADAM17/sangre , Adulto , Secretasas de la Proteína Precursora del Amiloide/sangre , Ligando CD30/genética , Células Cultivadas , Citocinas/metabolismo , Femenino , Factor de Transcripción GATA3/genética , Humanos , Mediadores de Inflamación/metabolismo , Isoantígenos/inmunología , Antígeno Ki-1/genética , Masculino , Proteínas de la Membrana/sangre , Persona de Mediana Edad , Proteínas de Dominio T Box/genéticaRESUMEN
BACKGROUND: Previous reports revealed the potential value of the soluble CD30 level (sCD30) as biomarker for the risk of acute rejection and graft failure after renal transplantation, here we examined its use for the prediction of safe tapering of calcineurin inhibitors as well as late acute rejection. METHODS: In a cohort of renal transplant patients receiving triple immunosuppressive therapy we examined whether sCD30 can be used as a marker for safe (rejection-free) discontinuation of tacrolimus at six months after transplantation (TDS cohort: 24 rejectors and 44 non-rejecting controls). Also, in a second cohort of patients (n=22, rejectors n=11 and non-rejectors n=11), participating in a clinical trial of rituximab as induction therapy after renal transplantation (RITS cohort), we examined whether sCD30 could predict the occurrence of late (>3months post-transplant) acute rejection episodes. sCD30 was measured by ELISA in serum taken before and at several time points after transplantation. RESULTS: Overall, in the TDS cohort sCD30 decreased after transplantation. No difference in sCD30 was observed between rejectors and non-rejecting controls at any of the time points measured. In addition, in the RITS cohort, sCD30 measured at three months after transplantation were not indicative for the occurrence of late acute rejection. CONCLUSION: In two prospectively followed cohorts of renal transplant patients we found no association between sCD30 and the occurrence of either late acute rejection or acute rejection after reduction of immunosuppression.
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Rechazo de Injerto/sangre , Terapia de Inmunosupresión , Antígeno Ki-1/sangre , Trasplante de Riñón , Enfermedad Aguda , Adulto , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Biomarcadores/sangre , Estudios de Cohortes , Femenino , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/inmunología , Humanos , Inmunosupresores/administración & dosificación , Antígeno Ki-1/inmunología , Masculino , Persona de Mediana Edad , Rituximab , Tacrolimus/administración & dosificación , Factores de TiempoRESUMEN
Several studies have shown association of high pre- or post-transplant levels of soluble CD30 (sCD30) with acute rejection and poor late kidney transplant outcome. Our goal was to investigate whether sCD30 levels at month-3 post-transplant are associated with subclinical rejection, presence of CD30(+) cells within the graft, and expression of immune response genes in peripheral blood mononuclear cells. The study comprised 118 adult first kidney graft recipients, transplanted at a single center, receiving tacrolimus in low concentration. All were submitted to a protocol biopsy at month-3. Subclinical rejection was identified in 10 biopsies and sCD30 levels ≥ 61.88 ng/mL (P = 0.004), younger recipient age (P = 0.030) and non-Caucasian ethnicity (P = 0.011) were independently associated with this outcome. Rare CD30(+) cells were present in only two biopsies. There was a correlation between sCD30 levels and CD30 gene expression in peripheral blood mononuclear cells (r = 0.385, P = 0.043). These results show that high sCD30 levels are independent predictors of graft dysfunction and may contribute to patient selection protocols by indicating those who could benefit from a more thorough evaluation.
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Regulación de la Expresión Génica , Rechazo de Injerto/sangre , Antígeno Ki-1/sangre , Trasplante de Riñón , Leucocitos Mononucleares/metabolismo , Adulto , Factores de Edad , Anciano , Femenino , Rechazo de Injerto/inmunología , Rechazo de Injerto/patología , Humanos , Antígeno Ki-1/inmunología , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/patología , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Factores de TiempoRESUMEN
The purpose of this study was to evaluate the association of post-transplant soluble CD30 (sCD30) levels, isolated or in combination with of anti-HLA class II antibodies and of serum creatinine levels, with kidney graft loss due to chronic allograft nephropathy (CAN), and type of lesions in graft biopsies for cause. The study comprised 511 first kidney graft recipients, transplanted at a single center, with a graft functioning for at least 2.8 years. A single blood sample was collected from each patient. sCD30 levels were determined by ELISA, and HLA antibodies by Luminex assay. The minimum follow-up after testing was 9.3 years. High sCD30 levels, set at sCD30 ≥ 34.15 ng/mL, the presence of HLA class II antibodies, and serum creatinine ≥ 1.9 mg/dL were independently associated with CAN-graft loss (P values <0.0001, 0.05, <0.0001, respectively), and the combined hazard ratio for CAN-graft loss was 20.2. Analyses of 166 biopsies for cause showed that high sCD30 levels and creatinine were independently associated with interstitial lesions. Post-transplant sCD30 serum levels, especially in conjunction with information regarding HLA class II antibodies and serum creatinine levels, provide valuable information regarding graft outcome and could be useful for the management of kidney transplant recipients.
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Rechazo de Injerto/sangre , Isoanticuerpos/sangre , Antígeno Ki-1/sangre , Enfermedades Renales/sangre , Trasplante de Riñón , Adolescente , Adulto , Anciano , Niño , Preescolar , Creatinina/sangre , Creatinina/inmunología , Femenino , Estudios de Seguimiento , Rechazo de Injerto/inmunología , Antígenos de Histocompatibilidad Clase II/inmunología , Antígenos de Histocompatibilidad Clase II/metabolismo , Humanos , Isoanticuerpos/inmunología , Antígeno Ki-1/inmunología , Enfermedades Renales/etiología , Enfermedades Renales/inmunología , Enfermedades Renales/prevención & control , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Objective To explore the significance of serum CD30 in predicting acute rejection in kidney transplant recipients.Method A total of 106 kidney transplant recipients were recruited in this prospective six months follow-up study from December 2010 to October 2012.According to the clinical outcome,the subjects were devided into stable renal function group (72 cases) and acute rejection group (34 cases).Twenty healthy subjects were choosed as controls.Serum sCD30 levels were detected by ELISA.The whole peripheral blood samples were collected from all recipients before transplantation,at days 7,14,21 and 28 post-transplantation,and at months 2,3,4,5 and 6 posttransplantation.Additional blood samples were collected for on the days that acute rejection occurred and reversed.Result Preoperative serum sCD30 levels were 33.42 ± 11.49 and 26.5 1 ± 13.70μg/L in AR group and stable group respectively.When acute rejection occurred,serum sCD30 levels in AR group was 50.38 ± 12.10μg/L,which was significantly higher than stable group (20.03 ± 6.68μg/L,P<0.05) and healthy control group (13.57 ± 5.56 ng/L,P<0.05).After the anti-rejection therapy,serum sCD30 levels decreased to 15.31 ± 6.37μg/L,which was lower than that before the therapy started (50.38± 12.10 μg/L,P<0.05).Elevated preoperative serum sCD30 levels suggested a higher risk of acute rejection in kidney transplant recipients,with Cutoff values of 24.96 μg/L,and the sensitivity and specificity were 91.30% and 84.21% respectively.Conclusion Serum sCD30 levels can predict and assess the risks of rejection episodes in kidney transplant recipients.
RESUMEN
PURPOSE: Serum level of soluble form CD30 (sCD30), a marker for T helper 2-type cytokine-producing T cells, is used as a marker of immunologic status of pre-transplant recipient that can predict graft rejection and graft survival. This study compared pre-transplant serum sCD30 levels with conventional pre-transplant immunologic parameter, such as panel- reactive antibodies (PRA) and lymphocyte cross matching (LCM). METHODS: Adult seventy two patients were enrolled this study. The blood for tests was sampled simultaneously. Measurement of serum sCD30 level was performed using enzyme-linked immunosorbent assay kit (Bender MedSystems, Co. CA, USA). We tested PRA using a commercial ELISA kit (Lambda Cell Tray Lymphocytotoxicity assay)(One Lambda Inc. CA, USA). We established LCM tests for T cells by Modified NIH (National institute center of health)/Johnson's Method/AHG (Anti human globulin), and for B cells by warm test. RESULTS: Mean score of sCD30 was 90.3+/-6.4 U/mL, ranged from 12.2 to 244.4 U/mL. There was no significant correlation between patient's age or sex and sCD30 level. The correlation between sCD30 and mode or duration of dialysis was not statistically significant clinical situation. The result of LCM didn't show significant correlation with sCD30 level (87.3+/-55.7 U/mL in LCM positive group versus 91.9+/-1.3 U/mL in LCM negative group, P=0.696). And sCD30 level equal to or more than 86 U/mL could not predict the positive result of LCM. The positive and negative predictive value of sCD30 to LCM was merely 27.8% and 58.3% (P=0.322). Also the correlation between sCD30 level and PRA was not significant (P=1.0). CONCLUCION: There was no significant correlation between serum sCD30 level and conventional immunologic parameter such as PRA or LCM. That means the pre-transplant monitoring of the sCD30 level can be used as an independent immunologic parameter.
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Adulto , Humanos , Anticuerpos , Linfocitos B , Diálisis , Ensayo de Inmunoadsorción Enzimática , Rechazo de Injerto , Supervivencia de Injerto , Linfocitos , Linfocitos TRESUMEN
0.05).The expression percentage of IL-4 of CD3+CD8-T lymphocytes cells in peripheral blood of the patients in group A(4.0%?2.8%)was significantly lower than that in group B and C(7.9%?5.5% and 10.2%?7.5%,P0.05).The level of serum sCD30 in the patients of group A(20.2?12.4ng/ml)was significantly higher than that of group B and C(7.8?3.1ng/ml and 7.6?3.0ng/ml,P0.05).ROC curve analysis indicated that when the ratio of Th1/Th2 was at the cut-off value of 1.95,the sensitivity and specificity to identify CRAD caused mainly by immune injury was 80% and 90%,respectively;and when the level of serum sCD30 was at the cut-off value of 10ng/ml,the sensitivity and specificity to identify CRAD caused mainly by immune injury was 93.3% and 86.7%,respectively.Conclusions Disequilibrium of Th1/Th2(drift to Th1)and raised level of serum sCD30 exist in most of the patients with CRAD which was caused mainly by immune injury.It is with high sensitivity and specificity to identify the CRAD by determining the ratio of Th1/Th2 of CD3+CD8-T lymphocytes cells in peripheral blood and the level of serum sCD30.