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INTRODUCTION: To describe the clinical and laboratory profile, natural course, treatment outcome, and risk factors of posttransplant esophageal and nonesophageal eosinophilic gastrointestinal disorders (EGIDs). METHODS: All children (aged <18 years) who underwent liver transplantation, between 2011 and 2019, in a single transplant center with a follow-up period of 1 year or more posttransplant and with a history of posttransplant endoscopic evaluation were included in this study. RESULTS: During the study period, 89 children met the inclusion criteria. Patients were followed for a median of 8.0 years. A total of 39 (44%) patients were diagnosed with EGID after transplantation. Of these, 29 (33%) had eosinophilic esophagitis (EoE), and 10 (11%) had eosinophilic gastritis, gastroenteritis or enterocolitis. In comparison with the non-EGID group, patients with EGID were younger at transplant (P ≤ 0.0001), transplanted more frequently due to biliary atresia (P ≤ 0.0001), and had higher rates of pretransplant allergy (P = 0.019). In the posttransplant period, they had higher rates of mammalian Target of Rapamycin inhibitor use (P = 0.006), Epstein-Barr virus viremia (P = 0.03), post-transplant lymphoproliferative disease (P = 0.005), and allergen sensitization (P ≤ 0.0001). In regression analysis, young age at transplant, age at diagnosis, pretransplant atopic dermatitis, and post-transplant lymphoproliferative disease were associated with an increased risk of EGID or EoE. Laboratory abnormalities such as anemia (P = 0.007), thrombocytosis (P = 0.012), and hypoalbuminemia (P = 0.031) were more commonly observed in the eosinophilic gastritis, gastroenteritis or enterocolitis group than in the EoE group. Following treatment, most patients had symptomatic resolution at 3 months and histologic resolution at 6 months postdiagnosis. Among the patients who had 5 years of follow-up, none recurred. DISCUSSION: EGID is a common posttransplant diagnosis, which seems to affect patients who are transplanted earlier and who have pretransplant atopy. Posttransplant EGID is responsive to treatment, but as histologic remission occurs after symptomatic resolution, the decision to perform control endoscopy should be delayed.
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Enteritis/epidemiología , Enterocolitis/epidemiología , Eosinofilia/epidemiología , Esofagitis Eosinofílica/epidemiología , Gastritis/epidemiología , Trasplante de Hígado , Complicaciones Posoperatorias/epidemiología , Factores de Edad , Antialérgicos/uso terapéutico , Atresia Biliar/cirugía , Budesonida/uso terapéutico , Niño , Preescolar , Colestasis Intrahepática/cirugía , Dermatitis Atópica/epidemiología , Progresión de la Enfermedad , Reducción Gradual de Medicamentos , Enteritis/tratamiento farmacológico , Enteritis/fisiopatología , Enterocolitis/tratamiento farmacológico , Enterocolitis/fisiopatología , Eosinofilia/tratamiento farmacológico , Eosinofilia/fisiopatología , Esofagitis Eosinofílica/tratamiento farmacológico , Esofagitis Eosinofílica/fisiopatología , Infecciones por Virus de Epstein-Barr/epidemiología , Femenino , Estudios de Seguimiento , Gastritis/tratamiento farmacológico , Gastritis/fisiopatología , Glucocorticoides/uso terapéutico , Rechazo de Injerto/prevención & control , Humanos , Hipersensibilidad/epidemiología , Inmunosupresores/uso terapéutico , Lactante , Cetotifen/uso terapéutico , Fallo Hepático Agudo/cirugía , Trastornos Linfoproliferativos/epidemiología , Masculino , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/fisiopatología , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Tacrolimus/uso terapéutico , Resultado del Tratamiento , Viremia/epidemiologíaRESUMEN
Biallelic mutations in neuroblastoma amplified sequence gene (NBAS) is a rare disease which is characterized by recurrent liver failure (RALF). We reported the novel mutations, clinical characteristics and long-term outcomes of 5 patients with novel biallelic NBAS variants. Four patients (80%) had acute, episodic liver crises (LC) triggered by fever, with a median age of onset of 8.5 months. The median age in the last episode was 34 months. Median number of liver episodes was 4. The course of ALF was complicated by hepatic encephalopathy and hypoglycaemia in all patients with ALF. Two patients recovered with conservative treatment, 2 required liver transplantation (LT) and 1 died during the fourth episode. Long-term post-transplant follow-up showed normal liver function and histology. There is no hepatic or extrahepatic recurrence after LT. Non-transplanted patients exhibited fibrosis in either biopsy or elastography. Despite a reduction in the frequency of clinically significant episodes, patients may exhibit ongoing liver injury and fibrosis. An acute on chronic liver failure with predominant cholestasis can be an alternative presentation.
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Fallo Hepático Agudo , Neuroblastoma , Preescolar , Fibrosis , Humanos , Lactante , Fallo Hepático Agudo/etiología , Mutación , Proteínas de Neoplasias/genética , Recurrencia Local de Neoplasia , Neuroblastoma/complicacionesRESUMEN
Background/aim: The presented study aimed to evaluate the utility of magnetic resonance angiography (MRA) in the pediatric population with nutcracker syndrome. Materials and methods: Patients with suggestive clinical symptoms and laboratory findings and got the diagnosis of nutcracker syndrome with Doppler ultrasonography between January 20112019 were included in the study. In addition, children who had renal MRA due to hypertension were evaluated as the control group. MRA images of all patients were examined retrospectively by three radiologists at different levels of experience, and the superior mesenteric artery angle, aorta-mesenteric distance, left renal vein diameter both in the regions of aorta-mesenteric, and renal hilum were recorded. Results: Forty-five patients diagnosed with nutcracker syndrome were included in the study. The mean age of patients was 12 (416) and 30 (67%) were female. As the control group, 25 patients with hypertension who had MRA were included and they had a mean age of 12 (118) and 19 (76%) were male. The mean superior mesenteric artery angle was 26.5 ° (1673 ± 12) in the patient group and 57.8 ° (25139, ± 33) in the control group (p < 0.001); the mean aorta-mesenteric distance was 3.3 mm (1.76.5, ± 1.1) in the patient group and 8 mm (3.432, ± 5.9) in the control group (p < 0.001). MRA measurements of three radiologists were consistent with each other. Conclusion: MRA imaging can be applied as an alternative diagnostic method for Doppler ultrasonography and multidetector CT examinations by radiologists with different experience levels in pediatric patients with nutcracker syndrome.
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Angiografía por Resonancia Magnética/estadística & datos numéricos , Síndrome de Cascanueces Renal/diagnóstico por imagen , Adolescente , Niño , Preescolar , Femenino , Humanos , Hipertensión , Angiografía por Resonancia Magnética/métodos , Masculino , Venas Renales/diagnóstico por imagen , Estudios RetrospectivosRESUMEN
Ataxia-telangiectasia (AT) is a hereditary recessive autosomal disorder following a course of progressive cerebellar ataxia, and oculocutaneous telangiectasia. Disease-specific telangiectasias are generally localized in the oculocutaneous region, while telangiectasias located within the bladder are rarely seen in patients with AT. The patient who had been followed-up with a diagnosis of AT since the age of 3 years was later diagnosed with acute lymphoblastic leukemia at the age of 8 years. The patient developed hematuria approximately in the 29th month of treatment. The cystoscopy revealed regions of extensive hemorrhagic telangiectasis, which was interpreted as the bladder involvement of AT. The case presented here underwent several cycles of intravesical steroid and tranexamic acid treatments and intravesical cauterization procedures, but the patient was unresponsive to all medical treatment approaches. The patient was consequently evaluated by an interventional radiology unit for a selective arterial embolization. The patient's hematuria resolved after embolization. Bladder wall telangiectasia may, on rare occasions, develop in patients with AT, and can result in life-threatening hemorrhages. We also suggest that a selective arterial embolectomy can be safely carried out in pediatric patients with treatment-resistant intravesical bleeding.
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Ataxia Telangiectasia/terapia , Embolización Terapéutica , Hematuria/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Niño , Preescolar , Humanos , Masculino , Vejiga UrinariaRESUMEN
WHAT IS KNOWN AND OBJECTIVE: Erlotinib is a small molecule tyrosine kinase inhibitor which blocks the activation of epidermal growth factor receptor (EGFR), a transmembrane receptor that is upregulated in many cancer types. Inhibition of angiogenesis with consequent impairments in intratumoral microcirculation is one of the mechanisms through which EGFR inhibition halts the progression of cancer. A consequence of impaired microcirculation is intratumoral hypoxia, which results in increases in serum uric acid levels. The goal of this study was to investigate the relationship between serum uric acid levels and response to erlotinib in metastatic non-small-cell lung cancer (NSCLC). METHODS: A total of 56 patients with metastatic non-small-cell lung cancer who received erlotinib for a duration of at least 3 months were included in this retrospective cohort study. Demographic characteristics, progression status, baseline serum uric levels and 3-month serum uric acid levels were recorded and analysed. RESULTS AND DISCUSSION: Of the study population, 21 (37.5%) were female and 35 (62.5%) were male patients. No significant difference in above demographic characteristics was observed among exitus, survivor with progression and survivor without progression groups. Patients who responded favourably to erlotinib with no progression of their disease had significantly increased uric acid levels at 3-month follow-up (P = .01). Such a correlation was not observed if the patient was exitus (P = .47) or had progressed on erlotinib therapy (P = .19). WHAT IS NEW AND CONCLUSION: In conclusion, this study is the first to demonstrate significant increases in serum uric acid levels in patients with metastatic NSCLC who responded favourably to erlotinib and had no progression under erlotinib therapy. Further studies are required to confirm and characterize serum uric acid as a novel biomarker in predicting the outcome in those with metastatic NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Clorhidrato de Erlotinib/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/administración & dosificación , Ácido Úrico/sangre , Anciano , Biomarcadores de Tumor/sangre , Carcinoma de Pulmón de Células no Pequeñas/patología , Estudios de Cohortes , Progresión de la Enfermedad , Receptores ErbB/antagonistas & inhibidores , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Renal hyperfiltration, defined as an increased glomerular filtration rate above normal values, is associated with early phases of kidney disease in the setting of various conditions such as obesity and diabetes. Although it is recognized that glomerular hyperfiltration, that is, increased filtration per nephron unit (usually studied at low glomerular filtration levels and often referred to as single nephron hyperfiltration), is a risk factor for the progression of chronic kidney disease, the implications of having renal hyperfiltration for cardiovascular disease and mortality risk are incompletely understood. Recent evidence from diverse populations, including healthy individuals and patients with diabetes or established cardiovascular disease, suggests that renal hyperfiltration is associated with a higher risk of cardiovascular disease and all-cause mortality. In this review, we critically summarize the existing studies, discuss possible mechanisms, and describe the remaining gaps in our knowledge regarding the association of renal hyperfiltration with cardiovascular disease and mortality risk.
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Enfermedades Cardiovasculares , Tasa de Filtración Glomerular/fisiología , Insuficiencia Renal Crónica , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/mortalidad , Complicaciones de la Diabetes/epidemiología , Complicaciones de la Diabetes/mortalidad , Complicaciones de la Diabetes/fisiopatología , Femenino , Humanos , Glomérulos Renales/fisiopatología , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/mortalidad , Insuficiencia Renal Crónica/fisiopatología , Factores de Riesgo , Adulto JovenRESUMEN
Acute alcoholic hepatitis is a syndrome of jaundice and hepatic decompensation that occurs with excessive alcohol consumption. The diagnosis can be made with a combination of clinical characteristics and laboratory studies, though biopsy may be required in unclear cases. Acute alcoholic hepatitis can range from mild to severe disease, as determined by a Maddrey discriminant function ≥32. Mild forms can be managed with supportive care and abstinence from alcohol. While mild form has an overall good prognosis, severe alcoholic hepatitis is associated with an extremely high short-term mortality of up to 50%. Additional complications of severe alcoholic hepatitis can include hepatic encephalopathy, gastrointestinal bleeding, renal failure, and infection; these patients frequently require intensive care unit admission. Corticosteroids may have short-term benefit in this group of patients if there are no contraindications; however, a subset of patients do not respond to steroids. New emerging therapies, which target hepatic regeneration, bile acid metabolism, and extracorporeal liver support, are being investigated. Liver transplantation for alcoholic liver disease was traditionally only considered in patients who have achieved 6 months of abstinence, in part due to social and ethical concerns regarding the use of a limited resource. However, the majority of patients with severe alcoholic hepatitis who fail medical therapy will not live long enough to meet this requirement. Recent studies have demonstrated that early liver transplantation in carefully selected patients with severe alcoholic hepatitis who fail medical therapy can provide a significant survival benefit and yields survival outcomes comparable to liver transplantation for other indications, with 6-month survival rates ranging from 77% to 100%. Alcohol relapse posttransplantation remains an important challenge, and heavy consumption can contribute to graft loss and mortality. Future investigation should address the substantial post-liver transplantation recidivism rate, from improving selection criteria to increasing posttransplantation substance abuse treatment resources.
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Hepatitis Alcohólica/cirugía , Trasplante de Hígado/mortalidad , Hepatitis Alcohólica/mortalidad , Humanos , Selección de Paciente , Periodo Posoperatorio , Recurrencia , Tasa de SupervivenciaRESUMEN
Primary hyperoxaluria type 1 (PH1) is a rare, autosomal recessive disease, caused by the defect of AGXT gene encoding hepatic peroxisomal alanine glyoxylateaminotransferase (AGT). This enzyme is responsible for the conversion of glyoxylate to glycine. The diagnosis of PH1 should be suspected in infants and children with nephrocalcinosis or nephrolithiasis. Early diagnosis and treatment is crucial in preventing disease progression to end stage kidney disease (ESKD). In this study, AGXT gene sequence analyses were performed in 82 patients who were clinically suspected (hyperoxaluria and nephrolithiasis or nephrocalcinosis with or without renal impairment) to have PH1. Disease causing mutations have been found in fifteen patients from thirteen families (18%). Novel mutations have been found (c.458T>A (p.L153X), c.733_734delAA (p.Lys245Valfs*11), c.52 C>T (p.L18F)) in three of 13 families. There were 3-year lag time between initial symptoms and the time of PH1 is suspected; additionally, 5.5-year lag time between initial symptoms and definitive diagnosis. Consanguinity was detected in 77% of the patients with mutation. After genetic diagnosis, one patient received combined kidney and liver transplantation. AGXT gene sequencing is now the choice of diagnosis of PH1 due to its non-invasive nature compared to liver enzyme assay. Early diagnosis and accurate treatment in PH1 is important for better patient outcomes.
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Diagnóstico Precoz , Hiperoxaluria Primaria/diagnóstico , Hiperoxaluria Primaria/genética , Transaminasas/genética , Adolescente , Adulto , Secuencia de Bases/genética , Niño , Preescolar , Consanguinidad , Exones/genética , Femenino , Humanos , Hiperoxaluria Primaria/fisiopatología , Lactante , Masculino , Mutación , Adulto JovenRESUMEN
Varicella infections are usually considered to be benign. Although very rare, infection of an immunocompetent patient by this virus may result in a severe illness. We describe a case of varicella infection in a previously healthy, immunocompetent 5-y-old boy, complicated with compartment syndrome, disseminated intravascular coagulation (DIC), pneumonia, and acute renal failure. He was treated successfully with aciclovir and intravenous immunoglobulins for the varicella infection, a fasciotomy for compartment syndrome, and fresh frozen plasma for DIC.
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Lesión Renal Aguda/virología , Varicela/fisiopatología , Síndromes Compartimentales/virología , Coagulación Intravascular Diseminada/virología , Neumonía/virología , Preescolar , Humanos , MasculinoRESUMEN
Introduction: The immunomodulatory properties of mesenchymal stromal cells (MSC) have been well-characterized in in-vitro and in-vivo models. We have previously shown that liver MSC (L-MSC) are superior inhibitors of T-cell activation/proliferation, NK cell cytolytic function, and macrophage activation compared to adipose (A-MSC) and bone marrow MSC (BM-MSC) in-vitro. Method: To test these observations in-vivo, we infused these types of MSC into mice with unilateral renal artery stenosis (RAS), an established model of kidney inflammation. Unilateral RAS was induced via laparotomy in 11-week-old, male 129-S1 mice under general anesthesia. Control mice had sham operations. Human L-MSC, AMSC, and BM-MSC (5x105 cells each) or PBS vehicle were injected intra-arterially 2 weeks after surgery. Kidney morphology was studied 2 weeks after infusion using micro-MRI imaging. Renal inflammation, apoptosis, fibrosis, and MSC retention were studied ex-vivo utilizing western blot, immunofluorescence, and immunohistological analyses. Results: The stenotic kidney volume was smaller in all RAS mice, confirming significant injury, and was improved by infusion of all MSC types. All MSC-infused groups had lower levels of plasma renin and proteinuria compared to untreated RAS. Serum creatinine improved in micetreated with BM- and L-MSC. All types of MSC located to and were retained within the stenotic kidneys, but L-MSC retention was significantly higher than A- and BM-MSC. While all groups of MSC-treated mice displayed reduced overall inflammation and macrophage counts, L-MSC showed superior potency in-vivo at localizing to the site of inflammation and inducing M2 (reparative) macrophage polarization to reduce inflammatory changes. Discussion: These in-vivo findings extend our in-vitro studies and suggest that L-MSC possess unique anti-inflammatory properties that may play a role in liver-induced tolerance and lend further support to their use as therapeutic agents for diseases with underlying inflammatory pathophysiology.
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Isquemia , Hígado , Macrófagos , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Animales , Ratones , Trasplante de Células Madre Mesenquimatosas/métodos , Masculino , Humanos , Hígado/patología , Hígado/inmunología , Isquemia/terapia , Isquemia/inmunología , Macrófagos/inmunología , Modelos Animales de Enfermedad , Inflamación/inmunología , Inflamación/terapia , Activación de Macrófagos , Obstrucción de la Arteria Renal/terapia , Obstrucción de la Arteria Renal/inmunología , Riñón/patología , Riñón/inmunologíaRESUMEN
Introduction: Autoimmune diseases are heterogeneous and often lack specific or sensitive diagnostic tests. Increased percentages of CD4+CXCR5+PD1+ circulating T follicular helper (cTfh) cells and skewed distributions of cTfh subtypes have been associated with autoimmunity. However, cTfh cell percentages can normalize with immunomodulatory treatment despite persistent disease activity, indicating the need for identifying additional cellular and/or serologic features correlating with autoimmunity. Methods: The cohort included 50 controls and 56 patients with autoimmune cytopenias, gastrointestinal, pulmonary, and/or neurologic autoimmune disease. Flow cytometry was used to measure CD4+CXCR5+ T cell subsets expressing the chemokine receptors CXCR3 and/or CCR6: CXCR3+CCR6- Type 1, CXCR3-CCR6- Type 2, CXCR3+CCR6+ Type 1/17, and CXCR3- CCR6+ Type 17 T cells. IgG and IgA autoantibodies were quantified using a microarray featuring 1616 full-length, conformationally intact protein antigens. The 97.5th percentile in the control cohort defined normal limits for T cell subset percentages and total number (burden) of autoantibodies. Results: This study focused on CD4+CXCR5+ T cells because CXCR5 upregulation occurs after cognate T-B cell interactions characteristic of autoimmune diseases. We refer to these cells as circulating T follicular memory (cTfm) cells to acknowledge the dynamic nature of antigen-experienced CXCR5+ T cells, which encompass progenitors of cTfh or Tfh cells as well as early effector memory T cells that have not yet lost CXCR5. Compared to controls, 57.1% of patients had increased CXCR5+CXCR3+CCR6+ cTfm1/17 and 25% had increased CXCR5+CXCR3-CCR6+ cTfm17 cell percentages. Patients had significantly more diverse IgG and IgA autoantibodies than controls and 44.6% had an increased burden of autoantibodies of either isotype. Unsupervised autoantibody clustering identified three clusters of patients with IgG autoantibody profiles distinct from those of controls, enriched for patients with active autoimmunity and monogenic diseases. An increased percentage of cTfm17 cells was most closely associated with an increased burden of high-titer IgG and IgA autoantibodies. A composite measure integrating increased cTfm1/17, cTfm17, and high-titer IgG and/or IgA autoantibodies had 91.1% sensitivity and 90.9% specificity for identifying patients with autoimmunity. Percentages of cTfm1/17 and cTfm17 percentages and numbers of high-titer autoantibodies in patients receiving immunomodulatory treatment did not differ from those in untreated patients, thus suggesting that measurements of cTfm can complement measurements of other cellular markers affected by treatment. Conclusions: This study highlights two new approaches for assessing autoimmunity: measuring CD4+CXCR5+ cTfm subsets as well as total burden of autoantibodies. Our findings suggest that these approaches are particularly relevant to patients with rare autoimmune disorders for whom target antigens and prognosis are often unknown.
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Chronic liver disease incidence is increasing among children worldwide due to a multitude of epidemiological changes. Most of these chronic insults to the pediatric liver progress to fibrosis and cirrhosis to different degrees. Liver and immune physiology differs significantly in children from adults. Because most of pediatric liver diseases have no definitive therapy, a better understanding of population and disease-specific fibrogenesis is mandatory. Furthermore, fibrosis development has prognostic significance and often guide treatment. Evaluation of liver fibrosis continues to rely on the gold-standard liver biopsy. However, many high-quality studies put forward the high diagnostic accuracy of numerous diagnostic modalities in this setting. Herein, we summarize and discuss the recent literature on fibrogenesis with an emphasis on pediatric physiology along with a detailed outline of disease-specific signatures, noninvasive diagnostic modalities, and the potential for antifibrotic therapies.
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Síndrome Hemolítico-Urémico/fisiopatología , Sistema Nervioso/fisiopatología , Adolescente , Factores de Edad , Biomarcadores/metabolismo , Niño , Preescolar , Diarrea/epidemiología , Diarrea/fisiopatología , Diarrea/terapia , Susceptibilidad a Enfermedades , Femenino , Estudios de Seguimiento , Síndrome Hemolítico-Urémico/epidemiología , Síndrome Hemolítico-Urémico/terapia , Humanos , Modelos Logísticos , Masculino , Paresia/epidemiología , Paresia/fisiopatología , Paresia/terapia , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Análisis de SupervivenciaRESUMEN
Liver-resident mesenchymal stem cells (L-MSCs) are superior inhibitors of alloreactive T cell responses compared to their counterparts from bone marrow (BM-MSCs) or adipose tissue (A-MSCs), suggesting a role in liver's overall tolerogenic microenvironment. Whether L-MSCs also impact NK cell functions differently than other MSCs is not known. We generated and characterized L-MSCs, A-MSCs and BM-MSCs from human tissues. The mass spectrometry analysis demonstrated that L-MSC secretome is uniquely different than that of A-MSC/BM-MSC, with enriched protein sets involved in IFNγ responses and signaling. When co-cultured with primary human NK cells, L-MSCs but not other MSCs, decreased surface expression of activating receptors NKp44 and NKG2D. L-MSCs also decreased IFNγ secretion by IL-2-stimulated NK cells more effectively than other MSCs. Cytolytic function of NK cells were reduced significantly when co-cultured with L-MSCs, whereas A-MSCs or BM-MSCs did not have a major impact. Mechanistic studies showed that the L-MSC-mediated reduction in NK cell cytotoxicity is not through changes in secretion of the cytotoxic proteins Perforin, Granzyme A or B, but through increased production of HLA-C1 found in L-MSC secretome that inhibits NK cells by stimulating their inhibitory receptor KIRDL2/3. L-MSCs are more potent inhibitors of NK cell functions than A-MSC or BM-MSC. Combined with their T cell inhibitory features, these results suggest L-MSCs contribute to the tolerogenic liver microenvironment and liver-induced systemic tolerance often observed after liver transplantation.
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Células Madre Mesenquimatosas , Subfamilia K de Receptores Similares a Lectina de Células NK , Granzimas/metabolismo , Humanos , Interleucina-2/metabolismo , Células Asesinas Naturales/metabolismo , Hígado/metabolismo , Células Madre Mesenquimatosas/metabolismo , Subfamilia K de Receptores Similares a Lectina de Células NK/metabolismo , Perforina/metabolismo , SecretomaRESUMEN
Bone marrow-derived long-lived plasma cells (LLPCs) are thought to be a major source of alloantibody in sensitized transplant patients. However, studies of LLPCs have been hampered not only by the fact that they are rare and difficult to isolate and culture but also due to the lack of consensus regarding a definitive cell-surface phenotype. The goal of the current study was to determine if LLPCs have a specific, stable cell-surface phenotype. PCs were isolated from high-volume (120cc) bone marrow aspirates that were enriched first by negative selection then positive selection using anti-CD38 antibody-coated beads and purified by cell sorting. A typical isolation resulted in >100,000 PCs that were sorted into 4 populations with variable numbers of PCs: CD19+/CD138+/CD38Hi (64.1% of the PCs), CD19-/CD138+/CD38Hi (20.9%), CD19+/CD138-/CD38Hi (10.7%), and CD19-/CD138-/CD38Hi (4.3%). The purity of each subset was 96-99%. Each subset contained PCs secreting IgG and IgA. Measles- and tetanus-specific PCs (i.e. putative IgG secreting, antigen-specific LLPCs). LLPCs were identified in both the CD19+/CD138+/CD38Hi and CD19-/CD138+/CD38Hi subsets and in the smaller CD138- subsets (when pooled). Thus, all CD38Hi subsets contained LLPCs. Cultured PCs maintained viability (>50%) and function and could be retrieved for analyses. During 7 days of culture, cell surface expression changed from baseline in many PCs. For example, approximately 20% of CD19 + CD138+/CD38Hi cells (the largest PC subset) became CD19-. CFSE assays showed no division and only a small percentage of LLPCs were Ki-67 positive suggesting that the cells did not divide in culture and that the antibody detected was not from plasmablasts. We conclude that human bone marrow LLPCs have a heterogeneous expression of CD19 and CD138, which can change during cell culture. The fact that LLPCs were found in all four subsets raises the possibility that a large percentage of PCs in the bone marrow may be LLPCs.
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Médula Ósea , Células Plasmáticas , Humanos , Antígenos CD19/metabolismo , Inmunoglobulina G/metabolismo , FenotipoRESUMEN
BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) occurs due to defective regulation of the alternative complement pathway (ACP) on vascular endothelial cells. Plasma based therapy (PT) was the mainstay of the treatment for aHUS for many years until the introduction of therapies targeting blockage of the complement system. The aim of this study was to evaluate patients with aHUS who had been treated with plasma based therapies alone. METHODS: The outcomes of seven genetically confirmed aHUS patients (2 girls, 5 males) were evaluated by means of clinical presentation, response to plasma therapy, course of the disease during the follow-up period and last status. RESULTS: The median age of the patients at admission was 6.7 years (IQR 0.7-7.8). Three patients received plasma exchange therapy and the other four patients were treated with plasma infusions. One patient was lost to follow-up after one year; the median duration of follow-up for other patients was 3.7 years (IQR 2.7-6.5). During the follow up, two patients from our historical records when complement blocking therapies had not been in clinical use yet in Turkey, underwent kidney transplantation. One transplant patient experienced an acute rejection episode without graft loss. The remaining five patients had a glomerular filtration rate of more than 90 ml/min./1.73 m < sup > 2 < /sup > at the last visit. CONCLUSION: Although we had a relatively small patient population, our findings indicate that PT might still be considered in selected patients particularly in countries where complement blocking therapies are difficult to reach due to their unavailability or costs that are not covered by the health care systems.
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Síndrome Hemolítico Urémico Atípico , Trasplante de Riñón , Anticuerpos Monoclonales Humanizados , Síndrome Hemolítico Urémico Atípico/diagnóstico , Síndrome Hemolítico Urémico Atípico/terapia , Niño , Preescolar , Células Endoteliales , Femenino , Humanos , Lactante , Masculino , Intercambio PlasmáticoRESUMEN
BACKGROUND: Previous studies demonstrated critical deficits in diagnosis and management of childhood food allergy (FA), and recent developments in FA research support adopting a proactive approach in FA management. Our objective was to describe FA knowledge and management patterns of pediatricians. METHOD: We applied a 24-item survey to 170 general pediatricians, pediatric allergists and pediatric gastroenterologists practicing in Turkey. RESULTS: Some IgE-mediated symptoms of FA such as cough, urticaria, wheezing and anaphylaxis were falsely recognized as symptoms of non-IgE-mediated FA by 30%, 29%, 25% and 19% of the participants, respectively. By contrast, 50% of the participants falsely recognized bloody stool, a finding of IgE-mediated FA. Most frequently and least frequently used diagnostic tools were specific IgE (30.5%) and oral food challenge test (1.7%), respectively. Maternal diet restrictions and infant diet restrictions were advised by 82% and 82%, respectively. Percentages of physicians eliminating only 1 food were 21%, 19%; 2 foods were 15%, 11%; 3 foods were 7%, 8%; 4-5 foods were 8%, 11%; 5 to 10 foods were 21%, 26%; and > 10 foods were 28%, 25% from the maternal and infant diet, respectively. Cow`s milk, cheese, butter, yoghurt, baked milk products and hen`s egg were the most commonly restricted items. CONCLUSION: Overall, FA knowledge of pediatricians was fair. Pediatricians utilize an overly restrictive approach when advising diet eliminations in FA. Recent developments favor a more proactive approach to induce immune tolerance and need to be encouraged in pediatric clinical practice. Future educational efforts should focus on emphasizing the deleterious effects of injudicious and extensive eliminations.
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Hipersensibilidad a los Alimentos , Hipersensibilidad a la Leche , Alérgenos , Animales , Bovinos , Pollos , Niño , Femenino , Hipersensibilidad a los Alimentos/diagnóstico , Hipersensibilidad a los Alimentos/prevención & control , Humanos , Inmunoglobulina E , Lactante , LecheRESUMEN
Gastrointestinal bleeding is a rare but potentially life-threatening manifestation of eosinophilic gastrointestinal disorders (EGIDs). Here, we describe a case series comprising 5 pediatric patients between 7 and 12 years of age, who presented to the emergency department with hematemesis and were subsequently diagnosed with EGID. Accompanying allergic history, peripheral eosinophilia, and total IgE elevation were common. Despite a more severe presentation, response to medical and dietary therapy was favorable. A comprehensive review of the literature revealed 26 other cases with similar findings that reinforced the importance of prompt recognition and early dietary and immunomodulating therapy in the control of this disease.