Preferential association of hepatitis C virus with CD19+ B cells is mediated by complement system

Extrahepatic disease manifestations are common in chronic hepatitis C virus (HCV) infection. The mechanism of HCV-related lymphoproliferative disorders is not fully understood. Recent studies have found that HCV in peripheral blood mononuclear cells (PBMCs) from chronically infected patients is mainly associated with CD19+ B cells. To further elucidate this preferential association of HCV with B cells, we used in vitro cultured virus and uninfected PBMCs from healthy blood donors to investigate the necessary serum components that activate the binding of HCV to B cells. First, we found that the active serum components were present not only in HCV carriers, but also in HCV recovered patients and HCV negative healthy blood donors and that the serum components were heat labile. Second, the preferential binding activity of HCV to B cells could be blocked by anti-complement C3 antibodies. In experiments with complement-depleted serum and purified complement proteins, we demonstrated that complement proteins C1, C2, and C3 were required to activate such binding activity. Complement protein C4 was partially involved in this process. Third, using antibodies against cell surface markers, we showed that the binding complex mainly involved CD21 (complement receptor 2), CD19, CD20, and CD81; CD35 (complement receptor 1) was involved but had lower binding activity. Fourth, both anti-CD21 and anti-CD35 antibodies could block the binding of patient-derived HCV to B cells. Fifth, complement also mediated HCV binding to Raji cells, a cultured B cell line derived from Burkitt´s lymphoma.CONCLUSION:In chronic HCV infection, the preferential association of HCV with B cells is mediated by the complement system, mainly through complement receptor 2 (CD21), in conjunction with the CD19 and CD81 complex. This article is protected by copyright. All rights reserved.Fil: Wang, Richard. National Institutes of Health; Estados UnidosFil: Baré, Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. National Institutes of Health; Estados UnidosFil: De Giorgi, Valeria. National Institutes of Health; Estados UnidosFil: Matsuura, Kentaro. Nagoya City University Graduate School of Medicine; Japón. National Institutes of Health; Estados UnidosFil: Salam, Kazi Abdus. National Institutes of Health; Estados Unidos. University of Rajshahi; IndiaFil: Grandinetti, Teresa. National Institutes of Health; Estados UnidosFil: Schechterly, Cathy. National Institutes of Health; Estados UnidosFil: Alter, Harvey J.. National Institutes of Health; Estados Unido

Current Perspectives in ABO-Incompatible Kidney Transplant

For a long time, ABO incompatible living donor kidney transplantation has been considered contraindicated, due to the presence of isohemagglutinins, natural antibodies reacting with non-self ABO antigens. However, as the demand for kidney transplantation is constantly growing, methods to expand the donor pool have become increasingly important. Thus, in the last decades, specific desensitization strategies for ABOi transplantation have been developed. Nowadays, these regimens consist of transient removal of preformed anti-A or anti-B antibodies by using plasmapheresis or immunoadsorption and B-cell immunity modulation by CD20+ cells depletion with rituximab, in association with maintenance immunosuppression including corticosteroids, tacrolimus and mycophenolate mofetil. The outcome in ABOi kidney transplantation have markedly improved over the years. In fact, although randomized trials are still lacking, recent meta analysis has revealed that there is no difference in terms of graft and patient???s survival between ABOi and ABO compatible kidney transplant, even in the long term. However, many concerns still exist, because ABOi kidney transplantation is associated with an increased risk of bleeding and infectious complications, partly related to the effects of extracorporeal treatments and the strong immunosuppression. Thus, a continuous improvement in desensitization strategies, with the aim of minimize the immunosuppressive burden, on the basis of immune pathogenesis, antibodies titers and/or ABO blood group, is warranted. In this review, we discuss the main immune mechanisms involved in ABOi kidney transplantation, the pathogenesis of tolerance and the desensitization regimens, including immunoadsorption and plasmapheresis and the immunosuppressive protocol. Finally, we provide an overview on outcome and future perspectives in ABOi kidney transplant

Kidney transplantation in systemic sclerosis: Advances in graft, disease, and patient outcome

Systemic sclerosis (SSc) is an immune-mediated rheumatic disease characterized by vascular abnormalities, tissue fibrosis, and inflammation. Renal disease occurring in patients with SSc may have a variable clinicopathological picture. However, the most specific renal condition associated with this disease is the scleroderma renal crisis (SRC), characterized by acute onset of renal failure and severe hypertension. SRC develops in about 20% of cases of SSc, especially in those patients with diffuse cutaneous disease. The prognosis of this condition is often negative, with a rapid progression to end-stage renal disease (ESRD). The advent of the antihypertensive angiotensin-converting enzyme inhibitors in 1980 was associated with a significant improvement in patients’ survival and recovery of renal function. However, the prognosis of these patients can still be improved. The dialytic condition is associated with early death, and mortality is significantly higher than among patients undergoing renal replacement therapy (RRT) due to other conditions. Patients with SRC who show no signs of renal functional recovery despite timely blood pressure control are candidates for kidney transplantation (KT). In this review, we reported the most recent advances in KT in patients with ESRD due to SSc, with a particular overview of the risk of disease recurrence after transplantation and the evolution of other disease manifestations

Creación de un área pecuaria para productores familiares en la Facultad de Veterinaria

A mediados de marzo del 2011 y como propuesta de un grupo de estudiantes y docentes de la Facultad de Ciencias Veterinarias de la Universidad Nacional de La Plata se crea un espacio llamado Área Pecuaria, que busca dar respuesta a demandas de los productores familiares pertenecientes al proyecto de extensión “Banco Social” (BS). El BS surge en el 2005 con la idea de generar un sistema de Fondo Rotatorio (FFRR) para productores de la zona de influencia de la Universidad, que por diversos motivos no son sujetos de crédito del sistema formal. Este sistema de fondos rotatorios permitió, a través de montos pequeños de dinero, servir de impulso para comenzar el ciclo productivo.Educación, Formación y Desarrollo Rural.Universidad Nacional de La Plat

Creación de un área pecuaria para productores familiares en la Facultad de Veterinaria

A mediados de marzo del 2011 y como propuesta de un grupo de estudiantes y docentes de la Facultad de Ciencias Veterinarias de la Universidad Nacional de La Plata se crea un espacio llamado Área Pecuaria, que busca dar respuesta a demandas de los productores familiares pertenecientes al proyecto de extensión “Banco Social” (BS). El BS surge en el 2005 con la idea de generar un sistema de Fondo Rotatorio (FFRR) para productores de la zona de influencia de la Universidad, que por diversos motivos no son sujetos de crédito del sistema formal. Este sistema de fondos rotatorios permitió, a través de montos pequeños de dinero, servir de impulso para comenzar el ciclo productivo.Educación, Formación y Desarrollo Rural.Universidad Nacional de La Plat

Creación de un área pecuaria para productores familiares en la Facultad de Veterinaria

A mediados de marzo del 2011 y como propuesta de un grupo de estudiantes y docentes de la Facultad de Ciencias Veterinarias de la Universidad Nacional de La Plata se crea un espacio llamado Área Pecuaria, que busca dar respuesta a demandas de los productores familiares pertenecientes al proyecto de extensión “Banco Social” (BS). El BS surge en el 2005 con la idea de generar un sistema de Fondo Rotatorio (FFRR) para productores de la zona de influencia de la Universidad, que por diversos motivos no son sujetos de crédito del sistema formal. Este sistema de fondos rotatorios permitió, a través de montos pequeños de dinero, servir de impulso para comenzar el ciclo productivo.Educación, Formación y Desarrollo Rural.Universidad Nacional de La Plat

Genetic analysis of neuroblastoma in African-Americans

Dottorato di Ricerca in: Ricerca Operativa, XXIV Ciclo, a.a. 2008-2011Università della Calabri

Aspetti genetici della cataratta congenita

Gli autori dopo la descrizione delle recenti acquisizioni sullo sviluppo embriologico del cristallino riportano i fattori di crescita e genetici implicati nella trasformazione catarattosa delle fibre lenticolari. In particolare, FGF è in grado di indurre, a seconda della sua concentrazione, tre risposte diverse: proliferazione, migrazione e differenziazione. Tale ipotesi del gradiente di FGF spiega come il gradiente di stimolazione di FGF sia diverso in senso anteroposteriore, cioè con concentrazioni maggiori a livello posteriore rispetto a quelle anteriori. Gli autori hanno preso in esame un modello transgenico per lo studio dei cambiamenti cellulari a lungo termine indotti da TGF e cioè la transizione epiteliale-mesenchimale. Le cellule lenticolari stimolate da questo fattore di crescita cambiano totalmente la loro morfologia. Sono due i markers coinvolti nella perdita del fenotipo epiteliale da parte di cellule lenticolari: Pax-6 e a-cristallina. Entrambi sono sotto-regolati nella placca neoformata. Pax-6 è particolarmente degno di osservazione, in quanto esso è un fattore fondamentale per lo sviluppo lenticolare e mantiene la stabilità delle cellule differenziate. La sua sottoregolazione potrebbe essere un requisito in grado di scatenare la transizione epiteliale-mesenchimale e la progressione verso una differenziazione anomala e patologica delle fibre lenticolari

Hematopoietic Cell and Renal Transplantation in Plasma Cell Dyscrasia Patients.

Gammopathies, multiple myeloma, and amyloidosis are plasma dyscrasias characterized by clonal proliferation and immunoglobulin overproduction. Renal impairment is the most common and serious complication with an incidence of 20-30% patients at the diagnosis. Kidney transplant has not been considered feasible in the presence of plasma dyscrasias because the immunosuppressive therapy may increase the risk of neoplasia progression, and paraproteins may affect the graft. However, recent advances in clinical management of multiple myeloma and other gammopathies allow considering kidney transplant as a possible alternative to dialysis. Numerous evidence indicates the direct relationship between hematological remission and renal function restoring. The combination of kidney and hematopoietic cell transplant has been reported as a promising approach to reestablish end-organ function and effectively treat the underlying disease. This review describes current protocols used to perform kidney transplantation in patients with plasma dyscrasias

Anti-neutrophil cytoplasmic autoantibody-associated vasculitis in the very elderly: a 90-year-old iron lady

Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides are characterized by blood vessel inflammation resulting in organ dysfunction or in the patient\u2019s death. The peak of incidence was observed in patients over 75 years of age. We describe an unusual ANCA vasculitis presentation in a 90-year old patient admitted to the emergency room for severe dyspnea, oliguria and a recent onset cutaneous purple rush. Plain chest radiography disclosed pulmonary edema and diffuse bilateral reticulonodular infiltrates. Creatinine was 7.3 mg/dl, azotemia 202 mg/dl, hemoglobin 6.8 g/dl. CPAP (continuous positive airway pressure), furosemide 20 ml/h, nitroglycerin 8\u3b3/kg/min, blood transfusions and i.v. methylprednisolone 60 mg/day were administered. On day 1 a femoral venous catheter was placed and hemodialysis (HD) treatment started for acute renal failure. The patient underwent 13 HD sessions without heparin (EVAL dialyzer). On day 7 renal function had still not recovered and a new plain chest radiogram was unchanged. Proteinase 3(PR3) ANCA were 81 IU/ml (ELISA), C-reactive protein (CRP) was 18 mg/dl, C3 42 mg/dl, C4 5 mg/dl. A high resolution computed tomography considering that the 53% of cases were managed with glucocorticoids alone. Nonetheless, Walsh et al\u2019s metanalysis showed that patients who received a course of glucocorticoid therapy for more than 12 months suffered fewer relapses of ANCA vasculitis. In patients older than 80 years any immunosuppressive therapy is associated with a significantly lower risk of ESRD and death, but the rate of infections is higher than in younger patients. In our patient the CY dose related to the body surface area was reduced to 200 mg in view of age, risk of infection and renal failure, but glucocorticoid therapy was maintained. During the 2 year follow-up no infections were reported, the Birmingham vasculitis score was lower than 10 and reached the 50% reduction of the initial disease activity score recommended. A good outcome was obtained and it seems to be related both to CY and to the long-term maintenance therapy with glucocorticoids