RESUMEN

Plasma cell hepatitis (PCH), also known as "de novo autoimmune" hepatitis, is an increasingly recognized, but suboptimally named and poorly understood, category of late allograft dysfunction strongly resembling autoimmune hepatitis (AIH): They share plasma-cell-rich necro-inflammatory activity on biopsy, autoantibodies and steroid responsiveness, but overlap with rejection is problematic. A retrospective study of clinical, serological, histopathological and IgG4 immunohistological features of PCH (n = 20) in liver allograft recipients, native liver AIH (n = 19) and plasma-cell-rich renal allograft rejection (n = 20) showed: (1) high frequency (44%) of HLA-DR15; (2) less female predominance (p = 0.03) and (3) n = 9/20 PCH recipients showed >25 IgG4+ plasma cells/high-power field (IgG4+ PCH) versus AIH (n = 1/19, p = 0.008) or plasma-cell-rich kidney rejection (n = 2/20, p = 0.03). The IgG4+ PCH (n = 9) subgroup showed lower alanine transaminase (ALT) (p < 0.01) and aspartate transaminase (AST) (p < 0.05) at index biopsy but (a) higher plasma cell number/percentage, (b) more aggressive-appearing portal/periportal and perivenular necro-inflammatory activity and (c) more severe portal/periportal fibrosis than IgG4- PCH (n = 11). Significant demographic, histopathologic and plasma cell phenotype differences between PCH and AIH suggest distinct pathogenic mechanisms for at least the IgG4+ PCH subgroup likely representing an overlap between allo- and auto-immunity. IgG4+ PCH was associated with fibrosis, but also highly responsive to increased immunosuppression.

Asunto(s)

Hepatitis C/patología , Hepatitis Autoinmune/patología , Inmunoglobulina G/inmunología , Trasplante de Hígado/efectos adversos , Células Plasmáticas/patología , Complicaciones Posoperatorias , Adulto , Anciano , Anciano de 80 o más Años , Aloinjertos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/patología , Femenino , Estudios de Seguimiento , Factores de Transcripción Forkhead/metabolismo , Hepacivirus/aislamiento & purificación , Hepatitis C/inmunología , Hepatitis C/virología , Hepatitis Autoinmune/inmunología , Hepatitis Autoinmune/virología , Humanos , Técnicas para Inmunoenzimas , Inmunoglobulina G/metabolismo , Hepatopatías/inmunología , Hepatopatías/cirugía , Hepatopatías/virología , Masculino , Persona de Mediana Edad , Células Plasmáticas/inmunología , Células Plasmáticas/virología , Pronóstico , Estudios Retrospectivos , Adulto Joven

RESUMEN

Mammalian target of rapamycin kinase inhibitor (mTORi) rapamycin (RAPA) use in transplantation can lead to inflammatory complications in some patients. Our goal was to better understand how mTORi-exposed human monocyte-derived dendritic cells (DC) stimulated with pro-inflammatory cytokines shape T cell allo-immunity. RAPA-conditioned-DC (RAPA-DC) displayed a more immature phenotype than untreated, control (CTRL)-DC. However, subsequent exposure of RAPA-DC to an inflammatory cytokine cocktail (ICC) plus IFN-γ induced a mature Type-1 promoting phenotype, consisting of elevated HLA-DR and co-stimulatory molecules, augmented IL-12p70 and IL-27 production, but decreased IL-10 secretion compared to CTRL-DC. Co-culture of mature (m)RAPA-DC with allogeneic peripheral blood mononuclear cells resulted in significantly increased Type-1 (IFN-γ) responses by T cells. Moreover, NK cells acted as innate modulators that conveyed activating cell-to-cell contact signals in addition to helper (IFN-γ) and/or regulatory (IL-10) soluble cytokines. We conclude that production of IL12-p70, IL-27 and low IL-10 by RAPA-DC allowed us to elucidate how these cytokines as well as NK-DC interaction shapes T cell allo-immunity. Thus, lack of inhibitory NK cell function during allo-specific T cell activation by human ICC + IFN-γ-stimulated RAPA-DC may represent an unwanted effector mechanism that may underlie RAPA-induced inflammatory events in transplant patients undergoing microbial infection or allograft rejection.

Asunto(s)

Células Dendríticas/inmunología , Interleucina-12/metabolismo , Interleucina-27/metabolismo , Células Asesinas Naturales/inmunología , Sirolimus/farmacología , Linfocitos T/inmunología , Diferenciación Celular , Técnicas de Cocultivo , Células Dendríticas/efectos de los fármacos , Células Dendríticas/metabolismo , Humanos , Interferón gamma/biosíntesis , Interleucina-10/biosíntesis , Leucocitos Mononucleares/fisiología

RESUMEN

I/R injury is a major deleterious factor of successful kidney transplantation (KTx). Carbon monoxide (CO) is an endogenous gaseous regulatory molecule, and exogenously delivered CO in low concentrations provides potent cytoprotection. This study evaluated efficacies of CO exposure to excised kidney grafts to inhibit I/R injury in the pig KTx model. Porcine kidneys were stored for 48 h in control UW or UW supplemented with CO (CO-UW) and autotransplanted in a 14-day follow-up study. In the control UW group, animal survival was 80% (4/5) with peak serum creatinine levels of 12.0 +/- 5.1 mg/dL. CO-UW showed potent protection, and peak creatinine levels were reduced to 6.9 +/- 1.4 mg/dL with 100% (5/5) survival without any noticeable adverse event or abnormal COHb value. Control grafts at 14 days showed significant tubular damages, focal fibrotic changes and numerous infiltrates. The CO-UW group showed significantly less severe histopathological changes with less TGF-beta and p-Smad3 expression. Grafts in CO-UW also showed significantly lower early mRNA levels for proinflammatory cytokines and less lipid peroxidation. CO in UW provides significant protection against renal I/R injury in the porcine KTx model. Ex vivo exposure of kidney grafts to CO during cold storage may therefore be a safe strategy to reduce I/R injury.

Asunto(s)

Monóxido de Carbono/administración & dosificación , Trasplante de Riñón , Daño por Reperfusión/prevención & control , Animales , Western Blotting , Carboxihemoglobina/metabolismo , Modelos Animales de Enfermedad , Supervivencia de Injerto , Malondialdehído/metabolismo , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Soluciones , Porcinos

RESUMEN

La leucemia mieloide crónica (LMC) es una enfermedad mieloproliferativa caracterizada por la expansión clonal de células mieloides que expresan la proteína de fusión BCR-ABL, responsable de los efectos oncogénicos de la LMC. La terapia actual en el tratamiento de LMC es el inhibidor de la BCR-ABL tirosín-kinasa, imatinib. Aunque este fármaco ha demostrado mejorar la supervivencia en pacientes con LMC, su papel en el contexto del trasplante renal no ha sido ampliamente descrito en la literatura. Presentamos un caso de remisión molecular de LMC en un varón de 55 años con un segundo trasplante renal, hepatitis C y con riesgos cardiovascularese inmunológicos asociados (AU)

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Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by clonal expansion of cells in the myeloid line, expressing the BCRABL fusion protein responsible for the oncogenic effect of CML. The current frontline therapy in CML is the BCR-ABL tyrosine kinase inhibitor, Imatinib. Although this drug has been shown to improve survival in CML patients, its role in the context of a transplant setting has not been widely described in the literature. We report on the long termmolecular remission of CML in a 55 year old man with a second renal transplant who is hepatitis C virus positive,and has associated cardiovascular and immunological riskfactors (AU)

Asunto(s)

Humanos , Masculino , Persona de Mediana Edad , Leucemia Mielógena Crónica BCR-ABL Positiva , Trasplante de Riñón , Glomerulonefritis Membranoproliferativa/complicaciones , Diálisis Renal , Hepatitis C Crónica/complicaciones , Factores de Riesgo , Enfermedades Cardiovasculares/epidemiología

RESUMEN

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by clonal expansion of cells in the myeloid line, expressing the BCR-ABL fusion protein responsible for the oncogenic effect of CML. The current frontline therapy in CML is the BCR-ABL tyrosine kinase inhibitor, Imatinib. Although this drug has been shown to improve survival in CML patients, its role in the context of a transplant setting has not been widely described in the literature. We report on the long term molecular remission of CML in a 55 year old man with a second renal transplant who is hepatitis C virus positive, and has associated cardiovascular and immunological risk factors.

Asunto(s)

Trasplante de Riñón , Leucemia Mielógena Crónica BCR-ABL Positiva/cirugía , Hepatitis C/complicaciones , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/complicaciones , Masculino , Persona de Mediana Edad , Inducción de Remisión , Reoperación

RESUMEN

HLA-B*4068 shares exon 2 with HLA-B*4008 and exon 3 with HLA-B*4004.

Asunto(s)

Alelos , Antígenos HLA-B/genética , Secuencia de Bases , Exones , Femenino , Antígeno HLA-B40 , Humanos , Masculino , Datos de Secuencia Molecular , Alineación de Secuencia , Análisis de Secuencia de ADN