Tratamiento de inducción combinando inmunoglobulinas, plasmaféresis y rituximaben pacientes hipersensibilizados que reciben trasplante renal de cadáver / Induction treatment by combining immunoglobulins, plasmapheresis and rituximab in hypersensitive patients receiving cadaveric renal allograft

En el Hospital Universitario de Canarias pusimos en marcha, en mayo de 2008, un protocolo de tratamiento de inducción para pacientes hipersensibilizados que reciben injerto renal de cadáver utilizando inmunoglobulinas intravenosas, plasmaféresis y rituximab más una inmunosupresión triple con prednisona, tacrolimus y micofenolatomofetil. Presentamos los resultados de 4 pacientes. Todo sellos presentaban una tasa de anticuerpos anti-HLA (PARA por CDC) superior al 75%, llevaban en lista de espera de 4a 17 años, el tiempo de seguimiento posterior al trasplante fue de 10-14 meses y la supervivencia de paciente y del injerto en este período fue del 100%. Sólo un paciente sufrió un rechazo agudo mediado por anticuerpos y otro uno celular, en ambos casos reversibles con el tratamiento. En la evolución no se objetivó aparición de novo de anticuerpos donante-específicos. Todos los pacientes habían reducido significativamente el número de células CD19+ después de la infusión de rituximab. No se han detectado síntomas neurológicos indicativos de leucoencefalopatía multifocal progresiva ni infecciones virales graves después del trasplante y tampoco se han observado efectos secundarios inmediatos tras la administración de la medicación. En resumen, el tratamiento de inducción combinado con inmunoglobulinas, plasmaféresis y rituximab en pacientes (..) (AU)

In our Universitary Hospital of Canarias we iniciated in May2008 a induction therapy protocol for sensitized patients receiving cadaveric renal graft using intravenous immunoglobulins, plasmapheresis and rituximab plusimmuno suppression with prednisone, tacrolimus and mycophenolate mofetil. We present the results of four patients. Everyone had anti-HLA antibodies rate (PRA by CDC) more than 75%, were on a waiting list during 4 to 17 years and follow-up time was 10-14 months after transplantation. Patient and graft survival in this period was 100%. Only one patient suffered a humoral acute rejection and another one cellular rejection, in both cases reversible with treatment. During the first year, no evidence of de novo donor-specific antibodies was detected. All patients had significantly reduced the CD19+ cells percentage after infusion of rituximab. Neurological symptoms suggestive of progressive multifocal leukoencephalopathy or serious viral infections after transplantation have not been observed. Additionally, no immediate side effects were observed after administration of medication. In summary, induction therapy by combining immunoglobulin, plasmapheresis and rituximab in hypersensitive patients allows the realization of deceased kidney transplantation with good results in the short and medium-term without serious side effects. It remains to know whether this success will continue in the long term (AU)

[Induction treatment by combining immunoglobulins, plasmapheresis and rituximab in hypersensitive patients receiving cadaveric renal allograft]. / Tratamiento de inducción combinando inmunoglobulinas, plasmaféresis y rituximab en pacientes hipersensibilizados que reciben trasplante renal de cadáver.

In our Universitary Hospital of Canarias we iniciated in May 2008 a induction therapy protocol for sensitized patients receiving cadaveric renal graft using intravenous immunoglobulins, plasmapheresis and rituximab plus immunosuppression with prednisone, tacrolimus and mycophenolate mofetil. We present the results of four patients. Everyone had anti-HLA antibodies rate (PRA by CDC) more than 75%, were on a waiting list during 4 to 17 years and follow-up time was 10-14 months after transplantation. Patient and graft survival in this period was 100%. Only one patient suffered a humoral acute rejection and another one cellular rejection, in both cases reversible with treatment. During the first year, no evidence of de novo donor-specific antibodies was detected. All patients had significantly reduced the CD19+ cells percentage after infusion of rituximab. Neurological symptoms suggestive of progressive multifocal leukoencephalopathy or serious viral infections after transplantation have not been observed. Additionally, no immediate side effects were observed after administration of medication. In summary, induction therapy by combining immunoglobulin, plasmapheresis and rituximab in hypersensitive patients allows the realization of deceased kidney transplantation with good results in the short and medium-term without serious side effects. It remains to know whether this success will continue in the long term.

Sobre "La Inmunología en nuestros hospitales" / On "Immunology in our hospitals"

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Detection of hepatitis B virus in the liver by in situ hybridization (ISH) in HBsAg seropositive and seronegative patients.

The presence of hepatitis B virus (HBV) DNA in the liver of 119 patients was studied to assess the diagnostic value of in situ hybridization (ISH) and its relationship with viral replication and histological liver damage. Liver biopsies of 119 patients (55 hepatitis B surface antigen -HBsAg- seropositive and 64 HBsAg seronegative) were studied retrospectively. Among the HBsAg seropositive patients, the ISH was positive in 26 cases (47%) and negative in 29 (53%) and the former group had higher levels of serum transaminases. The hepatocyte number with positivity for HBsAg and hepatitis B core antigen (HBcAg) in the liver were similar in both ISH-positive and -negative patients. The histological activity index (Knodell) was higher in ISH-positive patients (11 vs 7, p < 0.001). Six patients out of 12 were positive by PCR. In the HBsAg seronegative patients, the ISH was negative in 57 cases and positive in 7. These 7 were positive for anti-HBs (5 cases) and/or anti-HBc (6 cases); 4 were confirmed by PCR. Thus, our data suggest that the ISH technique is useful for detecting viral nucleic acid in the liver, but that the HBV-DNA cannot always be considered as a replication marker, because we also show that some HBsAg seronegative patients with chronic liver disease do have HBV-DNA in their liver cells.

[DNA papillomavirus detection in head and neck benign proliferative lesions]. / Detección de dna papilomavirus en lesiones proliferativas benignas de cabeza y cuello

In a retrospective study, human papillomavirus (HPV) (6/11, 16 and 18 types) were tested using polymerase chain reaction (PCR), in stored formalin-fixed, paraffin-embedded tissue sections, from 36 head and neck adult papillomata. The results, only 20 percent of positive cases, are non consistent with the role of the HPV infection in the etiology of head and neck papillomata in adult patients. However we detect HPV-18 positivity in papillomata with dysplasia.