RESUMEN
A 28-year-old female patient underwent allogeneic PBSCT from her HLA-identical sister for AML in first CR. CD34+ cells were positively selected from PBPC using immunoaffinity columns. She received 8.0 x 10(6) CD34+ cells/kg and 1.74 x 10(6) CD3+ cells/kg body weight (BW). The patient developed acute GVHD III and mild limited chronic GVHD. Thirteen months after transplantation severe thyrotoxicosis requiring plasmapheresis occurred. Immune thyroiditis was confirmed cytologically by lymphocytic infiltration in a fine needle aspirate and by elevated thyroid-Ab-titers. The patient's donor had received thyroid hormone substitution for 10 years for hypothyroidism. The most probable cause of immune thyroiditis after allogeneic BMT is the transfer of antithyroid donor lymphocytes. These lymphocytes can also be transferred with a CD34+ selected peripheral stem cell graft. The transplantation of lymphocyte-depleted autologous bone marrow or PBPC grafts after myeloablative treatment is increasingly considered as potential treatment of severe autoimmune diseases. This case demonstrates that even low numbers of lymphocytes are capable of transferring autoimmune disorders.
Asunto(s)
Antígenos CD34/análisis , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Tiroiditis Autoinmune/etiología , Adulto , Separación Celular , Femenino , Prueba de Histocompatibilidad , Humanos , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/terapia , Donadores Vivos , Depleción Linfocítica , Acondicionamiento PretrasplanteRESUMEN
Most cases of low-grade cervical intraepithelial neoplasia (CIN) associated with oncogenic human papillomavirus (HPV) types regress spontaneously within years. Unknown co-factors seem to be necessary for a progression to malignancy. To determine the possible role of cellular immunodeficiency as such a co-factor in the genesis of genital neoplasia, 48 HIV-infected women and 52 allograft recipients were examined periodically during a 3-year period. Colposcopy, cytology and HPV-DNA typing (ViraType) were performed at each visit. Each cervical lesion was matched prospectively with 2 lesions from immunocompetent controls. In all, 29/100 patients suffered from cervical neoplasms, including 2 advanced cervical cancers and 9 CIN3 lesions. Correlation between grade of lesion and HPV DNA 16/18 was significant. Low-grade lesions among patients progressed more often than among controls and recurrent lesions after destructive treatment were seen more frequently among patients than among controls. All patients with CD4-lymphocyte counts of < 400/microliters or immunosuppression for more than 3 years suffered from progressive lesions. We conclude that malfunction of the cellular immune response following either HIV-induced depletion or iatrogenic inhibition of CD4-lymphocyte activation, enhances the progression of HPV-induced cervical lesions to malignancy.
Asunto(s)
Huésped Inmunocomprometido , Papillomaviridae/patogenicidad , Infecciones por Papillomavirus/complicaciones , Neoplasias del Cuello Uterino/inmunología , Linfocitos T CD4-Positivos/inmunología , ADN Viral/análisis , Femenino , Humanos , Terapia de Inmunosupresión/efectos adversos , Recuento de Leucocitos , Infecciones por Papillomavirus/inmunología , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virología , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/virologíaRESUMEN
A liposome formulation containing a distearoylphosphatidylethanolamine analog was developed that was endocytosed by both lymphocytes and monocytes. This formulation was used to encapsulate sense and antisense 20-mer oligodeoxynucleotides to the 5' tat splice acceptor site of human immunodeficiency virus type 1. At a DNA concentration of 140 nM, the liposome-encapsulated sense DNA inhibited p24 production by as much as 84% in human peripheral blood leukocytes infected with "wild-type" virus. This treatment also reduced the number of peripheral blood leukocytes producing intracellular viral antigen by 71%. Of interest, no reduction in either parameter was observed for the antisense-containing liposomes. The results demonstrate the promise of a new liposomal delivery vehicle to inhibit human immunodeficiency virus replication by an entrapped oligodeoxynucleotide.