RESUMO
In this report we describe a patient who, after allogeneic bone marrow transplantation from her HLA-identical sister, developed polyendocrine failure in the form of Type 1 (insulin-dependent) diabetes mellitus and hypothyroidism. This was the result of the transfer of donor lymphoid cells which were activated by allogeneic bone marrow transplantation. The full chimerism of the recipient was demonstrated by restriction fragment length polymorphism analysis from nucleated blood cells and fibroblast DNA. During the 9-year follow-up, the donor developed hypothyroidism and signs of pre-Type 1 diabetes. This clinical observation resembles the adoptive transfer of diabetes observed in non-obese-diabetic mice and BB rats and confirms the role of immune processes in the pathogenesis of this disease.
Assuntos
Autoanticorpos/sangue , Transplante de Medula Óssea/imunologia , Diabetes Mellitus Tipo 1/etiologia , Hipotireoidismo/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Adolescente , Glicemia/metabolismo , Quimera , DNA/sangue , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/imunologia , Feminino , Seguimentos , Humanos , Hipotireoidismo/complicações , Hipotireoidismo/imunologia , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina G/classificação , Ilhotas Pancreáticas/imunologia , Polimorfismo de Fragmento de Restrição , Mapeamento por Restrição , Glândula Tireoide/imunologia , Doadores de Tecidos , Transplante HomólogoRESUMO
Cytosol fraction(s) from McFiFi2(s) fibrosarcoma cells (Fcc), isolated from either cultured cells or solid tumors induced in F344 rats, produced a dose-related inhibition of lymphoproliferative responses to several mitogens, whatever the lymphoid organ or the animal species used as the source of lymphocytes. Only stimulated human lymphocytes were not Fcc inhibited; instead, Fcc was a potent stimulator of their spontaneous proliferation. Fcc cytostatic activity was not effective in various cycling cell lines and was restricted to mitogen-stimulated lymphocytes. Fcc, a primary tumor product, did not induce suppressive cells and was unable to prevent mitogen cell surface binding. However, expression of its modulating effect was accelerated by the simultaneous presence of the mitogen. Moreover, Fcc produced its suppression by interrupting lymphocyte activation at some point within the G0-G1-phase transition. Molecular sieving showed that Fcc contains at least two factors with suppressive (mol wt, approximately 3,000) and stimulatory (mol wt, greater than 5,000) activities, respectively.
