RESUMEN
We evaluated a patient with disseminated Mycobacterium tuberculosis and Mycobacterium chelonae infection, of which he died. He also developed autoimmune (type I) diabetes and primary hypothyroidism. His serum contained a high titer of immunoglobulin G autoantibody to interferon-gamma (IFN-gamma) capable of blocking in vitro responses to this cytokine by peripheral blood mononuclear cells from normal donors. These results suggest that autoantibodies to IFN-gamma can induce susceptibility to disseminated mycobacterial infection, which may be refractory to chemotherapy.
Asunto(s)
Autoanticuerpos/sangre , Inmunoglobulina G/sangre , Interferón gamma/inmunología , Infecciones por Mycobacterium no Tuberculosas/inmunología , Tuberculosis/inmunología , Autoinmunidad , Diabetes Mellitus Tipo 1/etiología , Susceptibilidad a Enfermedades , Humanos , Hipotiroidismo/etiología , Masculino , Persona de Mediana Edad , Infecciones por Mycobacterium no Tuberculosas/complicaciones , Mycobacterium chelonae/efectos de los fármacos , Mycobacterium tuberculosis/efectos de los fármacos , Tuberculosis/complicacionesRESUMEN
We report a case in which an HIV-positive man developed general malaise, skin rash and biochemical hepatitis within days of starting a nevirapine-based antiretroviral treatment regimen. At the same time, his syphilis serology proved positive. We discuss the diagnostic dilemma: was this a nevirapine hypersensitivity reaction, secondary syphilis or both?
Asunto(s)
Fármacos Anti-VIH/efectos adversos , Exantema/inducido químicamente , Infecciones por VIH/tratamiento farmacológico , Nevirapina/efectos adversos , Sífilis/diagnóstico , Adulto , Fármacos Anti-VIH/uso terapéutico , Recuento de Linfocito CD4 , Diagnóstico Diferencial , Hepatitis/complicaciones , Hepatitis/tratamiento farmacológico , Humanos , Hipersensibilidad/complicaciones , Hipersensibilidad/tratamiento farmacológico , Kenia , Nevirapina/uso terapéutico , Sífilis/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Toll-like receptors (TLRs) are important in the initiation of immune responses in both health and disease. How TLR activity alters with age, gender, and also with immunosuppressive agents is still largely unexplored. We studied TLR activity in 49 healthy individuals as well as in 26 patients receiving immunosuppressive drugs. TLR activity did not alter significantly between the ages of 2 and 67 years. However, females had twice the TLR7 ligand-induced interferon-I response of males (OR [95% CI] 2.7 [1.4-5.1]), whereas TLR3 and four activities were not significantly different between the sexes. The T-cell immunosuppressant agents cyclosporine, tacrolimus, and azathioprine, as well as low dose glucocorticosteroids did not significantly alter TLR pathway responses. In contrast, high dose glucocorticosteroids reduced in vivo TLR responses by 70%-90%. We suggest that gender differences in TLR responses may help to explain the female preponderance of some autoimmune disorders. Furthermore, an understanding the effects of immunosuppressive agents on TLR-pathway activity should allow more focused therapy for autoimmune disorders.
Asunto(s)
Células Sanguíneas/efectos de los fármacos , Huésped Inmunocomprometido/inmunología , Transducción de Señal/efectos de los fármacos , Receptores Toll-Like/metabolismo , Adolescente , Adulto , Factores de Edad , Anciano , Células Sanguíneas/inmunología , Células Sanguíneas/metabolismo , Células Sanguíneas/patología , Células Cultivadas , Niño , Preescolar , Citocinas/metabolismo , Femenino , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Masculino , Persona de Mediana Edad , Factores Sexuales , Transducción de Señal/inmunología , Receptores Toll-Like/inmunologíaRESUMEN
Early bone marrow transplant is now standard treatment for infants with severe immunodeficiencies such as Wiskott-Aldrich Syndrome (WAS), but results in older children and adults are poor. Non-myeloablative transplant has shown promise in the treatment of older children, who are likely to have active infections and organ damage. We describe a non-myeloablative transplant of a 26-year-old man with WAS, undertaken because of severe infections and vasculitis. Partial engraftment and immunorestoration were achieved. The patient is well 1 year post transplantation.