ABSTRACT
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?
Subject(s)
Anti-HIV Agents/adverse effects , Exanthema/chemically induced , HIV Infections/drug therapy , Nevirapine/adverse effects , Syphilis/diagnosis , Adult , Anti-HIV Agents/therapeutic use , CD4 Lymphocyte Count , Diagnosis, Differential , Hepatitis/complications , Hepatitis/drug therapy , Humans , Hypersensitivity/complications , Hypersensitivity/drug therapy , Kenya , Nevirapine/therapeutic use , Syphilis/drug therapy , Treatment OutcomeABSTRACT
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.
Subject(s)
Blood Cells/drug effects , Immunocompromised Host/immunology , Signal Transduction/drug effects , Toll-Like Receptors/metabolism , Adolescent , Adult , Age Factors , Aged , Blood Cells/immunology , Blood Cells/metabolism , Blood Cells/pathology , Cells, Cultured , Child , Child, Preschool , Cytokines/metabolism , Female , Humans , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects , Male , Middle Aged , Sex Factors , Signal Transduction/immunology , Toll-Like Receptors/immunologyABSTRACT
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.
Subject(s)
Autoantibodies/blood , Immunoglobulin G/blood , Interferon-gamma/immunology , Mycobacterium Infections, Nontuberculous/immunology , Tuberculosis/immunology , Autoimmunity , Diabetes Mellitus, Type 1/etiology , Disease Susceptibility , Humans , Hypothyroidism/etiology , Male , Middle Aged , Mycobacterium Infections, Nontuberculous/complications , Mycobacterium chelonae/drug effects , Mycobacterium tuberculosis/drug effects , Tuberculosis/complicationsABSTRACT
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.
