RESUMO
Acute generalized exanthematous pustulosis (AGEP) is an uncommon disease, which presents as a nonfollicular erythematous sterile pustular eruption. More than 90% of the cases are induced by adverse drug reactions, often triggered by anti-infectious systemic drugs. We report a case of itraconazole-induced AGEP in a 22-year-old man, with an assessment of his cytokine/chemokine production and drug-specific cell reactivity. We found that AGEP, like other T cell-mediated drug eruptions, alters the immunological status of the patient, probably favouring T-cell activation, recruitment and regulation. Few cases of itraconazole-induced AGEP have been described in the literature, and to our knowledge, this is the first report in which the cellular immunological features are assessed.
Assuntos
Pustulose Exantematosa Aguda Generalizada/imunologia , Antifúngicos/efeitos adversos , Toxidermias/imunologia , Itraconazol/efeitos adversos , Ativação Linfocitária/imunologia , Pustulose Exantematosa Aguda Generalizada/induzido quimicamente , Humanos , Masculino , Linfócitos T/fisiologia , Adulto JovemRESUMO
We describe how hookworms interact with their human hosts by comparing lymphocyte phenotyping, proliferative responses, and cytokine and chemokine secretion patterns in adults who are either mono-infected with Necator americanus or egg-negative controls resident in an area of high transmission in Brazil. Cellular immune responses against crude hookworm antigen extracts from different developmental stages were evaluated simultaneously. Principal component analysis (PCA) was used to reduce the standardized immune responses. Random effects multivariate regression was then used to investigate whether principal components (PC) differ between the two groups once potential confounders and effect modifiers have been accounted for. Although hookworm patients had reduced percentages of T and B cells, they had higher levels of activated CD4(+) T and CD19(+) B cells. This state of 'immune activation' coincided with lower proliferative responses, especially to third-stage larval antigen. Cytokine levels in mono-infected adults were also lower and characterized by a mixed Th1/Th2-type profile. Excretory/secretory antigen from adult worms was a potent modulator of the immune response, resulting in diminished TNF-alpha and IL-10 secretion in peripheral blood mononuclear cells (PBMC) from hookworm infected patients. We propose that the longevity of hookworms in their human hosts results from a stage-specific, down-modulation of the immune response.
Assuntos
Estágios do Ciclo de Vida , Ativação Linfocitária/imunologia , Subpopulações de Linfócitos/imunologia , Necator americanus/crescimento & desenvolvimento , Necator americanus/imunologia , Necatoríase/imunologia , Adolescente , Adulto , Idoso , Animais , Antígenos de Helmintos/imunologia , Brasil , Citocinas/biossíntese , Feminino , Interações Hospedeiro-Parasita , Humanos , Masculino , Pessoa de Meia-Idade , Necator americanus/patogenicidade , Necatoríase/parasitologia , Análise de Componente PrincipalRESUMO
This paper summarises the progress towards vaccine development against the major blood-feeding nematodes of man and livestock, the hookworms and Haemonchus contortus, respectively. The impact of the diseases and the drivers for vaccine development are summarized as well as the anticipated impact of the host immune response on vaccine design. The performance requirements are discussed and progress towards these objectives using defined larval and adult antigens, many of these being shared between species. Specific examples include the Ancylostoma secreted proteins and homologues in Haemonchus as well as proteases used for digestion of the blood meal. This discussion shows that many of the major vaccine candidates are shared between these blood-feeding species, not only those from the blood-feeding stages but also those expressed by infective L3s in the early stages of infection. Challenges for the future include: exploiting the expanding genome information for antigen discovery, use of different recombinant protein expression systems, formulation with new adjuvants, and novel methods of field testing vaccine efficacy.