RESUMO
Leukocyte adhesion deficiency type 1 (LAD 1 - CD18 deficiency) is a rare disease characterized by disturbance of phagocyte function associated with less severe cellular and humoral dysfunction. The main features are bacterial and fungal infections predominantly in the skin and mucosal surfaces, impaired wound healing and delayed umbilical cord separation. The infections are indolent, necrotic and recurrent. In contrast to the striking difficulties in defense against bacterial and fungal microorganisms, LAD 1 patients do not exhibit susceptibility to viral infections and neoplasias. The severity of clinical manifestations is directly related to the degree of CD18 deficiency. Here, a 20 year-old female presenting a partial CD18 deficiency that developed a megakaryocytic (M7) acute myeloid leukemia is described for the first time. The clinical features of the patient included relapsing oral thrush due to Candida, cutaneous infections and upper and lower respiratory tract infections, followed by a locally severe necrotic genital herpetic lesion. The patient's clinical features improved for a period of approximately two years, followed by severe bacterial infections. At that time, the investigation showed a megakaryocytic acute myeloid leukemia, treated with MEC without clinical improvement. The highly aggressive evolution of the leukemia in this patient suggests that adhesion molecules could be involved in the protection against the spread of neoplastic cells.
Assuntos
Antígenos CD18/genética , Candidíase/complicações , Herpes Genital/complicações , Leucemia Mieloide Aguda/complicações , Síndrome da Aderência Leucocítica Deficitária/complicações , Antígeno CD11a/genética , Antígeno CD11b/genética , Candidíase/genética , Candidíase/microbiologia , Candidíase/virologia , Progressão da Doença , Evolução Fatal , Feminino , Expressão Gênica , Herpes Genital/genética , Herpes Genital/microbiologia , Herpes Genital/virologia , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/microbiologia , Leucemia Mieloide Aguda/virologia , Síndrome da Aderência Leucocítica Deficitária/genética , Síndrome da Aderência Leucocítica Deficitária/microbiologia , Síndrome da Aderência Leucocítica Deficitária/virologia , Pele , Adulto JovemRESUMO
BACKGROUND: Dendritic cells (DC) have been proposed to mediate sexual HIV-1 transmission by capturing the virus in the mucosa and subsequently presenting it to CD4+ T cells. We have demonstrated before that DC subsets expressing higher levels of intercellular adhesion molecule-1 (ICAM-1) are better HIV-1 transmitters. ICAM-1 binds leukocyte function-associated molecule-1 (LFA-1) on T cells, an integrin responsible for adhesion and signaling at the immunological synapse. To corroborate the importance of the ICAM-1- LFA-1 interaction, we performed transmission experiments to LFA-1 negative leukocytes from Leukocyte Adhesion Deficiency type 1 (LAD-1) patients. RESULTS: We clearly show that DC-mediated HIV-1 transmission to LAD-1 T cells is impaired in comparison to healthy controls. Furthermore, HIV-1 transmission to T cells from a unique LAD-1 patient with a well characterized LFA-1 activation defect was impaired as well, demonstrating that activation of LFA-1 is crucial for efficient transmission. Decreased cell adhesion between DC and LAD-1 T cells could also be illustrated by significantly smaller DC-T cell clusters after HIV-1 transmission. CONCLUSION: By making use of LFA-1 defect cells from unique patients, this study provides more insight into the mechanism of HIV-1 transmission by DC. This may offer new treatment options to reduce sexual transmission of HIV-1.
