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HIV induced AIDS and related cancers: chronic immune activation and future therapeutic strategies
Martin Cadogan1, Angus G Dalgleish
1Laboratory of Oncology, Department of Cellular and Molecular Medicine, St George's University of London, London, United Kingdom.
Chronic generalized immune activation represents one of the most critical features determining progression to AIDS. This may result in the manifestation of malignancy, with lymphoma and Karposi's sarcoma being the first to be recognised. In this regard, the manifestation of lymphoma is very similar to that seen in transplant patients and those with graft versus host disease (GVHD) where both chronic immune activation and immune suppression are present. Unlike the latter conditions which involve HLA mismatch, the source of this phenomenon during HIV infection remains elusive. Despite a lifecycle adapted to the host and possessing a plethora of survival strategies, HIV promotes disease progression in a manner that is consistently associated with the HLA repertoire suggesting pathogenic features relating to immunological incompatibility may be at the root of disease. Here we review the influence of immune activation on progression to AIDS with particular reference to molecular mimicry and autoimmune phenomenon and highlight the therapeutic potential of non-neutralizing antibodies and strategies designed to diffuse immune activation.
Chronic generalized immune activation represents one of the most critical features determining progression to AIDS. This may result in the manifestation of malignancy, with lymphoma and Karposi's sarcoma being the first to be recognised. In this regard, the manifestation of lymphoma is very similar to that seen in transplant patients and those with graft versus host disease (GVHD) where both chronic immune activation and immune suppression are present. Unlike the latter conditions which involve HLA mismatch, the source of this phenomenon during HIV infection remains elusive. Despite a lifecycle adapted to the host and possessing a plethora of survival strategies, HIV promotes disease progression in a manner that is consistently associated with the HLA repertoire suggesting pathogenic features relating to immunological incompatibility may be at the root of disease. Here we review the influence of immune activation on progression to AIDS with particular reference to molecular mimicry and autoimmune phenomenon and highlight the therapeutic potential of non-neutralizing antibodies and strategies designed to diffuse immune activation.
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