HIV infection and rheumatic diseases - Autoimmune mechanisms in immunodeficient hosts

The recognition of a newly acquired immunodeficiency syndrome (AIDS) in 1981 has had dramatic social and economic implications. Eventually, an epidemic of the viral infection developed with a potential to spread globally. The extraordinary breadth of AIDS research lead to the early identification of the causative agent: the human immunodeficiency virus (HIV) is a member of the lentivirus family and is characterized by its ability to remain latent within the genome of the infected host. The primary targets for the HIV are helper T-lymphocytes and monocytes/macrophages, which results in the progressive destruction of immune functions in the infected hosts. Binding to and entry into the cells is facilitated by a high-affinity interaction of a viral glycoprotein and the CD4 molecule. Signs of the immunodeficient state, manifested as a broad spectrum of opportunistic infections initially dominated the clinical presentations of HIV infected patients. Over the last decade, however, the manifestations of HIV infection have steadily grown and, surprisingly, include many rheumatic syndromes and autoimmune phenomena. The finding that HIV-infected individuals present with a highly progressive form of Reiter's syndrome and psoriasis has challenged our understanding of immune functions in HLA-B27 associated disorders. Obviously, CD8⁺ T-cells can maintain function despite the depletion of CD4⁺ helper T-cells. Consistent with the current model of the pathogenesis of rheumatoid arthritis and systemic lupus erythematosus, patients with these syndromes were described to go into remission when CD4⁺ T-cells were selectively depleted in active HIV infection. There is growing evidence that complex mechanisms arise from the interaction of the HIV and the human host which extend beyond the initial expectation that the virus only kills CD4⁺ helper T-cells. Indicating yet another aspect of HIV disease, a new syndrome mimicking Sjogren's syndrome has been encountered in HIV-infected patients and has been named the diffuse infiltrative lymphocytosis syndrome. Dense infiltrates of CD8⁺, potentially antiviral killer cells, are characteristically found in the salivary glands of patients who express a certain HLA genotype and who are, typically, longterm survivors of the disease. Recent reports have stressed a new mechanism of disease induction in HIV infected patients. Inappropriate induction of potentially destructive cytokines appears to be initiated by the viral infection and the expression of the viral genome seems to be effectively modulated by cytokines. In summary, HIV infection may provide important insights in the pathogenesis of rheumatic diseases co-occurring with HIV infections. Studying immunopathogenic mechanisms in HIV-infected individuals presenting with rheumatic diseases preceding or following the viral infection represents a unique opportunity to understand the immune dysfunctions in patients with rheumatic diseases.