CUTANEOUS AUTOIMMUNE PHENOMENA IN HIV+ PATIENTS

Autoimmune diseases are characterized by a misdirected immune response against self, thereby inflicting damage to various organs. Paradoxically, such autoimmune phenomena are also common in patients with human immunodeficiency virus (HIV) infection. Essentially, HIV infects immune cells key to orchestrating immune responses, so called helper T cells. Over time, these cells diminish and, as a consequence, the functionality of the immune system deteriorates, eventually leading to opportunistic infections unknown to healthy persons. The loss of these helper T cells is accompanied by a dysbalance in immune regulation, possibly explaining the frequent occurrence of autoimmune phenomena in HIV infected patients. Owing to highly efficacious modern treatment regimens, HIV infected patients have an increasingly good immune status and an estimated life expectancy that is approaching that of age matched controls, potentially causing this increase in frequency of autoimmune phenomena. A subgroup of autoimmune diseases is autoimmune blistering skin diseases, which are caused by specific proteins in the patients blood termed autoantibodies. In these heterogeneous groups of acquired diseases blistering occurs after binding of these autoantibodies to distinct molecules in the skin and disrupting the highly complex structures involved in the attachment of the skin. To date, only very limited data exists regarding frequency and clinical course of autoimmune blistering skin disease in HIV infected patients. As HIV infected patients become older and owing to better treatment regimens concomitantly possess a less compromised immune system, it can be assumed that autoimmune blistering diseases will be diagnosed more frequently in the near future. The aim of this project is to investigate the frequency and significance of various autoantibodies specific for the multiple autoimmune blistering diseases using various laboratory techniques in HIV infected patients. By assessing the clinical relevance, we also hope to define cut-off levels for these autoantibodies in HIV infected patients. In total, knowledge about the frequency of specific autoantibodies associated with autoimmune blistering disease might prove to be supportive in the diagnosis of these conditions in the future. Hopefully, the results of this study will provide guidance to clinicians when prescribing and analyzing results of antibodies tests for autoimmune blistering skin diseases in HIV infected patients.

In HIV-infected patients, owing to the immune system's imbalances associated with the retroviral infection, numerous immune phenomena against "self" have been described. We have investigated one subtype of these so called autoimmune phenomena, namely proteins called autoantibodies binding to important structures in the skin, thereby potentially causing skin disease. Our results indicate that the frequency of these autoantibodies directed at skin structures is nowadays similar to HIV-infected patients and uninfected controls, probably because of the effectiveness of modern antiretroviral treatments. Now that effective and tolerable antiretroviral treatment is available, many patients infected with HIV can expect to have a more or less normal life expectancy and a virtually recovered immune system. As a consequence thereof, the occurrence of a group of diseases called autoimmune blistering diseases, some of which are associated with higher age, may be destined to increase. These diverse diseases are caused by autoantibodies that bind highly complex structures in the skin required for the attachment of skin cells, eventually leading to the formation of blisters, causing significant physical and psychological burden to the patients. Before effective HIV treatments were available, it has been shown that autoantibodies associated with the most common autoimmune blistering skin disease, bullous pemphigoid, were present in up to 38% of HIV-infected patients, especially in later stages of HIV infection. We have found in a large sample of HIV-infected patients with mostly well control viral infection that the frequency of a number of cutaneous autoantibodies is low and comparable to that of uninfected controls. Interestingly, autoantibody levels indicative of the most common autoimmune blistering disease, bullous pemphigoid, could be predicted based on the patients' history of a past syphilis infection, a common sexually transmitted disease, but not a single demographic, HIV or infectious laboratory marker. It is possible that inflammation in the brain or in peripheral nerves in the course of a syphilis infection elicits an (auto)immune response, leading to cross-reactions between structures in the nerves and the skin, giving rise to the formation of these autoantibodies. We therefore recommended that patients expressing high levels of these autoantibodies lacking typical clinical signs of bullous pemphigoid should therefore be further evaluated for, among other aspects, syphilis. In addition, with the vast majority of patients with positive results showing only reactivity to only one structure in the skin, no specific combinational pattern of the studied autoantibodies was observed in HIV-infected patients or control patients. Overall, the results of this project may potentially support clinicians in their decision-taking when considering autoimmune blistering diseases as potential differential diagnoses and provide guidance and help when analyzing and interpreting results of antibodies tests required for the diagnosis of various autoimmune blistering skin diseases in patients infected with HIV.