Kanikah Mehndiratta
Transcriptomic analysis has been a recent approach to identify biomarkers associated with normal or diseased physiology in patients. An obvious approach to targeting any infection or disease through treatment strategies or prophylaxis requires a proper understanding of the mechanisms of its pathogenesis. Researching on better and more effective treatment approaches towards a deadly condition like Acquired Immune Deficiency Syndrome (AIDS) similarly requires attention towards the pathophysiological changes in affected cells and tissues. A useful approach could be transcriptomic analysis to identify prognostic biomarkers as has been done in a recent study conducted by scientists at the University of Minnesota, USA, and the Infectious Disease Institute in Uganda.
The HIV’s attack on the Immune system
The infection by the Human immunodeficiency virus (HIV) can eventually lead to AIDS where the immune system is believed to be compromised. The virus targets the CD4+ T cell machinery leading to a cell count of 200 or fewer cells/μL as defined by the US Centre for Disease Control (CDC) and prevention diagnostic criteria for AIDS. This weakening of the body’s defensive response makes an HIV+ patient more prone to Opportunistic Infections (OIs). More than 20 different OIs have been identified that lead to hospitalization and disability, eventually causing death in patients with AIDS.
Cryptococcal Meningitis pathogenesis
Cryptococcal meningitis (CM) accounts for about 1 million cases worldwide with a report of 600,000 deaths because of the condition. It usually presents in patients with less-apparent immunosuppression. Cryptococcal Meningitis (CM) is considered to be the most prevalent fungal OI and quite disseminated in the brain and spinal cord in AIDS patients. Mainly caused by Cryptococcus neoformans and Cryptococcus gattii, it begins with symptoms of headache, fever and uneasiness, lethargy, and memory loss due to meningitis that adds to unnecessary intracranial pressure. Antifungal therapies here seem to be a good option but have reported conflicting studies leading to death in about 20% of CM patients just after they follow it up with Antiretroviral Therapy (ART) to target HIV. It involves a cocktail of drugs that prevents the progression to death of an AIDS patient.
Transcriptomic analysis of disease pathways
The study published in the BMC Medical Genomics in 2021 aimed to identify biomarker pathways at the transcriptomic level in peripheral blood of AIDS patients to understand the cause of fatality. It reports Cryptococcal Immune Reconstitution Syndrome (C-IRIS) during immune system recovery as the cause for a dysregulated inflammatory response that rather leads to worsening of the health of the patient. The blood samples for the study were obtained from a randomized clinical trial where the execution of ART after about a month of antifungal therapy had reported a 15% improvement in patient survival. Longitudinal transcriptomic analysis was performed using NGS mRNA sequencing of CM patients that experienced C-IRIS condition during therapy where the study found an upregulation of STAT pathways and interferon type 1 involved in immune cell division and activation during the survival phase from C-IRIS before initiation of the ART. Patients who died without any reporting of C-IRIS were observed with elevated regulation of pro-inflammatory pathways that could lead to oxidative stress. And tissue damage resulting in death. The study concluded with an emphasis on the presence of unique transcriptomic signatures that can help develop novel treatments and prevent associated deaths.
Also read: Vaccine for Covid positive HIV patients
References-
- Vlasova-St Louis, I., Musubire, A. K., Meya, D. B., Nabeta, H. W., Mohei, H., Boulware, D. R., & Bohjanen, P. R. (2021). Transcriptomic biomarker pathways associated with death in HIV-infected patients with cryptococcal meningitis. BMC medical genomics, 14(1), 108. https://doi.org/10.1186/s12920-021-00914-1
- Tugume, L., Rhein, J., Hullsiek, K. H., Mpoza, E., Kiggundu, R., Ssebambulidde, K., Schutz, C., Taseera, K., Williams, D. A., Abassi, M., Muzoora, C., Musubire, A. K., Meintjes, G., Meya, D. B., Boulware, D. R., & COAT and ASTRO-CM teams (2019). HIV-Associated Cryptococcal Meningitis Occurring at Relatively Higher CD4 Counts. The Journal of infectious diseases, 219(6), 877–883. https://doi.org/10.1093/infdis/jiy602
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