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(148) Global Immune Cell Analysis Reveals Plasma B-cell Infiltration in the Frontal Lobe of Patients Experiencing Cognitive Impairment and Encephalitis Secondary to HIV Infection


Authors:

Ashley Harvin, MD – Resident Physician, Virginia Commonwealth University

Roxanne Sholevar, MD – Resident Physician, Virginia Commonwealth University Health System

Christopher Kogut, MD, MSW – Associate Professor and Director of Residency Education, Virginia Commonwealth University


Co-Authors:

Presenting Author: Ashley Harvin, MD, Virginia Commonwealth University
Co-Author: Roxanne Sholevar, MD, Virginia Commonwealth University Health System
Co-Author: Christopher Kogut, MD, MSW, Virginia Commonwealth University

Abstract:

Background/Significance: In addition to opportunistic infections, a major driver of morbidity and mortality due to HIV infection is caused by central nervous system (CNS) pathology. Aberrant immune responses have long been implicated in CNS pathology secondary to HIV infection1. This study performs a top-down, unsupervised analysis of global immune cell infiltration in the brains of HIV-1 infected patients experiencing neurocognitive impairment vs healthy controls and patients with HIV infection but no neurological symptoms.


Methods: We analyzed publicly available microarray data1 within the NIH Gene Expression Ominobus (GEO)2 of twenty-four human subjects and separated into four groups: 1) Uninfected controls; 2) HIV-1 infected subjects with no substantial neurocognitive impairment (NCI); 3) HIV-1 infected with substantial NCI without HIV encephalitis (HIVE); 4) Infected with substantial NCI and HIVE. Arrays were analyzed using robust multichip averaging analysis (RMA). Immune cell populations were evaluated using CIBERSORT support vector regression. Statistical significance was assessed using a standard student t-test with a p value < 0.05 deemed significant.


Results: Plasma B-cells were the most robustly upregulated immune cells in the frontal cortex of patients with neurocognitive impairment alone (p = 0.003), and in patients with neurocognitive impairment and encephalitis (p=0.007) compared to healthy control patients. Additionally, patients with HIV-1 infection alone but without cognitive sequelae demonstrated negligible plasma cell presence, similar to healthy control patients (p=0.80). These changes were maintained in samples of white matter. Little difference in immune cell infiltration was detected in the basal ganglia.


Discussion: Our top-down analysis of immune cell infiltration in healthy patients, HIV-1 infected patients, and patients with cognitive sequelae of HIV-1 reveals that a humoral response and plasma cell infiltration in the frontal lobe and white matter is robustly upregulated in patients experiencing cognitive symptoms secondary to HIV. These data potentially implicate antibody production and plasma cell secretion as drivers of immune responses in the brain known to cause neurocognitive impairment and encephalitis. In addition to opportunistic infections, CNS pathology is a major player in morbidity and mortality secondary to HIV infection. Thus, our data suggests that targeting the humoral response in the brain in the future may potentially modulate the morbidity of HIV infection.

Conclusion/Implications: Plasma cell infiltration is robustly upregulated in patients with HIV-1 infection experiencing neurocognitive impairment and patients with neurocognitive impairment and encephalitis relative to healthy controls, and patients with HIV-1 infection but no cognitive sequelae. Future efforts to modulate the humoral response in the brain may reduce the morbidity associated with HIV-1 infection.

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