Preliminary Evidence for a Relationship between Elevated Plasma TNFα and Smaller Subcortical White Matter Volume in HCV Infection Irrespective of HIV or AUD Comorbidity

Abstract

Classical inflammation in response to bacterial, parasitic, or viral infections such as HIV includes local recruitment of neutrophils and macrophages and the production of proinflammatory cytokines and chemokines. Proposed biomarkers of organ integrity in Alcohol Use Disorders (AUD) include elevations in peripheral plasma levels of proinflammatory proteins. In testing this proposal, previous work included a group of human immunodeficiency virus (HIV)-infected individuals as positive controls and identified elevations in the soluble proteins TNFα and IP10; these cytokines were only elevated in AUD individuals seropositive for hepatitis C infection (HCV). The current observational, cross-sectional study evaluated whether higher levels of these proinflammatory cytokines would be associated with compromised brain integrity. Soluble protein levels were quantified in 86 healthy controls, 132 individuals with AUD, 54 individuals seropositive for HIV, and 49 individuals with AUD and HIV. Among the patient groups, HCV was present in 24 of the individuals with AUD, 13 individuals with HIV, and 20 of the individuals in the comorbid AUD and HIV group. Soluble protein levels were correlated to regional brain volumes as quantified with structural magnetic resonance imaging (MRI). In addition to higher levels of TNFα and IP10 in the 2 HIV groups and the HCV-seropositive AUD group, this study identified lower levels of IL1β in the 3 patient groups relative to the control group. Only TNFα, however, showed a relationship with brain integrity: in HCV or HIV infection, higher peripheral levels of TNFα correlated with smaller subcortical white matter volume. These preliminary results highlight the privileged status of TNFα on brain integrity in the context of infection.

Serum albumin and white matter hyperintensities

“…Socioeconomic status (SES) was derived from the Four-Factor Index of Social Status , which considers education and occupation level and wherein a lower score reflects higher status [ 85 ]. As in our other studies, the diagnostic groups relative to the healthy control group were less educated, had worse SES, and were more likely to include men, Black individuals, nicotine use, and hepatitis C virus (HCV) infection ( Table 1 ) [ 81 , 82 , 86 , 87 ].…”

Multi‐atlas thalamic nuclei segmentation on standard T1‐weighed MRI with application to normal aging

“…Current study participants had served as healthy control subjects in earlier projects (e.g., Sullivan et al, 2018 ; Zahr et al, 2021 ). The subset of participants who had taken the Grooved Pegboard test near the time of MRI acquisition enabled testing of the functional meaningfulness of the aging thalamic nuclei.…”

“…A separate set of T1‐contrast scans acquired in 238 (117 female and 121 male) well characterized normal control volunteers from our earlier studies (e.g., Sullivan et al, 2018 ; Zahr et al, 2021 ), ages 19 to 86 years old, were analyzed with THOMAS. On average, this group (29 Asian, 26 African American, 158 Caucasian, 25 other) had 16.4 years of education (range = 11–21) and a socioeconomic status of 24.3 (range = 11–65).…”

“…Current study participants had served as healthy control subjects in earlier projects (e.g., Sullivan et al, 2018;Zahr et al, 2021). The subset Neurons of the medial pulvinar were found to be responsive while animals were engaged in goal-directed movements involving eyes, limbs, and selective attention (for review, Phillips et al, 2021).…”

“…A separate set of T1-contrast scans acquired in 238 (117 female and 121 male) well characterized normal control volunteers from our earlier studies (e.g., Sullivan et al, 2018;Zahr et al, 2021), ages 19 to 86 years old, were analyzed with THOMAS. On average, this group (sICV) (Pfefferbaum et al, 2013).…”