Unveiling neuroimmunology profile of immunological non-responders in HIV: a multimodal MRI approach

Front Immunol. 2024 Dec 13:15:1452532. doi: 10.3389/fimmu.2024.1452532. eCollection 2024.

Abstract

Background: People living with HIV (PLWH), especially immunological non-responders (INRs), may experience adverse neurologic events. However, the extent of neurological impairment in INRs remains uncertain. This study evaluates brain structure and function, immune dysregulation, and peripheral immunomarkers in INRs and immunological responders (IRs) among PLWH, classified according to immunological response criteria, within a clinical research setting.

Methods: This study utilized multi-modal MRI to assess brain structure and function in INRs (n = 25) and IRs (n = 53). Mass cytometry and Luminex/ELISA assays were employed to analyze peripheral blood monocytes, T cell subpopulations, cytokines, chemokines, neurotrophic factors, and endocrine factors.

Results: Neuroimaging findings revealed notable changes in brain structure and function in INRs, including increased fractional amplitude of low-frequency fluctuations and regional homogeneity in the left middle temporal gyrus, as well as decreased grey matter volume in the left middle temporal gyrus, left lingual gyrus, and right rolandic operculum. Furthermore, INRs exhibited significant alterations in functional connectivity in the temporal and occipital gyrus. Mass cytometry analysis demonstrated significant immune dysregulation in INRs, characterised by increased levels of senescent and activated T cells, and heightened monocyte activation. Additionally, noteworthy associations were found between neurological abnormalities and peripheral levels of immunomarkers, inflammatory cytokines, chemokines, neurotrophic factors, and endocrine factors in INRs.

Conclusion: These findings underscore the associations between immune dysfunction and changes in brain structure and function, emphasizing the importance of further investigations in this field.

Keywords: human immunodeficiency virus; immunological non-responders; mass cytometry; multimodal magnetic resonance; neuroimmune.

MeSH terms

  • Adult
  • Brain* / diagnostic imaging
  • Brain* / immunology
  • Brain* / pathology
  • Cytokines / blood
  • Female
  • HIV Infections* / diagnostic imaging
  • HIV Infections* / immunology
  • Humans
  • Magnetic Resonance Imaging* / methods
  • Male
  • Middle Aged
  • Multimodal Imaging / methods
  • Neuroimmunomodulation

Substances

  • Cytokines

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by Beijing Research Ward Excellence Program (BRWEP2024W042180103 to YZ), the National Natural Science Foundation of China (82072271 to TZ, 82241072 to TZ, 82072294 to ZL), the Beijing Natural Science Foundation (7222095 to YLZ, 7222091 to YZ), the High-level Public Health Technical Personnel Construction Project (2022-1-007 to TZ), and the Beijing Key Laboratory for HIV/AIDS Research (BZ0089 to TZ), the High-level Public Health Specialized Talents Project of Beijing Municipal Health commission(2022-02-20 to ZL), the Peak Talent Program of Beijing Hospital Authority (DFL20191701 to TZ), National Key Research and Development Program of China (2021YFC0122601), the Capital’s Funds for Health Improvement and Research (2022-1-1151 to TZ), the Research and Translational Application of Clinical Characteristic Diagnostic and Treatment Techniques in Capital City (Z221100007422055 to TZ), Beijing research center for respiratory infectious diseases project(BJRID2024-001 to YLZ), the Beijing Hospitals Authority Innovation Studio of Young Staff Funding Support (2021037 to YZ).