| 1. |
- Cheng, D., et al.
(författare)
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Elevated Cerebrospinal Fluid Anti-CD4 Autoantibody Levels in HIV Associate with Neuroinflammation
- 2022
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Ingår i: Microbiology Spectrum. - : American Society for Microbiology. - 2165-0497. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- The mechanisms of persistent central nervous system (CNS) inflammation in people with HIV (PWH) despite effective antiretroviral therapy (ART) are not fully understood. We have recently shown that plasma anti-CD4 IgGs contribute to poor CD41 T cell recovery during suppressive ART via antibody-mediated cytotoxicity (ADCC) against CD41 T cells, and that plasma anti-CD4 IgG levels are associated with worse cognitive performance and specific brain area atrophy. However, the role of anti-CD4 IgGs in neuroinflammation remains unclear. In the current study, plasma and cerebrospinal fluid (CSF) samples from 31 ART-naive and 26 treated, virologically suppressed PWH, along with 16 HIV-seronegative controls, were evaluated for CSF levels of antiCD4 IgG, white blood cell (WBC) counts, soluble biomarkers of neuroinflammation, and neurofilament light chain (NfL). We found that 37% of the PWH exhibited elevated CSF anti-CD4 IgG levels, but few or none of the PWH were observed with elevated CSF antiCD4 IgM, anti-CD8 IgG, or anti-double-strand DNA IgG. CSF anti-CD4 IgG levels in PWH were directly correlated with neuroinflammation (WBC counts, neopterin, and markers of myeloid cell activation), but not with CSF NfL levels. Using cells from one immune nonresponder to ART, we generated a pathogenic anti-CD4 monoclonal IgG (JF19) presenting with ADCC activity; JF19 induced the production of soluble CD14 (sCD14) and interleukin-8 (IL-8) in human primary monocyte-derived macrophages via CD4 binding in vitro. This study demonstrates for the first time that elevated CSF anti-CD4 IgG levels present in a subgroup of PWH which may play a role in neuroinflammation in HIV. IMPORTANCE This study reports that an autoantibody presents in the CNS of HIV patients and that its levels in the CSF correlate with some markers of neuroinflammation. © 2022 Cheng et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
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| 2. |
- Joseph, S. B., et al.
(författare)
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Biotypes of Central Nervous System Complications in People With Human Immunodeficiency Virus: Virology, Immunology, and Neuropathology
- 2023
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 227:SUPP1
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Tidskriftsartikel (refereegranskat)abstract
- Despite viral suppression with antiretroviral therapy (ART), people with human immunodeficiency virus (HIV) continue to experience central nervous system (CNS) complications, primarily in the form of mild cognitive impairment and mental health disorders (eg, depression, anxiety, other neuropsychiatric problems). The multifactorial pathogenesis and heterogeneity of mechanisms likely underlying CNS complications must be addressed in the development of preventive interventions and effective treatments. The biotyping approach has previously been useful to define phenotypes of other CNS diseases based on underlying mechanisms and could be translated to the field of neuroHIV. The purpose of the Biotype Workshop series, and the Virology, Immunology and Neuropathology Working Group in particular, is to capitalize on current and new technologies and guide future research efforts using the wealth of available immunological, virologic, and neuropathological data collected from people with HIV on and off ART.
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| 3. |
- Premeaux, Thomas A, et al.
(författare)
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Elevated cerebrospinal fluid Galectin-9 is associated with central nervous system immune activation and poor cognitive performance in older HIV-infected individuals.
- 2019
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Ingår i: Journal of neurovirology. - : Springer Science and Business Media LLC. - 1538-2443 .- 1355-0284. ; 25:2, s. 150-161
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Tidskriftsartikel (refereegranskat)abstract
- We previously reported that galectin-9 (Gal-9), a soluble lectin with immunomodulatory properties, is elevated in plasma during HIV infection and induces HIV transcription. The link between Gal-9 and compromised neuronal function is becoming increasingly evident; however, the association with neuroHIV remains unknown. We measured Gal-9 levels by ELISA in cerebrospinal fluid (CSF) and plasma of 70 HIV-infected (HIV+) adults stratified by age (older >40years and younger <40years) either ART suppressed or with detectable CSF HIV RNA, including a subgroup with cognitive assessments, and 18 HIV uninfected (HIV-) controls. Gal-9 tissue expression was compared in necropsy brain specimens from HIV- and HIV+ donors using gene datasets and immunohistochemistry. Among older HIV+ adults, CSF Gal-9 was elevated in the ART suppressed and CSF viremic groups compared to controls, whereas in the younger group, Gal-9 levels were elevated only in the CSF viremic group (p<0.05). CSF Gal-9 positively correlated with age in all groups (p<0.05). CSF Gal-9 tracked with CSF HIV RNA irrespective of age (β=0.33; p<0.05). Higher CSF Gal-9 in the older viremic HIV+ group correlated with worse neuropsychological test performance scores independently of age and CSF HIV RNA (p<0.05). Furthermore, CSF Gal-9 directly correlated with myeloid activation (CSF-soluble CD163 and neopterin) in both HIV+ older groups (p<0.05). Among HIV+ necropsy specimens, Gal-9 expression was increased in select brain regions compared to controls (p<0.05). Gal-9 may serve as a novel neuroimmuno-modulatory protein that is involved in driving cognitive deficits in those aging with HIV and may be valuable in tracking cognitive abnormalities.
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