Cerebrospinal fluid (β2-microglobulin in patients with AIDS dementia complex

Brew, Bruce J.; Bhalla, Ravi; Paul, M.; Sidtis, John J.; Keilp, John J.; Sadler, Abigail E.; Gallardo, Humilidad F.; McArthur, Justin C.; Schwartz, Morton K.; Price, Richard W.

doi:10.1097/00002030-199205000-00004

Cited by 92 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CCL2 (MCP-1, monocyte chemokine protein 1) a CSF marker for HIV and SIV encephalitis (Cinque et al 1998; Kelder et al 1998; Mankowski et al 2004); CXCL10 (IP-10, interferon protein 10) likely the main chemokine for CSF lymphocytes (Cinque et al 2005); beta-2-microglobulin (β2M), component of the MHC-I complex increased in CSF in HAD (Brew et al 1992); TNFα (tumor necrosis factor alpha) also increased in the CSF in HAD (Mastroianni et al 1990; Nolting et al 2009); sCD14, the soluble LPS ligand increased in the CSF in HIV (Kamat et al 2012); sCD163, a macrophage chemokine increased in blood in HIV (Kamat et al 2012); sVCAM (soluble vascular adhesion molecule 1) mediates lymphocye and monocyte adhesion to vascular endothelium; MMP-9 (matrix metallopeptidase 9) and TIMP-1 (tissue inhibitor of metalloproteinases one) are involved in integrity of the extracellular matrix. T-tau (total tau) and p-tau (phosphorolated tau) are different states of the neuronal tau protein that are elevated in CSF in Alzheimer’s disease while amyloid beta 1–42 (Aβ1-42) is an amyloid cleavage product depressed in the CSF of Alzheimer’s disease (Blennow et al 2010); sAPPα, sAPPβ are soluble degradation products of the amyloid precursor protein that are reduced in CSF in HAD (Gisslen et al 2009)…”

Section: Disease Framework For Approaching Csf Biomarkersmentioning

confidence: 99%

Approach to Cerebrospinal Fluid (CSF) Biomarker Discovery and Evaluation in HIV Infection

Price

Peterson

Fuchs

et al. 2013

J Neuroimmune Pharmacol

Self Cite

View full text Add to dashboard Cite

Central nervous system (CNS) infection is a nearly universal facet of systemic HIV infection that varies in character and neurological consequences. While clinical staging and neuropsychological test performance have been helpful in evaluating patients, cerebrospinal fluid (CSF) biomarkers present a valuable and objective approach to more accurate diagnosis, assessment of treatment effects and understanding of evolving pathobiology. We review some lessons from our recent experience with CSF biomarker studies. We have used two approaches to biomarker analysis: targeted, hypothesis-driven and non-targeted exploratory discovery methods. We illustrate the first with data from a cross-sectional study of defined subject groups across the spectrum of systemic and CNS disease progression and the second with a longitudinal study of the CSF proteome in subjects initiating antiretroviral treatment. Both approaches can be useful and, indeed, complementary. The first is helpful in assessing known or hypothesized biomarkers while the second can identify novel biomarkers and point to broad interactions in pathogenesis. Common to both is the need for well-defined samples and subjects that span a spectrum of biological activity and biomarker concentrations. Previously-defined guide biomarkers of CNS infection, inflammation and neural injury are useful in categorizing samples for analysis and providing critical biological context for biomarker discovery studies. CSF biomarkers represent an underutilized but valuable approach to understanding the interactions of HIV and the CNS and to more objective diagnosis and assessment of disease activity. Both hypothesis-based and discovery methods can be useful in advancing the definition and use of these biomarkers.

show abstract

Section: Disease Framework For Approaching Csf Biomarkersmentioning

confidence: 99%

Approach to Cerebrospinal Fluid (CSF) Biomarker Discovery and Evaluation in HIV Infection

Price

Peterson

Fuchs

et al. 2013

J Neuroimmune Pharmacol

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, increases in these factors have either been subjected to limited investigation or have been correlated more with infection, stage of infection, or bloodbrain barrier dysfunction than with neurological disease, so their links to dementia are unclear. CSF factors that are indicative of HIV-associated dementia when elevated are: neopterin, ␤ 2 -microglobulin, prostaglandin E2, quinolinic acid, plateletactivating factor, and monocyte chemotactic protein-1 (MCP-1) (27)(28)(29)(30)(31). All are products of activated macrophages, which further highlights the role of macrophages in the pathogenesis of HIV-associated dementia.…”

Section: Immunologic Insights Into Hiv-associated Dementiamentioning

confidence: 96%

Cytokines in the brain during viral infection: clues to HIV-associated dementia.

Griffin

1997

J. Clin. Invest.

106

View full text Add to dashboard Cite

Immune responses induced by virus infections of the central nervous system Control of virus infection of the central nervous system (CNS) 1 is a complicated task for the host because of the potentially damaging consequences of immune responses in the brain and spinal cord. Neurological damage can be associated with cellular cytotoxicity, altered vascular permeability, and the influx of inflammatory cells into an enclosed space containing nonrenewable cells of vital importance to the host. Not surprisingly, therefore, the CNS has a number of mechanisms for controlling and regulating the development of local inflammatory processes. These include the blood-brain barrier, limited capability for antigen presentation, and functional modulation of immune reactions by gangliosides and astrocytes. The blood-brain barrier is composed of nonreactive endothelial cells linked by tight junctions, a basement membrane, and apposing astrocytic foot processes (see Licinio perspective, Fig. 1, in this issue of The Journal). This barrier effectively excludes most circulating soluble factors and circulating leukocytes from the parenchyma of the brain and spinal cord. In addition, cells within the CNS do not normally express class I or class II antigens of the MHC, which are necessary for recognition of antigens by T cells. However, T cells activated in the periphery do cross the blood-brain barrier and enter the CNS in an antigen-nonspecific manner as a part of routine immunologic surveillance. These activated T cells express the adhesion molecules and matrix metalloproteases necessary to traverse resting cerebral capillary endothelial cells and the basement membrane. Only T cells specific for an antigen present in the brain or spinal cord are retained within the CNS. Cells without such specificity leave within a few hours (1). Antigen-presenting cells which promote retention of specific lymphocytes within the CNS are most likely to be perivascular macrophages or microglial cells, both of which can quickly upregulate MHC antigen expression in response to stimulation.

show abstract

“…Plasma B2M levels are higher in ADC patients compared to non-ADC patients and serves as a risk factor for ADC progression (Sánchez-Portocarrero et al 1996 ; Stern et al 2001 ); however, it cannot independently predict neurological outcomes following HIV infection (Childs et al 1999 ). In contrast, B2M in the CSF was increased in ADC patients and has been proved to be a valuable indicator of ADC severity (Brew et al 1992 ). Interestingly, while non-ADC patients display a strong correlation between serum and CSF B2M levels, ADC patients show increased CSF B2M levels independently of their serum levels (McArthur et al 1992 ), suggesting that B2M production in ADC patients originates from the brain.…”

Section: Role Of B2m In Specific Cns Diseasesmentioning

confidence: 99%

The Role of Beta2-Microglobulin in Central Nervous System Disease

Liu,

Tang,

Yang

et al. 2024

Cell Mol Neurobiol

View full text Add to dashboard Cite

Central nervous system (CNS) disorders represent the leading cause of disability and the second leading cause of death worldwide, and impose a substantial economic burden on society. In recent years, emerging evidence has found that beta2 -microglobulin (B2M), a subunit of major histocompatibility complex class I (MHC-I) molecules, plays a crucial role in the development and progression in certain CNS diseases. On the one hand, intracellular B2M was abnormally upregulated in brain tumors and regulated tumor microenvironments and progression. On the other hand, soluble B2M was also elevated and involved in pathological stages in CNS diseases. Targeted B2M therapy has shown promising outcomes in specific CNS diseases. In this review, we provide a comprehensive summary and discussion of recent advances in understanding the pathological processes involving B2M in CNS diseases (e.g., Alzheimer's disease, aging, stroke, HIV-related dementia, glioma, and primary central nervous system lymphoma).

show abstract

Cerebrospinal fluid (β2-microglobulin in patients with AIDS dementia complex

Cited by 92 publications

References 0 publications

Approach to Cerebrospinal Fluid (CSF) Biomarker Discovery and Evaluation in HIV Infection

Approach to Cerebrospinal Fluid (CSF) Biomarker Discovery and Evaluation in HIV Infection

Cytokines in the brain during viral infection: clues to HIV-associated dementia.

The Role of Beta2-Microglobulin in Central Nervous System Disease

Contact Info

Product

Resources

About