Intrathecal synthesis of anti‐HIV IgG

Wielink, Gina; McArthur, Justin C.; Moench, Thomas R.; Farzadegan, Homayoon; McArthur, Justin; Johnson, Richard T.; Saah, A. J.

doi:10.1212/wnl.40.5.816

Cited by 20 publications

(3 citation statements)

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“…However, the observed increase in CSF B cells with HIV-infection was considerably less than previously reported for other inflammatory diseases such as multiple sclerosis and neuromyelitis optica, [8], [18], [19], [34], [35] or CNS infection, such as Lyme disease or neurosyphilis [36], [37]. The presence of IgG in the CSF of a majority of HIV-infected individuals [38] suggests that local B cell immune responses occur in response to HIV infection of the CNS. Thus, the changes we observed in response to HIV-infection and treatment may reflect a B cell response to intrathecal HIV replication.…”

Section: Discussionmentioning

confidence: 58%

Cellular Composition of Cerebrospinal Fluid in HIV-1 Infected and Uninfected Subjects

Ronquillo

Altmeppen

et al. 2013

PLoS ONE

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In order to characterize the cellular composition of cerebrospinal fluid (CSF) in a healthy state and in the setting of chronic pleocytosis associated with HIV-1 (HIV) infection, multi-parameter flow cytometry was used to identify and quantitate cellular phenotypes in CSF derived from HIV-uninfected healthy controls and HIV-infected subjects across a spectrum of disease and treatment. CD4+ T cells were the most frequent CSF population and the CD4:CD8 ratio was significantly increased in the CSF compared to blood (p = 0.0232), suggesting preferential trafficking of CD4+ over CD8+ T cells to this compartment. In contrast, in HIV-infection, CD8+ T cells were the major cellular component of the CSF and were markedly increased compared to HIV-uninfected subjects (p<0.001). As with peripheral blood, the CSF CD4:CD8 ratio was reversed in HIV-infected subjects compared to HIV-uninfected subjects. Monocytes, B cells and NK cells were rare in the CSF in both groups, although absolute counts of CSF NK cells and B cells were significantly increased in HIV-infected subjects (p<0.05). Our studies show that T cells are the major cellular component of the CSF in HIV-infected and uninfected subjects. The CSF pleocytosis characteristic of HIV infection involves all lymphocyte subsets we measured, except for CD4+ T cells, but is comprised primarily of CD8+ T cells. The reduced proportion of CD4+ T cells in the CSF may reflect both HIV-related peripheral loss and changes in trafficking patterns in response to HIV infection in the central nervous system.

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Section: Discussionmentioning

confidence: 58%

Cellular Composition of Cerebrospinal Fluid in HIV-1 Infected and Uninfected Subjects

Ronquillo

Altmeppen

et al. 2013

PLoS ONE

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“…However, even if the median IgG index is normal in cohorts, the proportion of naïve patients with an abnormal IgG index is about 56% (Abdulle et al, 2005). The IgG index is globally stable (Elovaara et al, 1993b) or slowly increases in three stages: at less than one year, the mean IgG index is mainly normal, at 1-3 years, it increases to 1.05, and at more than 3 years it reaches 1.16 (Andersson et al, 1988;Marshall et al, 1989;Van Wielink et al, 1990). A possible decrease or reversion of intrathecal secretion may occur during late profound immunosuppression (Elovaara et al, 1987;Marshall et al, 1988;Singer et al, 1994;Gisslen et al, 1999a), unless patients are neurologically symptomatic (Elovaara et al, 1988).…”

Section: Intrathecal Igg Synthesismentioning

confidence: 98%

“…From an historical point of view, the possibility of a coexistent intrathecal synthesis against a non-disease-relevant virus like measles has been considered so unlikely that older papers either excluded such patients or inappropriately used the ratio IgG CSF /IgG serum against measles to normalize data for passive diffusion (Lloyd et al, 1988;Mathiesen et al, 1988a;Van Wielink et al, 1990). Moreover, AIDS is characterized by a profound immune suppression impeding or even abolishing the capacity to develop an immune reaction against opportunistic infections.…”

Section: Non-hiv-related Intrathecal Igg Synthesismentioning

confidence: 99%

Compartmentalized intrathecal immunoglobulin synthesis during HIV infection — A model of chronic CNS inflammation?

Bonnan¹,

Barroso²,

Demasles³

et al. 2015

Journal of Neuroimmunology

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HIV infects the central nervous system (CNS) during primary infection and persists in resident macrophages. CNS infection initiates a strong local immune response that fails to control the virus but is responsible for by-stander lesions involved in neurocognitive disorders. Although highly active anti-retroviral therapy now offers an almost complete control of CNS viral proliferation, low-grade CNS inflammation persists. This review focuses on HIV-induced intrathecal immunoglobulin (Ig) synthesis. Intrathecal Ig synthesis early occurs in more than three-quarters of patients in response to viral infection of the CNS and persists throughout the course of the disease. Viral antigens are targeted but this specific response accounts for <5% of the whole intrathecal synthesis. Although the nature and mechanisms leading to non-specific synthesis are unknown, this prominent proportion is comparable to that observed in various CNS viral infections. Cerebrospinal fluid-floating antibody-secreting cells account for a minority of the whole synthesis, which mainly takes place in perivascular inflammatory infiltrates of the CNS parenchyma. B-cell traffic and lineage across the blood-brain-barrier have not yet been described. We review common technical pitfalls and update the pending questions in the field. Moreover, since HIV infection is associated with an intrathecal chronic oligoclonal (and mostly non-specific) Ig synthesis and associates with low-grade axonal lesions, this could be an interesting model of the chronic intrathecal synthesis occurring during multiple sclerosis.

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Viral load determines the B‐cell response in the cerebrospinal fluid during human immunodeficiency virus infection

Cepok

Geldern

Nolting

et al. 2007

Annals of Neurology

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Intrathecal synthesis of anti‐HIV IgG

Cited by 20 publications

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Cellular Composition of Cerebrospinal Fluid in HIV-1 Infected and Uninfected Subjects

Cellular Composition of Cerebrospinal Fluid in HIV-1 Infected and Uninfected Subjects

Compartmentalized intrathecal immunoglobulin synthesis during HIV infection — A model of chronic CNS inflammation?

Viral load determines the B‐cell response in the cerebrospinal fluid during human immunodeficiency virus infection

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