Binding Sites for Immune Components in Human Choroid Plexus

Peress, Nancy S.; Roxburgh, Vivian A.; Gelfand, Michael

doi:10.1002/art.1780240312

Cited by 45 publications

(11 citation statements)

References 21 publications

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“…Similarly, clinical reports point to the possibility that the choroid plexus is a site for immune complex and leukocyte deposition (Atkins et al, 1972;Gershwin et al, 1975;Peress et al, 1981;Duprez et al, 2001). In the present study, we provide a direct comparison of animal and human brain pathology by using the same protocols and reagents for FJB staining.…”

Section: Discussionmentioning

confidence: 95%

Hippocampal damage in mouse and human forms of systemic autoimmune disease

Ballok¹,

Woulfe

Sur

et al. 2004

Hippocampus

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Systemic lupus erythematosus (SLE) is frequently accompanied by neuropsychiatric (NP) and cognitive deficits of unknown etiology. By using autoimmune MRL-lpr mice as an animal model of NP-SLE, we examine the relationship between autoimmunity, hippocampal damage, and behavioral dysfunction. Fluoro Jade B (FJB) staining and anti-ubiquitin (anti-Ub) immunocytochemistry were used to assess neuronal damage in young (asymptomatic) and aged (diseased) mice, while spontaneous alternation behavior (SAB) was used to estimate the severity of hippocampal dysfunction. The causal relationship between autoimmunity and neuropathology was tested by prolonged administration of the immunosuppressive drug cyclophosphamide (CY). In comparison to congenic MRL +/+ controls, SAB acquisition rates and performance in the "reversal" trial were impaired in diseased MRL-lpr mice, suggesting limited use of the spatial learning strategy. FJBpositive neurons and anti-Ub particles were frequent in the CA3 region. Conversely, CY treatment attenuated the SAB deficit and overall FJB staining. Similarly to mouse brain, the hippocampus from a patient who died from NP-SLE showed reduced neuronal density in the CA3 region and dentate gyrus, as well as increased FJB positivity in these regions. Gliosis and neuronal loss were observed in the gray matter, and T lymphocytes and stromal calcifications were common in the choroid plexus. Taken together, these results suggest that systemic autoimmunity induces significant hippocampal damage, which may underlie affective and cognitive deficits in NP-SLE.

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Section: Discussionmentioning

confidence: 95%

Hippocampal damage in mouse and human forms of systemic autoimmune disease

Ballok¹,

Woulfe

Sur

et al. 2004

Hippocampus

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“…These pathogenic autoantibodies are a prelude to immune complex disease, a common feature of lupus (Peress et al, 1981). Indeed, deposition of antigen-antibody complexes (immune aggregates) in choroidal blood vessels have been associated with neuropsychiatric dysfunction, and vascular deposits within the choroid plexus (CP) are accompanied by histopathologic evidence of inflammation (Schwartz and Roberts, 1983).…”

Section: Prelude To Cns Damage: Disruption Of the Blood-brain Barriermentioning

confidence: 99%

Neuroimmunopathology in a murine model of neuropsychiatric lupus

Ballok

2007

Brain Research Reviews

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Animal models are extremely useful tools in defining pathogenesis and treatment of human disease. For many years researchers believed that structural damage to the brain of neuropsychiatric (NP) patients lead to abnormal mental function, but this possibility was not extensively explored until recently. Imaging studies of NP-systemic lupus erythematosus (SLE) support the notion that brain cell death accounts for the emergence of neurologic and psychiatric symptoms, and evidence suggests that it is an autoimmunity-induced brain disorder characterized by profound metabolic alterations and progressive neuronal loss. While there are a number of murine models of SLE, this article reviews recent literature on the immunological connections to neurodegeneration and behavioral dysfunction in the Fas-deficient MRL model of NP-SLE. Probable links between spontaneous peripheral immune activation, the subsequent central autoimmune/inflammatory responses in MRL/MpJ-Tnfrsf6 lpr (MRL-lpr) mice and the sequential mode of events leading to Fas-independent neurodegenerative autoimmune-induced encephalitis will be reviewed. The role of hormones, alternative mechanisms of cell death, the impact of central dopaminergic degeneration on behavior, and germinal layer lesions on developmental/regenerative capacity of MRL-lpr brains will also be explored. This model can provide direction for future therapeutic interventions in patients with this complex neuroimmunological syndrome.

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“…TOXICOLOGIC PATHOLOGY predilection for vascular/perivascular IC deposition in human SLE patients, newborn Finnish-Landrace lambs with mesangiocapillary GN (interstitial IgG, IgM granular deposits), and New Zealand mice, and BSA-injected rabbits with acute ICD/serum sickness (Gardiner 1976;Harbeck et al 1979). FcgR for IgG- coated sheep erythrocytes have been described in human, rabbit, and monkey choroid plexus (Braathen et al 1979;Peress, Roxburgh, and Gelfand 1981).…”

Section: Localized Drug-ada Ic Formation and Localized Deposition In mentioning

confidence: 99%

Formation, Clearance, Deposition, Pathogenicity, and Identification of Biopharmaceutical-related Immune Complexes

et al. 2014

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Vascular inflammation, infusion reactions, glomerulopathies, and other potentially adverse effects may be observed in laboratory animals, including monkeys, on toxicity studies of therapeutic monoclonal antibodies and recombinant human protein drugs. Histopathologic and immunohistochemical (IHC) evaluation suggests these effects may be mediated by deposition of immune complexes (ICs) containing the drug, endogenous immunoglobulin, and/or complement components in the affected tissues. ICs may be observed in glomerulus, blood vessels, synovium, lung, liver, skin, eye, choroid plexus, or other tissues or bound to neutrophils, monocytes/macrophages, or platelets. IC deposition may activate complement, kinin, and/or coagulation/fibrinolytic pathways and result in a systemic proinflammatory response. IC clearance is biphasic in humans and monkeys (first from plasma to liver and/or spleen, second from liver or spleen). IC deposition/clearance is affected by IC composition, immunomodulation, and/or complement activation. Case studies are presented from toxicity study monkeys or rats and indicate IHC-IC deposition patterns similar to those predicted by experimental studies of IC-mediated reactions to heterologous protein administration to monkeys and other species. The IHC-staining patterns are consistent with findings associated with generalized and localized IC-associated pathology in humans. However, manifestations of immunogenicity in preclinical species are generally not considered predictive to humans.

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Binding Sites for Immune Components in Human Choroid Plexus

Cited by 45 publications

References 21 publications

Hippocampal damage in mouse and human forms of systemic autoimmune disease

Hippocampal damage in mouse and human forms of systemic autoimmune disease

Neuroimmunopathology in a murine model of neuropsychiatric lupus

Formation, Clearance, Deposition, Pathogenicity, and Identification of Biopharmaceutical-related Immune Complexes

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