Evaluation of Cerebrospinal Fluid for the Presence of Anticardiolipin Antibodies (aCL) in NP-SLE Patients

Jędryka-Góral, Anna; Ząbek, Jakub; Wojciechowska, Bożena; Zaborski, Jacek; Chwalińska-Sadowska, H; Członkowska, Anna

doi:10.1007/s100670070051

Cited by 10 publications

(4 citation statements)

References 25 publications

(32 reference statements)

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“…Although the former possibility is viable when serum antibodies (originally directed towards peripheral antigens) are considered, our studies and clinical evidence (Lai and Lan, 2000) suggest that neuroactive antibodies are synthesized intrathecally. Similar to the present lack of discriminative value in the MRL model, in some clinical studies ACA could not be detected in the CSF of patients with NP-SLE, even when found in their sera (Jedryka-Goral et al, 2000). With respect to pro-inflammatory cytokines measured in the present study, we infer that they do not play a key role in cytotoxicity towards proliferating cells.…”

Section: Discussionsupporting

confidence: 81%

Proliferating brain cells are a target of neurotoxic CSF in systemic autoimmune disease

Šakić

Kirkham

Ballok

et al. 2005

Journal of Neuroimmunology

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Brain atrophy, neurologic and psychiatric (NP) manifestations are common complications in the systemic autoimmune disease, lupus erythematosus (SLE). Here we show that the cerebrospinal fluid (CSF) from autoimmune MRL-lpr mice and a deceased NP-SLE patient reduce the viability of brain cells which proliferate in vitro. This detrimental effect was accompanied by periventricular neurodegeneration in the brains of autoimmune mice and profound in vivo neurotoxicity when their CSF was administered to the CNS of a rat. Multiple ionic responses with microfluorometry and protein peaks on electropherograms suggest more than one mechanism of cellular demise. Similar to the CSF from diseased MRL-lpr mice, the CSF from a deceased SLE patient with a history of psychosis, memory impairment, and seizures, reduced viability of the C17.2 neural stem cell line. Proposed mechanisms of cytotoxicity involve binding of intrathecally synthesized IgG autoantibodies to target(s) common to different mammalian species and neuronal populations. More importantly, these results indicate that the viability of proliferative neural cells can be compromised in systemic autoimmune disease. Antibody-mediated lesions of germinal layers may impair the regenerative capacity of the brain in NP-SLE and possibly, brain development and function in some forms of CNS disorders in which autoimmune phenomena have been documented. AbbreviationsACA, anti-cardiolipin antibodiesx; Abbreviations, anti-nuclear antibodies; CSF, cerebrospinal fluid; FJB, Fluoro Jade B stain; NP-SLE, neuropsychiatric systemic lupus erythematosus; PBS, phosphate buffered saline

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Section: Discussionsupporting

confidence: 81%

Proliferating brain cells are a target of neurotoxic CSF in systemic autoimmune disease

Šakić

Kirkham

Ballok

et al. 2005

Journal of Neuroimmunology

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“…A stronger association between aPL and neurological disorders might be easier to establish if aPL are sought and detected in the cerebral spinal fluid (CSF) of patients experiencing neurologic symptoms. Historically, scarce reports of aPL in CSF are limited mostly to IgG and IgM anticardiolipin (aCL) detection (Marchiorri, 1990;Lolli et al, 1991;Wang et al, 1992;Gallo et al, 1994;Yeh et al, 1994;Martinez-Cordero, 1997;Jedryka-Goral et al, 2000;Lai and Lan, 2000;Baraczka et al, 2002). Rarely are IgA aCL sought (Wang et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Testing for Antiphospholipid Antibody (aPL) Specificities in Retrospective “Normal” Cerebral Spinal Fluid (CSF)

Sokol

Wagenknecht

McIntyre

2004

Journal of Immunology Research

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Antiphospholipid antibodies (aPL) have been found in the blood of patients with systemic and neurological disease. The rare reports of aPL in cerebral spinal fluid (CSF) have been limited mostly to IgG and IgM anticardiolipin (aCL). Our published finding of IgA aPE in the CSF of a young stroke victim prompted us to establish "normal" CSF aPL values for a panel of aPL, which included aCL, antiphosphatidylserine (aPS), antiphosphatidylethanolamine (aPE) and antiphosphatidylcholine (aPC). CSF samples were tested by ELISA for IgG, IgM and IgA aPL. In addition, the CSF samples were tested for activity in the presence and absence of phospholipid (PL) binding plasma-proteins. A total of 24 data points were obtained for each CSF sample. We tested 59 CSF samples obtained from 59 patients who were undergoing evaluation for systemic or neurologic diseases. All CSF samples had normal protein, glucose and cell counts. Ten of the 59 CSF samples (17%) had elevated aPL optical density (OD) values an order of magnitude higher than the other 49 CSF samples for one or more aPL specificity and/or isotype. One CSF sample had both PL-binding protein dependent and independent IgG aPE activity. Another CSF sample showed both IgG aPE and aPC reactivity. The remaining eight CSF samples showed single aPL findings; IgG aPE (5), IgG aPC (1), IgG aCL (1) and IgM aPC (1). Seven of 10 patients with elevated CSF values were females. As expected, most "normal" aPL OD values were substantially lower in CSF than those we have reported in blood samples from volunteer blood donors. Jacobson et al., 1999). The associations of aPL with neurologic conditions other than thromboocclusive events have been considered "weak" and attributable to an "epiphenomenon" rather than to pathophysiologic mechanisms (Brey, 2000). A stronger association between aPL and neurological disorders might be easier to establish if aPL are sought and detected in the cerebral spinal fluid (CSF) of patients experiencing neurologic symptoms. Historically, scarce reports of aPL in CSF are limited mostly to IgG and IgM anticardiolipin (aCL) detection (Marchiorri, 1990;Lolli et al., 1991;Wang et al., 1992;Gallo et al., 1994;Yeh et al., 1994;Martinez-Cordero, 1997;Jedryka-Goral et al., 2000;Lai and Lan, 2000;Baraczka et al., 2002). Rarely are IgA aCL sought (Wang et al., 1992). To our knowledge only one report included testing for IgG and IgM antiphosphatidylserine (aPS) and antiphosphatidylethanolamine (aPE) in CSF; the results were negative (Gallo et al., 1994). Our finding of IgA aPE in the CSF of a young stroke victim (Sokol et al., 2000), together with our intent to continue testing additional CSF samples, prompted us to undertake and establish "normal" aPL values for CSF. Our findings form the basis of this report. PATIENTS AND METHODSBecause of the potential risks associated with spinal taps to healthy individuals we were unable to obtain CSF samples from random donors. We opted to perform a retrospective analysis using residual CSF that was collected for diagnostic purposes a...

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“…For a long time, the leakage of the BBB was believed to be the only mechanism allowing peripheral autoantibodies to enter the brain parenchyma and start an immune response to neuronal components. Goral and colleagues studying patients affected by NPSLE have discovered that the presence of aCL, commonly associated with thrombosis risk in patients with SLE [ 63 ], is not associated with BBB disruption or intrathecal antibody production [ 64 ]. These results suggest that the disruption of BBB is not due to prothrombotic events, but rather it is related to the overexpression of proinflammatory cytokines promoting the infiltration of leukocytes within the CNS (Fig.…”

Section: Neuropsychiatric Systemic Lupus Erythematosusmentioning

confidence: 99%

Autoantibodies in Neuropsychiatric Systemic Lupus Erythematosus (NPSLE): Can They Be Used as Biomarkers for the Differential Diagnosis of This Disease?

Manca

2021

Clinic Rev Allerg Immunol

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Systemic lupus erythematosus is a complex immunological disease where both environmental factors and genetic predisposition lead to the dysregulation of important immune mechanisms. Eventually, the combination of these factors leads to the production of self-reactive antibodies that can target any organ or tissue of the human body. Autoantibodies can form immune complexes responsible for both the organ damage and the most severe complications. Involvement of the central nervous system defines a subcategory of the disease, generally known with the denomination of neuropsychiatric systemic lupus erythematosus. Neuropsychiatric symptoms can range from relatively mild manifestations, such as headache, to more severe complications, such as psychosis. The evaluation of the presence of the autoantibodies in the serum of these patients is the most helpful diagnostic tool for the assessment of the disease. The scientific progresses achieved in the last decades helped researchers and physicians to discover some of autoepitopes targeted by the autoantibodies, although the majority of them have not been identified yet. Additionally, the central nervous system is full of epitopes that cannot be found elsewhere in the human body, for this reason, autoantibodies that selectively target these epitopes might be used for the differential diagnosis between patients with and without the neuropsychiatric symptoms. In this review, the most relevant data is reported with regard to mechanisms implicated in the production of autoantibodies and the most important autoantibodies found among patients with systemic lupus erythematosus with and without the neuropsychiatric manifestations.

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Evaluation of Cerebrospinal Fluid for the Presence of Anticardiolipin Antibodies (aCL) in NP-SLE Patients

Cited by 10 publications

References 25 publications

Proliferating brain cells are a target of neurotoxic CSF in systemic autoimmune disease

Proliferating brain cells are a target of neurotoxic CSF in systemic autoimmune disease

Testing for Antiphospholipid Antibody (aPL) Specificities in Retrospective “Normal” Cerebral Spinal Fluid (CSF)

Autoantibodies in Neuropsychiatric Systemic Lupus Erythematosus (NPSLE): Can They Be Used as Biomarkers for the Differential Diagnosis of This Disease?

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