Relationship between elevated cerebrospinal fluid levels of plasminogen activator inhibitor 1 and neuronal destruction in patients with neuropsychiatric systemic lupus erythematosus

Authors

  • Jakub Kwieciński,

    1. Göteborg University and Sahlgrenska University Hospital, Göteborg, Sweden
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    • Mr. Kwieciński, Mr. Kłak, and Dr. Trysberg contributed equally to this work.

  • Marcin Kłak,

    1. Göteborg University and Sahlgrenska University Hospital, Göteborg, Sweden
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    • Mr. Kwieciński, Mr. Kłak, and Dr. Trysberg contributed equally to this work.

  • Estelle Trysberg,

    1. Karolinska University Hospital, Huddinge, Sweden
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    • Mr. Kwieciński, Mr. Kłak, and Dr. Trysberg contributed equally to this work.

    • Dr. Trysberg has received consulting fees and speaking fees from Roche (less than $10,000).

  • Kaj Blennow,

    1. Göteborg University and Sahlgrenska University Hospital, Göteborg, Sweden
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  • Andrej Tarkowski,

    1. Göteborg University and Sahlgrenska University Hospital, Göteborg, Sweden
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    • Dr. Tarkowski is deceased.

  • Tao Jin

    Corresponding author
    1. Göteborg University and Sahlgrenska University Hospital, Göteborg, Sweden
    • Department of Rheumatology and Inflammation Research, Göteborg University, Guldhedsgatan 10, S-413 46 Göteborg, Sweden
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Abstract

Objective

A homeostatic imbalance between coagulation and fibrinolysis might occur intrathecally in neuropsychiatric systemic lupus erythematosus (NPSLE). However, there are no published data on levels of fibrinolytic factors in the cerebrospinal fluid (CSF) of patients with NPSLE. The present study was undertaken to assess CSF levels of fibrinolytic molecules, including urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA), D-dimer, and plasminogen activator inhibitor 1 (PAI-1), in SLE patients with clinically verified neuropsychiatric involvement and to compare these levels with those in SLE patients without neuropsychiatric involvement and in healthy subjects.

Methods

Levels of uPA, tPA, and PAI-1 were assessed in CSF from 94 patients with SLE (33 who had NPSLE, 56 who did not have NPSLE, and 5 who were positive for antiphospholipid antibody [not included in the NPSLE or non-NPSLE group]) and from 53 age-matched controls. Patients were evaluated clinically, with magnetic resonance imaging of the brain, analyses of neuronal/glial degradation products in CSF, and neuropsychiatric testing.

Results

In the group of patients with NPSLE, intrathecal PAI-1 levels were significantly elevated compared with levels in SLE patients without overt neuropsychiatric involvement (P < 0.05) and in healthy controls (P < 0.001). In contrast, intrathecal levels of uPA did not differ significantly. Intrathecal levels of PAI-1 correlated significantly with CSF levels of interleukin-6 (IL-6) (r = 0.34, P < 0.001) and IL-8 (r = 0.33, P < 0.001). Importantly, increased PAI-1 and D-dimer levels were observed in SLE patients who had pathologically elevated levels of glial fibrillary acidic protein, neurofilament triplet protein, and tau protein in CSF.

Conclusion

Intrathecal release of PAI-1 is increased in patients with NPSLE. This results in impaired fibrinolysis, which might contribute to neuronal and astrocytic damage in NPSLE.

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