RESEARCH - Relationship between elevated CSF levels of PAI-1 and neuronal destruction in neuropsychiatric SLE

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Arthritis Rheum. 2009 Jun 29;60(7):2094-2101.

Relationship between elevated cerebrospinal fluid levels of

plasminogen activator inhibitor 1 and neuronal destruction in patients

with neuropsychiatric systemic lupus erythematosus.

Kwieciński J, Kłak M, Trysberg E, Blennow K, Tarkowski A, Jin T.

Göteborg University and Sahlgrenska University Hospital, Göteborg, Sweden.

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.

PMID: 19565516

http://www.ncbi.nlm.nih.gov/pubmed/19565516

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