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

Abstract

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...

Redox‐Reactive Autoantibodies in Cerebrospinal Fluids

“…Previous data 7 have shown that CSF from a normal adult male was observed to be within normal aPL limits, the latter defined by our earlier studies of 59 surgical‐excess CSF samples 18 . After 20 h exposure to hemin, however, we observed a significant redox unmasking in his CSF aPL reactivity, which was greatest for aCL, intermediate for aPS and aPE, and borderline for aPC.…”