Measurement of Glial Fibrillary Acidic Protein in Human Blood: Analytical Method and Preliminary Clinical Results

Abstract

Glial fibrillary acidic protein (GFAP), found only in glial cells of the central nervous system (CNS) (1)(2), was first isolated by Eng et al. (1) in 1971. GFAP is a monomeric molecule with a molecular mass between 40 and 53 kDa (3)(4) and an isoelectric point between 5.7 and 5.8 (2). GFAP represents the major part of the cytoskeleton of astrocytes. DeArmond et al. (5) reported on the spontaneous degradation of GFAP in vitro and in vivo; under physiological conditions, GFAP polymerizes spontaneously to astrofibrils with a length of 0.8–1.06 μm. Numerous reports in the literature document the usefulness of measuring GFAP in cerebrospinal fluid (CSF) as a specific indicator of CNS pathology (6)(7)(8)(9)(10)(11)(12)(13). Measuring GFAP in blood would have clinical advantages over CSF measurements; however, to our knowledge, the only method attempted to date to measure GFAP in blood (14) was not successful. We describe the results of measuring the concentrations of both GFAP and S-100 protein in the blood of patients with acute severe head trauma and healthy controls, using the dissociation-enhanced lanthanide fluorescence immunoassay (DELFIA) system for detection of GFAP (DELFIA can also be used to measure the concentration of GFAP in CSF). Blood samples were obtained from 25 patients (19 males and 6 females; ages, 16–72 years; mean age, 38.6 ± 19.0 years) who were admitted <24 h after severe head trauma (a Glasgow Coma Scale score of ≤6 on admission). Three samples were obtained from each patient: the first sample was obtained on admission to the hospital, the second was obtained 24 h after the head injury, and the third was obtained 48 h after the injury. Blood samples were also obtained from 70 healthy blood donors …