Identification of histidine-rich glycoprotein, a potential autoantigen, in human and rat brain preparations

Beta(2)-glycoprotein-I (beta(2)-GPI, also known as apolipoprotein H) is a major autoantigen in the antiphospholipid syndrome (APS), a disease commonly affecting the central nervous system. We examined whether beta2-GPI and similar proteins exist in rat and human brains. No expression was found on Northern blot analysis of human brain. Utilizing a standard procedure for the isolation of serum beta2-GPI we purified a 100 kD human brain protein, which was found by peptide sequencing to have full homology with the serum protein, histidine-rich glycoprotein (HRGP). Expression of HRGP in rat and human brain was established by RT-PCR studies and a partial sequence of rat brain HRGP was obtained showing 68% homology with the human protein. IgG from most APS patients bound to HRGP, which shares distinct biochemical properties with beta2-GPI, is present in the brain and may be an important autoantigen.