TYPE-IIA (ANTI-HU) ANTINEURONAL ANTIBODIES PRODUCE DESTRUCTION OF RATCEREBELLAR GRANULE NEURONS IN-VITRO

We reacted dispersed cultures of newborn rat cerebellar granule cells with serum, purified IgG, and CSF from patients with type IIa (''anti- Hu'') antibody response accompanying paraneoplastic neurologic syndrom es. All type Ila sera, IgGs, and CSFs, but not those of normal or canc er controls, produced bright nuclear immunofluorescence of cultured gr anule neurons. Type IIa serum and CSF labeled proteins of 35-42 kd in rat granule cell blots, identical in molecular weight to proteins labe led by type IIa antibodies in blots of human granule cells. IgGs elute d from the 35-42 kd band in blots of rat granule cells labeled protein s of similar molecular weights in blots of human granule cells and pro duced typical type IIa immunostaining of human cerebellar sections. Hu man IgG could be identified in nuclei and cytoplasm of neurons incubat ed for 72 hours with 2/4 type IIa sera tested, but not with normal ser a. Type IIa sera or IgGs from 4/7 patients produced specific lysis of rat granule cells in the presence of complement, as compared with cont rols using normal serum or heat-inactivated complement. Prolonged (7-d ay) incubation of cultures with type Ila antibody without complement a lso resulted in specific lysis, whereas incubation with normal serum o r serum from neurologically normal patients with small-cell carcinoma of the lung did not. Rat granule cell cultures provide a valuable in v itro system with which to study the interaction of type IIa antibody w ith neurons. The present study provides the first reported evidence th at type IIa antibodies may cause cell injury directly, in the absence of lymphocyte-mediated immune response.