Ma1, a novel neuron- and testis-specific protein, is recognized by the serum of patients with paraneoplastic neurological disorders

The identification of antineuronal antibodies has facilitated the diagnosis of paraneoplastic neurological disorders and the early detection of the as sociated tumours, It has also led to the cloning of possibly important neur on-specific proteins, In this study we wanted to identify novel antineurona l antibodies in the sera of patients with paraneoplastic neurological disor ders and to clone the corresponding antigens, Serological studies of 1705 s era from patients with suspected paraneoplastic neurological disorders resu lted in the identification of four patients with antibodies that reacted wi th 37 and 40 kDa neuronal proteins (anti-Ma antibodies), Three patients had brainstem and cerebellar dysfunction, and one had dysphagia and motor weak ness, Autopsy of two patients showed loss of Purkinje cells, Bergmann glios is and deep cerebellar white matter inflammatory infiltrates, Extensive neu ronal degeneration, gliosis and infiltrates mainly composed of CD8(+) T cel ls were also found in the brainstem 'of one patient, In normal human and ra t tissues, the anti-Ma antibodies reacted exclusively with neurons and with testicular germ cells; the reaction was mainly with subnuclear elements (i ncluding the nucleoli) and to a lesser degree the cytoplasm, Anti-Ma antibo dies also reacted with the cancers (breast, colon and parotid) available fr om three anti-Ma patients, but not with 66 other tumours of varying histolo gical types, Preincubation of tissues with any of the anti-Ma sera abrogate d the reactivity of the other anti-Ma immunoglobulins. Probing of a human c omplementary DNA library with anti-Ma serum resulted in the cloning of a ge ne that encodes a novel 37 kDa protein (Mal), Recombinant Mal was specifica lly recognized by the four anti-Ma sera but not by 337 control sera, includ ing those from 52 normal individuals, 179 cancer patients without paraneopl astic neurological symptoms, 96 patients with paraneoplastic syndromes and 10 patients with non-cancer-related neurological disorders, The expression of Mal mRNA is highly restricted to the brain and testis, Subsequent analys is suggested that Mal is likely to be a phosphoprotein, Our study demonstra tes that some patients with paraneoplastic neurological disorders develop a ntibodies against Ma1, a new member of an expanding family of 'brain/testis ' proteins.