Localization of the neuronal antigen recognized by anti-Tr antibodies from patients with paraneoplastic cerebellar degeneration and Hodgkin's disease in the rat nervous system

Abstract

Patients with paraneoplastic cerebellar degeneration and Hodgkin's disease develop autoantibodies (Tr-Ab) that immunoreact with the cytoplasm of the Purkinje cells and produce a characteristic punctate pattern in the molecular layer of the cerebellum. In the present study, we analyzed the structures of the adult rat cerebellar cortex identified by Tr-Ab and the expression of the antigen recognized by Tr-Ab in the developing rat brain. By laser confocal microscopy and immunoelectron microscopy, Tr-Ab immunoreactivity was found localized in the cytosol and outer surface of the endoplasmic reticulum of the perikarya of neurons of the molecular layer and the cell body and dendrites of Purkinje cells without a particular concentration in dendritic spines. Tr-Ab reactivity was more widespread in the developing rat brain. Tr-Ab labeling of Purkinje cells was already observed at P0 (day of birth). The staining of the molecular layer followed the development of the dendritic tree. The internal and inner level of the external granule cell layer were labeled with Tr-Ab with a dotted pattern that became almost negative by the 2nd postnatal week. The staining probably corresponded to granule cells as suggested by the positive Tr-Ab labeling of cultures of embryonic granule neurons. The present findings suggest that the antigen recognized by Tr-Ab appears early and is widely expressed in the developing rat brain. In the adult cerebellum, the antigen is localized in the cell body and dendrites of the Purkinje cells but is not concentrated in the dendritic spines.

Adapting a transforming growth factor β–related tumor protection strategy to enhance antitumor immunity

“…23,48,54 Hodgkin cells also secrete the chemokine TARC, which specifically recruits IL-4-secreting Th2 cells, and a Th2 growth factor, IL-13. [55][56][57][58] Both favor the creation of a noncytotoxic Th2 environment. Although this is a daunting list of evasion mechanisms, their very profligacy argues that multiple defenses are required to protect the tumor cells from attack.…”

Paraneoplastic cerebellar degeneration associated with antineuronal antibodies: analysis of 50 patients

“…All positive sera were con®rmed by western blotting, using rat cerebellar extract (Moll et al, 1993;Honnorat et al, 1998) and puri®ed recombinant HuD, CDR62, amphiphysin and NOVA-1 antigens (Fathallah-Shaykh et al, 1991;Buckanovich et al, 1993;De Camilli et al, 1993;Manley et al, 1995). Anti-Tr was diagnosed by strict immunohistochemical criteria when Purkinje cell cytoplasmic staining was combined with a characteristic punctuated staining of Purkinje cell dendrites (Graus et al, 1998). Anti-mGluR1 was con®rmed by reactivity with mGluR1-expressing Chinese hamster ovary (CHO) cells (Sillevis Smitt et al, 2000).…”

New Purkinje cell antibody (PCA-2): Marker of lung cancer-related neurological autoimmunity

“…9,10 The most common presentations of ANNA-1-positive patients are subacute sensory neuronopathy, encephalomyeloneuropathy, or gastrointestinal dysmotility. 3,5,11 Less common neuronal cytoplasmic and nuclear autoantibody specificities have been reported, [12][13][14][15][16][17][18][19][20] and a minority of patients with paraneoplastic neurological disorders have no currently recognized autoantibody markers. The earliest described Purkinje cell cytoplasmic antibody specificity is associated with Hodgkin's lymphoma.…”