Anti-Tr antibodies as markers of paraneoplastic cerebellar degeneration and Hodgkin's disease.
BACKGROUND
Preliminary studies suggested that anti-Tr antibodies identify patients with paraneoplastic cerebellar degeneration (PCD) and Hodgkin disease (HD).


OBJECTIVE
To extend the clinical-immunologic analysis to 28 patients with anti-Tr antibodies.


METHODS
Anti-Tr antibodies were detected by immunohistochemistry. A competitive inhibition assay was used to ascertain if anti-Tr antibodies of different sera identify common epitopes. Anti-Tr immunoglobulin G (IgG) subclass distribution was determined by immunohistochemistry using monoclonal antibodies against human IgG isotypes. Tr immunoreactivity was analyzed in tumor sections using biotinylated anti-Tr IgG.


RESULTS
Median age of the 28 patients was 61 years (range 14 to 75 years) and 22 were male. A cerebellar syndrome was present in 27 patients and a possible limbic encephalitis in one. HD was diagnosed in 25 patients. No tumor was found in three patients; the autopsy of one of them disclosed severe loss of Purkinje cells without inflammatory infiltrates. Anti-Tr antibodies spontaneously disappeared in all patients without tumor and in 10/10 patients after successful HD treatment. Anti-Tr antibodies were absent in the serum but positive in the CSF of two patients. All positive anti-Tr sera inhibited the immunoreactivity of biotinylated anti-Tr IgG. The predominant isotypes of anti-Tr were IgG1 and IgG3. Only 1 out of the 15 HD samples studied presented anti-Tr positivity that was localized in some Reed-Sternberg cells.


CONCLUSIONS
This study confirms the strong association between anti-Tr antibodies and PCD associated with HD. Anti-Tr antibodies from different patients recognize similar epitopes. Unlike other antineuronal antibodies, anti-Tr antibodies can be detected in the CSF but not in the serum and may spontaneously disappear during the follow-up, and Tr immunoreactivity is usually lacking in the tumor.
Bernal
F
F
Service of Neurology and Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Spain.
Shams'ili
S
S
Rojas
I
I
Sanchez-Valle
R
R
Saiz
A
A
Dalmau
J
J
Honnorat
J
J
Sillevis Smitt
P
P
Graus
F
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000096:biosynthesis; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D005260:Female; D006689:Hodgkin Disease / Q000150:complications* / Q000175:diagnosis* / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020362:Paraneoplastic Cerebellar Degeneration / Q000150:complications* / Q000175:diagnosis* / Q000276:immunology; D011237:Predictive Value of Tests; D011689:Purkinje Cells / Q000276:immunology / Q000473:pathology; D051381:Rats; D016539:Reed-Sternberg Cells / Q000276:immunology / Q000473:pathology; D012074:Remission Induction
D015703:Antigens, CD; D001323:Autoantibodies; D015415:Biomarkers