B-111 Parallel Detection of Antibodies Against CDR2L and CDR2 Increases the Diagnostic Specificity in Serological Diagnostics of Paraneoplastic Cerebellar Degeneration

Background Onconeuronal anti-Yo antibodies are key diagnostic markers for paraneoplastic cerebellar degeneration (PCD) and often associated with gynaecologic/breast cancer. Cerebellar degeneration-related protein 2-like (CDR2L), but not cerebellar degeneration-related protein 2 (CDR2), has recently been shown to be the major anti-Yo target (1, 2). This study investigated if inclusion of CDR2L in diagnostic tests results in increased specificity for PCD. Methods Three panels were examined for reactivity against CDR2L and CDR2 by line blot analysis (EUROLINE). Panel A comprised 14 preselected sera from women with Yo-specific reactivity by indirect immunofluorescence assay (IFA) on rat cerebellum, presenting with cerebellar ataxia (n = 13) or peripheral neuropathy (n = 1) and underlying gynaecologic/breast cancers (n = 14). Panel B included 2132 non-selected consecutive serum/CSF samples from patients with neurological symptoms. Panel C consisted of 150 samples from healthy blood donors. Results In Panel A, all samples (100%) from patients with typical clinical characteristics for Yo-associated PCD showed strong positive reactivity to both CDR2L and CDR2. In Panel B, seven (0.3%) sera were anti-CDR2 negative, but anti-CDR2L positive, all of them from patients (6M/1F) without PCD and two with cancer or pre-cancerous condition. Eleven (0.5%) patients (9M/2F) were found to be anti-CDR2 positive, but anti-CDR2L negative, including two with cerebellar ataxia and three with cancer or pre-cancerous condition. In all 18 cases, IFA on rat cerebellum was negative, suggesting non-specific line blot reactivity to CDR2L or CDR2. In Panel C, 0/150 sera were anti-CDR2L and 1/150 anti-CDR2 positive, corresponding to specificities of 100% and 99.3%, respectively. The anti-CDR2 positive blood donor was male with negative IFA result. Conclusion Using CDR2L in addition to CDR2 increases the specificity in diagnosing anti-Yo-associated PCD. Positive line blot reactivity against both parameters seems to confirm the diagnosis. In contrast, results showing isolated reactivity against either CDR2L or CDR2 have to be interpreted carefully as they may apply to non-PCD cases.