Year: 2024
Type: article
Study design: Observational Study
Abstract: Objective To compare the performance of cerebellar degeneration-related protein 2 (CDR2) and CDR2-like (CDR2L) antigens in a line blot format. Background Purkinje cytoplasmic autoantibody type 1 (PCA-1)/anti-Yo autoimmunity is a common high-risk paraneoplastic neurological disorder, traditionally attributed antigenically to cerebellar degeneration-related protein 2 (CDR2). Single-modality CDR2 testing may produce false-positive results. Design/Methods CDR2 and CDR2L were tested in six specimen groups. Group 1, PCA-1/Yo mouse brain indirect immunofluorescence assay (IFA) positives; Group 2, PCA-1/Yo IFA mimics; Group 3, suspected CDR2 line blot false positives; Group 4, consecutive patient samples tested for neural antibodies over one year; Group 5, healthy subject serums; and Group 6, polyclonal (non-specific) immunoglobulin G (IgG)-positive serums. Results Group 1: Of 64 samples tested, all but two were positive for CDR2, and all were positive for CDR2L, with consistently higher CDR2L values compared to CDR2. The two “CDR2L-only” positives were CSFs with low titers by IFA, serum negativity, but a typical clinical phenotype. Group 2: All 51 PCA-1/Yo mimics tested negative for CDR2/CDR2L. Group 3: Nine samples (6/1289 serums and 3/700 CSFs) were PCA-1/Yo IFA negative/CDR2 positive; 2/6 were also CDR2L positive; 4 were CDR2L negative with low CDR2 values (17-22). Group 4: 22 patients showed unexpected CDR2 or CDR2L positivity/ tissue IFA negativity; 11/2,132 serums and 3/677 CSFs were CDR2 positive; median value=19 (range, 11-48); 7/2,132 serums and 3/677 CSFs were CDR2L positive; median value=18 (range, 11-96). Group 5: All 151 healthy serums tested negative. Group 6: One of 46 polyclonal serums was positive for CDR2L. Optimal overall performance was achieved by requiring both CDR2 and CDR2L positivity in serum (sensitivity, 100%; specificity, 99.9%) and positivity for CDR2L in CSF (sensitivity, 100%; specificity, 99.6%). Conclusions CDR2L provides additional PCA-1/anti-Yo sensitivity in CSF, and dual positivity with CDR2 provides additional specificity assurance in serum. Combining antigen-specific and tissue-based assays optimizes PCA-1/anti-Yo testing.
Source: Neurology
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funder: National Institutes of Health
OpenAlex ID: W4403206640