Case report: Seropositive myasthenia gravis complicated by limbic encephalitis positive for antibodies to AMPAR and Lgi1.

Objectives: Autoantibodies to the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and leucine-rich glioma-inactivated 1 (Lgi1) are associated with autoimmune encephalitis. We described an acetylcholine receptor (AChR)-positive patient with myasthenia gravis who developed limbic encephalitis with antibodies to AMPAR and Lgi1.

Methods: A single-case report with detailed, prospective clinical and biomarker data including serial laboratory testing and histopathology.

A cerebellar degeneration-related protein 2-like cell-based assay for anti-Yo detection in patients with paraneoplastic cerebellar degeneration.

Background And Purpose: Commercially available tests for Yo antibody detection have low specificity for paraneoplastic cerebellar degeneration (PCD) because these assays use cerebellar degeneration-related protein 2 (CDR2) as the antigen, not CDR2-like (CDR2L). We aimed to test the hypothesis that use of a CDR2L cell-based assay (CBA), as an additional screening technique, would increase the accuracy of Yo-PCD diagnosis.

Methods: An in-house CBA to test for anti-CDR2L antibodies was developed and used to screen sera from 48 patients with confirmed anti-Yo-associated PCD.

Case report: Pain in anti-DPPX encephalitis.

Encephalitis due to antibodies targeting dipeptidyl-peptidase-like protein 6 (DPPX), a potassium channel subunit, is rare. The illness is typically characterized by a triad of weight loss, CNS hyperexcitability and cognitive symptoms, but recent reports suggest that the clinical picture may be more heterogeneous. Here, we describe the case of a 63-year-old female who was admitted to the hospital with severe extremity pain, which had been preceded by diarrhea and weight loss.

Expression of cerebellar degeneration-related proteins CDR2 and CDR2L in human and rat brain tissue.

Patients with ovarian cancer and paraneoplastic cerebellar degeneration, a cancer-related immune disorder, often have anti-Yo antibody. Here we studied the distributions of anti-Yo antigens CDR2L and CDR2 in rat and human brain using immunohistochemistry and western blot. CDR2L localized mainly to the Purkinje cells and large neurons scattered in the brain stem.

CRMP5 Antibodies-Diagnostic Challenges.

CRMP5-associated paraneoplastic neurological syndromes (PNS) are rare, and only few studies describe larger cohorts of patients with CRMP5 antibodies. We have included 24 patients with CRMP5 antibodies and compared clinical findings with diagnostic findings from two different line assays (Ravo and Euroimmun), staining of cerebellar sections and results of a newly developed cell-based assay for detection of CRMP5 antibodies, CRMP5-CBA. We found that peripheral neuropathy and cerebellar ataxia together with lung cancer were the most common diagnoses associated with CRMP5 antibodies.

Paraneoplastic Cerebellar Degeneration: The Importance of Including CDR2L as a Diagnostic Marker.

Objective: Investigate the value of including cerebellar degeneration-related protein 2-like (CDR2L) as a marker in commercial diagnostic tests for anti-Yo-associated paraneoplastic cerebellar degeneration (PCD).

Methods: We included sera and CSF samples from 24 patients with suspected PCD (6 of whom had PCD with underlying gynecologic or breast cancer), who were positive for Yo antibodies using the commercially available, paraneoplastic neurologic syndromes (PNS) 14 Line Assay from Ravo Diagnostika. The samples were further evaluated using the EUROLINE PNS 12 Ag Line Assay and a cell-based assay (CBA) from Euroimmun.

CDR2L Is the Major Yo Antibody Target in Paraneoplastic Cerebellar Degeneration.

The pathogenesis of Yo-mediated paraneoplastic cerebellar degeneration (PCD) is unclear. We applied cerebrospinal fluid and serum from PCD patients as well as CDR2 and CDR2L antibodies to neuronal tissue, cancer cell lines, and cells transfected with recombinant CDR2 and CDR2L to elucidate which is the major antigen of Yo antibodies. We found that Yo antibodies bound endogenous CDR2L, but not endogenous CDR2.

Expression of the onconeural protein CDR1 in cerebellum and ovarian cancer.

Cerebellar degeneration related protein 1 (CDR1) is expressed in the cerebellum, and CDR1 antibodies have been associated with paraneoplastic cerebellar degeneration (PCD). In this study, we examined CDR1 expression in cerebellum and in ovarian and breast tumors, as well as the intracellular localization of CDR1 in cancer cells in culture. CDR1 was strongly expressed in the cytosol and dendrites of Purkinje cells and in interneurons of the molecular layer in cerebellum.

Cerebellar degeneration-related proteins 2 and 2-like are present in ovarian cancer in patients with and without Yo antibodies.

Background: Cerebellar degeneration-related protein 2 (CDR2) has been presumed to be the main antigen for the onconeural antibody Yo, which is strongly associated with ovarian cancer and paraneoplastic cerebellar degeneration (PCD). Recent data show that Yo antibodies also target the CDR2-like protein (CDR2L). We, therefore, examined the expression of CDR2 and CDR2L in ovarian cancer tissue from patients with and without Yo antibodies and from various other cancerous and normal human tissues.

Paraneoplastic CDR2 and CDR2L antibodies affect Purkinje cell calcium homeostasis.

Paraneoplastic cerebellar degeneration (PCD) is characterized by loss of Purkinje cells (PCs) associated with progressive pancerebellar dysfunction in the presence of onconeural Yo antibodies. These antibodies recognize the cerebellar degeneration-related antigens CDR2 and CDR2L. Response to PCD therapy is disappointing due to limited understanding of the neuropathological mechanisms.

CDR2L Antibodies: A New Player in Paraneoplastic Cerebellar Degeneration.

Objective: Yo antibodies are associated with paraneoplastic cerebellar degeneration (PCD). We have characterized Yo sera by measuring CDR2 and CDR2L antibodies and the localization of their antigens.

Methods: Forty-two Yo sera from patients with paraneoplastic neurological syndromes (PNS), 179 sera from ovarian and 114 sera from breast cancer patients without PNS and 100 blood donors were screened for CDR2 and CDR2L antibodies by radioactive immune assay (RIA).

Avidity of onconeural antibodies is of clinical relevance.

Onconeural antibodies are important in the detection of paraneoplastic neurological syndromes (PNS). The avidity of Hu, Yo, and CRMP5 antibodies from 100 patients was determined by immunoprecipitation (IP), and 13 of the Yo positive sera were also tested by surface plasmon resonance (SPR). There was a significant association between the results from IP and SPR.

Progressive striatal necrosis associated with anti-NMDA receptor antibodies.

Background: We report a case of childhood onset, generalized dystonia due to slowly progressive bilateral striatal necrosis associated with anti-N-methyl-D-aspartate receptor (NMDAR) antibodies. This clinical phenotype has not been previously associated with NMDA receptor autoimmunity.

Case Presentation: An eighteen year old man presented with a history of childhood-onset, progressive generalized dystonia.

Onconeural antibodies: improved detection and clinical correlations.

Onconeural antibodies are found in many patients with paraneoplastic neurological syndromes (PNS) and define the disease as paraneoplastic. The study describes the presence of onconeural antibodies and PNS in 555 patients with neurological symptoms and confirmed cancer within five years, and compares the diagnostic accuracy of different antibody assays (immunoprecipitation, immunofluorescence and immunoblot). Onconeural antibodies were found in 11.

CDR2 antigen and Yo antibodies.

Paraneoplastic cerebellar degeneration (PCD) is often associated with Yo antibodies that are directed against human cerebellar degeneration-related protein 2 (CDR2). Such antibodies may also be found in ovarian cancer patients without PCD. We studied if there was an association between Yo antibody production and differences in CDR2 cDNA sequence, mRNA or CDR2 expression in ovarian cancers.

Antibody to CCDC104 is associated with a paraneoplastic antibody to CDR2 (anti-Yo).

Patients with cancer may develop paraneoplastic neurological syndromes (PNS) in which onconeural antibodies are important diagnostic findings. As the functional role of onconeural antibodies is largely unknown, insight gained by identifying associated antibodies may help to clarify the pathogenesis of the PNS. In this study, we identified patients with Yo antibodies who also had antibodies to an uncharacterized protein called coiled-coil domain-containing protein 104 (CCDC104).