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

Vernino, Steven; Lennon, Vanda A.

doi:10.1002/1531-8249(200003)47:3<297::aid-ana4>3.0.co;2-4

Cited by 168 publications

(72 citation statements)

References 21 publications

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“…Stored samples were coded and tested retrospectively by blinded technicians who used contemporary clinical assay methods. Muscle and neuronal ganglionic AChR binding, muscle AChR blocking, neuronal voltage-gated potassium channel (VGKC, ␣-dendrotoxin receptor), P/Q-and N-type calcium channel, and glutamic acid decarboxylase (GAD65) antibodies were detected with radioimmunoprecipitation assays (27)(28)(29)(30). The normal range for muscle AChR binding, P/Q-and N-type calcium channel and GAD65 antibody was 0.00 to 0.02 nmol/L.…”

Section: Methodsmentioning

confidence: 99%

Autoantibody Profiles and Neurological Correlations of Thymoma

Vernino

Lennon

2004

Clinical Cancer Research

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Purpose: Determine muscle and neuronal autoantibody frequencies in patients with thymoma, with and without paraneoplastic neurological accompaniments.Experimental Design: Analysis of IgG autoantibodies in stored serum collected between 1985 and 2003 from 201 patients with histologically diagnosed thymoma (including six with thymic carcinoma). Contemporary assays quantitated antibodies reactive with muscle and neuronal cation channels, muscle sarcomeric proteins and neuronal cytoplasmic, and nuclear proteins.Results: Neurological diagnoses included myasthenia gravis (MG), myositis, encephalitis, neuromuscular hyperexcitability, autonomic neuropathy, and subacute hearing loss, a previously unrecognized accompaniment of thymoma. Muscle acetylcholine receptor (AChR) binding antibodies were found in all patients with a diagnosis of MG. Muscle autoantibodies (AChR-binding, AChR-modulating, or striational) were also found in 59% of patients without any neurological disorder. One or more neuronal autoantibodies were found in 41% of patients without any neurological disorder, 43% of patients with MG only, and 78% of patients with other neurological disorders. Neuronal autoantibody specificities were, in descending order of frequency, as follows: glutamic acid decarboxylase, voltagegated potassium channel, collapsin response-mediator protein-5, ganglionic AChR, and antineuronal nuclear antibody-type 1 (ANNA-1).Conclusions: Neuronal autoantibodies complement skeletal muscle autoantibodies as serological markers of thymoma in patients with and without clinical evidence of a neurological disorder. The high prevalence of glutamic acid decarboxylase autoantibody, not previously considered a paraneoplastic marker, justifies its consideration as a marker of thymoma-related neurological autoimmunity. Serological evaluation of a patient's profile of neuronal and muscle autoantibodies may aid in preoperative identification of an indeterminate mediastinal mass.

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Section: Methodsmentioning

confidence: 99%

Autoantibody Profiles and Neurological Correlations of Thymoma

Vernino

Lennon

2004

Clinical Cancer Research

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“…Other antibodies associated with paraneoplastic encephalomyelitis include anti-CRMP5/CV2 [16], antiamphiphysin [34], and the less well-characterized ANNA-3 [35] and Purkinje cell antibody, PCA-2 [36].…”

Section: Antineuronal Antibodiesmentioning

confidence: 99%

“…The more recently discovered PCA-2 antibody and the ANNA-3 antibody are associated with lung cancer and a variety of neurological syndromes including cerebellar degeneration [36]. Anti-Zic4 antibodies are strongly associated with SCLC, and most patients have paraneoplastic encephalomyelitis, often presenting with cerebellar dysfunction [51].…”

Section: Antineuronal Antibodiesmentioning

confidence: 99%

Managing Paraneoplastic Neurological Disorders

2006

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“…2 The neurological associations initially reported for PCA-2 were mixed, of subacute onset and predominantly central (brainstem and limbic encephalitis, cerebellar ataxia), but some patients had peripheral manifestations (Lambert-Eaton myasthenic syndrome [LEMS] or autonomic or motor neuropathy). 1 Our study extends the immunochemical characteristization of PCA-2 IgG and identifies its antigen as MAP1B, a member of the microtubule-associated protein family. We also provide clinical and oncologic correlative information gained for this paraneoplastic autoantibody in the past 2 decades.…”

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confidence: 55%

Microtubule‐associated protein 1B: Novel paraneoplastic biomarker

Gadoth¹,

Kryzer²,

Fryer³

et al. 2017

Annals of Neurology

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Objective: To report the identification of microtubule-associated protein (MAP) 1B as the antigen of the previously described Purkinje cell cytoplasmic antibody type 2 (PCA-2) antibody, its frequency, and clinical, oncological, and serological associations. Methods: Archival serum or cerebrospinal fluid (CSF) specimens were available from 96 of 118 consecutive PCA-2-IgG-seropositive patients identified during 1993-2016. The autoantigen, defined in mouse brain lysate by Western blot and mass spectrometry, was confirmed by dual immunohistochemical staining using commercial antibodies. The major antigenic region was defined by Western blot using recombinant protein fragments. Results: IgG in 95 of 96 patients' serum or CSF (but in none of 98 healthy or disease control subjects' serum specimens) bound to recombinant MAP1B. A minority (17.5%) of patients' IgG also bound to MAP1A. PCA-2 was often accompanied by additional neural autoantibody markers of small-cell carcinoma, including collapsin responsemediated protein 5 (CRMP5) IgG (26%) or antineuronal nuclear antibody type 1 (ANNA-1) IgG (also known as antiHu; 13%). Neurological manifestations in 95 patients were (in decreasing frequency): peripheral neuropathy, 53%; cerebellar ataxia, dysmetria, or dysarthria, 38%; and encephalopathy, 27%. Cancer (majority small-cell lung carcinoma [SCLC]) was detected in 66 of 84 evaluated patients (79%). The MAP1B (PCA-2) autoantibody detection rate, among approximately 70,000 patients undergoing service neural autoantibody evaluation in 2015, was 0.024%, equaling amphiphysin IgG (0.026%) and more common than ANNA-2 (also known as anti-Ri; 0.016%) and PCA-Tr (also known as delta/notch-like epidermal growth factor-related receptor [DNER]; 0.006%). Interpretation: MAP1B, the PCA-2 autoantigen, represents a novel target in paraneoplastic neurological disorders and has high predictive value for SCLC. Its relatively high prevalence, compared with other recognized paraneoplastic neural autoantibodies, justifies its testing in comprehensive paraneoplastic neural autoantibody evaluation. ANN NEUROL 2017;81:266-277 I n 2000, Vernino and Lennon 1 reported 10 patients with neurological autoimmunity, 9 of whom had imaging or histopathologic evidence of lung cancer (8 biopsyproven small-cell lung carcinoma [SCLC]). Their serum IgG bound to a protein of 280kDa mass in both rodent brain and a SCLC line and yielded a characteristic staining pattern on rodent neural tissues. The autoantibody was named Purkinje cell cytoplasmic antibody type 2 (PCA-2), to distinguish it from a biomarker of ovarian and breast cancer-related cerebellar degeneration, PCA-1 (also known as anti-Yo). 2 The neurological associations initially reported for PCA-2 were mixed, of subacute onset and predominantly central (brainstem and limbic encephalitis, cerebellar ataxia), but some patients had peripheral manifestations (Lambert-Eaton myasthenic syndrome [LEMS] or autonomic or motor neuropathy). 1 Our study extends the immunochemical characteristization of PCA-2 IgG an...

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

Cited by 168 publications

References 21 publications

Autoantibody Profiles and Neurological Correlations of Thymoma

Autoantibody Profiles and Neurological Correlations of Thymoma

Managing Paraneoplastic Neurological Disorders

Microtubule‐associated protein 1B: Novel paraneoplastic biomarker

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