ANNA-3 anti-neuronal nuclear antibody: Marker of lung cancer-related autoimmunity

Koon Ho Chan, Steven Vernino, Vanda A Lennon

Research output: Contribution to journalArticle

133 Citations (Scopus)

Abstract

Two anti-neuronal nuclear antibodies (ANNA-1 and ANNA-2) are markers of paraneoplastic neurological autoimmunity related to small-cell carcinoma. ANNA-2 is also related to breast carcinoma. Here we define a third IgG specificity (ANNA-3), identified in 11 patients (10 adults) by immunofluorescence screening of sera from approximately 68,000 patients with suspected paraneoplastic neurological syndromes. ANNA-3 binds prominently to nuclei of cerebellar Purkinje neurons, not to cytoplasm, granular neurons, or enteric neurons, but distinctively to renal glomerular podocytes. Western blots revealed an approximately 170 kDa antigen, in cerebellum and small-cell carcinoma. IgG eluted from this protein reproduced Purkinje and podocyte nuclear staining. ANNA-2 in 8 of 32 cases bound to podocyte nuclei but not to the 170 kDa protein. Healthy subjects and control neurological and cancer patients lack ANNA-3. Neurological accompaniments, subacute and usually multifocal, included sensory/sensorimotor neuropathies, cerebellar ataxia, myelopathy, brain stem and limbic encephalopathy. All of 9 adults followed had an intrathoracic neoplasm, seven biopsied within 7 months (five small-cell lung carcinomas and two adenocarcinomas, one lung, one esophagus) and two imaged, one early, the other 3 years later. Thus, immunohistochemical and Western blot criteria can now identify six IgG markers of neurological autoimmunity related to small-cell carcinoma, their frequency being ANNA-1 > collapsin response-mediator protein-5 > amphiphysin > Purkinje cell cytoplasmic antibody-2 = ANNA-2 = ANNA-3.

Original languageEnglish (US)
Pages (from-to)301-311
Number of pages11
JournalAnnals of Neurology
Volume50
Issue number3
DOIs
StatePublished - 2001

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Podocytes
Small Cell Carcinoma
Autoimmunity
Lung Neoplasms
Immunoglobulin G
Purkinje Cells
Antibodies
Western Blotting
Semaphorin-3A
Neurons
Paraneoplastic Syndromes
Cerebellar Nuclei
Cerebellar Ataxia
Proteins
Spinal Cord Diseases
Small Cell Lung Carcinoma
Brain Diseases
Cerebellum
Esophagus
Brain Stem

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

ANNA-3 anti-neuronal nuclear antibody : Marker of lung cancer-related autoimmunity. / Chan, Koon Ho; Vernino, Steven; Lennon, Vanda A.

In: Annals of Neurology, Vol. 50, No. 3, 2001, p. 301-311.

Research output: Contribution to journalArticle

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