Neural autoantibody clusters aid diagnosis of cancer

Erika S. Horta, Vanda A Lennon, Daniel H Lachance, Sarah M. Jenkins, Carin Y. Smith, Andrew B McKeon, Christopher Jon Klein, Sean J Pittock

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Purpose: Clustering of neural autoantibodies in patients with paraneoplastic neurologic disorders may predict tumor type. A mathematical analysis of neural autoantibody clusters was performed in 78,889 patients undergoing evaluation for a suspected paraneoplastic autoimmune neurologic disorder. Tumor predictive autoantibody profiles were confirmed in sera from patients with histologically proven tonsillar cancer, thymoma, and lung cancer. Patients and Methods: Of note, 78,889 patient sera were tested for 15 defined neural autoantibodies (1.2 million tests). The observed and hypothesized frequencies of autoantibody clusters were compared and their tumor associations defined. A tumor validation study comprised serum from 368 patients with a variety of tumors (thymoma, lung, or tonsil). Results: Informative oncological associations included (i) thymoma in 85% of patients with muscle striational, acetylcholine receptor antibodies plus CRMP5 autoantibodies; (ii) lung carcinoma in 80% with both P/Q-type and N-type calcium channel antibodies plus SOX1-IgG; and (iii) in men, prostate carcinoma frequency more than doubled when striational and muscle AChR specificities were accompanied by ganglionic AChR antibody. In women, amphiphysin-IgG alone was associated commonly with breast carcinoma, but amphiphysin-IgG, coexisting with antineuronal nuclear autoantibody-type 1 or CRMP5-IgG, was associated with lung cancer (P < 0.0001). In the validation cohorts, many tumor-associated profiles were encountered that matched the clusters identified in the screening study (e.g., 15% of thymoma patients had striational, acetylcholine receptor antibodies plus collapsin response-mediator protein-5 autoantibodies). Conclusions: Neural autoantibodies commonly coexist in specific clusters that are identifiable by comprehensive screening. Signature autoantibody clusters may predict a patient's cancer risk and type.

Original languageEnglish (US)
Pages (from-to)3862-3869
Number of pages8
JournalClinical Cancer Research
Volume20
Issue number14
DOIs
StatePublished - Jul 15 2014

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Autoantibodies
Thymoma
Neoplasms
Immunoglobulin G
Lung Neoplasms
Antibodies
Cholinergic Receptors
Nervous System Diseases
Tonsillar Neoplasms
Serum
Semaphorin-3A
N-Type Calcium Channels
Carcinoma
Muscles
Lung
Validation Studies
Palatine Tonsil
Cluster Analysis
Prostate
Breast Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Neural autoantibody clusters aid diagnosis of cancer. / Horta, Erika S.; Lennon, Vanda A; Lachance, Daniel H; Jenkins, Sarah M.; Smith, Carin Y.; McKeon, Andrew B; Klein, Christopher Jon; Pittock, Sean J.

In: Clinical Cancer Research, Vol. 20, No. 14, 15.07.2014, p. 3862-3869.

Research output: Contribution to journalArticle

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abstract = "Purpose: Clustering of neural autoantibodies in patients with paraneoplastic neurologic disorders may predict tumor type. A mathematical analysis of neural autoantibody clusters was performed in 78,889 patients undergoing evaluation for a suspected paraneoplastic autoimmune neurologic disorder. Tumor predictive autoantibody profiles were confirmed in sera from patients with histologically proven tonsillar cancer, thymoma, and lung cancer. Patients and Methods: Of note, 78,889 patient sera were tested for 15 defined neural autoantibodies (1.2 million tests). The observed and hypothesized frequencies of autoantibody clusters were compared and their tumor associations defined. A tumor validation study comprised serum from 368 patients with a variety of tumors (thymoma, lung, or tonsil). Results: Informative oncological associations included (i) thymoma in 85{\%} of patients with muscle striational, acetylcholine receptor antibodies plus CRMP5 autoantibodies; (ii) lung carcinoma in 80{\%} with both P/Q-type and N-type calcium channel antibodies plus SOX1-IgG; and (iii) in men, prostate carcinoma frequency more than doubled when striational and muscle AChR specificities were accompanied by ganglionic AChR antibody. In women, amphiphysin-IgG alone was associated commonly with breast carcinoma, but amphiphysin-IgG, coexisting with antineuronal nuclear autoantibody-type 1 or CRMP5-IgG, was associated with lung cancer (P < 0.0001). In the validation cohorts, many tumor-associated profiles were encountered that matched the clusters identified in the screening study (e.g., 15{\%} of thymoma patients had striational, acetylcholine receptor antibodies plus collapsin response-mediator protein-5 autoantibodies). Conclusions: Neural autoantibodies commonly coexist in specific clusters that are identifiable by comprehensive screening. Signature autoantibody clusters may predict a patient's cancer risk and type.",
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