26149 Dysautonomia, Autoimmune/Paraneoplastic Evaluation, Serum

If the indirect immunofluorescence assay (IFA) patterns suggest collapsin response-mediator protein (CRMP)-5-IgG, then CRMP-5-IgG IFA titer and CRMP-5-IgG Western blot will be performed at an additional charge.

If the IFA pattern suggests antineuronal nuclear antibody type 1 (ANNA-1), then ANNA-1 immunoblot, ANNA-1 IFA titer, and ANNA-2 immunoblot will be performed at an additional charge.

If the IFA pattern suggests adaptor protein 3 beta 2 (AP3B2) antibody, then AP3B2 cell-binding assay (CBA) and AP3B2 IFA titer will be performed at an additional charge.

If the IFA pattern suggests dipeptidyl-peptidase-like protein-6 antibody (DPPX) antibody, then DPPX antibody CBA and DPPX IFA titer will be performed at an additional charge.

If the IFA pattern suggests Purkinje cytoplasmic antibody type 2 (PCA-2), then PCA-2 titer is performed at an additional charge.

For more information see Autoimmune/Paraneoplastic Dysautonomia Evaluation Algorithm.

Investigating idiopathic dysautonomic symptoms

Directing a focused search for cancer in patients with idiopathic dysautonomia

Investigating autonomic symptoms that appear in the course or wake of cancer therapy and are not explainable by recurrent cancer or metastasis (detection of autoantibodies in this profile helps differentiate autoimmune dysautonomia from the effects of chemotherapy)

Patient Preparation:

1. For optimal antibody detection, specimen collection is recommended before initiation of immunosuppressant medication or intravenous immunoglobulin treatment.

2. This test should not be requested in patients who have recently received radioisotopes, therapeutically or diagnostically, because of potential assay interference. The specific waiting period before specimen collection will depend on the isotope administered, the dose given, and the clearance rate in the individual patient. Specimens will be screened for radioactivity prior to analysis. Radioactive specimens received in the laboratory will be held 1 week and assayed if sufficiently decayed, or canceled if radioactivity remains.​

Necessary Information: 

Provide the following information:

-Relevant clinical information

-Ordering provider name, phone number, mailing address, and e-mail address

Negative results do not exclude autoimmune dysautonomia or cancer.

Intravenous immunoglobulin (IVIg) treatment prior to the serum collection may cause a false-positive result.

​Autoimmune dysautonomia encompasses disorders of peripheral autonomic synapses, ganglionic neurons, autonomic nerve fibers, and central autonomic pathways mediated by neural-specific IgG or effector T cells. These disorders may be idiopathic or paraneoplastic, subacute or insidious in onset, and may present as a limited disorder or generalized pandysautonomia. Pandysautonomia is usually subacute in onset and severity and includes impaired pupillary light reflex, anhidrosis, orthostatic hypotension, cardiac arrhythmias, gastrointestinal dysmotility, sicca manifestations, and bladder dysfunction. Limited dysautonomia is confined to one or just a few domains, is often mild, and may include sicca manifestations, postural orthostatism and cardiac arrhythmias, bladder dysfunction, or gastrointestinal dysmotilities. Diagnosis of limited dysautonomia requires documentation of objective abnormalities by autonomic reflex testing, thermoregulatory sweat test, or gastrointestinal motility studies.​

The most frequently encountered autoantibody marker of autoimmune dysautonomia is the neuronal ganglionic alpha-3-acetylcholine receptor (AChR) autoantibody. This autoantibody to date is the only proven effector of autoimmune dysautonomia. A direct relationship has been demonstrated between antibody titer and severity of dysautonomia in both alpha-3-AChR-immunized animals and patients with autoimmune dysautonomia. Patients with high alpha-3-AChR autoantibody values (>1.0 nmol/L) generally have profound pandysautonomia. Dysautonomic patients with lower alpha-3-AChR autoantibody values (0.03-0.99 nmol/L) have limited dysautonomia.

Importantly, cancer is detected in 30% of patients with alpha-3-AChR autoantibody. Cancers recognized include small-cell lung carcinomas, thymoma, lymphoma, and adenocarcinomas of breast, lung, prostate, and gastrointestinal tract. Cancer risk factors include a previous or family history of cancer, history of smoking, or social or environmental exposure to carcinogens. Early diagnosis and treatment of the neoplasm favors neurologic improvement and lessens morbidity.

Autoantibodies to other onconeural proteins shared by neurons, glia, or muscle (eg, antineuronal nuclear antibody-type 1 [ANNA-1], collapsin response-mediator protein-5 neuronal [CRMP-5-IgG]) serve as additional markers of paraneoplastic or idiopathic dysautonomia. A specific neoplasm is often predictable by the individual patient's autoantibody profile.

See Interpretive Report

Antibodies directed at onconeural proteins shared by neurons, muscle, and glia are valuable serological markers of a patient's immune response to cancer. These autoantibodies are not found in healthy subjects and are usually accompanied by subacute neurological symptoms and signs. It is not uncommon for more than one autoantibody to be detected in patients with autoimmune dysautonomia. These include:

-Plasma membrane cation channel antibodies (neuronal ganglionic [alpha-3]). All of these autoantibodies are potential effectors of autonomic dysfunction.

-Antineuronal nuclear autoantibody-type 1

-Neuronal and muscle cytoplasmic antibodies (CRMP-5 IgG)

A rising autoantibody titer in previously seropositive patients suggests cancer recurrence.