Test ID: GID2 Gastrointestinal Dysmotility, Autoimmune/Paraneoplastic Evaluation, Serum
Ordering Guidance
Multiple neuroimmunology profile tests are available. For testing that is performed with each profile, see Autoimmune Neurology Antibody Matrix.
Necessary Information
Provide the following information:
-Relevant clinical information
-Ordering provider name, phone number, mailing address, and e-mail address
Specimen Required
Patient Preparation:
1. For optimal antibody detection, specimen collection is recommended prior to initiation of immunosuppressant medication or intravenous immunoglobulin (IVIg) 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.
3. Patient should have no general anesthetic or muscle-relaxant drugs in the previous 24 hours.
Collection Container/Tube:
Preferred: Serum gel
Acceptable: Red top
Submission Container/Tube: Plastic vial
Specimen Volume: 4 mL
Useful For
Investigating unexplained weight loss, early satiety, anorexia, nausea, vomiting, constipation, or diarrhea in a patient with a past or family history of cancer or autoimmunity
Directing a focused search for cancer
Investigating gastrointestinal symptoms that appear in the course or wake of cancer therapy, not explainable by recurrent cancer, metastasis, or therapy; detection of autoantibodies on this profile helps differentiate autoimmune gastrointestinal dysmotility from the effects of chemotherapy
Detecting early evidence of cancer recurrence in previously seropositive patients who have a rising titer of 1 or more autoantibodies
Profile Information
Test ID | Reporting Name | Available Separately | Always Performed |
---|---|---|---|
AGIDI | GI Dysmotility, Interpretation, S | No | Yes |
GANG | AChR Ganglionic Neuronal Ab, S | No | Yes |
ANN1S | Anti-Neuronal Nuclear Ab, Type 1 | No | Yes |
CS2CS | CASPR2-IgG CBA, S | No | Yes |
CRMS | CRMP-5-IgG, S | No | Yes |
DPPIS | DPPX Ab IFA, S | No | Yes |
LG1CS | LGI1-IgG CBA, S | No | Yes |
PCAB2 | Purkinje Cell Cytoplasmic Ab Type 2 | No | Yes |
Reflex Tests
Test ID | Reporting Name | Available Separately | Always Performed |
---|---|---|---|
AMPCS | AMPA-R Ab CBA, S | No | No |
AMPIS | AMPA-R Ab IF Titer Assay, S | No | No |
AMPHS | Amphiphysin Ab, S | No | No |
AMIBS | Amphiphysin Immunoblot, S | No | No |
AN1BS | ANNA-1 Immunoblot, S | No | No |
AN2BS | ANNA-2 Immunoblot, S | No | No |
CRMWS | CRMP-5-IgG Western Blot, S | Yes | No |
DPPCS | DPPX Ab CBA, S | No | No |
DPPTS | DPPX Ab IFA Titer, S | No | No |
GABCS | GABA-B-R Ab CBA, S | No | No |
GABIS | GABA-B-R Ab IF Titer Assay, S | No | No |
NMDCS | NMDA-R Ab CBA, S | No | No |
NMDIS | NMDA-R Ab IF Titer Assay, S | No | No |
PC1BS | PCA-1 Immunoblot, S | No | No |
PCTBS | PCA-Tr Immunoblot, S | No | No |
PCABP | Purkinje Cell Cytoplasmic Ab Type 1 | No | No |
PCATR | Purkinje Cell Cytoplasmic Ab Type Tr | No | No |
Testing Algorithm
If immunofluorescence assay (IFA) patterns suggest collapsin response-mediator protein-5-IgG (CRMP-5-IgG), then CRMP-5-IgG Western blot is performed at an additional charge.
If IFA patterns suggest amphiphysin antibody, then amphiphysin titer and/or amphiphysin immunoblot is performed at an additional charge.
If IFA pattern suggests antineuronal nuclear antibody (ANNA)-1, then ANNA-1 immunoblot and ANNA-2 immunoblot are performed at an additional charge.
If IFA pattern suggests Purkinje cytoplasmic antibody (PCA)-1, then PCA-1 IFA and immunoblot are performed at an additional charge.
If IFA pattern suggests PCA-2 antibody, then PCA-2 IFA is performed at an additional charge.
If IFA pattern suggests PCA-Tr antibody, then PCA-Tr IFA and immunoblot are performed at an additional charge.
If IFA pattern suggests N-methyl-D-aspartate (NMDA)-receptor, then NMDA- receptor cell-binding assay (CBA) and NMDA-R titer are performed at an additional charge.
If IFA pattern suggests alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-receptor then AMPA-receptor CBA and AMPA-receptor titer are performed at an additional charge.
If IFA pattern suggests gamma-aminobutyric acid B (GABA-B)-receptor, then GABA-B-receptor CBA and GABA-B-receptor titer are performed at an additional charge.
If IFA pattern suggests dipeptidyl-peptidase-like protein-6 antibody (DPPX) antibody, then DPPX CBA and DPPX titer are performed at an additional charge.
For more information, see Autoimmune/Paraneoplastic Gastrointestinal Dysmotility Evaluation Algorithm.
Method Name
AMPHS, AMPIS, ANN1S, CRMS, DPPIS, DPPTS, GABIS, NMDIS, PCAB2, PCABP, PCATR: Indirect Immunofluorescence Assay (IFA)
AMPCS, CS2CS, DPPCS, GABCS, LG1CS, NMDCS: Cell Binding Assay (CBA)
CRMWS: Western Blot (WB)
AMIBS, AN1BS, AN2BS, PC1BS, PCTBS: Immunoblot (IB)
GANG: Radioimmunoassay (RIA)
Reporting Name
GI Dysmotility, Autoimm/Paraneo, SSpecimen Type
SerumSpecimen Minimum Volume
2 mL
Specimen Stability Information
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Serum | Refrigerated (preferred) | 28 days | |
Frozen | 28 days | ||
Ambient | 72 hours |
Clinical Information
Autoimmune gastrointestinal dysmotility (AGID) is a limited form of dysautonomia (also known as autoimmune autonomic ganglionopathy or neuropathy) that is sometimes a paraneoplastic disorder. Neoplasms most commonly found are lung cancer, thymoma, and miscellaneous adenocarcinomas. Diagnosis is confirmed by objective abnormalities on gastrointestinal (GI) motility studies (eg, gastric, small intestinal, or colonic nuclear transit studies; esophageal, gastroduodenal, or colonic manometry or anorectal manometry with balloon expulsion). These disorders target autonomic postganglionic synaptic membranes and, in some cases, ganglionic neurons and autonomic nerve fibers, and may be accompanied by sensory small fiber neuropathy. Onset may be subacute or insidious. There may be additional manifestations of dysautonomia (eg, impaired pupillary light reflex, anhidrosis, orthostatic hypotension, sicca manifestations, and bladder dysfunction) or signs of other neurologic impairment. Autonomic reflex testing and a thermoregulatory sweat test are valuable aids in the documentation of objective abnormalities.
The serological profile of AGID may include autoantibodies specific for onconeural proteins found in the nucleus, cytoplasm, or plasma membrane of neurons or muscle. Some of these autoantibodies are highly predictive of an underlying cancer. A commonly encountered autoantibody marker of AGID is the ganglionic neuronal alpha-3- acetylcholine receptor (alpha-3-AChR) autoantibody. The pathogenicity of this autoantibody was demonstrated in rabbits immunized with a recombinant extracellular fragment of the alpha-3-AChR subunit and in mice injected with IgG from high-titered alpha-3-AChR autoantibody-positive rabbit or human sera. A direct relationship between antibody titer and severity of dysautonomia occurs in both experimental animals and patients. Patients with high alpha-3-AChR autoantibody values (>1.0 nmol/L) generally present with profound pandysautonomia, and those with lower alpha-3-AChR autoantibody values may have limited autoimmune dysautonomia or other neurological signs and symptoms.
Importantly, cancer is detected in 30% of patients with alpha-3-AChR autoantibody. Cancer risk factors include the patient's past or family history of cancer, history of smoking, or social and environmental exposure to carcinogens. Early diagnosis and treatment of the neoplasm favor less morbidity from the GI dysmotility disorder. The cancers recognized most commonly with alpha-3-AChR autoantibody include lymphoma and adenocarcinomas of breast, lung, prostate, and GI tract. A specific neoplasm is often predictable when a patient's autoantibody profile includes other autoantibodies to onconeural proteins shared by neurons, glia, or muscle. Small-cell lung carcinoma is found in 80% of antineuronal nuclear antibody-type 1 (ANNA-1; anti-Hu)-positive patients and 23% of ANNA-1-positive patients have GI dysmotility. The most common GI manifestation is gastroparesis, but the most dramatic is pseudoobstruction.
Reference Values
Test ID |
Reporting Name |
Methodology* |
Reference Value |
AGIDI |
GI Dysmotility, Interpretation, S |
Medical interpretation |
NA |
GANG |
AChR Ganglionic Neuronal Ab, S |
RIA |
≤0.02 nmol/L |
ANN1S |
Anti-Neuronal Nuclear Ab, Type 1 |
IFA |
<1:240 |
CS2CS |
CASPR2-IgG CBA, S |
CBA |
Negative |
CRMS |
CRMP-5-IgG, S |
IFA |
<1:240 |
DPPIS |
DPPX Ab IFA, S |
IFA |
Negative |
LG1CS |
LGI1-IgG CBA, S |
CBA |
Negative |
PCAB2 |
Purkinje Cell Cytoplasmic Ab Type 2 |
IFA |
<1:240 |
Reflex Information:
Test ID |
Reporting Name |
Methodology* |
Reference Value |
AMPCS |
AMPA-R Ab CBA, S |
CBA |
Negative |
AMPIS |
AMPA-R Ab IF Titer Assay, S |
IFA |
<1:120 |
AMPHS |
Amphiphysin Ab, S |
IFA |
<1:240 |
AMIBS |
Amphiphysin Immunoblot, S |
IB |
Negative |
AN1BS |
ANNA-1 Immunoblot, S |
IB |
Negative |
AN2BS |
ANNA-2 Immunoblot, S |
IB |
Negative |
CRMWS |
CRMP-5-IgG Western Blot, S |
WB |
Negative |
DPPCS |
DPPX Ab CBA, S |
CBA |
Negative |
DPPTS |
DPPX Ab IFA Titer, S |
IFA |
<1:240 |
GABCS |
GABA-B-R Ab CBA, S |
CBA |
Negative |
GABIS |
GABA-B-R Ab IF Titer Assay, S |
IFA |
<1:120 |
NMDCS |
NMDA-R Ab CBA, S |
CBA |
Negative |
NMDIS |
NMDA-R Ab IF Titer Assay, S |
IFA |
<1:120 |
PC1BS |
PCA-1 Immunoblot, S |
IB |
Negative |
PCTBS |
PCA-Tr Immunoblot, S |
IB |
Negative |
PCABP |
Purkinje Cell Cytoplasmic Ab Type 1 |
IFA |
<1:240 |
PCATR |
Purkinje Cell Cytoplasmic Ab Type Tr |
IFA |
<1:240 |
*Methodology abbreviations used:
Immunofluorescence assay (IFA)
Cell-binding assay (CBA)
Western blot (WB)
Radioimmunoassay (RIA)
Immunoblot (IB)
Neuron-restricted patterns of IgG staining that do not fulfill criteria for ANNA-1, ANNA-2, PCA-1, PCA-2, or PCA-Tr may be reported as "unclassified anti-neuronal IgG." Complex patterns that include nonneuronal elements may be reported as "uninterpretable."
CRMP-5 titers lower than 1:240 are detectable by recombinant CRMP-5 Western blot analysis. CRMP-5 Western blot analysis will be done on request on stored serum (held for 4 weeks). This supplemental testing is recommended in cases of chorea, vision loss, cranial neuropathy, and myelopathy. Call 1-800-533-1710 to request CRMP-5 Western blot.
Interpretation
Antibodies directed at onconeural proteins shared by neurons, muscle, and certain cancers are valuable serological markers of a patient's immune response to cancer. They are not found in healthy subjects and are usually accompanied by subacute symptoms and signs. It is not uncommon for more than one antibody to be detected. Three classes of antibodies are recognized (the individual antibodies from each class included in the profile are denoted in parentheses):
-Antineuronal nuclear autoantibody-type 1
-Neuronal and muscle cytoplasmic (collapsin response-mediator protein-5)
-Plasma membrane cation channel (neuronal ganglionic alpha-3-acetylcholine receptor).
All of these autoantibodies are potential effectors of autoimmune gastrointestinal dysmotility.
Clinical Reference
1. Lennon VA, Sas DF, Busk MF, et al: Enteric neuronal autoantibodies in pseudoobstruction with small cell lung carcinoma. Gastroenterology. 1991 Jan;100(1):137-142. doi: 10.1016/0016-5085(91)90593-a
2. Lucchinetti CF, Kimmel DW, Lennon VA: Paraneoplastic and oncologic profiles of patients seropositive for type 1 antineuronal nuclear autoantibodies. Neurology. 1998 Mar;50(3):652-657. doi: 10.1212/wnl.50.3.652
3. Vernino S, Adamski J, Kryzer TJ, Fealey RD, Lennon VA: Neuronal nicotinic ACh receptor antibody in subacute autonomic neuropathy and cancer-related syndromes. Neurology. 1998 Jun;50(6):1806-1813. doi: 10.1212/wnl.50.6.1806
4. Vernino S, Low PA, Fealey RD, Stewart JD, Farrugia G, Lennon VA: Autoantibodies to ganglionic acetylcholine receptors in autoimmune autonomic neuropathies. N Engl J Med. 2000 Sep;343(12):847-855. doi: 10.1056/NEJM200009213431204
5. Dhamija R, Tan KM, Pittock SJ, Foxx-Orenstein A, Benarroch A, Lennon VA: Serological profiles aiding the diagnosis of autoimmune gastrointestinal dysmotility. Clin Gastroenterol Hepatol. 2008 Sep;6(9):988-992. doi: 10.1016/j.cgh.2008.04.009
6. McKeon A, Lennon VA, Lachance DH, Fealey RD, Pittock SJ: The ganglionic acetylcholine receptor autoantibody: oncological, neurological, and serological accompaniments. Arch Neurol. 2009 Jun;66(6):735-741. doi: 10.1001/archneurol.2009.78
7. Kraichely RE, Farrugia G, Pittock SJ, Castell DO, Lennon VA: Neural autoantibody profile of primary achalasia. Dig Dis Sci. 2010 Feb;55(2):307-311. doi: 10.1007/s10620-009-0838-9
Day(s) Performed
Report Available
10 to 13 daysTest Classification
This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
83519
86255 x 6
86255-AMPCS (if appropriate)
86256-AMPIS (if appropriate)
86255-AMPHS (if appropriate)
84182-AMIBS (if appropriate)
84182-AN1BS (if appropriate)
84182-AN2BS (if appropriate)
84182-CRMWS (if appropriate)
86255-DPPCS (if appropriate)
86256-DPPTS (if appropriate)
86255-GABCS (if appropriate)
86256-GABIS (if appropriate)
86255-NMDCS (if appropriate)
86256-NMDIS (if appropriate)
84182-PC1BS (if appropriate)
84182-PCTBS (if appropriate)
86255-PCABP (if appropriate)
86255-PCATR (if appropriate)
LOINC Code Information
Test ID | Test Order Name | Order LOINC Value |
---|---|---|
GID2 | GI Dysmotility, Autoimm/Paraneo, S | 97557-3 |
Result ID | Test Result Name | Result LOINC Value |
---|---|---|
34269 | GI Dysmotility, Interpretation, S | 69048-7 |
64279 | LGI1-IgG CBA, S | 94287-0 |
64281 | CASPR2-IgG CBA, S | 94285-4 |
64930 | DPPX Ab IFA, S | 82976-2 |
80150 | ANNA-1, S | 94342-3 |
83077 | CRMP-5-IgG, S | 94815-8 |
84321 | AChR Ganglionic Neuronal Ab, S | 94694-7 |
83138 | PCA-2, S | 94351-4 |
36349 | Reflex Added | 77202-0 |
Special Instructions
Forms
If not ordering electronically, complete, print, and send Gastroenterology and Hepatology Client Test Request (T728) with the specimen