The University of Iowa (UIHC)
Department of Pathology
LABORATORY SERVICES HANDBOOK


Paraneoplastic Autoantibody Evaluation
Order Code: PNSER
Epic Lab Code: LAB3800
Order Form: A-1a Miscellaneous Request or Epic Req
  Commercial "Mail-out" Laboratory
6240 RCP
356-3527
Specimen:
Serum
Collection Medium:
and
Red top tube Red top tube
Minimum:
Adult minimum: 12 mls whole blood in two 6 ml red top tubes to yield
  (min: 4.0 mL serum)

Pediatric minimum: 6 mls whole blood in one red top tube to yield
  (min: 2.0 mL serum)
Analytic Time:
2 weeks
Reference Range:
NEURONAL NUCLEAR ANTIBODIES
      Antineuronal Nuclear Antibody-Type 1 (ANNA-1)
                  <1:240
      Antineuronal Nuclear Antibody -Type 2 (ANNA-2)
                  <1:240
      Antineuronal Nuclear Antibody -Type 3 (ANNA-3)
                  <1:240
      Anti-Glial/Neuronal Nuclear Antibody-Type 1 (AGNA-1)
                  <1:240

NEURONAL AND MUSCLE CYTOPLASMIC ANTIBODIES
      Purkinje Cell Cytoplasmic Antibody, Type 1 (PCA-1)
                  <1:240
      Purkinje Cell Cytoplasmic Antibody, Type 2 (PCA-2)
                  <1:240
      Purkinje Cell Cytoplasmic Antibody, Type Tr  (PCA-Tr)
                  <1:240
      Amphiphysin Antibody
                  <1:240
      CRMP-5-IgG
                  <1:240
Note:  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 4 weeks). This supplemental testing is 
recommended in cases of chorea, vision loss, cranial neuropathy, and 
myelopathy. Call the Neuroimmunology Laboratory at 800-533-1710 or 
507-266-5700 to request CRMP-5 Western blot.
      Striational (Striated Muscle) Antibodies
                  <1:60

CATION CHANNEL ANTIBODIES
      N-Type Calcium Channel Antibody
                  < or = 0.03 nmol/L
      P/Q-Type Calcium Channel Antibody
                  < or = 0.02 nmol/L
      ACh Receptor (Muscle) Binding Antibody
                  < or = 0.02 nmol/L
      AChR Ganglionic Neuronal Antibody
                < or = 0.02 nmol/L
      Voltage-Gated Potassium Channel Antibody
                < or = 0.02 nmol/L
      GAD65 Antibody
                < or = 0.02 nmol/L

Neuron-restricted patterns of IgG staining that do not fulfill criteria 
for amphiphysin, ANNA-1, ANNA-2, ANNA-3, PCA-1, PCA-2, PCA-Tr, or 
CRMP-5-IgG may be reported as "unclassified antineuronal IgG."  Complex 
patterns that include non-neuronal elements may be reported as 
"uninterpretable."
Interpretive Data:
Antibodies directed at onconeural proteins shared by neurons, glia, 
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 neurological symptoms 
and signs. Several autoantibodies have a syndromic association, but no 
autoantibody predicts a specific neurological syndrome. Conversely, a 
positive autoantibody profile has 80% to 90% predictive value for a 
specific cancer. It is not uncommon for more than 1 paraneoplastic 
autoantibody to be detected, each predictive of the same cancer.

Cautions:  Negative results do not exclude cancer.

The neuronal voltage-gated potassium channel Ab assay will not be 
performed for children (aged 18 years or younger) because normal values 
are not yet established for the pediatric population.

This evaluation does not include Ma2 autoantibody (alias: MaTa) or the 
NMDA receptor (NR2B). Ma2 autoantibody has been described in patients 
with brainstem and limbic encephalitis in the context of testicular 
germ cell neoplasms. Scrotal ultrasound is advisable in men who present 
with unexplained subacute encephalitis.  NMDA receptor antibodies have 
been reported in women with paraneoplastic encephalitis related to 
ovarian teratoma.
Comments:
Testing Algorithm
If IFA patterns are indeterminate, paraneoplastic autoantibody Western 
blot is performed at an additional charge.

If client requests or if IFA patterns suggest CRMP-5-IgG, CRMP-5-IgG 
Western blot is performed at an additional charge.

If P/Q-Type or N-Type calcium channel is >0.02, CRMP-5-IgG Western blot 
is performed at an additional charge.

If IFA pattern is suggestive of neuromyelitis optica (NMO), NMO-IgG is 
performed at an additional charge.

If IFA patterns suggest amphiphysin antibody, amphiphysin Western blot 
is performed at an additional charge.

If IFA patterns suggest GAD65 antibody, GAD65 antibody RIA is performed 
at an additional charge.

If ACh receptor binding antibody is >0.02 or if striational antibodies 
are > or = 1:60, ACh receptor modulating antibodies and CRMP-5-IgG 
Western blot are performed at an additional charge.

If ACh receptor modulating antibodies are > or =40% loss, RIA for ACh 
receptor blocking antibodies is performed at an additional charge.

If AChR ganglionic neuronal antibodies are >0.02, CRMP-5-IgG Western 
blot is performed at an additional charge.

If neuronal voltage-gated potassium channel (VGKC) autoantibody is 
>0.02 nmol/L, CRMP-5-IgG Western blot is performed at an additional 
charge.

Please refer to the Paraneoplastic Evaluation Algorithm from the 
Mayo Medical Laboratories.
Methodology:
Indirect Immunofluorescence (IFA)
Enzyme Immunoassay (EIA)
Radioimmunoassay (RIA)
Western Blot
CPT Code:
83519-59/ACh receptor (muscle) binding antibody
83519-59/AChR ganglionic neuronal antibody
83519-59/N-type calcium channel antibody
83519-59/P/Q-type calcium channel antibody
83520/Striational (striated muscle) antibodies
86256/AGNA-1
86256/Amphiphysin
86256/ANNA-1
86256/ANNA-2
86256/ANNA-3
86256/CRMP-5-IgG
86256/PCA-1
86256/PCA-2
86256/PCA-Tr
83519-59/ACh receptor (muscle) blocking antibodies (if appropriate)
83519-59/ ACh receptor (muscle) modulating antibodies (if appropriate)
83519-59/Neuronal (V-G) K Channel Ab, S (if appropriate)
84182/CRMP-5-IgG Western blot (if appropriate)
84182/Paraneoplastic autoantibody Western blot confirmation (if
  appropriate)
86341/GAD65 antibody assay (if appropriate)
84182/Amphiphysin Western Blot (if appropriate)
 
See also:
Paraneoplastic Autoantibody Evaluation, CSF

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Updated: 05/20/2009

Note: The information contained in this handbook is for use by personnel of University of Iowa Health Care. No other use is implied or intended.