LABORATORY TESTING: SERUM ANTIBODIES
GM1 ganglioside

Indications
Lower motor neuron syndromes
Motor neuropathy: Chronic; Acute
Clinical features
  Distal; Asymmetric
  Upper extremity onset: Often
Treatment follow-up
  Document sufficient cytoxan
    Best prognosis: Anti-GM1
      titers ê by > 70%
é Likelihood of positive test:
  Asymmetry
  No upper motor neuron signs
  No prominent sensory Δ
  Motor conduction block

+ Results
ELISA
  IgM vs GM1 or NP-9 > 1,800
    Low IgM vs Histone H3
  IgG vs GM1 > 1,000
    Low IgG vs Sulfatide
Clinical correlations
  IgM +
    Motor neuropathy: Chronic
      85% sensitivity
      99% specificity vs ALS
  IgG +
    Motor neuropathy: Acute
      50% sensitivity
      90% specificity

Lab standards: IgM
> 80% sensitivity for MMN
> 95% clinical specificity

Interpretation
Diagnosis
  Dx of immune neuropathy
    Distinguish vs CIDP & ALS
Prognosis: Not ALS;
  Slow progression
Treatment
  Cytoxan or HIG often useful
  Prednisone not useful
Follow-up: Cytoxan Rx
  é anti-GM1 titer ® ? Relapse
Myelin-associated glycoprotein

Indications
Adult onset neuropathy:
  Clinical:
    Distal; Symmetric;
    Sensory > Motor
  Electrodiagnostic: Demyelination
    Usually with
      é distal latency
      No conduction block
  Serum: IgM M-protein
Treatment follow-up
  Document sufficient cytoxan
  Best prognosis:
    Anti-MAG titers ê by > 60%
    Usually with cytoxan Rx
é Likelihood of positive test:
  Age > 50
  Gait disorder
  Tremor
  Disability 2° sensory
    or motor loss
  Demyelination
  Serum IgM M-protein: 85%

+ Results
ELISA
  IgM vs MAG > 1,500
  Low IgM vs Histone H3
Western blot confirmation
Clinical correlation: Titer > 6,000
  Demyelinating neuropathy
  90% specificity; 95% sensitivity

Lab standards
Document 90% clinical specificity

Interpretation
Diagnosis
  Dx of immune neuropathy
    Distinguish from CIDP
Prognosis: Slow progression
Treatment
  Cytoxan may be useful
  Prednisone & HIG not useful
Follow-up
  é anti-MAG titer ® ? Relapse
Sulfatide

Indications
Adult onset neuropathy:
  Clinical:
    Distal; Symmetric;
    Sensory > Motor
é Likelihood of positive test:
  Age > 50
  Gait disorder
  Tremor
  Disability 2° sensory
    or motor loss
  Demyelination
  Serum IgM M-protein: 50%

+ Results
IgM vs Sulfatide > 5,000
    Low IgM vs Histone H3
    IgM M-protein
  Clinical correlation
    Sensory-motor neuropathy
    ± Gait Δ (GALOP)
    Demyelination
    Specificity: 85%
IgM vs Sulfatide > 5,000
    Low IgM vs Histone H3
    No M-protein
  Clinical correlation
    Sensory neuropathy
    Axonal
    Specificity: 85%
IgG vs Sulfatide > 6,000
    Low IgG vs GM1
  Clinical correlation
    Sensory neuropathy
    Specificity: 80%

Lab standards
80% to 85% clinical specificity

Interpretation
Diagnosis
  Dx of immune neuropathy
    Distinguish from CIDP
Prognosis: Slow progression
Treatment: ? HIG or cytoxan
Hu

Indications
Sensory neuronopathy
é Likelihood of positive test:
  Asymmetry; Rapid progression
  Sensory ê:
    Proximal; All modalities
  CNS signs: Cerebellar; Limbic
  Neoplasm: Small cell lung
Low likelihood of positive test:
  Sensory neuropathy
    Distal only; Chronic
    Normal proprioception
  Weakness: Distal

+ Result
Clinical correlation
  Low titer: Neoplasm
  High titer: Also PNS & CNS Δ
  Specificity > 95%

Lab standards
2 methods confirm IgG vs Hu
  Western blot: 35 to 40 kDa bands
  Immunocytochemistry
    IgG vs neuronal nuclei

Interpretation
Neuronopathy: No response to Rx
Neoplasm: Small cell
  Work-up indicated
  Small size; Slow-growing
Other Ab (usually IgG) targets

Yo: Cerebellar; Female Ca
Tr: Cerebellar; Hodgkin's
Ri: Opsoclonus; Ataxia; Breast Ca
GQ1b: Miller-Fisher (80%)
GalNAc-GD1a: AMAN; Demyelinating PN
GAD: Stiffman; Diabetes
Tubulin: IgM; CIDP; Asymmetry
GD1b: IgM; Ataxic neuropathy
P-type Ca++ channel: LEMS
Striation: MG; Thymoma
K+ channel (KCNA6): Isaac's
Decorin (BJ): Myopathy; IgM
Jo-1: Myositis; Lung Δ
Mi-2: Dermatomyositis; Nail Δ
ANCA: Vasculitis
SSA (Ro): Sjögren's
GALOP

Indications
Neuropathy & Gait Δ
  Onset > 50
  Sensory ± motor PN
  Gait Δ; Falling

+ Result
IgM vs GALOP antigen > 10,000
    Low IgM vs Histone H3
  Specificity > 90%

Interpretation
Diagnosis
  Dx of immune neuropathy
    Distinguish from CIDP
Prognosis: Slow progression
Treatment: HIG or cytoxan
M-protein

Indications
Adult-onset neuropathy
  Clinical: Numerous syndromes

+ Result
IgM, IgG, or IgA M-protein

Lab standards
Immunofixation method
NOT protein electrophoresis

Interpretation
Diagnosis
  r/o Myeloma
    Skeletal survey
    ± Bone marrow biopsy
Acetylcholine receptor

Indications
Fatigue; Weakness;
  Thymoma

+ Result
Clinical correlation
  Myasthenia gravis
    Sensitivity:
      MG + Thymoma: 100%
      Adult generalized: 90%
      Child & Ocular: 50%
    Specificity
      Young: 99%;
      > 70 yrs: 97%
Lab standard
IgG binding to AChR
  by immunoprecipitation

Interpretation
Diagnosis: Myasthenia gravis
  r/o Thymoma; Thyroid Δ
  No relation: Absolute titer
    vs MG severity
Treatment
  ê titer in patient ® ê severity
Laboratory standard testing
Neuromuscular Clinical Lab
Washington University
660 South Euclid
Box 8111
St. Louis, MO 63110
314-362-6981
Testing: GM1; MAG; Sulfatide
  Hu; Yo; GALOP; BJ
Oklahoma Medical Research Foundation
Clinical Immunology Laboratory
825 N.E. 13th Street, C-323
Oklahoma City OK 73104
405-271-7771
Testing: Myositis antibodies
Athena Diagnostics
Four Biotech Park
377 Plantation Street
Worcester, MA 01605
800-394-4493
Testing: Sulfatide; GALOP;
  Hu & Yo (Western blot only);
  CMT 1A & X
Mayo Medical Lab
200 First Street SW
Rochester, Minnesota 55905
800-533-1710
Testing: AChR antibody;
  LEMS antibody;
  Hu (Immunocytochemistry only)
Alan Pestronk 6/5/00: More information at Neuromuscular Website: http://www.neuro.wustl.edu/neuromuscular/