Autoimmune Neuropathies - Neuropathic Disease

Last Literature Review: February 2020 Last Update:

Autoimmune neuropathies present with a broad range of symptoms, including subacute progression, asymmetric or multifocal deficits, and selective involvement of motor, sensory, or autonomic nerves.  The overlap of symptoms among syndromes often makes diagnosis difficult. Presumptive diagnosis is based on patient history and clinical presentation. Initial laboratory testing aims to rule out underlying etiologies, including potential infection, metabolic disturbances, and brain tumors; if nothing is uncovered, further evaluation, including imaging, nerve conduction studies, and cerebrospinal fluid (CSF) analysis may be required.  Autoimmune neuropathies can also arise as paraneoplastic disorders in the setting of cancer. The detection of an autoantibody in the right clinical setting provides some evidence that the peripheral nerve disturbance is immune mediated and may direct treatment, but antibody testing cannot be used as the sole diagnostic tool. 

Quick Answers for Clinicians

What is the role of antibody testing in suspected autoimmune neuropathies?

Antibody testing is not part of accepted diagnostic criteria or management strategies for autoimmune neuropathies. In most cases, such as in Guillain-Barré syndrome (GBS), the initial diagnosis is based on clinical presentation and is established if cerebrospinal fluid (CSF) and electrodiagnostic studies (eg, nerve conduction studies) show abnormalities.  Antibody testing may help to clarify the diagnosis, but cannot be used as the sole diagnostic tool.

Are certain biomarkers associated with specific neuropathies?

Some antibodies show statistically significant associations with specific neuropathic syndromes. For example, antimyelin-associated glycoprotein (anti-MAG) antibodies are often present in patients with predominant sensory symptoms, and anti-GM1 antibodies are present in patients with predominant motor symptoms. Refer to the Nonparaneoplastic Markers and Paraneoplastic Markers tables for more examples.

Do antibody titers correlate with the level of disease activity?

Most antibody titers do not correlate with the level of disease activity in autoimmune neuropathies.

Should all patients with monoclonal gammopathy of undetermined significance be tested for autoimmune neuropathy?

Monoclonal gammopathy of undetermined significance (MGUS) has a prevalence of 3-4% among those older than 50 years, and the presence of an M protein does not automatically indicate a causal relationship to the neuropathy.  Additional investigation is required to differentiate monoclonal gammopathy-associated peripheral neuropathy from specific plasma cell disorders (eg, immunoglobulin light chain amyloidosis, POEMS [polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes] syndrome) that are known to have a definite causal relationship. 

Which differential diagnoses should be considered when investigating autoimmune neuropathies?

Frequent differential diagnoses include infections (eg, West Nile virus, enterovirus, and poliovirus), myasthenia gravis, and other autoimmune diseases (eg, rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome, and mixed connective tissue disease).

Indications for Testing

Autoantibody testing can be considered in individuals presenting with severe or rapidly progressive muscle weakness and sensory symptoms and no known underlying infection or etiology.


Autoimmune neuropathies are categorized as acute or chronic. Acute neuropathies include Guillain-Barré syndrome (GBS) and its variants. Chronic autoimmune neuropathies are described in relation to classic chronic inflammatory demyelinating polyneuropathy (CIDP). Neuropathies are further distinguished by their dominant presentation: motor, sensory, or a combination of both. Test choice depends on both the clinical manifestation and the risk of malignancy.

Nonparaneoplastic Markers
AutoantibodyExamples of Associated Neuropathic Syndromes
GM2GBS variants
GD1aAxonal GBS
GD1bSensory peripheral neuropathy, MND, GBS
GQ1bMFS, acute ophthalmoplegia, cerebellar ataxia
MAG/SGPGInflammatory (often demyelinating) neuropathy with IgM gammopathy, gait ataxia, hand tremor
SulfatideChronic sensory peripheral neuropathy, GALOP syndrome

ALS, amyotrophic lateral sclerosis; AMAN, acute motor axonal neuropathy; GALOP, gait disorder, antibody, late-age onset polyneuropathy; IgM, immunoglobulin M; MAG, myelin-associated glycoprotein; MFS, Miller-Fisher syndrome; MMN, multifocal motor neuropathy; MND, motor neuron disease; SGPG, sulfate-3-glucuronyl paragloboside

Source: Vernino, 2007 

Paraneoplastic Markers
AutoantibodyExamples of Associated Neuropathic SyndromesAssociated Malignancies
Hu (ANNA-1)PN, limbic encephalitis, ataxia, sensory neuronopathy, autonomic and sensorimotor neuropathies, GI dysmotilitySCLC
CV2 (CRMP5)PN, limbic encephalitis, ataxia, chorea, optic neuritisSCLC, thymoma
AmphiphysinEncephalomyelitis, neuropathy, stiff-person syndromeLung, breast
Ri (ANNA-2)Ataxia, opsoclonus-myoclonus, neuropathyLung, breast
ANNA-3Ataxia, limbic encephalitis, neuropathyLung, breast
N-type calcium channel antibodiesPN, other syndromesLung, breast

GI, gastrointestinal; PN, peripheral neuropathy; SCLC, small cell lung cancer

Source: Vernino, 2007 

Laboratory Test Selection

Appropriate laboratory test selection depends on both the clinical manifestation and the risk of malignancy. Generally, laboratory panels for autoimmune neuropathy investigation are designed to include appropriate antibody components for various clinical manifestations (eg sensory, motor, or a combination) and malignancies. The table below details four ARUP-specific panels and their included antibody components.

Antibody ComponentsPrimary Tests for Autoimmune Neuropathies
Test Components (Standalone Test Number)Sensory Neuropathy Antibody Panel (2007965)Motor and Sensory Neuropathy Evaluation (2007966)Motor and Sensory Neuropathy Evaluation with IFE (2007967)Motor Neuropathy Panel (0051225)
Purkinje cell/neuronal nuclear, IgGa


Purkinje cell antibody titera


Neuronal nuclear (Hu, Ri, and Yo, and Tr/DNER), IgG (3002917)a


Neuronal nuclear antibody (ANNA), IgG titera


MAG, IgM (0051285)

SGPG, IgM (0051284)

Asialo-GM1, IgG and IgM


GM1, IgG/IgM


GD1a, IgG/IgM


GD1b, IgG/IgM


GQ1b, IgG/IgM


Total protein, serum






Alpha-1 globulin



Alpha-2 globulin



Beta globulins



Gamma globulins



IgA (0050340)b



IgG (0050350)b



IgM (0050355)b



aThese components are available as a directed PCCA/ANNA by IFA with Reflex to Titer and Immunoblot panel (2007961).

bThese components are available as a directed Immunoglobulins (IgA, IgG, IgM), Quantitative panel (0050630).

ARUP Laboratory Tests

Panels for Suspected Malignancy

Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Quantitative Immunoturbidimetry/Quantitative Capillary Electrophoresis/Qualitative Immunofixation Electrophoresis/Colorimetry

Other Tests (Single and Combined Antibodies)

Medical Experts




Joshua M. Klonoski, MD, PhD
Neuropathology Fellow, Department of Pathology, University of Utah
Former Assistant Medical Director of Informatics and Content Editor at ARUP Laboratories


Tammy Smith, MD, PhD
Assistant Professor of Neurology, University of Utah
Clinical Consultant, Autoimmune Neurology, ARUP Laboratories
GRECC Investigator, George E. Wahlen Department of Veterans Affairs Medical Center