What is the significance and appropriate treatment approach for a patient with abnormal results in ANA (Antinuclear Antibody), ENA (Extractable Nuclear Antigens) panel, dsDNA (double-stranded DNA), ESR/CRP (Erythrocyte Sedimentation Rate/C-Reactive Protein), ACE (Angiotensin-Converting Enzyme), Lyme serology, HIV (Human Immunodeficiency Virus), syphilis panel, B12 (Vitamin B12), Vit D (Vitamin D), TSH (Thyroid-Stimulating Hormone), AQP4-IgG (Aquaporin-4 Immunoglobulin G), and MOG-IgG (Myelin Oligodendrocyte Glycoprotein Immunoglobulin G) tests?

Diagnostic Workup Panel for Neurologic and Systemic Autoimmune Evaluation

Purpose and Clinical Context

This comprehensive laboratory panel is designed to evaluate for autoimmune, infectious, metabolic, and demyelinating disorders, particularly in patients presenting with neurologic symptoms or suspected immune-mediated conditions. 1

Individual Test Significance

Autoimmune Markers

• ANA (Antinuclear Antibody): Screens for systemic autoimmune diseases including systemic lupus erythematosus, though positive results can occur with infections (both acute and chronic) and autoimmune thyroid disease without indicating systemic disease 2, 3

• ENA (Extractable Nuclear Antigens) Panel: Identifies specific autoantibodies (anti-Ro, anti-La, anti-Sm, anti-RNP) that help differentiate between various connective tissue diseases when ANA is positive 1, 3

• dsDNA (double-stranded DNA): Highly specific for systemic lupus erythematosus; used to confirm diagnosis when ANA is positive and to monitor disease activity 1, 3

Inflammatory Markers

• ESR/CRP (Erythrocyte Sedimentation Rate/C-Reactive Protein): Non-specific markers of inflammation used to assess for active inflammatory processes, vasculitis, or infection; particularly useful in evaluating encephalitis or other CNS inflammatory conditions 1

• ACE (Angiotensin-Converting Enzyme): Elevated in sarcoidosis and other granulomatous diseases; helps evaluate for neurosarcoidosis when neurologic symptoms are present 1

Infectious Disease Screening

• Lyme Serology: Detects Borrelia burgdorferi antibodies; essential for evaluating neurologic symptoms that may represent Lyme neuroborreliosis 1

• HIV Testing: Identifies human immunodeficiency virus infection, which can cause neurologic complications and secondary immunodeficiency; recommended in all patients with new immune thrombocytopenia or Evans syndrome 1, 4

• Syphilis Panel (RPR/VDRL): Screens for Treponema pallidum infection, which can cause neurosyphilis presenting with diverse neurologic manifestations 1

Nutritional and Metabolic Markers

• B12 (Vitamin B12): Deficiency causes subacute combined degeneration of the spinal cord, peripheral neuropathy, and cognitive changes; must be evaluated in myelopathy workup 1

• Vitamin D: Deficiency associated with autoimmune disease risk and bone health; commonly checked in comprehensive autoimmune evaluations 1

• TSH (Thyroid-Stimulating Hormone): Screens for thyroid dysfunction, which can cause neurologic symptoms and is associated with other autoimmune conditions; thyroid disease commonly produces positive ANA without systemic autoimmune disease 1, 3

Demyelinating Disease-Specific Antibodies

• AQP4-IgG (Aquaporin-4 Immunoglobulin G): Diagnostic for AQP4-positive neuromyelitis optica spectrum disorders (NMOSD); mandatory in evaluation of transverse myelitis, optic neuritis, or area postrema syndrome 1, 5, 6

• MOG-IgG (Myelin Oligodendrocyte Glycoprotein Immunoglobulin G): Identifies MOG-associated disease (MOGAD), which presents similarly to AQP4-NMOSD but has distinct pathophysiology with less blood-brain barrier breakdown and lower peripheral plasmablast elevation during acute attacks 5, 6

Key Diagnostic Distinctions

AQP4-NMOSD vs. MOGAD Differentiation

MOG-associated disease shows significantly less blood-brain barrier compromise compared to AQP4-positive NMOSD, with lower CSF protein, myelin basic protein, albumin quotient, and IgG quotient. 5

• MOGAD patients demonstrate lower plasmablast elevation during acute phases (2.1 ± 2.4) compared to AQP4-NMOSD (7.8 ± 7.2), indicating different B-cell pathogenesis 5

• MOG-IgG can be CSF-restricted in approximately 29% of cases, whereas AQP4-IgG is never found exclusively in CSF 6

• Intrathecal MOG-IgG production occurs more frequently than AQP4-IgG production, with elevated antibody index (>4.0) in 57% of MOG-IgG cases versus only 6% of AQP4-IgG cases 6

Clinical Application Algorithm

When to Order This Panel

Order this comprehensive panel for patients presenting with:

• Unexplained transverse myelitis, optic neuritis, or brainstem syndromes 1
• Encephalitis or aseptic meningitis after excluding infectious causes 1
• Immune-mediated cytopenias (particularly Evans syndrome) requiring underlying etiology evaluation 7, 4
• Peripheral neuropathy or Guillain-Barré-like syndromes in the context of possible autoimmune disease 1

Interpretation Pitfalls

Common pitfalls to avoid:

• Positive ANA occurs in 46% of Hashimoto's thyroiditis and is significantly elevated in Graves' disease without indicating systemic lupus erythematosus or other systemic autoimmune disease 3

• ANA positivity increases with acute and chronic infections, particularly in children with non-specific symptoms like fever, joint pain, or fatigue 2

• Isolated positive ANA without specific ENA antibodies or clinical symptoms does not warrant treatment or diagnosis of autoimmune disease 2, 3

Required Additional Testing

When specific antibodies are positive, additional workup includes:

• For positive AQP4-IgG or MOG-IgG: MRI brain and spine with contrast, lumbar puncture with cell count, protein, glucose, oligoclonal bands, and viral PCRs 1, 6

• For cytopenias: Bone marrow examination to exclude lymphoproliferative disorders, myelodysplastic syndromes, or aplastic anemia 1, 7, 4

• For positive HIV: CD4 count, viral load, and hepatitis B/C co-infection screening before initiating treatment 1, 4