Acetyl Choline Receptor Antibodies (AChRab)

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Critical diagnostic tool in evaluating neuromuscular disorders, especially myasthenia gravis

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Acetyl Choline Receptor Antibodies (AChRab) - Comprehensive Test Information Guide

Section 1: Why is it done?
- Test Purpose: Detects antibodies against acetylcholine receptors at the neuromuscular junction. These autoimmune antibodies attack and damage the AChR, leading to impaired neuromuscular transmission and characteristic muscle weakness.
- Primary Indications: Diagnosis of Myasthenia Gravis (MG) in patients presenting with ptosis, diplopia, bulbar weakness, or generalized muscle weakness; Confirmation of suspected autoimmune neuromuscular disorder; Evaluation of treatment response in diagnosed MG patients
- Clinical Presentation Triggers: Patients with fluctuating ocular symptoms (drooping eyelids, double vision); Progressive muscle fatigue throughout the day; Bulbar symptoms (difficulty swallowing, speaking, chewing); Respiratory muscle involvement; Family history of myasthenia gravis or autoimmune disorders
- Typical Timing: Initial diagnostic workup when myasthenia gravis is suspected; Before starting immunosuppressive therapy; Periodically during disease monitoring (typically 6-12 months in stable patients); When assessing treatment efficacy or disease progression; Prior to thymectomy in seropositive patients
Section 2: Normal Range
- Reference Range/Normal Values: Negative/Undetectable: <0.4 nmol/L (typical cutoff varies by laboratory: generally <0.3-0.5 nmol/L)
- Units of Measurement: nmol/L (nanomoles per liter) using radioimmunoprecipitation assay (RIA); Some laboratories may report in IU/mL (International Units per milliliter) with cutoff typically <0.4-1.0 IU/mL
- Negative Result Interpretation: No detectable antibodies against acetylcholine receptors; Does not exclude myasthenia gravis diagnosis (15-20% of generalized MG cases and up to 50% of ocular MG cases are seronegative); Associated with lower disease severity in some patients
- Positive Result Interpretation: Detectable AChR antibodies present; Highly specific for myasthenia gravis; Indicates autoimmune attack on neuromuscular junction; Value >0.4 nmol/L confirms diagnosis
- Result Stratification: 0.0-0.4 nmol/L: Negative (Normal); 0.4-1.5 nmol/L: Mildly positive (generally indicative); 1.5-5.0 nmol/L: Moderately positive (significant immune response); >5.0 nmol/L: Strongly positive (substantial autoimmune activity)
Section 3: Interpretation
- Positive AChRab Results (>0.4 nmol/L): Diagnostic of myasthenia gravis with >99% specificity; Indicates autoimmune destruction of acetylcholine receptors; Correlates with disease severity (higher titers often associated with more generalized disease); Present in 80-85% of generalized MG; Present in 50% of purely ocular MG; Suggests thymoma association in 10-15% of seropositive patients
- Negative AChRab Results (<0.4 nmol/L): Does not exclude myasthenia gravis; May indicate seronegative MG (requires additional testing); Suggests consideration of MuSK antibody testing; Patient may have double seronegative MG if MuSK is also negative; Warrants repeat testing if high clinical suspicion persists
- Serial Monitoring Changes: Decreasing titers typically indicate therapeutic response to immunosuppressive treatment; Persistent or increasing titers suggest inadequate disease control; Conversion from seropositive to seronegative rare but possible with remission; Rising titers may precede clinical deterioration
- Factors Affecting Results: Timing of testing (early disease may have lower titers); Immunosuppressive therapy (reduces titers); Recent thymectomy (may temporarily increase or decrease titers); Disease duration (longer duration may show higher titers); Patient age (juveniles often have lower titers); Concurrent infection or immunological stress
- Clinical Correlation Importance: Antibody titer does not always correlate with symptom severity; Some patients with high titers may have mild symptoms; Clinical examination findings must be integrated with serologic results; Diagnosis requires combination of serology, clinical presentation, and confirmatory tests (edrophonium test, electromyography, repetitive nerve stimulation)
Section 4: Associated Organs
- Primary Organ Systems Involved: Neuromuscular junction (primary site of autoimmune attack); Skeletal muscles (affected by impaired neurotransmission); Thymus gland (often hyperplastic or contains thymoma in AChRab-positive patients); Central nervous system (mood disorders, cognitive effects in some cases); Respiratory system (respiratory muscles affected in myasthenic crisis)
- Myasthenia Gravis Classifications: Ocular MG: Affects eye muscles (ptosis, diplopia); bulbar symptoms limited to eyes; Generalized MG: Extends beyond ocular muscles to limbs and respiratory muscles; Seronegative MG: No detectable AChRab (may have MuSK antibodies); Thymoma-associated: 10-15% of AChRab-positive patients have thymoma
- Diseases/Conditions Associated with Abnormal Results: Myasthenia Gravis (primary disorder); Thymoma (especially in seropositive patients); Lambert-Eaton myasthenic syndrome (related but distinct); Thyroid disorders (common association with MG); Lupus and other autoimmune diseases (increased incidence in MG patients); Sjögren's syndrome; Rheumatoid arthritis
- Potential Complications of Abnormal Results: Myasthenic crisis (respiratory failure requiring mechanical ventilation); Oculomotor complications (permanent ocular muscle damage); Bulbar dysfunction (aspiration, feeding difficulties); Respiratory muscle paralysis; Cholinergic crisis (from excessive treatment); Thymoma-related complications if present; Cardiovascular involvement (rare but serious)
- Thymic Involvement: Thymic hyperplasia present in 65% of AChRab-positive MG; Thymoma present in 10-15% of seropositive patients; Thymic imaging (CT or MRI) recommended in AChRab-positive patients; Thymectomy beneficial in AChRab-positive generalized MG; Thymic abnormalities require monitoring and potential intervention
Section 5: Follow-up Tests
- Confirmatory Tests (if Positive AChRab): Repetitive nerve stimulation (RNS) - shows decremental response in 60-70% of generalized MG; Single fiber electromyography (SFEMG) - most sensitive test, abnormal in 90-95% of generalized MG; Edrophonium test (rarely used now, replaced by other modalities); Muscle-specific kinase (MuSK) antibody testing (for seronegative patients)
- Confirmatory Tests (if Negative AChRab): MuSK antibody testing (positive in 40-50% of AChRab-negative patients); Repetitive nerve stimulation (abnormal in seronegative patients with generalized MG); Single fiber electromyography (highly sensitive for seronegative MG); Ice pack test (bedside clinical test for ocular MG); Neostigmine test (clinical assessment)
- Imaging Studies Recommended: Chest CT (evaluate for thymoma in AChRab-positive patients); Thyroid ultrasound (screen for thyroid disorders); Brain MRI (if atypical neurological presentation); Chest X-ray (initial screening for mediastinal abnormalities)
- Associated Autoimmune Screening: Thyroid function tests (TSH, free T4); Thyroid peroxidase antibodies (TPO); Thyroglobulin antibodies; Antinuclear antibody (ANA); Rheumatoid factor; Anti-muscle-specific kinase (anti-MuSK) if seronegative; Complete blood count; Liver and kidney function tests (baseline for immunosuppressive therapy)
- Monitoring During Treatment: Serial AChRab titers every 6-12 months in stable patients; More frequent testing if treatment adjusted; Antibody levels help assess treatment efficacy; Clinical myasthenia gravis composite scores; Pulmonary function tests (for respiratory involvement)
- Pre-Treatment Baseline Testing: Complete metabolic panel (before corticosteroids or immunosuppressants); Hepatitis and HIV screening (before biologics); Complete blood count with differential; Pulmonary function tests (before thymectomy); Cardiac assessment (if considering certain medications)
Section 6: Fasting Required?
- Fasting Requirement: NO - Fasting is NOT required for AChRab testing
- Specimen Collection Requirements: Blood draw: 5-10 mL venous blood sample; Serum collection tube (usually SST/gold top or similar); No special preparation needed; Can be collected any time of day; Sample should be processed within 24 hours for optimal results
- Medications to Avoid: No medications need to be held before testing; Immunosuppressive therapy does NOT interfere with test (may lower titers but testing can proceed); Anticholinesterase medications (pyridostigmine, neostigmine) do not affect serology; Continue all regular medications unless specifically instructed otherwise
- Patient Preparation Instructions: No fasting required - can eat and drink normally; No special clothing requirements; Comfortable attire recommended for easy blood draw access; Inform phlebotomist of any blood draw difficulties or arm restrictions; Stay hydrated (helps with venipuncture); Arrive without excessive exercise or stress if possible
- Timing Considerations: No time-of-day restrictions; Test can be performed morning or afternoon; Symptoms may be worse at end of day (fatigue) but this does not affect antibody levels; If patient is in myasthenic crisis, urgent care protocols apply
- Special Instructions: Inform laboratory if currently receiving plasma exchange or IVIG (affects antibody levels); Notify if on experimental immunotherapy; Report recent infections or vaccinations (theoretical immune stimulation); Inform if pregnant (elevated antibodies may persist); Inform if symptomatic - helps with interpretation

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