Autoimmune Blood Tests for Nonspecific Body Pains
For patients presenting with nonspecific body pains, ANA testing should be the first-line autoimmune blood test, followed by more specific antibody tests based on clinical suspicion and ANA results. 1
Initial Testing Approach
First-Line Test
- Antinuclear Antibody (ANA) test:
- Gold standard method: Indirect Immunofluorescence Assay (IIFA) on HEp-2 cells 1
- Screening dilution typically 1:160 (abnormal ANA is a titer above the 95th percentile of healthy control population) 1
- Report should include pattern (nuclear, cytoplasmic, or mitotic) and highest dilution showing reactivity 1
Second-Line Tests (Based on ANA Results and Clinical Presentation)
- If ANA positive:
- Anti-dsDNA antibodies: Especially if SLE is suspected 1
- Extractable Nuclear Antigens (ENA) panel:
- Anti-Ro/SSA and Anti-La/SSB: For Sjögren's syndrome
- Anti-Sm: Highly specific for SLE
- Anti-RNP: Mixed connective tissue disease
- Anti-Scl-70: Systemic sclerosis
- Anti-Jo-1: Polymyositis/dermatomyositis
Testing Based on Specific Clinical Suspicion
For Inflammatory Arthritis Suspicion
- Rheumatoid Factor (RF): Present in rheumatoid arthritis (RA), but also in other conditions 2
- Anti-Cyclic Citrullinated Peptide (anti-CCP): Higher specificity for RA than RF 2
- Sensitivity: 53.1%, Specificity: 95.3% 2
For Vasculitis Suspicion
- Anti-neutrophil Cytoplasmic Antibodies (ANCA):
- c-ANCA (PR3-ANCA): Granulomatosis with polyangiitis
- p-ANCA (MPO-ANCA): Microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis 1
For Autoimmune Liver Disease Suspicion
- Anti-mitochondrial Antibodies (AMA): Primary biliary cholangitis 1
- Anti-Smooth Muscle Antibodies (SMA): Autoimmune hepatitis 1
- Anti-Liver Kidney Microsomal type 1 (anti-LKM1): Autoimmune hepatitis type 2 1
For Inflammatory Myopathy Suspicion
- Creatine Kinase (CK): Elevated in inflammatory myopathies 1
- Myositis-specific antibodies: Jo-1, Mi-2, SRP 1
Important Considerations
ANA Testing Limitations
- ANA positivity can occur in healthy individuals (especially at low titers) 3
- Positive predictive value of ANA for lupus is only about 2.1% and 9.1% for any ANA-associated rheumatic disease 3
- ANA titers <1:160 rarely indicate ANA-associated rheumatic disease 3
- ANA can be positive in non-autoimmune conditions, including infections 4
Pattern Interpretation
- Homogeneous pattern: Associated with SLE, drug-induced lupus
- Speckled pattern: Various connective tissue diseases
- Nucleolar pattern: Systemic sclerosis
- Centromere pattern: Limited cutaneous systemic sclerosis (CREST syndrome) 5
Testing Pitfalls to Avoid
- Ordering ANA without clinical suspicion: Most common reason for ANA testing is widespread pain (23.2%), but this has low yield 3
- Failing to consider non-autoimmune causes: Infections can cause positive ANA 4
- Over-reliance on a single test: No single test is diagnostic; clinical correlation is essential
- Ignoring titer levels: Higher titers generally have greater clinical significance 5
When to Refer to Rheumatology
- Positive ANA with symptoms suggestive of autoimmune disease
- Positive ANA with specific autoantibodies
- Suspected inflammatory arthritis with positive RF or anti-CCP 5
By following this structured approach to autoimmune testing in patients with nonspecific body pains, clinicians can improve diagnostic accuracy while avoiding unnecessary testing and false positive results.