Which conditions are the Crithidia test, Myeloperoxidase (MPO), Proteinase 3 (PR3), Immunoglobulin E (IgE) profile, Extractable Nuclear Antigens (ENA), and Immunoglobulins most useful for diagnosing?

Diagnostic Utility of Specialized Blood Tests in Autoimmune and Inflammatory Conditions

Each specialized blood test is most useful for diagnosing specific conditions, with MPO and PR3 being essential for diagnosing ANCA-associated vasculitides, Crithidia test for systemic lupus erythematosus, IgE profile for allergic disorders, ENA for connective tissue diseases, and immunoglobulins for immune deficiencies and plasma cell disorders. 1, 2

ANCA-Associated Tests (MPO and PR3)

Myeloperoxidase (MPO) Antibodies

• Primary diagnostic utility:
  • Microscopic polyangiitis (MPA)
  • Eosinophilic granulomatosis with polyangiitis (EGPA) - found in 30-40% of cases
  • Some cases of granulomatosis with polyangiitis (GPA)
• Clinical associations:
  • Associated with peripheral neuropathy, renal involvement, and purpura
  • Less commonly associated with pulmonary infiltrates and cardiac manifestations
• Testing approach: Should be performed using enzyme-linked immunosorbent assay (ELISA) for highest specificity 1

Proteinase 3 (PR3) Antibodies

• Primary diagnostic utility:
  • Granulomatosis with polyangiitis (GPA) - highly specific
  • Rarely in other ANCA-associated vasculitides
• Clinical associations:
  • Associated with lung nodules and skin manifestations
  • Less commonly associated with active asthma, peripheral neuropathy, and hypereosinophilia
• Testing approach: Should be performed alongside MPO testing in suspected vasculitis 1

Crithidia luciliae Test

• Primary diagnostic utility: Systemic lupus erythematosus (SLE)
• Mechanism: Detects anti-double-stranded DNA (anti-dsDNA) antibodies using kinetoplast of Crithidia luciliae
• Clinical value:
  • Highly specific for SLE diagnosis
  • Particularly useful for identifying patients at risk for lupus nephritis
  • Titers correlate with disease activity and severity of nephritis
• Advantages over other methods:
  • More specific than ELISA for anti-dsDNA
  • Comparable sensitivity to Farr radioimmunoassay but simpler and less expensive
  • Can detect complement-fixing antibodies to native DNA 3, 4, 5, 6

Extractable Nuclear Antigens (ENA)

• Primary diagnostic utility:
  • Systemic lupus erythematosus (SLE)
  • Sjögren's syndrome
  • Mixed connective tissue disease
  • Polymyositis/dermatomyositis
  • Systemic sclerosis
• Specific antibodies and their associations:
  • Anti-Ro/SSA: Sjögren's syndrome, SLE, neonatal lupus
  • Anti-La/SSB: Sjögren's syndrome, SLE
  • Anti-Sm: Highly specific for SLE
  • Anti-RNP: Mixed connective tissue disease, SLE
  • Anti-Jo-1: Polymyositis, antisynthetase syndrome
  • Anti-Scl-70: Diffuse systemic sclerosis
  • Anti-centromere: Limited systemic sclerosis (CREST syndrome)
• Clinical value: Helps identify subgroups of patients at risk for specific clinical manifestations 3

Immunoglobulin E (IgE) Profile

• Primary diagnostic utility:
  • Allergic disorders
  • Parasitic infections
  • Eosinophilic disorders including EGPA
• Clinical applications:
  • Total IgE: Elevated in allergic disorders, parasitic infections, and EGPA
  • Specific IgE: Identifies allergen triggers in allergic rhinitis, asthma, food allergies
  • Component-resolved diagnostics: Differentiates between primary sensitization and cross-reactivity
• In EGPA: Elevated IgE levels are common but not specific; must be interpreted alongside eosinophil count and clinical features 1

Immunoglobulins (IgG, IgA, IgM)

• Primary diagnostic utility:
  • Primary immunodeficiency disorders
  • Secondary immunodeficiencies
  • Monoclonal gammopathies
  • Monitoring treatment response in autoimmune conditions
• Specific patterns and their associations:
  • Low IgG, IgA, IgM: Common variable immunodeficiency
  • Low IgG with normal/elevated IgM: Hyper-IgM syndrome
  • Isolated IgA deficiency: Most common primary immunodeficiency
  • Elevated polyclonal immunoglobulins: Chronic infections, autoimmune diseases
  • Monoclonal spike: Multiple myeloma, monoclonal gammopathy of undetermined significance (MGUS)
• Monitoring applications:
  • Assess for hypoimmunoglobulinemia after rituximab treatment
  • Monitor response to immunoglobulin replacement therapy 2

Practical Approach to Testing

1. For suspected vasculitis:

   • Order both MPO-ANCA and PR3-ANCA using high-quality antigen-specific assays
   • Consider additional testing for anti-GBM antibodies in pulmonary-renal syndrome
   • Monitor inflammatory markers (ESR, CRP) and renal function alongside ANCA levels 1, 2

2. For suspected SLE:

   • Begin with ANA testing on HEp-2 cells (highly sensitive)
   • If positive, proceed with Crithidia luciliae test for anti-dsDNA (highly specific)
   • Include ENA panel to identify specific antibody patterns 3

3. For suspected allergic or eosinophilic disorders:

   • Order total IgE and specific IgE panels based on clinical presentation
   • Include complete blood count with differential to assess eosinophil count
   • Consider ANCA testing if EGPA is suspected 1, 2

4. For suspected immunodeficiency:

   • Order quantitative immunoglobulins (IgG, IgA, IgM)
   • Include IgG subclasses if specific deficiencies are suspected
   • Consider protein electrophoresis if monoclonal gammopathy is suspected 2

Important Clinical Considerations

• ANCA status alone should not determine treatment choice in vasculitis but may have prognostic implications 1
• The Crithidia luciliae test should be used in the diagnostic phase for SLE due to its high specificity 3, 4
• A negative ANCA does not exclude a diagnosis of vasculitis, particularly in limited forms of disease 1
• Immunoglobulin levels should be checked before potential IVIG therapy and monitored after rituximab treatment 2
• Serial testing of these markers is valuable for monitoring disease activity and treatment response 2