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Rheumatology Lab Testing

Raeann Whitney

Lab Test Quick Associations Additional Facts
ANA SLE, many others (NOT specific)
dsDNA SLE High level (>150) usually specific for SLE, correlates with disease activity, associated with renal disease
Anti-Smith SLE Specific for SLE but not sensitive
Anti-SSA / Ro Sjogrens (fetal heart block); also seen in SLE, MCTD, myositis Maternal positivity for SSA is associated with congenital heart block in infants.
Anti-SSB / La Sjogrens Specific for systemic sclerosis, most associated with diffuse cutaneous disease
Anti-RNP Mixed connective tissue disease Can be positive in SLE
Anti-Scl70 Scleroderma (diffuse)
Anti-centromere* Scleroderma (limited) Associated with pulmonary HTN
Anti-Jo Dermatomyositis
Anti-histone Drug-induced lupus
RF RA (not specific; also HBV/HCV, cryoglobulinemia, etc.)
Anti-CCP RA
C3/C4 SLE (hypocomplementemia)
ANCA Granulomatosis with polyangiitis, microscopic polyangiitis

At VUMC, the ANA may show a centromere pattern but does not reflex to anti-centromere Ab testing. The specific Ab should be sent to confirm if the pattern states centromere

Serologic testing must be interpreted in the clinical context. ANA, ANCA, and even specific antibodies without typical manifestations of the disease are of unclear clinical significance

Anti-nuclear Antibodies (ANA)

  • Always send with reflex (if ≥ 1:80, will check for dsDNA, Sm, SSA, SSB, Scl70, RNP)
    • At VUMC, 1:80 is considered “positive”; a higher titer is more specific for ANA-associated rheumatologic disease
      • ~30% of the general population has a “positive” ANA at 1:40, most clinically significant ANAs are at least 1:160
    • Common patterns
      • Smooth/homogenous: associated with anti-dsDNA and anti-histone antibodies
      • Speckled: associated with anti-RNP, anti-Smith, anti-SSA/Ro, anti-SSB/La
      • Nucleolar: associated with anti-Scl-70; notably many other scleroderma and overlap Ab produce a nucleolar patter but are not included on reflex such as anti-RNA-polymerase 3, anti-PM/SCL, and anti-U3-RNP

Anti-neutrophil Cytoplasmic Antibodies (ANCA)

  • Qualitative: p-ANCA, c-ANCA, negative, or indeterminate
  • Quantitative titers: anti-proteinase 3 (PR3), anti-myeloperoxidase (MPO) IgG antibodies

C3 and C4

  • Hypocomplementemia in active SLE (due to increased consumption)
  • Complement may also be low in diseases that decreases the liver’s synthetic function
  • ↓ C3/C4 in other diseases that form immune complexes or activates the classic complement pathway: mixed cryoglobulinemia, Sjogren’s, MPGN, and antiphospholipid syndrome

C-reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR)

  • Both tests are non-specific markers of inflammation
  • CRP measures a specific acute phase protein made by the liver
    • IL-6 dependent (pts on anti-IL6 therapy will have falsely decreased CRP)
    • Typically changes more rapidly (24h) than ESR (7-14d)
  • ESR is the rate at which RBCs settle to the bottom of a test tube
    • Presence of positively charged proteins disrupt the self-repelling negative charges of RBCsà clumping (rouleaux formation)à increased rate of sedimentation
      • ESR will increase in states with increased antibodies, acute phase proteins,
    • Falsely high ESR: sickle cell (microcytosis and anemia leads to fewer and smaller cells that can therefore fall fast)
    • Falsely low ESR: low fibrinogen states (DIC, HLH), polycythemia

Creatinine Kinase (CK)

  • CK can be elevated by vigorous exercise, rhabdomyolysis, endocrinopathy, cardiac disease, renal disease, malignancy, medication effect, neuromuscular disease, connective tissue disease
  • Consider inflammatory myopathies if there is ↑ CK and objective proximal muscle weakness
  • CK is normal in polymyalgia rheumatica

Extended Myositis Panel

  • Ordered as “Myositis extended Pnl-ARUP”; includes 19 separate Abs
  • Can be sent when suspecting various forms of myositis such as dermatomyositis, polymyositis, anti-synthetase syndrome (e.g. ILD work-up)

Cryoglobulins

  • Cryoglobulins are immunoglobulins that spontaneously precipitate at low temperatures and become soluble again with rewarming
  • Reported as qualitative (positive or negative) and quantitative (percentage = “cryocrit”)
    • Cryoglobulin last test is highly prone to collection error; must be collected in pre-warmed tubes and maintained at body temperature during collection and delivery to the lab;
    • At VUMC can only be obtained at certain times M-F; lab and nursing staff can coordinate
  • Cryoglobulins are classified into three types: Type I, II, and III
  • Type I cryoglobulins: monoclonal immunoglobulin (IgM or IgG)
    • Lymphoproliferative disorders: Waldenström’s, MM, CLL, B cell lymphomas
    • Types II and III are mixed cryoglobulins (they contain polyclonal components)
    • Essentially all mixed cryoglobulinemias will be RF+ *
    • Commonly associated with HCV (~90%); also CTD
    • Type II: monoclonal Ig with RF activity against polyclonal Igs
    • Type III: polyclonal Ig with RF against polyclonal Igs
  • *RF activity by definition is the reactivity of an IgM component with the Fc portion of an IgG
  • Cryoglobulinemic vasculitis: small vessel vasculitis resulting from vascular deposition of cryoprecipitates (immune complexes)
    • Skin most common: palpable purpura, usually in lower extremities (colder areas), immune-complex mediated leukocytoclastic vasculitis on biopsy
    • Additional manifestations: arthralgias, peripheral motor or sensory neuropathy, sicca, glomerulonephritis (usually MPGN)
    • Treatment: B cell depletion (rituximab) and treatment of underlying cause (e.g. Hep C)