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Rheumatology Lab Testing

Raeann Whitney

Lab Test Quick Associations
ANA SLE, many others (NOT specific)
Anti-Smith SLE
Anti-SSA / Ro Sjogrens (fetal heart block)
Anti-SSB / La Sjogrens
Anti-RNP Mixed Connective Tissue Disease
Anti-Scl70 Scleroderma (diffuse)
Anti-Centromere Scleroderma (limited)
Anti-Jo Dermatomyositis
Anti-histone Drug-induced lupus
RF RA (not specific; also HBV/HCV, cryoglobulinemia, etc.)
C3/C4 SLE (hypocomplementemia)
ANCA Granulomatosis with polyangiitis, microscopic polyangiitis

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

  • Specific types of ANAs:

    • Anti-dsDNA: High levels (>150) are usually specific for SLE. Can correlate with disease activity, a/w renal disease

    • Anti-Smith (Qualitative): Very specific for SLE but not sensitive

    • Anti-SSA/Ro

      • Classic for Sjogren’s but non-specific; can also be seen in SLE, MCTD, myositis, etc

      • Maternal positivity for SSA is associated with congenital heart block in infants

    • Anti-SSB/La: Similar profile to Anti-SSA/Ro but less common

    • Anti-Scl-70: Specific for systemic sclerosis, most associated with diffuse cutaneous disease

    • Anti-RNP: Required for MCTD diagnosis, can also be seen in SLE

    • Anti-histone: drug-induced lupus

    • Anti-centromere: limited scleroderma, a/w pulmonary HTN

    • Anti-RNA polymerase III: increased risk of scleroderma renal disease

Anti-neutrophil Cytoplasmic Antibodies (ANCA)

  • Qualitative: p-ANCA, c-ANCA, negative, or indeterminate

  • Quantitative titers: anti-proteinase 3 (PR3), anti-myeloperoxidase (MPO) IgG antibodies

  • See vasculitis section for further details

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, activating 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 anti-IL6 therapy will have falsely decreased CRP)

    • Typically changes more rapidly than ESR as it is a direct measure of acute phase reactant

  • 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 RBCs clumping (rouleaux formation) increased rate of sedimentation

      • ESR will increase in states with increased antibodies, acute phase proteins, etc
    • Falsely low ESR: low fibrinogen states (DIC, HLH), sickle cell, 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 elevated CK and objective proximal muscle weakness

  • Notably, 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 (ex- ILD work-up)


  • 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 & nursing staff can coordinate

  • Cryoglobulins are classified into three types: Type I, II, and III

    • Type I Cryoglobulins: Monoclonal immunoglobulins (IgM or IgG)

      • A/w 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, vascular deposition of cryoprecipitates

    • Skin most common: palpable purpura, usually in lower extremities (colder areas), immune-complex mediated leukocytoclastic vasculitis on biopsy

    • Additional manifestations include: Arthralgias, peripheral motor or sensory neuropathy, sicca, glomerulonephritis (usually MPGN)

Last update: 2022-06-26 16:41:25