Rheumatology Lab Testing

Meridith Balbach

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Additional Facts

ANA w/ reflex (performed if ANA 1:80 and includes antidsDNA, SSA, SSB, ScL 70, Smith, RNP) Screening for connective tissue disease Not disease-specific; pattern (homogeneous, speckled, nucleolar, centromere) may help narrow differential; in particular, consider addtl workup if centromere or nucleolar pattern (i.e. anti-centromere, anti-Pm/Scl)
  • Anti-dsDNA
 SLE Specific but low sensitivity (~20–30%)
  • Anti-Smith
 SLE Good 1st line agent
Less BP effect than dilt
  • Anti-SSA (Ro)
 Sjögren’s, SLE, neonatal lupus Associated with congenital heart block in neonates if maternal +SSA
  • Anti-SSB (La)
 Sjögren’s (almost always with SSA) Less sensitive; typically coexists with SSA
  • Anti-RNP
 MCTD, SLE Seen in Raynaud’s, swollen hands; overlaps with myositis
  • Anti-Scl-70 (Topo I)
 Diffuse systemic sclerosis Associated with ILD and aggressive skin disease
Anti-centromere Limited systemic sclerosis Associated with PAH, CREST features, slower progression; consider if +ANA with centromere pattern (not part of reflex)
Anti-histone Drug-induced lupus Classically associated with hydralazine, procainamide, isoniazid
Anti-Jo-1 Antisynthetase syndrome (ILD + myositis + Raynaud’s) Associated with mechanic’s hands, poor ILD prognosis
Anti-CCP RA High specificity (~95%); predictive of erosive disease
RF RA (nonspecific) Marker of chronic humoral immune stimulation; seen in HCV, cryoglobulinemia, aging
C3 / C4 SLE, cryoglobulinemia Low C3/C4 suggests active immune complex disease; C4 often falls first
ANCA / PR3 / MPO GPA, MPA, EGPA PR3 (c-ANCA) → GPA; MPO (p-ANCA) → MPA/EGPA; can be drug- or infection-induced
Antiphospholipid antibody panel (includes INR, PTT, anticardiolipin, antibeta-2-glycoprotein, lupus anticoagulant) Antiphospholipid syndrome (may be primary or secondary to autoimmune disease—about 50% of all cases) medium/high titers and persistent IgG or IgM positivity ≥12 weeks required for diagnosis

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 hbuh7 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 overlab 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 (perinuclear staining) and c-ANCA (diffuse cytoplasmic staining)
  • Quantitative titers: anti-proteinase 3 (PR3) and 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

  • - Reported as qualitative (positive or negative) and quantitative (percentage = “cryocrit”)
    • Cryoglobulin 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
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