Rheumatology Lab Testing¶
Raeann Whitney
| Lab Test | Quick Associations |
|---|---|
| ANA | SLE, many others (NOT specific) |
| dsDNA | SLE |
| 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.) |
| Anti-CCP | RA |
| 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)¶
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Always send with reflex (if ≥ 1:80, will check for dsDNA, Sm, SSA, SSB, Scl70, RNP)
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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
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Common Patterns
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Smooth/homogenous – associated with Anti-dsDNA and Anti-histone antibodies
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Speckled – associated with Anti-RNP, Anti-Smith, Anti-SSA/Ro, Anti-SSB/La
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Nucleolar – associated with Anti-Scl-70
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Specific types of ANAs:
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Anti-dsDNA: High levels (>150) are usually specific for SLE. Can correlate with disease activity, a/w renal disease
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Anti-Smith (Qualitative): Very specific for SLE but not sensitive
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Anti-SSA/Ro
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Classic for Sjogren’s but non-specific; can also be seen in SLE, MCTD, myositis, etc
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Maternal positivity for SSA is associated with congenital heart block in infants
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Anti-SSB/La: Similar profile to Anti-SSA/Ro but less common
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Anti-Scl-70: Specific for systemic sclerosis, most associated with diffuse cutaneous disease
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Anti-RNP: Required for MCTD diagnosis, can also be seen in SLE
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Anti-histone: drug-induced lupus
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Anti-centromere: limited scleroderma, a/w pulmonary HTN
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Anti-RNA polymerase III: increased risk of scleroderma renal disease
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Anti-neutrophil Cytoplasmic Antibodies (ANCA)¶
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Qualitative: p-ANCA, c-ANCA, negative, or indeterminate
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Quantitative titers: anti-proteinase 3 (PR3), anti-myeloperoxidase (MPO) IgG antibodies
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See vasculitis section for further details
C3 and C4¶
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Hypocomplementemia in active SLE (due to increased consumption)
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Complement may also be low in diseases that decreases the liver’s synthetic function
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↓ 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)¶
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Both tests are non-specific markers of inflammation
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CRP measures a specific acute phase protein made by the liver
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IL-6 dependent (pts anti-IL6 therapy will have falsely decreased CRP)
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Typically changes more rapidly than ESR as it is a direct measure of acute phase reactant
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ESR is the rate at which RBCs settle to the bottom of a test tube
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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
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Falsely low ESR: low fibrinogen states (DIC, HLH), sickle cell, polycythemia
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Creatinine Kinase (CK)¶
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CK can be elevated by vigorous exercise, rhabdomyolysis, endocrinopathy, cardiac disease, renal disease, malignancy, medication effect, neuromuscular disease, connective tissue disease
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Consider inflammatory myopathies if there is elevated CK and objective proximal muscle weakness
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Notably, CK is normal in polymyalgia rheumatica
Extended Myositis Panel¶
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Ordered as “Myositis extended Pnl-ARUP”; includes 19 separate Abs
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Can be sent when suspecting various forms of myositis such as dermatomyositis, polymyositis, anti-synthetase syndrome (ex- ILD work-up)
Cryoglobulins¶
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Cryoglobulins are immunoglobulins that spontaneously precipitate at low temperatures and become soluble again with rewarming
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Reported as qualitative (positive or negative) and quantitative (percentage = “cryocrit”)
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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;
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At VUMC can only be obtained at certain times M-F; lab & nursing staff can coordinate
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Cryoglobulins are classified into three types: Type I, II, and III
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Type I Cryoglobulins: Monoclonal immunoglobulins (IgM or IgG)
- A/w lymphoproliferative disorders (Waldenström’s, MM, CLL, B cell lymphomas)
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Types II and III are Mixed Cryoglobulins (they contain polyclonal components)
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Essentially all mixed cryoglobulinemias will be RF+ *
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Commonly associated with HCV (~90%); also CTD
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Type II: monoclonal Ig with RF activity against polyclonal Igs
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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
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Cryoglobulinemic vasculitis: small vessel vasculitis, vascular deposition of cryoprecipitates
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Skin most common: palpable purpura, usually in lower extremities (colder areas), immune-complex mediated leukocytoclastic vasculitis on biopsy
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Additional manifestations include: Arthralgias, peripheral motor or sensory neuropathy, sicca, glomerulonephritis (usually MPGN)
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