Unifying Concepts

Clinical Laboratory Testing in the Rheumatic Diseases

The diagnosis of rheumatologic diseases is based on clinical information, blood and imaging tests, and in some cases on histology. Blood tests are useful in confirming clinically suspected diagnosis and monitoring the disease activity. The tests should be used as adjuncts to a comprehensive history and physical examination.

Acute-phase reactants
Acute-phase reactants are proteins whose plasma concentration increases (positive acute-phase proteins) or decreases (negative acute-phase proteins) by at least 25% during inflammatory states.
Positive Acute-Phase Reactants

  • Alpha1-antitrypsin
  • Ceruloplasmin
  • Complement components
  • Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
  • Ferritin
  • Fibrinogen
  • Haptoglobin
  • Serum amyloid A

Negative Acute-Phase Reactants

  • Albumin
  • Transferrin
  • Transthyretin

Antinuclear antibodies
Antinuclear antibodies (ANAs) directed against a variety of nuclear antigens have been detected in the serum of patients with many rheumatic and nonrheumatic diseases as well as in healthy persons.
Sensitivity and Specificity of Antinuclear Antibody in Various Connective Tissue Diseases

Disease Sensitivity (%) Specificity (%)
Systemic lupus erythematosus 93-95 57
Scleroderma 85 54
Polymyositis, dermatomyositis 61 63
Rheumatoid arthritis 41 56
Sjögren’s syndrome 48 52
Raynaud’s phenomenon 64 41
Juvenile chronic arthritis 57 39
Juvenile chronic arthritis with uveitis 80 53

There are different types of ANAs based on their target antigen, including single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA), nuclear histone and nonhistone nuclear proteins, and RNA protein complexes. The staining pattern seen on indirect immunofluorescence (IIF) gives some indication of the specificity of the antibodies in the sample.
Identifying Antinuclear Antibodies

Antigen Disease Association
Homogenous and Diffuse
DNA-histone complex (nucleosome) SLE (60%)
Drug-induced lupus (95%)
Peripheral Rim
RNA polymerase types II and III Systemic sclerosis
RNP MCTD (100%)
Scl-70 Systemic sclerosis (15%-70%)
Sm SLE (25%-30%)
SS-A Sjögren’s syndrome (8%-70%)
SLE (35%-40%)
SS-B Sjögren’s syndrome (14%-60%)
SLE (15%)
Nucleolar RNA, RNA polymerase 1 Systemic sclerosis
Pm-scl Polymyositis
CENP Limited scleroderma

MCTD, mixed connective tissue disease; SLE, systemic lupus erythematosus.

Rheumatoid factor
Rheumatoid factor (RF) autoantibodies are directed against the Fc portion of IgG. RF is detected in a wide variety of rheumatic and nonrheumatic conditions.
Rheumatic Conditions (Sensitivity)

  • Cryoglobulinemia (40%-100%)
  • Polymyositis and dermatomyositis (5%-10%)
  • Rheumatoid arthritis (50%-90%)
  • Sjögren’s syndrome (75%-95%)
  • Systemic lupus erythematosus (15%-35%)
  • Systemic sclerosis (20%-30%)

Nonrheumatic Conditions

  • Bacterial endocarditis
  • Infections
    • Hepatitis
    • Leprosy
    • Parasites
    • Syphilis
    • Tuberculosis
  • Malignancy
  • Pulmonary disease
    • Interstitial pulmonary fibrosis
    • Sarcoidosis
    • Silicosis
  • Primary biliary cirrhosis

Other Antibodies
Serum antibody testing may help distinguish some causes, such as:

  • Antiglomerular basement membrane antibodies: Goodpasture’s syndrome
  • Antibodies to double-stranded DNA and reduced serum complement levels: SLE
  • Antineutrophil cytoplasmic antibodies (ANCA) directed against proteinase-3 (PR3-ANCA or cytoplasmic ANCA [c-ANCA]): Wegener’s granulomatosis
  • Antineutrophil cytoplasmic antibodies directed against myeloperoxidase (MPO-ANCA, or perinuclear ANCA [p-ANCA]): Microscopic polyangiitis



  1. Morley JJ, Kushner I. Serum C-reactive protein levels in disease. Ann N Y Acad Sci. 1982, 389: 406-418. [Medline]
  2. Sheldon J. Laboratory testing in autoimmune rheumatic diseases. Best Pract Res Clin Rheumatol. 2004, 18: 249-269. [Medline]
  3. Hoffman GS, Specks U. Antineutrophil cytoplasmic antibodies. Arthritis Rheum. 1998, 41: 1521-1537. [Medline]
  4. Kerr GS, Fleisher TA, Hallahan CW, et al: Limited prognostic value of changes in antineutrophil cytoplasmic antibody titer in patients with Wegener’s granulomatosis. Arthritis Rheum. 1993, 36: 365-371. [Medline]
  5. Colglazier CL, Sutej PG. Laboratory testing in the rheumatic diseases: a practical review. South Med J. 2005 Feb;98(2):185-91. [Medline]


Created: Nov 1, 2010

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