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Antinuclear antibody patterns Internal Medicine ,Rheumatology

OVERVIEW
• Antinuclear antibodies (ANA): autoantibodies directed against histones, double-stranded and single-stranded DNA, ribonucleoprotein (RNP) complexes, and other nuclear components.
• Indirect immunofluorescence assays detect antibodies that bind to various nuclear antigens, and are used to report the titer of the ANA and the pattern of nuclear staining of the ANA.
• Titers 1:40 are considered positive.
• Titers 1:320 are more likely to represent true-positive results.
• There are various staining patterns

ANA-pattern-ready.gif

STAINING PATTERNS
• Diffuse / homogeneous: antibodies to histone (see bubbles in glass “think of histone subunits floating in the glass”)
• Rim: antibodies to nuclear envelope proteins and to double-stranded (ds) DNA (see salt on the rim of the glass)
• Speckled: antibodies to Sm, RNP, Ro/SS-A, La/SS-B, and other antigens (see speckled particle in the glass)
• Nucleolar: associated with diffuse scleroderma
• Centromeric: highly specific for the CREST syndrome


ANTIBODIES TO HISTONE
• Drug induced lupus: Anti-histone antibodies are sensitive but nonspecific for drug-induced lupus
• Anti-histone antibody testing may be useful in patients with a positive ANA test and a history of exposure to medications associated with drug-induced lupus (i.e. procainamide, isoniazid, hydralazine).


ANTIBODIES TO DOUBLE-STRANDED DNA (dsDNA)
• Antibodies to dsDNA recognize its base pairs, its ribose-phosphate backbone, and the structure of its double helix
• Systemic Lupus Erythematous (SLE): High titers of anti-double-stranded DNA (anti-dsDNA) antibodies are highly specific SLE (present in 60% of patients with SLE)
• Antibodies to dsDNA should be measured when there is clinical suspicion of SLE and the ANA is positive
• Specificity of anti-dsDNA antibodies for SLE is 97% overall and approaches 100% when the antibody titer is high

ANTI-SMALL NUCLEAR RIBONUCLEOPROTEINS

• Anti-Sm (anti-Smith) antibodies: specific for SLE (20 - 30 % of SLE patients)
• Anti-U1 snRNP : SLE (30 - 40 %); myositis; esophageal hypomotility; sclerodactyly; Raynaud's phenomenon; arthralgias; arthritis; and mixed connective tissue disease (MCTD)
• Testing for anti-U1 snRNP should be limited to patients with a positive ANA test who are suspected of having SLE or MCTD


ANTI- Ro/SS-A and ANTI -La/SS-B
• Antibodies to La almost always occur in association with anti-Ro antibodies
• Anti-Ro/SS: Primary Sjögren's syndrome (SS); positive in 40-50%
• Anti-La : SLE (10 to 15 percent of patients); late-onset SLE; secondary Sjögren's syndrome; congenital complete heart block (90%);and neonatal lupus syndrome (70%)
• RNA-protein conjugates
• Ro and La refer to the antigen as localized to the cytoplasm
• SS-A and SS-B are nuclear antigens

ANTI-CENTROMERE
• Antibody to the kinetechore of chromosomes
• Scleroderma (22 – 36%)
• Raynaud's phenomenon
• CREST syndrome (15%)
• Primary biliary cirrhosis

September 25, 2006