Clinical significance of antinuclear antibody staining patterns and associated autoantibodies
- Donald B Bloch, MD
Donald B Bloch, MD
- Associate Professor of Medicine
- Harvard Medical School
The indirect immunofluorescence (IIF) test for antinuclear antibodies (ANA), using the human cell line HEp-2 as substrate, is a commonly used assay to detect human autoantibodies. The results of ANA testing are reported in two parts: the titer of the antibodies and the staining pattern produced by the antibodies. The titer of the antibodies refers to the highest dilution of serum that produces visible fluorescence. The ANA pattern refers to the distribution of staining produced by autoantibodies reacting with antigens in the HEp-2 cell nucleus and cytoplasm. The measurement and clinical significance of ANA titer is reviewed elsewhere. (See "Measurement and clinical significance of antinuclear antibodies".)
Unfortunately, there is limited agreement among laboratories as to which ANA staining patterns should be identified and reported to clinicians. The patterns to be reported are determined by individual laboratory directors. The directors also choose from among HEp-2 cell slides prepared by different companies. These companies may use different fixative and permeabilization techniques. Depending on the preparation of the HEp-2 cell substrate, some autoantibodies may or may not be detected by IIF. The clinician should know which staining patterns are recognized and reported by their reference laboratory.
An international workshop attempted to arrive at a consensus on the nomenclature of ANA staining patterns . The participants suggested that there are 11 staining patterns that “must” be reported by all “competent-level” laboratories. An additional 22 ANA staining patterns should be reported by “expert-level” laboratories. Whether or not the recommendations of the workshop will become widely accepted remains to be determined.
This topic review will cover three broad categories of ANA staining patterns: nuclear, cell cycle-associated, and cytoplasmic. Within each of these categories, individual patterns will be defined and autoantibodies that produce the staining patterns will be identified. The disease associations of autoantibodies producing the staining patterns will be described as well as additional laboratory tests that may be used to further characterize the autoantibodies.
ANA STAINING PATTERNS INVOLVING THE NUCLEUS
●Definition – The homogenous antinuclear antibody (ANA) pattern refers to diffuse staining of the nucleus in resting cells. There is also diffuse staining of the chromosome region in dividing cells. The homogenous staining pattern was reported in 36 percent of more than 9200 ANA-positive serum samples tested at the University Hospitals in Leuven, Belgium .
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- ANA STAINING PATTERNS INVOLVING THE NUCLEUS
- Nuclear speckled
- - Fine speckled
- - Coarse speckled
- - Dense fine speckled pattern
- Nuclear dot staining patterns
- - Centromere
- - PML-Sp100 nuclear body
- - Cajal body
- Nuclear envelope
- - Nuclear envelope pattern
- - Nuclear pore complex pattern
- CELL CYCLE-ASSOCIATED STAINING PATTERNS
- Mitotic spindle apparatus
- - NuMA1 staining pattern
- - NuMA2 staining pattern
- CYTOPLASMIC STAINING PATTERNS
- Antimitochondrial antibody
- Cytoplasmic fine speckled
- Cytoskeletal staining
- Golgi apparatus
- Rods and rings