What is the clinical significance and management of a positive Antinuclear Antibody (ANA) test showing a mitotic intercellular bridge pattern?

Mitotic Intercellular Bridge Pattern in ANA Testing

Pattern Recognition and Reporting

The mitotic intercellular bridge pattern is a specific mitotic apparatus pattern that should be reported when detected on ANA testing, as both nuclear and mitotic apparatus patterns are clinically relevant according to international consensus guidelines. 1

Clinical Significance

• The mitotic intercellular bridge pattern falls under the category of mitotic apparatus patterns, which should be reported and specified when possible during ANA testing 1
• This pattern represents antibodies targeting structures involved in cell division, specifically the intercellular bridge that forms between dividing cells during cytokinesis 1
• Mitotic patterns, including the mitotic spindle and intercellular bridge patterns, have been documented in approximately 0.89% of ANA-positive patients, with higher prevalence in females 2

Associated Clinical Conditions

• Systemic lupus erythematosus (SLE) and rheumatoid arthritis are the two most common autoimmune disorders associated with mitotic patterns, including mitotic spindle fibers and related mitotic apparatus antibodies 2
• The clinical relevance of uncommon ANA patterns like the mitotic intercellular bridge has not been as well established as common patterns (homogeneous, speckled), but they warrant reporting and clinical correlation 2

Recommended Management Approach

Initial Steps

• Report both the pattern (mitotic intercellular bridge) and the highest dilution demonstrating reactivity, as recommended by international consensus 1
• Document the specific mitotic apparatus pattern terminology in standardized format 1

Follow-up Testing Strategy

• If ANA is positive with a mitotic pattern, perform specific testing for anti-extractable nuclear antigen (ENA) antibodies depending on the titer and clinical setting 1
• If clinical suspicion for SLE exists, add anti-dsDNA antibody testing using either Crithidia luciliae immunofluorescence test (CLIFT) or Farr assay for high specificity 1
• Consider testing for specific ENAs including anti-Sm, anti-RNP, anti-SSA/Ro, and anti-SSB/La based on clinical presentation 1

Clinical Correlation Requirements

• The presence of a mitotic intercellular bridge pattern requires correlation with clinical symptoms and other laboratory findings, as ANA positivity alone is not diagnostic 3
• In cases of high clinical suspicion for specific autoimmune diseases, request determination of antibodies to specific ENAs regardless of the ANA result, as some autoantibodies may be present even with atypical patterns 1, 3

Important Caveats

• Uncommon mitotic patterns are not routinely reported by all clinical laboratories, so explicit communication with the laboratory about pattern recognition is essential 2
• The screening dilution of 1:160 on HEp-2 substrates provides optimal specificity (86.2%) while maintaining high sensitivity (95.8%) for systemic autoimmune rheumatic diseases 1, 3
• ANA testing is primarily for diagnostic purposes, not for monitoring disease progression once a diagnosis is established 3
• Up to 31.7% of healthy individuals may have positive ANA at 1:40 dilution, decreasing to 5.0% at 1:160, emphasizing the importance of titer interpretation 3

Reporting Standards

• The method used for ANA detection (indirect immunofluorescence assay on HEp-2 cells) should be included in the test result 1
• Results of subsequent specific antibody assays should be reported separately, including negative results 1
• Quantitative or semi-quantitative reporting is preferred for anti-dsDNA and anti-ENA antibodies 1