Rare Antinuclear Antibody Patterns: Relevance in Routine Laboratory Reporting

Abstract

Introduction: Uncommon patterns on Human Epithelial 2 (Hep 2) substrate during Antinuclear Antibody (ANA) screening by Indirect Immunofluorescence (IIF) microscopy are not routinely reported by many laboratories since their clinical relevance is not well established. Aim: To elucidate rare ANA patterns on Hep 2 and their possible association with clinical presentation. Materials and Methods: A retrospective study was conducted on ANA reports in the duration January 2021 to March 2022 at the Department of Laboratory Medicine, Dr. Sulaiman Al Habib Medical Group, Olaya Medical Complex, Riyadh, Saudi Arabia, to recognise rare ANA patterns. Gold standard method of IIF on Hep 2 was used for screening. Statistical evaluation was done to obtain frequencies of various ANA patterns. Those with frequency of less than 1% were classified as rare patterns. Results: Overall, 4207 consecutive ANA reports were evaluated out of which 1388 were positive and 210 (4.99%) demonstrated rare ANA patterns including nuclear, cytoplasmic and mitotic subtypes. Most commonly encountered among the rare ANA patterns was intercellular bridge (AC 27) with frequency of 0.78% (n=33). Systemic Lupus Erythematosus (SLE) (10/210) was the most often observed clinical association with rare cytoplasmic and mitotic patterns at titer ≥1:160. Conclusion: Uncommon ANA patterns may be useful in initial work-up of autoimmune illness hence, should be routinely reported. Further studies to enlighten the significance of these patterns, analogous antibodies could be of diagnostic relevance in autoimmune and other diseases.

Clinical Significance of Uncommon, Non-Clinical, and Novel Autoantibodies

“… 77 Interestingly, SLE was linked to rare cytoplasmic and mitotic cellular patterns mostly at autoantibody titer ≥1:160. 76 …”

“…27 Furthermore, intercellular bridge or midbody patterns may be also related to SSc, SLE, vasculitis, and cancers. 63,76 One preliminary study stated an elevated occurrence of liver disease in MSA-positive individuals. 77 Interestingly, SLE was linked to rare cytoplasmic and mitotic cellular patterns mostly at autoantibody titer ≥1:160.…”

“…77 Interestingly, SLE was linked to rare cytoplasmic and mitotic cellular patterns mostly at autoantibody titer ≥1:160. 76 The International Consensus on ANA Patterns states that the cytoplasmic and to a lesser extent the mitotic HEp-2 IFA staining patterns, are clinically important and should "demand dedicated follow-up testing in daily clinical practice". 66 Finally, it is important to note that the International Consensus on Standardized Nomenclature of HEp-2 cell staining patterns in IFA demands that autoantibodies detected in HEp-2 cells must be verified by supplementary monospecific assays.…”